1 15 6 https://www.nal.usda.gov/exhibits/speccoll/files/original/18e316bef07da71f9df02c5519c300e1.pdf 9cbfa08f7cf70f8ad0a01bd3e24864b4 PDF Text Text Item D Number °5598 D Not Scanned Lathrop, George D. Epidemiology Division, Data Sciences, Division, USAF S Report/ArtldO TitlB Pr °iect Ranch Hand II: An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides, Baseline Mortality Study Results Journal/Book Title Year 1983 Month/Day June3 Color ° D Number of Images ° DOSCrlptOD NOtQS Also included are summaries of the baseline mortality study results (June 30,1983), the baseline morbidity study results (February 24, 1984), and the mortality update (December 10, 1984. Alvin L. Young filed these documents together with others in a folder labeled, "Agent Orange Working Group Science Panel, Current Folder." Tuesday, March 19, 2002 Page 5598 of 5611 �I PROJECT RANCH HAND II AN EPIDEMIOLOGIC INVESTIGATION OF HEALTH EFFECTS IN AIR FORCE PERSONNEL FOLLOWING EXPOSURE TO HERBICIDES BASELINE MORTALITY STUDY RESULTS 30 JUNE 1983 Prepared for: The Surgeon General United States Air Force Washington, D.C. 20314 Approved for public release; distribution unlimited EPIDEMIOLOGY DIVISION DATA SCIENCES DIVISION USAF SCHOOL OF AEROSPACE MEDICINE (AFSC) BROOKS AIR FORCE BASE, TEXAS 78235 �Unclassified SECURITY CLASSIFICATION OF THIS PAGE (When DatafEntered)i REPORT DOCUMENTATION PAGE 1. REPORT NUMBER «. Tl T L t 2. GOVT ACCESSION NO READ INSTRUCTIONS BEFORE COMPLETING FORM 3. RECIPIENT'S CATALOG NUMBER 5. TYPK OF REPORT A PKRIon C O V K R I n («"</ S AN EPIDEMIOLOGIC INVESTIGATION OF HEALTH EFFECTS IN AIR FORCE PERSONNEL FOLLOWING EXPOSURE TO HERBICIDES: BASELINE MORTALITY STUDY RESULTS Annual Report, Initial Report 6. PERFORMING OHG, REPORT NUMBER 7. AUTHORfs) 6. CONTRACT OR GRANT NUMBERS; 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT, PROJECT, TASK AREA ft WORK UNIT NUMBERS George D. Lathrop, Colonel, USAF, MC; Patricia M, Moynahan; Colonel, USAF, NC; Richard A. Albanesei M.D.; William H. Wolfe, Lt Colonel, USAF, MC USAF School of Aerospace Medicine (EK) Aerospace Medical Division (AFSC) Brooks Air Force Base, Texas 78235 11. CONTROLLING OFFICE NAME AND ADDRESS The Surgeon General United States Air Force Washington, D.C. 20311* 1Z. REPORT DATE U. MONITORING AGENCY N'AME ft ADDRESSfff dltterent Irom Controlling Ottice) 15. SECURITY CLASS, (ol thti report) 30 June 1983 13. NUMBER OF PAGES 61 Unclassified I5«. DECLASSIFI CATION/DOWN GRADING SCHEDULE 16. DISTRIBUTION STATEMENT (oi this Report) Approved for public release; distribution unlimited. 17. DISTRIBUTION STATEMENT (of the abstract entered In Block 20. It different from Report) IB. SUPPLEMENTARY NOTES 19. KEY WORDS (Continue on reverse side H necessary and Identity by block number) Epidemiologic investigation Air Force Health Study Mortality study RANCH HAND Matched cohort design Nonconcurrent prospective design '0. ABSTRACT (Continue on reverse side if necessary and identify by block number) In 1979 the United States Air Force (USAF) made the commitment to Congress and to the White House to conduct an epidemiologic study of the possible health effects from chemical exposure in Air Force personnel who conducted aerial herbicide dissemination missions in Vietnam (Operation RANCH HAND). The purpose of this epidemiologic investigation is to determine whether long-term health effects exist and can be attributed to occupational exposure to herbicides. This study uses a matched cohort design in a nonconcurrent prospective setting, incorporating mortality, morbidity, and follow-up studle; DD , F O R M73 <|.|« EDITION OF 1 NOV 65 IS OBSOLETE JAN WO Unclassified 7 SECURITY CLASSIFICATION OF THIS PAGE (When Data Entered) �unclassified SECURITY CLASSIFICATION OF THIS PAGE(HTi«n Data Entertd) The purpose of this report is to present the baseline mortality study results. As of December 31» 1982, 50 Ranch Hand and 250 comparison subjects had died (certified on/before April 27, 1983). Data analysis showed that the mortality experience of the Ranch Hand group is nearly identical to that of this comparison group. However, this mortality report can in no way be regarded as conclusively negative since the study population may not yet have reached the latency period. Subsequent mortality reports will include additional anaylses and will be updated annually for the next 20 years. Unclassified S E C U R I T Y C L A S S I F I C A T I O N OF T U I ' PAGEfWien Dalf Entered) �EXECUTIVE SUMMARY Baseline Mortality Study The Ranch Hand II epidemiclogic study uses a matched cohort design in a nonconcurrent prospective setting, incorporating mortality, morbidity, and follow-up studies. The purpose of this report is to present the baseline mortality study results. Since 1979, a detailed population ascertainment process has enumerated a total of 1269 Ranch Hand personnel who served in Vietnam during the period of 1962-1971. As described in the protocol, this total is believed to comprise, the entire exposed study population. The eligibility of each Ranch Hander was verified by a hand review of his personnel record, A comparison group was formed by identifying all individuals assigned to selected Air Force organizational units with a mission of flying cargo to, from, and in Vietnam during the same period. All Ranch Hand and comparison subjects designated as killed in action were removed from the study population. By a computerized nearest neighbor selection process, up to 10 comparison individuals were matched to each Ranch Hander by job category, race, and age to the closest month of birth. A hand record review of the matched comparison sets revealed that on the average, 8.2 comparison individuals were fully suitable for study. From each matched comparison set, five individuals were randomly selected for the mortality study, yielding a 1:5 design. Every Ranch Hander and his set of comparisons will be the subjects of annual mortality updates throughout the entire 20 years of the follow-up study so that emerging mortality patterns or disease clusters may be detected with maximal sensitivity. Each living Ranch Hander and his first and willing comparison match were selected to participate in a comprehensive physical examination and an in-home interview; the results of this study will be presented in a subsequent report in late 1983. A mortality determination on 1,247 Ranch Handers and 6,171 comparison subjects was made, sequentially using the data sources of the Air Force, Veterans Administration, Social Security Administration, Internal Revenue Service, and personal contact efforts. As of December 31, 1982, 50 Ranch Hand and 250 comparison subjects had died (certified on/before April 27, 1983). Death certificates were obtained on all 300 deceased subjects and were coded by an Air Force nosologist (ICD, 9th ED). All codings were verified by the National Center for Health Statistics. Autopsy results are currently being sought for future analyses. Statistical analyses of noncause specific death emphasized survival curve estimates, linear rank procedures, relative risk estimates, and standardized mortality ratios (SMRs). Cause specific analyses were limited to relative risk estimates because of small cell sizes. In addition to these approaches, three other data bases were contrasted to the Ranch Hand population, where possible; the 1978 US White Male Mortality experience, the 1978 Department of Defense (DoD) Nondisability Retired Life Table, and the mortality experience of the West Point Class of 1956. These additional comparison groups have substantial comparability or sample size limitations, rendering conclusions to the weakest order. Analyses with these "external" comparison groups were accomplished to crudely define the healthy worker effect and to determine if the Ranch Hand group mortality was drastically out of line with that of other military populations. �Data analysis showed that the mortality experience of the Parch Hand group is nearly identical to that of the comparison group. Analyses showed that, officers are living longer than enlisted personnel in both Ranch Hand and comparison groups. This difference between officers and enlisted personnel was statistically significant in the comparison group whereas it was not in the Ranch Hand cohort. A contrast of the Ranch Hand and comparison group to the 1978 DoD Life Table showed significantly less mortality for Ranch Hand officers, comparison officers and comparison enlisted men, however, there was not a statistically significant favorable mortality rate for Ranch Hand enlisted personnel. This pattern of mortality was also seen in a contrast of the Ranch Hand and comparison groups to the 1978 U.B. white male mortality experience. That is, highly favorable mortality differentials for Ranch Hand officers, comparison officers and comparison enlisted personnel were observed, but not for Ranch Hand enlisted. This trend is consistent with the self perceptions of differential herbicide exposures reported by many of the Ranch Hand subjects. The reason(s) for these observations are speculative at present, but may include the related items of sample size, socioeconomic differences, access to medical care, and health education and possible herbicide effects. Cause specific analyses were statistically nonsignificant. The Ranch Handers showed a relative paucity of overall cancer but an excess of digestive disorder deaths, both statistically nonsignificant. No soft tissue sarcoma deaths were detected in either group. Analyses of both the Ranch Hand and the comparison groups to the 1978 US White male mortality experience showed highly significant favorable findings. Most of these differences are speculatively attributed to the healthy worker effect. A contrast of the Ranch Hand and comparison groups to the 1978 DoD Life Table showed significantly less mortality for Ranch Hand officers and comparison officers and enlisted men. The West Point comparison showed nonsignificant SMRs of 0.530 and 0.778 for the Ranch Hand officers and the comparison group officers, respectively. Overall, the limitations of the statistical power calculations in most of these analyses were substantial in most analyses due to 1) the low mortality rate (4%) in the Ranch Hand and comparison groups to date, 2) the inherently small group of Ranch Handers (as described in the study protocol), and 3) the observed relative risks which approached unity in most categories. This baseline mortality report can in no way be regarded as conclusively negative because this small, young, and relatively healthy cohort may not have yet reached the latency period wherein attributable fatal disease might be expected and detected within limited power boundaries of this study. Future commitments for the annual mortality updates include detailed covariate analyses for disease risk factors, herbicide exposure, and confounding industrial chemical exposures. Further, subsequent morbidity reports will include full spectrum, disease specific analyses, e.g., cancer (fatal, ongoing, cured) in an effort to enhance study sensitivity to emerging herbicide effects, if they occur. ii �PREFACE In October 1978, the United States Air Force (USAF) Surgeon General made the commitment to the Congress and to the White House to conduct an epidemiologic study of the possible adverse health effects arising from the herbicide exposure of Air Force personnel who conducted aerial dissemination missions in Vietnam (Operation Ranch Hand). The purpose of this epidemiologic investigation is to determine whether long-term adverse health effects exist and whether they can be attributed to occupational exposure to herbicides and their contaminants. The study protocol (1) for this effort incorporates a matched cohort design placed in a nonconcurrent prospective setting. The study approach includes mortality, morbidity, and follow-up elements linked tightly in time, in order to produce the most data in the shortest period of time. The study addresses the question: Has there been, or are there currently, or will there be any adverse health effects among former Ranch Hand personnel caused by repeated occupational exposure to 2,4,5-T containing herbicides and the contaminant, TCDD? At the request of the Principal Investigators (see Appendix I) the study protocol was extensively and independently peer reviewed. The review agencies included: The University of Texas School of Public Health, Houston Texas; the USAF Scientific Advisory Board; the Armed Forces Epidetniological Board; and the National Research Council of the National Academy of Sciences. In 1980, the Science Panel of the Agent Orange Working Group was created as an additional peer review agency. This group, redesignated as the Advisory Committee on Special Studies Relating to the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants, has consented to the oversight responsibility of the Ranch Hand study and continues to monitor the conduct of this epidemiologic investigation (see Appendix II). The approved and official protocol for this effort is available to the public through the National Technical Information Services, 5285 Port Royal Road, Springfield, Virginia 22161. The Ranch Hand II Study protocol heralds the suboptimal statistical power of the mortality study. The mortality study was motivated by the desire to use a full spectrum epidemiologic approach to the herbicide question. Additionally, the investigators were scientifically obliged to pursue the mortality study because of previous and emerging studies (some with small sample sizes) which suggested the possibility of a soft tissue sarcoma end point (2,3,4). Within the inherent sample size limitation of the Ranch Hand population, detection of such a rare condition will be missed unless there is marked case clustering and correspondingly high relative risks. Also, because of sample size limitations as well as the myriad of proposed clinical end points, a case-control design was not entertained. The investigators have attempted to enhance statistical power and analytic sensitivity where possible by using ] a large comparison group, 2) precise ) matching procedures, 3) annual mortality updates, A) mortality-morbidity linkages, 5) a lengthy follow-up study, 6) external comparison groups, and 7) state-of-the-art statistical methodology. A final assessment of overall mortality must necessarily await substantially more data and covariate approaches to identify and isolate unusual emerging mortality patterns, if they occur. iii �This report is primarily directed to individuals with statistical and epidemiologic backgrounds. It also assumes that the reader has a familiarity with the herblcide/dioxin issue and a detailed 'knowledge of the protocol of the Air Force study. In the interest of brevity, the reader is referred to the protocol published as US Air Force School of Aerospace Medicine Technical Report 82-44. iv �Page Executive Summary Preface ............................. ............................... Table of Contents Chapter I. . . .iii ............................. THE MORTALITY STUDY DESIGN 1 . The Study Population 2. The Mortality Population Chapter II. i .......................... ........................ THE MORTALITY DETERMINATION PROCESS 1. Introduction ....................... . ...... 2. United States Air Force Data Sources .................. 3. Veterans Administration Death Beneficiary Identification and Record Location Subsystem ........................... 1. Other Governmental Data Sources .................... 5. Morbidity Population Tracking ..................... 6. Receipt and Coding of Death Certificates ................ 7. Results ................... ............. Chapter III. RANCH HAND VERSUS COMPARISON GROUP ANALYSES 1. Introduction v 1 1 2 4 4 4 6 6 6 7 8 9 9 2. Overall Comparisons 9 3. Noncause Specific Occupational Comparisons 15 4. 17 Cause Specific Ranch Hand Versus Comparison Mortality Chapter IV. NONCAUSE SPECIFIC COMPARISONS WITH EXTERNAL POPULATIONS 1. Background and Motivation 2. Adjustment Difficulties A. Adjustment for Calendar Year of Death 20 20 20 20 B. Adjustment for Military Status (Active Duty, Separated, Retired). . 20 C. Adjustment for Selection D. Adjustment for Branch of Service 21 21 �3. Comparisons with 1978 DoD Life Tables ................. 4. Comparisons with U.S. 1978 White Male Life Table ......... 21 . . . 24 Chapter V. COMPARISONS WITH THE WEST POINT STUDY GROUP 1 . Background and Motivation ..... . ................. 2. Noncause Specific Comparisons of Ranch Hand and Comparison Subgroups with the West Point Study Group .................... 3. Cause Specific Comparisons ....................... Chapter VI. STATISTICAL ASPECTS 1. 2. 3. 4. 5. 6. 28 28 31 34 Purpose ................................ 3^ Survival Curve Estimates and Confidence Bands ............. 34 Linear Rank Procedures ......................... 35 Relative Risk Estimation ....... . ............ .... 36 Indirect Standardization ........... . ............ 37 Comparing Observed Life Table Data with a Known Survival Curve. .... 37 Chapter VII. CONCLUSION 1. 2. 3. 4. 5. 28 39 Introduction .................. . ...... . . . . . 39 Internal Comparison Group . . . . . . . ..... . .......... 42 External Comparisons. . . . . ......... . . . . . . . . . . . . 42 Power Considerations. . . . ....... . . . . . . . . ....... 42 Consistency Patterns ...... . ................... 43 APPENDICES I. Ranch Hand II Principal Investigators, Coinvestigators, Contributors, and Management Personnel 45 II. Advisory Committee on Special Studies Relating to the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants . . 47 III. Matching Results in the Mortality Population 48 IV. Year of Birth, Occupational and Race Specific Mortality 51 V. The Extended E j i gou-McHugh Relative Risk Estimator ..53 VI. Survival Curves and Confidence Bands for Ranch Hand and Comparison Subgroups 54 REFERENCES 59 VI �Chapter I THE MORTALITY STUDY DESIGN 1. The Study Population The exposed study population, termed "Ranch Hand", was defined as those individuals who were formally assigned to the USAF organizations responsible for the aerial dissemination of herbicides and insecticides in the Republic of Vietnam from 1962 to 1971. These individuals were identified from historical data sources at the National Personnel Records Center (NPRC), St. Louis, Missouri and the USAF Human Resources Laboratory, Brooks Air Force Base, Texas. A total of 1,269 Ranch Hand personnel were eventually identified through this process. The comparison population was defined as those individuals who were assigned to a variety of cargo mission organizations throughout Southeast Asia during the same time period. Cargo mission aircrew members and support personnel were selected because of sufficient population size, similar training and military background experiences, and psychologic similarities to the Ranch Hand group. The comparison population was not occupationally exposed to herbicides or insecticides in the Republic of Vietnam. Identification of this population was completed using the same historical data sources as were used with the Ranch Hand population; 2*1,971 individuals were so identified. In preparation for matching the study and comparison populations, all subjects killed in action (KIA) were removed from the data base. The rationale for this action is the assumption that combat death in the Ranch Hand group was not caused by the immediate effects of herbicide exposure; KIA's were removed from the comparison group for comparability purposes. A KIA analysis will be performed in a subsequent report. The Ranch Hand KIA subgroup, numbering 22 individuals, although not matched, was maintained in the data base but was deleted from the mortality analysis, leaving 12M7 Ranch Hand subjects. The Ranch Hand population was matched to the comparison population with an iterative nearest-neighbor computer program (1). Up to 10 comparison subjects were matched to each Ranch Hander by year of birth, race (Black versus non-Black), and occupational category (officer pilot, navigator and other; enlisted flight, engineer and other), thus creating matched sets of one study subject and up to 10 comparison subjects. All subjects are males. The mean age of the study subjects is *J5 years. Following the original match, the majority of Ranch Handers had 10 comparisons. The exceptions were the group of non-Black pilots who had a mean of only 9.5 comparisons per exposed subject due to the extreme ages of several individuals, and the strata of Black pilots and other Black officers who only had means of 2.7 and 5.0, respectively. In December 1981, the USAF Principal Investigators learned that several morbidity study comparison subjects had reported no experience in Southeast Asia, suggesting that overselection of the comparison population had occurred (1). Manual review of the comparison subjects' military personnel records revealed that 18 percent of the 12,193 comparison individuals in the original match were ineligible for study. The inadvertent inclusion of several non-Southeast Asia organizations resulted in the selection of these inappropriate individuals. These ineligible subjects were found to be randomly distributed throughout the matched sets and were removed from the study. Following the removal of the �ineligible subjects, the study was reduced to a 1:8 design. Also during this period, five Ranch Hand subjects were identified through personnel record sources and Veterans Administration Education Benefits and Financial Records. These five individuals had not been identified earlier because the majority of their military personnel records had been destroyed in a fire at the NPRC in St. Louis. Three of these five were newly found Ranch Handers and two were comparisons subsequently identified as Ranch Handers. No attempt was made to match comparisons to these five new Ranch Handers. During the removal of ineligible subjects, one Ranch Hander, a Black officer pilot, lost his only comparison and remains unmatched, giving a total of six unmatched Ranch Handers. All six of these unmatched Ranch Handers are included in the morbidity and mortality studies. They were used in the analyses where appropriate, in order to improve statistical power. 2. The Mortality Population Five comparisons per exposed subject were considered more than adequate for mortality analyses; this estimate has recently been verified under a multiplicative model by Breslow, et al. (5). Up to five comparisons in each matched set, were identified from the 1:8 cohort as the mortality comparisons. Since the positions of the individuals in the matched sets had already been randomized in the data file, the selection of the first five positions in each matched set array for membership in the mortality comparison resulted in a random selection of the mortality comparison cohort. If a Ranch Hander had at least one but no more than five comparisons after removal of the ineligibles, then all of his matched set were used in the mortality component of this study. The mortality population is, therefore, defined as the 1241 matched Ranch Handers and their randomly chosen mortality comparisons (6171 individuals) and the six unmatched Ranch Handers. Table 1 summarizes the mortality population by occupational category and race. Here, and elsewhere in this report, non-Black is defined as Caucasian, Mexican or Oriental. Table 1 MORTALITY POPULATION SUMMARY BY OCCUPATION AND RACE Occupation, Race Officer-Pilot, Non-Black Officer-Pilot, Black Ranch Hand Counts Comparison 349 6 1740 13 Officer-Navigator, Non-Black Officer-Navigator, Black 80 2 390 10 Officer-Other, Non-Black Officer-Other, Black 25 1 123 2 189 15 935 75 528 52_ 1247 2628 255 6171 Enlisted-Fit Eng, Non-Black Enlisted-Fit Eng, Black Enlisted-Other, Non-Black Enlisted-Other, Black �The overall match ratio, 6171/1247=4.95, reflects the lack of suitable controls in some strata, the subsequent removal of ineligible comparisons and the addition of five unmatched Ranch Handers. A detailed description of the matching results is given in Appendix III. Those Ranch Handers having fewer than five matched mortality controls are summarized in Table 2. Table 2 RANCH HAND SUBJECTS WITH LESS THAN FIVE COMPARISON SUBJECTS Counts Occupation, Race Officer-Pilot, Non-Black Ranch Hand Comparisons-^ Notes Officer-Navigator, Non-Black Officer-Other, Non-Black Officer-Other, Black Enlisted-Fit Eng, Non-Black Enlisted-Other, Non-Black Enlisted-Other, Black 2 3 1 1 0 1 1 2 1 Officer-Pilot, Black 1 1 1 2 3 1 1 1 2 2 1 2 12 1 0 4 2 0 J» 0 2 1 1 2 1 2 27 Note 1. Lack of suitable comparison subject or loss due to ineligibility. Note 2. New Ranch Hander, no attempt to match. Note 3. Comparisons per Ranch Hander 1 �Chapter II THE MORTALITY DETERMINATION PROCESS 1. Introduction The mortality status of the Ranch Hand group and their mortality comparisons are, and will continue to be, ascertained using four major data sources: USAF, Veterans Administration (VA), other Governmental and morbidity population tracking. The mortality determination process using these data sources is presented in Figure 1. Figure 1. RANCH HAND II MORTALITY DETERMINATION ALGORITHM RANCH HAND II MORTALITY STUDY ENTIRE STUDY POPULATION 1 U.S. AIR FORCE ACTIVE DUTY ^ RETIRED PERSONNEL CENTER ACCOUNTING t FIKAHM CASUALTY BRANCH WSC FACILITY IHFUR. BENEFICIARY^ DIED ACTIVE DIED AF HQSP^ ALL I i DEATH BFJiEFIT ' SOCIAI SECURITY AOVIS. CLOSED BY DEATH INTEMIAL RLTOUE ACTIVE ACCT. CLOSED BY DEATH 3E 5 JE 3 X Ut ALIVE f ,__ TRACKING CONTACT UTTER LOWS HARRIS DEAD EAO - REOtiESf DEATH CERTIFICATE VETERml'S ADMIN. (GIRLS, SGI.I) The entire study population was matched or checked against the first three sections of this algorithm while only the morbidity population was contacted and tracked. A description of the data sources within the algorithm follows. 2. United States Air Force Data Sources The USAF data sources include the USAF Military Personnel Center (MFC) records, the USAF Accounting and Finance Center records, and the USAF Medical �Service Center Facility Use Data. The USAF MFC records include the individual's military personnel record and the data accumulated by the Casualty Branch of the MFC. Individual military personnel records are created at the time of induction into the USAF, and reflect a chronological history of the individual's military career. Epidemiologically, these records are an invaluable data source as they can be used for the development of occupational histories, identification of race, sex, and date of birth as well as for location of personnel, and for determining vital status. Hard copy records of these data are maintained at the individual's base of assignment while on active duty; a computer copy of these records is maintained at the USAF military personnel center, Randolph AFB, Texas. Following retirement and/or separation from the USAF, these records are forwarded to the National Personnel Records Center (NPRC), St Louis, Missouri, the record repository for all military personnel records. They are indexed by Social Security Account Number or Air Force Serial Number at the NPRC. If an individual should die while on active duty, after retirement, or within 120 days of separation from active duty, it is the responsibility of the Casualty Branch of the USAF Military Personnel Center to update the hard copy military personnel record and the MFC computer data base and to inform the USAF Accounting and Finance Center of this fact. At the same time, USAF MFC personnel initiate a copy of the USAF Form 1312, Report of Retired Casualty, or Department of Defense DD Form 1300, Report of Casualty. The selection of the appropriate form is based on the current status of the individual concerned. The DD Form 1300 also clarifies an individual's casualty status which can be either battle or nonbattle. Copies of the appropriate death form are sent to appropriate agencies while the original is placed in the individual's military personnel record. Since the initial review of military personnel records, a system has been established with the Casualty Branch of the Military Personnel Center wherein all active duty and retired death forms are forwarded monthly to the Occupational Epidemiology Section of the USAF School of Aerospace Medicine Epidemiology Division. In this way, the mortality status of all active duty and retired study subjects is systematically determined on a continuing basis. The USAF Accounting and Finance Center data base was used as a resource to update individual Air Force serial numbers to Social Security numbers. The Social Security number is required for all other aspects of the mortality algorithm. The Air Force Medical Service Center (AFMSC) Facility Use Data is a computer data base containing information regarding all active duty and retired deaths that .occur in Department of Defense (DOD) Medical Facilities. This data base identified no additional deaths in the mortality population, but did verify the deaths known to have occurred in DOD hospitals. In addition to the USAF data bases, the Ranch Hand Association, a reunion association of approximately 850 Ranch Handers, has contributed to the success of this study. This group has assisted the Principal Investigators in the ascertainment of the exposed population, and in the determination of the current location and the mortality status of the group. The association contacts all of its members yearly through newsletters and provides updated information to the Air Force investigators. �3. Veterans Administration Death Beneficiary Identification and Record Location Subsystem The Beneficiary Identification and Record Locator Subsystem (BIRLS) is a Veterans Administration data base generated by the Veterans Administration for determination of funeral allowance. If the family of the deceased informs the funeral director that the deceased served in the US military, the funeral director submits the required data to the Veterans Administration. In January 1981, August 1982,and January 1983,the BIRLS data base was searched for Ranch Hand and comparison deaths. In addition to these searches, the Department for Veterans Benefits, Veterans Administration, coordinated the gathering of death certificates from VA regional offices. 4. Other Governmental Data Sources A. Internal Revenue Service Public Law 96-126, Section 502, 28 November 1979, authorized the use of Internal Revenue Service (IRS) addresses for individuals who had been exposed to occupational hazards in order to determine the status of their health. The National Institute for Occupational Safety and Health (NIOSH) coordinated the USAF requests for these IRS addresses. This system is based on the address shown on individual tax returns and is corrected once a year. The addresses are verified by NIOSH through use of a post card mailed to the post office responsible for the individual's mail delivery. NIOSH assumes that the individual is alive if he files a tax return and if the verification scheme confirms his address for mail delivery. The IRS assumes an individual ia dead if the individual is so reported on a joint tax return. The IRS data base search provides an incomplete mortality determination, however, since absence of an individual tax return does not necessarily imply death of that individual. B. Social Security Administration The Social Security Administration (SSA) is a source of mortality information based on data maintained by the Office of Remuneration and Earnings. The basis for this data is employer-reported earnings. The SSA assumes that an individual is living if there is no indication of death on the individuals record and earnings are recorded for the last calendar year or retirement, disability, black lung or supplemental security income payments are being made. The SSA did inform us that they do not conduct an exhaustive search, and all deaths are not necessarily reported to SSA. Therefore, this mortality information may not be complete. 5. Morbidity Population Tracking Individual tracking techniques apply only to the morbidity population, defined as those selected and compliant to questionnaire. The morbidity population for this effort is defined as all Ranch Handers and their morbidity comparisons. The morbidity comparisons are, in general, also mortality comparisons. The selection procedure for the morbidity study is presented in Figure 2. �Figure 2. SELECTION PROCEDURE FOR THE QUESTIONNAIRE, PHYSICAL EXAMINATION, AND FOLLOW-UP STUDY Living Ranch Hand Comparison Individuals Randomly Ordered Mortality Comparisons r -A—"^ r~ 1 t i 1 11 +-* #* 1:1 Morbidity Match + Dead - Unwilling * Volunteer ** Replacement candidates In this figure, the first randomly ordered comparison was found to be dead. The second was contacted but was unwilling to participate and the third volunteered to participate in the questionnaire component of the morbidity effort. This contacting process for the morbidity effort was the final step in the baseline mortality determination. The original contact was made by certified mail. Each Ranch Hander and a random living comparison were sent an introductory letter and fact sheet signed by the USAF Surgeon General. A Louis Harris and Associates (LHA) interviewer then accomplished an in-home interview. LHA identified two Ranch Handers and nine comparisons who could not be located. All eleven unlocatable subjects were assumed living and remain included in the mortality study. 6. Receipt and Coding of Death Certificates Death certificates were ordered from the vital statistics department of the appropriate state, trust territory, or foreign country. Death certificates or their equivalent were obtained on all appropriate subjects. All death certificates were coded by two individuals, trained by the National Center for Health Statistics (NCHS) in underlying and multiple cause of death coding procedures, using the International Classification of Diseases, Ninth Edition (1977) coding system. Classification of the underlying cause of death was in accordance with NCHS decision tables. Each coder independently classified the underlying and multiple, causes of death and gave the coding worksheet, with each corresponding death certificate, to the coding supervisor, a trained nosologist, for reconciliation. Following reconciliation, one of the coders placed the death code information, by computer terminal, in the death certificate mortality file via a blind verification program designed to mimic the NCHS underlying multiple cause of death coding sheet. At the �conclusion of this initial input of the death codes, a copy of the death certificate was forwarded to NCHS for further validation. The NCHS returned coded death certificates, which were then compared with the Air Force classification. Discordances were resolved in cooperation with NCHS and entered into the data base. 7. Results Chapter II has reviewed the comprehensive, cohesive, sequential ascertainment process of death in the study populations. This process has resulted in the identification of 50 dead Ranch Hand subjects and 250 dead comparison subjects. Although it is understood that early differential ascertainment occurred in the Ranch Hand members (because of detailed knowledge of the study group), it is judged that the overall comprehensive ascertainment process is currently balanced with respect to the two groups. Table 3 and Appendix IV contain summary counts by age, job, and race category for all Ranch Handers and their mortality comparisons; these counts reflect mortality as of 31 December 1982, as known on 27 April 1983. In the stratified analyses, the term "at risk" is defined as simply the number of subjects within a specific stratum, and in life table analyses, as the number of subjects entering a specific age bracket. The term "rate" is the proportion of those individuals "at risk" who are dead. Table 3 OCCUPATIONAL AND RACE SPECIFIC MORTALITY Race Occupation Non-Black Officer-pilot Officer-navigator Officer-other Enlisted-fit eng Enlisted-other Black Officer-pilot Officer-navigator Officer-other Enlisted-fit eng Enlisted-other TOTAL Ranch Hand At Risk Dead Rate Comparisons At Risk Dead Rate 3*»9 80 25 189 528 12 2 1 6 25 .03* .025 .040 .032 .047 1740 390 123 935 2628 72 13 3 46 97 .041 .033 .024 .049 .037 6 0 0 0 2 2 50 .000 .000 .000 .133 .038 .040 13 10 2 75 255 6171 0 0 0 9 10 250 .000 .000 .000 .120 .039 .041 2 1 15 52 1247 �Chapter III RANCH HAND VERSUS COMPARISON GROUP ANALYSES 1. Introduction Overall survival comparisons, without regard to cause of death, were made via survival curve estimation, linear rank procedures, relative risk estimation and standardized mortality ratios. Survival curves were estimated and plotted using the method of Kaplan and Meier (6); 95% confidence bands (7) for each survival curve estimate were also plotted on each graph. Linear rank testing was carried out using the logrank test and Prentice's censored data extension of the Wilcoxon test (8). All linear rank tests were carried out with matched sets merged when Ranch Hands differed by less than one year relative to date of birth, within each stratum of job and race (9). These merged matched sets were regarded as separate strata for testing purposes (9, 10, 11). Relative risk estimates and confidence intervals were computed using an extension of the method of Ejigou and McHugh (12) to variable length, one-to-many matched sets (see Appendix V). Here, due to the one-to-many limitation of the algorithm, matched sets were not merged as when testing procedures were performed. Standardized mortality ratios and associated tests and plots were carried out as in Gail (13). These analyses are fully adjusted for the matching variables, age, race and occupation, but are unadjusted for other variables of interest, such as length of time in Vietnam or Southeast Asia, herbicide dose, time since exposure, time in active duty military, and other medical or occupational risk factors. Some of these variables, such as herbicide dose and time since exposure will be adjusted for in the next analyses, after such data become available. In particular, latency analyses cannot be undertaken at this time but will be included in the next mortality report. In these analyses, we have used summary statistics for which underlying modeling assumptions can be tested. For this reason, we have used the Breslow-Day (13) approach to SMR calculation, rather than the more traditional person-years method. A detailed explanation of this choice is given in Chapter VI. 2. Overall Comparisons Survival time in these analyses was regarded as independent of censorship, if any, and was taken to be age at death. All subjects not certifiably dead, as of 31 December 1982, at the time of analysis, were considered censored at their age on that date. Contact has been lost with two Ranch Handers and nine comparisons as described in Chapter II, but these are not assumed lost to follow-up for the purpose of mortality determination. They are assumed to have been alive on 31 December 1982. With this assumption, no subjects were lost to mortality follow-up before 31 December 1982 in this study. Ranch Hand and comparison group survival curve estimates and their associated 95% confidence bands are shown in Figure 3 and Appendix VI for the five groups: pooled, officers, enlisted, flying and ground personnel, as defined in Table 4. The curves for the pooled groups are shown in Figure 3 with the 95% confidence interval bands deleted in the interest of legibility, but they are included in the group1 specific curves in Appendix VI. Review of �Ranch Hand operations has strongly suggested that Ranch Hand enlisted personnel were more heavily exposed to herbicide than Ranch Hand officers. Further, there is a perception of possible exposure differential between flying and ground Ranch Hand personnel. These notions prompted the above groupings and analyses seen in this and subsequent chapters. Analyses of latency are not possible at this time due to the as yet incomplete nature of the military service data base. These analyses will be performed after the hand review of military tour records has been completed. Figure 3 SURVIVAL CURVE ESTIMATES FOR POOLED RANCH HANDERS AND COMPARISON SUBJECTS 1 0.9 0.8 Z 0.7 t—i > > 0,6 a: co 0.5 0 « * 0.4 •-• 0.3 0.2 0-1 0 R - RANCH HAND C - COMPARISON 10 20 30 YEflRS 70 �Table 4 GROUP DEFINITIONS Group Definition Officer Enlisted Officer-pilot, navigator, other Enlisted-flight engineer, other Flying Officer-pilot, navigator Enlisted-flight engineer Ground Officer-other Enlisted-other Pooled All occupational categories Summary counts by group are shown in Table 5. Ignoring the matching, interaction between officer-enlisted categories and Ranch Hand membership, and interaction between flying-ground categories and Ranch Hand membership was evaluated using log-linear models. No statistically significant interactions were detected. Table 5 SUMMARY COUNTS BY GROUP Group Ranch Hand At Risk Dead Rate Comparisons At Risk Dead Rate Officer Enlisted 463 784 15 35 .032 .045 2278 3893 162 .039 .042 Flying Ground 641 606 22 28 .03** .046 3163 3008 140 110 .044 .037 Pooled 1247 50 .040 6171 250 .041 88 Linear rank procedures were carried out on the same five groups. The results, summarized by test statistics and two-sided P-values, are shown in Table 6. Small P-values, less than .05, indicate significant differences, at the 5% level, between the two groups. These procedures are designed so that the statistic will be positive when the Ranch Handers are dying before the comparison subjects and negative when the comparisons are dying prior to the Ranch Handers. The null hypothesis is that the actual survival distributions of Ranch Handers and their matched comparisons are identical. Each statistic is approximately null distributed as a standard normal random deviate. 11 �Table 6 TEST RESULTS AND P-VALUES FOR OVERALL COMPARISONS Group Logrank (Value) P-Value Wilcoxon (Value) P-Value Officer Enlisted (-0.631) (0.383)' .526 .702 (-0.722) (0.33D .470 .741 Flying Ground (-1.021) (1.023) .307 .306 (-1.116) (0.950) .264 .342 Pooled (-0.047) .962 (-0.123) .902 There is no significant difference, based on these data, between the Ranch Handers and their mortality comparison group. This means that, in particular, the mean ages-at-death of the Ranch Handers and their matched comparisons are not significantly different. In some groups, pooled, officer and flying, the statistics are negative, indicating that the Ranch Handers are living longer than the comparisons, but the differences are, again, insignificant, as evidenced by the large P-values. The situation is reversed for enlisted and ground personnel. These findings are consistent with the observation that, within each group, the comparison confidence bands are contained within the Ranch Hand confidence bands. When matched sets are stratified by five year intervals on year of birth, the same procedures give larger P-values than those in Table 6. Relative risk estimates, the associated 95$ confidence intervals, twosided P-values for testing the null hypothesis of relative risk equal to unity and the associated power are given in Table 7. Here, the power of the test is defined as the conditional probability of rejecting the null hypothesis at the 5% level of significance, given that the relative risk is equal to its estimated value. Table 7 RELATIVE RISKS AND 95$ CONFIDENCE INTERVALS, P-VALUES AND POWER Group Relative Risk 95% Confidence Interval P-Value Power Officer Enlisted 0.763 1.065 (.320- 1.207) (.660- 1.471) .373 .742 .105 .072 Flying Ground 0.734 1.232 (.387 - 1.081) (.694- 1.769) .211 .337 .197 .195 Pooled 0.964 (.658- .819 .051 12 1.269) �The confidence intervals and P-values in Table 7 indicate no significant difference, at the 5% level, between the mortality of the Ranch Handers and comparisons in each of the five groups. Year-of-birth specific mortality rates for each of the five groups are given in Tables 8 through 12, with the corresponding standardized mortality ratios (SMR). In each group, the comparisons are the internal standard. The SMR estimates relative risk in these comparisons if the year-of-birth specific relative risks are all equal (13). A likelihood ratio test for the hypothesis of equal year-of-birth specific relative risks was carried out for each comparison; its P-value is denoted by P1 . In addition, the hypothesis that relative risk is unity, given that relative risk is constant across strata, was tested via a likelihood ratio procedure (13); its P-value is denoted by P2. The SMR and both P-values are given with each comparison. Here, and elsewhere in this report, the denominator of the SMR where n^j is the number of individuals for the ith stratum population and r^ is the death rate, per person, in the standard for the ith stratum. In these calculations the data is stratified birth. Table 8 POOLED SPECIFIC MORTALITY RATES BY YEAR OF BIRTH (SMR - .996; P1-.389, P2-.955) Birth Year Ranch Handers At Risk Dead Rate Comparison At Risk Dead Rate 1905-14 5 2 .1100 1*1 2 .143 1915-19 17 4 .235 96 11 .115 1920-24 1925-29 48 84 3 2 .063 .024 241 501 24 40 .100 .080 1930-31 1935-39 304 207 15 7 .049 .034 1389 1020 67 33 .048 .032 1940-44 1945-54 208 374 5 j_2 50 .024 .032 1096 1814 23 50_ 250 .021 .028 13 is of the jth population on year of �Table 9 OFFICER SPECIFIC MORTALITY RATES BY YEAR OF BIRTH (SMR - .827; P1-.233, P2-.490) Ranch Hand Officers Rate At Risk Dead Birth Year 1910-24 1925-34 1935-39 1940-44 191)5-49 1*1 194 93 90 45 3 4 4 2 2 15 Comparison Officers At Risk Dead Rate 205 930 458 495 190 .073 .021 .043 .022 .044 17 49 11 6 5 88 .083 .053 .024 .012 .026 Table 10 ENLISTED SPECIFIC MORTALITY RATES BY YEAR OF BIRTH (SMR = 1.074; P1=.733, P2=.722) Birth Year Enlisted Ranch Handers At Risk Dead Rate 1905-14 1915-19 1920-24 1925-29 1930-34 1935-39 1940-44 1945-54 4 9 16 41 153 114 118 329 2 1 3 2 11 3 3 10 35 Enlisted Comparisons At Risk Dead Rate .500 .111 .188 .049 .072 .026 .025 .030 12 54 80 211 749 562 601 1624 2 7 11 22 36 22 17 45 .167 .130 .138 .104 .048 .039 .028 .028 162 Table 11 FLYING SPECIFIC MORTALITY RATES BY YEAR OF BIRTH (SMR = .769; P1-.678, P2-.238) Birth Year 1915-24 1925-34 1935-39 1940-44 1945-49 Flying Ranch Handers At Risk Dead Rate 44 272 142 120 63 4 8 6 2 2 22 .091 .029 .042 .017 .032 14 Flying Comparisons At Risk Dead Rate 220 1316 698 653 276 23 71 22 14 10 140 .105 .054 .032 .021 .036 �Table 12 GROUND SPECIFIC MORTALITY RATES BY YEAR OF BIRTH (SMR = 1.257; P1-.535, P2=.302) Birth Year Ground Ranch Handera At Risk Dead Rate Ground Comparisons At Risk Dead Rate 1905-14 1915-24 1925-29 1930-34 5 21 31 85 2 3 2 7 .1400 .143 .065 .082 14 117 151 423 2 12 19 17 .143 .103 .126 .040 1935-39 1940-44 1945-54 65 88 311 1 3 1£ 28 .015 .034 .032 322 443 1538 11 9 40 110 .034 .020 .026 These SMR comparisons are in agreement with the preceding relative risk and linear rank analyses; there is no significant difference in mortality, based on these data, between the Ranch Hand group and the comparison group. 3. Noncause Specific Occupational Comparisons Within-group comparisons by occupation via SMR's, with P-values for testing constant relative risk across year of birth strata (P1) and for testing relative risk equal to unity (P2) are given in Tables 13 through 16. The enlisted and ground personnel are the internal standards in these comparisons. Comparisons via the logrank procedure are given in Table 17. Table 13 RANCH HAND OFFICERS VERSUS RANCH HAND ENLISTED MORTALITY BY YEAR OF BIRTH (SMR «= .544; P1-.280, P2= .087) Birth Year 1905-24 1925-34 1935-39 1940-44 1945-54 Ranch Hand Officers At risk Dead Rate 41 194 93 90 45 3 4 4 2 _2 15 .073 .021 .043 .022 .044 15 Ranch Hand Enlisted At Risk Dead Rate 29 194 114 118 329 6 13 3 3 lp_ 35 .207 .067 .026 .025 .030 �Table 14 RANCH HAND FLYING PERSONNEL VERSUS RANCH HAND GROUND PERSONNEL MORTALITY BY YEAR OF BIRTH (SMR - .581; P1-.382, P2-.100) Birth Year Ranch Hand Fliers At Risk Dead Rate 1905-24 1925-34 1935-39 1940-44 1945-54 44 272 142 120 63 4 8 6 2 _2 22 Ranch Hand Ground At Risk Dead Rate .091 .029 .042 .017 .032 26 116 65 88 311 5 9 1 3 1P_ 28 .192 .078 .015 .034 .032 Table 15 COMPARISON GROUP OFFICERS VERSUS COMPARISON GROUP ENLISTED MORTALITY BY YEAR OF BIRTH (SMR - .697; P1-.640, P2-.015) Birth Year 1905-19 1920-24 1925-29 1930-34 1935-39 1940-44 1945-54 Comparison Officers At Risk Dead Rate 44 161 290 640 458 495 190 4 13 18 31 11 .091 .081 .062 .048 .024 .012 .026 6 5 Comparison Enlisted At Risk Dead Rate 66 80 211 749 562 601 9 11 22 36 22 17 1624 45 T52 M .136 .138 .104 .048 .039 .028 .028 Table 16 COMPARISON FLYING PERSONNEL VERSUS COMPARISON GROUND MORTALITY BY YEAR OF BIRTH (SMR - .930; P1-.305, P2-.867) Birth Year 1905-19 1920-24 1925-29 1930-34 1935-39 1940-44 1945-54 Comparison Fliers At Risk Dead Rate 45 175 350 966 698 653 276 6 17 21 50 22 14 10 140 .133 .097 .060 .052 .032 .021 .036 16 Comparison Ground At Risk Dead Rate 65 66 151 423 322 443 1538 7 7 19 17 11 9 40 110 .108 .106 .126 .040 .034 .020 .026 �Table 17 LOGRANK WITHIN GROUP COMPARISONS Comparison Logrank P-Value RH Officer vs RH Enlisted RH Flyers vs RH Ground Comparison Officer vs Comp Enlisted Comparison Flyers vs Comp Ground -1.468 -1.455 -2.597 -0.363 0.1*12 0.146 0.009 0.717 The SMR and logrank analyses are somewhat in agreement, with both procedures finding significant differences between comparison officers and comparison enlisted, with the officers living longer. The two methods approximately agree on the Ranch Hand fliers versus ground personnel and on Ranch Hand officer versus enlisted personnel with the logrank result near significance at the .10 level; the fliers appear to be living longer than the ground personnel within the Ranch Hand group. 4. Cause Specific Ranch Hand Versus Comparison Mortality Cause specific mortality, relative risks, two-sided P-values for testing relative risk equal to unity, power and 95? confidence intervals for relative risks are summarized in Table 18 for the 1241 matched Ranch Handers and their mortality comparisons. Mortality data for the six unmatched Ranch Handers were not used in this analysis. Of the six, one has died of an accident and the rest are still alive. In some categories, the data were too sparse for relative risk estimation. Table 18 CAUSE SPECIFIC MORTALITY AND RELATIVE RISKS Cause Dead Relative RJH Comparison Risk 95% Conf Int. Accidental 18 Suicide 3 Homicide 2 Infectious, Parasitic 0 Malignant Neoplasm 4 Uncertain Neoplasm 0 Endocrine 1 Mental Disorder 0 Nervous System 0 Circulatory 16 Respiratory 0 Digestive 5 Genitourinary 0 111 Defined 0 Unknown _0_ 92 14 3 49 250 P-value Power .959 1.071 3.333 (.466 - 1.453) (0 - 2.407) (0 - 9.297) .875 .913 .099 .047 .061 .489 .503 (0 - 1.024) .205 .153 5.000 (0 -18.859) .102 .562 1.002 (.411 - 1.594) .994 .050 2.273 (0 - 4.675) .085 .457 3 39 2 1 1 2 70 4 11 3 2 3_< 17 �The low powers in Table 18 reflect the sparseness of data or the fact that some of the observed relative risks approach unity. However, two categories do stand out as deserving further attention: malignant neoplasms and digestive system deaths. It should be noted that if matched sets are ignored and relative risk is estimated using the method of Mantel and Haenszel (14), these results remain essentially unchanged; using this'approach, the relative risk for malignant neoplasms, for example, is .506 with a P-value of .195 and power equal to .254. The 95/& confidence interval for relative risk using this approach is .180 to 1.419. The Mantel-Haenszel relative risk for the digestive system comparison is 2.254, with a P-value of .132 and a power equal to .325; the 95$ confidence interval for relative risk is .782 to 6.501. The digestive system deaths are further defined in Table 19. There has been an increase in deaths due to liver disease among the Ranch Handers; however, this observed difference is not statistically significant. These data are also based on death certificate diagnoses and will be subjected to verification and validation from medical record and autopsy reports. When all deaths from liver disease are considered as a whole, a relative risk of 2.50 is found, with a 95% confidence interval of 0 to 5.501. The P value is 0.083. Similarly, the relative risk for pancreatitis is 2.50 with a 95% confidence interval of 0 to 8.501.; the P value is 0.386. These observations are of interest and will be pursued in depth in subsequent reports. Table 19 DIGESTIVE SYSTEM MORTALITY Deaths Ranch Hand Comparison ICD Code (9th Ed) Pancreatitis (5770) Alcoholic cirrhosis (5712) Nonalcoholic cirrhosis (5715) Nonalcoholic fatty liver (5718) Chronic liver disease (5728) Alcoholic liver disease (5711) Duodenal ulcer (5325) 1 0 3 0 0 1 0_ 5 2 3 3 1 1 0 _J_ 11 Table 20 SITE SPECIFIC MALIGNANT NEOPLASM MORTALITY Deaths Ranch Hand Comparison Site ICD Code (9th Ed) Lip, oral cavity, Pharynx (140-149) Digestive organs, peritoneum (150-159) Respiratory, intrathoracic (160-165) Bone, connective tissue, skin, breast (170-175) Genitourinary organs (179-189) Brain (191-192) Lymphatic and hematopoietic tissue (200-208) No site specification (199) 18 0 0 2 4 8 15 0 1 0 0 J_ 4 1 3 3 4 J_ 39 �The malignant neoplasms are detailed in Table 20, the cell types or the neoplasms, as recorded on the death certificates, are summarized in Table 21. Table 21 MORPHOLOGY OF NEOPLASMS ICD Code 9th Ed. M800 M801-80*» M805-808 M8HJ-838 M872-879 M905 M938-948 M959-963 M965-966 M986 Deaths Ranch Hand Comparison Nomenclature Neoplasms not otherwise specified (NOS) Brain Bronchus and Lung Colon Intestinal Tract Epithelial neoplasms (NOS) Bronchus and Lung Esophagus Kidney Nasopharynx Pancreas Unspecified site Papillary and Squamous Cell Nasal Sinus Lip Tongue Tonsil Andenomas and Adenocarcinomas Appendix Bronchus and Lung Colon Kidney Stomach Nevi and Melanomas Skin (NOS) Mediastinal Mesothelioma Bronchus and Lung Gliomas Frontal Lobe Brain (NOS) Lymphomas NOS and Diffuse Lymphomas (NOS) Hodgkins disease Hodgkin's (NOS) Myeloid Leukemias Acute Myelocytic Leukemia 0 0 0 0 1 3 1 1 1 0 1 0 0 1 8 1 1 1 2 1 0 0 0 0 1 1 1 1 0 0 0 0 0 1 2 1 2 1 0 1 1 0 0 1 0 0 1 1 0 1 0 2 0 4 Epithelial, papillary and adenomas account for 6H% of the comparison neoplasms. Three Ranch Hand neoplasms arose from epithelial cells. There were no tumors in either group which were classified as soft tissue sarcoma. 19 �Chapter IV NONCAUSE SPECIFIC COMPARISONS WITH EXTERNAL POPULATIONS 1. Background and Motivation It is important to know, not only how the Ranch Handers and their matched comparisons relate to each other, but also how they compare with general military and male United States populations. Pitfalls inherent in these comparisons are well known and are briefly reviewed below for specific comparisons with 1978 DoD period life tables for nondisability retired military officer and enlisted personnel (15) and the 1978 U.S. White Male Life Table (16). Although there are difficulties in the use of these comparisons, their use does provide an additional indicator of trends in mortality when viewed in the context of the total analytic process. 2. Adjustment Difficulties Mortality rates in any military population are strongly dependent upon 1) calendar year of death, 2) military status (active duty, separated, retired), 3) selection and retention, and 4) branch of service. Adjustment for these effects was not made in these comparisons because published select Air Force life tables, by calendar year and by status, are not available. In addition, there is also a problem with the statistical method used, since the Gail and Ware (17) procedure assumes constant relative risk with respect to age; the selection effect has been shown to diminish sharply with time making this assumption untenable in these comparisons. The adjustment difficulties (1-4), and their likely consequences, are detailed below. These difficulties apply to all of the comparison groups, but these concerns have less effect on the comparisons of the Ranch Hand group to their matched cohort since these two groups are generally equivalent, relative to these key factors. A. Adjustment for Calendar Year of Death Due to the continuing decrease in overall mortality in the military (18) and in the United States (19), the referenced external age-specific rates are appropriate only for the calendar period of the referenced external life table, that is, 1977-79 for the 1978 period military table used in this analysis. The 1977-79 period rates would, for example, be too low for comparison with subjects dying in 1970 at the age of 40. These subjects would more properly be compared with the death rate for 40 year olds in a 1970 period life table or with a death rate for 40 year olds in a cohort military life table for subjects born in 1930. Calendar time is not taken into account in this analysis because period life tables covering the three decades from 1950 to 1980, for the the active duty, separated and retired Air Force subpopulations, are not currently available. This discrepancy is serious because the decline in death rates in the active duty Air Force during the period 1966 to 1980 has been very substantial (18). B. Adjustment for Military Status (Active Duty, Separated, Retired). The only published military life tables available at this writing are 1978 period tables for DoD nondisability retired officer and enlisted personnel (15) and a series of yearly abridged tables for the active duty Air Force, the first covering the period 1966-1968 and the last, 1978-1980 (18). With these data limitations, adjustment for military status is not possible. It is 20 �olear, however, that there are substantial differences between active duty and retired death rates with the active duty rates being lower than retired rates (15). C. Adjustment for Selection Entry into the military carries with it an effect known as selection, a lengthening of life expectancy due to health prerequisites upon entry into select status and periodic health checks thereafter. This effect is well known to insurance actuaries who have observed that, in insured populations, the effect diminishes as time passes unless there are continued checks on the state of health of the insured persons (20). If selection is to be adjusted for in this analysis, it would be necessary to know Air Force death rates as a function of both age and of time elapsed since entry into the Air Force. It would also be necessary, therefore, to know enlistment and discharge or retirement dates for all study subjects. It is the lack of these data that makes this adjustment impossible at this time. The consequences of this lack of adjustment are not known at this writing. D. Adjustment for Branch of Service Age specific active duty Air Force death rates are substantially lower than the corresponding rates for other services (18). Nonservice specific death rates are therefore too high for appropriate comparison with these two study groups. 3- Comparisons with 1978 DoD Life Tables In Tables 22 and 23, Ranch Hand officers and comparison group officers are contrasted to a 1978 DoD nondisability retired officer life table (15) and in Tables 24 and 25, Ranch Hand and comparison group enlisted personnel are compared with a 1978 DoD nondisability retired enlisted life table (15). In each table, the column labeled "At Risk" lists the number of subjects entering each five year age interval, the column labeled "Deaths" tabulates the numbers of deaths in the age intervals and the column labeled "Expected Deaths" gives the expected numbers of deaths in the age intervals if the study subjects had experienced the same death rates as those specified by the DoD table. The value of the test statistic (17) for testing the null hypothesis of equality is denoted by T; its two-sided P-value is denoted by P. While each table summarizes the findings with five year age intervals for ease of presentation, one year age intervals were used for the computation of the statistic T. All comparisons are conditioned on survival to age 35, since the DoD tables begin at that age. All comparisons are unadjusted for race since the DoD tables are not race specific. 21 �Table 22 RANCH HAND OFFICER VERSUS DOD NONDISABILITY RETIRED OFFICER LIFE TABLE (T - -3.962, P < .001) Age At Risk Deaths Expected Deaths 35-39 40-44 45-49 50-54 456 366 288 173 2 1 1 1 4.183 4.244 4.578 3.099 55-59 57 1 2.043 60-64 30 2 .823 65-68 1 £ 8 .076 19.046 Table 23 COMPARISON OFFICERS VERSUS DOD NONDISABILITY RETIRED OFFICER LIFE TABLE (T - -2.402, P = .016) Age At Risk Deaths Expected Deaths 35-39 40-44 45-49 50-54 2264 1822 1365 842 12 13 24 12 20.837 20.703 21.920 15.901 55-59 60-64 308 145 9 4 10.265 4.377 65-68 .19 JD .601 74 94.604 Table 24 ENLISTED RANCH HANDERS VERSUS DOD NONDISABILITY RETIRED ENLISTED LIFE TABLE (T = -.239, P = .811) Age At Risk Deaths 35-39 668 6 40-44 45-49 50-54 55-59 60-64 392 287 140 41 20 5 5 5 2 2 65-69 6 0 70-71 1 J_ 26 22 Expected Deaths �10UJ.C C-J ENLISTED COMPARISON SUBJECTS VERSUS DOD NONDISABILITY RETIRED ENLISTED LIFE TABLE (T = -3.214, P = .001) Age At Risk Deaths Expected Deaths 35-39 40-44 45-49 50-54 55-59 60-64 65-59 70-74 3299 1945 1437 695 203 103 35 5 21 20 31 14 12 3 1 0 102 33.370 27.681 31.450 20.076 10.980 7.515 2.593 .646 134.311 These findings suggest that, if the effects discussed in section 2 are assumed to be negligible, Ranch Hand officers and comparison officers and comparison enlisted personnel are living longer than expected relative to their respective external populations. Enlisted Ranch Hand personnel are not different from DoD enlisted personnel. In the above DoD comparison there is a suggestion of interaction between officer-enlisted categories and Ranch Hand versus comparison group membership. If matching and time of death are ignored, the following table can be constructed. The term "rate" is as defined on page 8 of this report. Table 26 DEATH AFTER 35 YEARS Ranch Hand Alive Dead Rate Officer Enlisted 448 642 8 26 Alive .018 .039 Comparison Dead Rate 2190 3197 74 102 .033 .031 Analysis using log-linear models shows a statistically significant interaction with pS 0.05. It appears that Ranch Hand officers have a lower mortality after age 35 than Ranch Hand enlisted or comparison officers or enlisted. However, the converse situation is noted considering mortality prior to age 35 and is significant with pSO.05. The data for this analysis of mortality prior to age 35 is set out below. Table 27 DEATHS BEFORE AGE 35 YEAR Alive Officer Enlisted 456 775 Ranch Hand Dead Rate 7 9 > Alive .015 .011 2264 3833 23 Comparison Dead Rate 14 60 .006 .015 �These interactions will require further detailed analysis and evaluation, with specific consideration of medical covariables including risk taking, other life patterns and herbicide. 4. Comparisons with U.S. 1978 White Male Life Table Non-Black Ranch Handera and non-Black comparisons are compared in this section with the population of White males, as represented by the 1978 U.S. White Male Life Table (16). Two serious and well known problems with the use of this table are the lack' of adjustments for the calendar year and selection effects just described; when comparing occupational cohorts with national populations, the selection effect is known as the "healthy worker" effect. The pitfalls of these kinds of comparisons are well documented (21, 22, 23). In Tables 28 and 29, non-Black Ranch Handers and non-Black comparisons are compared, via the method of Gail and Ware (17), with the 1978 U.S. White Male Life Table (16). In Tables 30 through 33, non-Black officers and enlisted personnel in both study groups are compared with the same 1978 U.S. White Male Table. Table 28 NON-BLACK RANCH HANDERS VERSUS 1978 U.S. WHITE MALE LIFE TABLE (T--4.588, P <.001) Age At Risk Deaths Expected Deaths 21-24 25-29 1171 1169 2 6 9.003 9;783 30-34 35-39 1163 1054 7 7 9.396 9.256 40-44 722 5 10.381 45-49 50-54 549 304 6 5 12.085 8.114 55-59 60-64 65-69 70-71 98 50 7 1 3 4 0 1 W 5.039 2.790 0.669 0.089 76.605 24 �Table 29 NON-BLACK COMPARISONS VERSUS THE 1978 U.S. WHITE MALE LIFE TABLE (T = -11.230, P <.001) Age At Risk Deaths Expected Death 19-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 5816 5815 5799 5772 5245 3593 2675 1487 509 248 54 5 1 16 27 23 31 29 50 26 20 7 1 0 231 10.325 55.444 48.592 46.719 46.124 51.041 58.810 40.529 25.210 11:161 3.403 0.601 354.540 Table 30 NON-BLACK RANCH HAND OFFICERS VERSUS 1978 U.S. WHITE MALE LIFE TABLE (T «= -4.575, P < .001 ) Age 25-29 30-31 35-39 40-44 45-49 50-54 55-59 60-64 65-68 At Risk Deaths 151 151 147 362 285 172 57 30 1 3 1 2 1 1 1 1 2 _0 15 25 Expected Deaths 3.794 3.710 4.42Q 5.304 6.370 4.541 3.019 1.302 0.110 32.570 �Table 31 NON-BLACK COMPARISON OFFICERS VERSUS 197$ U.S. WHITE MALE LIFE TABLE (T - -7.923, P < .001) Age At Risk Deaths Expected Deaths 25-29 2253 9 18.880 30-34 2244 5 18;530 35-39 2239 12 22.137 40-44 45-49 50-54 55-59 60-64 65-68 1801 1352 834 308 145 19 13 24 12 9 4 _0 25.841 30.468 23.328 15.157 6.923 0.887 88 162.151 Table 32 NON-BLACK RANCH HAND ENLISTED PERSONNEL VERSUS 1978 U.S. WHITE MALE LIFE TABLE (T - -1.753, P - .080) Age At Risk Deaths 21-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-71 717 715 712 607 360 264 132 41 20 6 1 2 3 3 5 4 5 4 2 2 0 J_ 5.510 5.988 5.686 4.836 5.077 5.716 3.573 2.020 1.488 0.588 0.089 33 40.571 26 Expected Deaths �Table 33 NON-BLACK COMPARISON ENLISTED PERSONNEL VERSUS THE 1978 U.S. WHITE MALE LIFE TABLE (T =-5.923, ? < .001) Age At Risk Deaths Expected Death 19-19 20-21 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 3563 3562 3546 3528 3006 1792 1323 653 201 103 35 5 1 16 18 18 19 16 26 14 11 3 1 0 6.325 33-938 29.713 28.189 23.987 25.200 28.341 17.201 10.053 7.538 2.515 0.601 T4~3 213.601 Given the cautions just described, these findings suggest that the non-Black Ranch Handers and comparisons are living much longer than expected relative to the 1978 U.S. White Male Life Table. The ratios of the observed to the expected deaths described in Tables 28 and 29 reveal that the Ranch Hand and comparison subjects are experiencing death at only 60 to 6556 of the rate of the U.S. White male population. The ratio is 0.461 for the subset of Ranch Hand officers, 0.543 for comparison officers, 0.813 for enlisted Ranch Handers, and 0.669 for enlisted comparison subjects. The healthy worker effect is very likely a major contributor to the undoubtedly real differences between these study groups and the general population. 27 �Chapter V '. COMPARISONS WITH THE WEST POINT STUDY GROUP 1. Background and Motivation The statistical and epidemiological literature is replete with warnings against the uncritical use of the SMR and related summary measures for comparing study groups with published vital statistics for national populations or subpopulations (5), (24), (25). Those cautions are based on the adjustment difficulties described in Chapter 4, Section 2, and departures from the assumption of constant relative risk across age intervals between the study group and the external population. These drawbacks can be avoided by not referencing an external standard at all, by using one of the study groups as the standard (13). or by using as an external standard a group of military personnel, born during approximately the same years, with the same mortality follow-up, as the Ranch Hand and comparison groups. An external group of sufficient size for meaningful statistical comparisons is not available at this time. Mortality and year of birth data are available, however, on a small group of West Point graduates, the subjects of the West Point Follow-up. Study. Although this group is too small for all but very crude statistical comparisons (1), it is the only known external data available at this time. The following comparisons are, therefore, primarily descriptive. The West Point Study Group consists of W members of the West Point graduation class of 1956. These men have been followed up since then for morbidity and mortality. All members of that class were, or still are, officers in the U.S. Armed Forces. The purpose of the West Point study is to investigate the relationship between blood lipid levels and cardiovascular disease. Each study subject is physically examined biennially and blood samples are obtained for lipid and lipoprotein analyses at the USAF School of Aerospace Medicine (26). 2. Noncause Specific Comparisons of Ranch Hand and Comparison with the West Point Study Group Subgroups For the purpose of these mortality comparisons, 15 of the 36 known West Point deaths occurring on or before 31 December 1982 were deleted, 9 of the 15 were killed in action, one was killed in 1959 in the line of duty and 5 were killed in automobile crashes prior to 1962. These deletions imitate the deletion of personnel killed in action from the Ranch Hand and comparison groups. Noncombat or accidental deaths prior to 1962 were deleted because death prior to 1962 would have precluded membership in the Ranch Hand or comparison groups. In addition, one West Pointer who is also a Ranch Hander, was deleted; that individual was alive on 31 December 1982. 28 �A summary of the remaining 21 deaths among the 458 West Point subjects used in these analyses is given by year of birth in Table 34 and by age in Table 35. In Table 35 the column headed "censored" lists by age, the number of West Pointers alive on 31 December 1982. Table 34 WEST POINT DEATHS BY YEAR OF BIRTH Year of Birth At Risk Dead 1930 1931 1932 1933 1934 1935 20 59 90 136 141 12 458 0 2 6 8 4 J_ 21 Table 35 WEST POINT DEATHS BY AGE Age 25-29 30-34 35-39 HO-44 H5-H9 50-52 At Risk Censored 458 456 451 4 4 8 lji)6 162 Dead 0 0 0 0 276 161 437 2 5 3 2 8 J_ 21 In this analysis, non-Black Ranch Hand and comparison officers are compared, without regard to cause of death, with the West Point study group; all of the West Point subjects are non-Black. Non-Black Ranch Hand Officers were matched, one-to-one, by year of birth, to West Point subjects. Due to the relatively small number of Ranch Hand officers and the limited year of birth range imposed by the age of the Class of 1956, only 283 of the 458 West Point subjects received a matched Ranch Hander. Matched sets with West Pointers having the same year of birth were then merged to create six matched sets, corresponding to the six years of birth, 1930 through 35, of the West Pointers. To compare West Pointers with comparison officers, two non-Black comparison officers were matched to each West Pointer by year of birth. All West Pointers received two matched comparison individuals. Matched sets with West Pointers having the same year of birth were merged, giving six. matched sets containing a total of 916 comparisons. 29 �Logrank teats were carried out on these two matched data sets, and the results are summarized in Table 36. In these analyses, survival time is age at death. Censorship is due to survival to 31 December 1982. For those still alive on 31 December 1982, censoring time is age on that day. Table 36 STUDY GROUP VERSUS WEST POINT GROUP LOGRANK COMPARISONS WITH TWO-SIDED P-VALUES Comparison P-Value Ranch Hand officer versus West Point Comparison officer versus West Point .218 .528 An SMR analysis, with the West Pointers being the standard, is summarized in Table 37. Table 37 SMR COMPARISON OF NON-BLACK RANCH HAND AND COMPARISON OFFICERS WITH THE WEST POINT STUDY GROUP (SMR = .530) Birth Year 25-31 32 33-34 35-40 (SMR = .778) Ranch Hand (SMR = 1) Comparison West Point At Risk Dead Rate At Risk Dead Rate At Risk Dead Rate 95 35 60 93 2 1 1 1 8 .021 .029 .017 .043 272 164 257 223 19 7 6 _5 37 .070 .043 .023 .022 79 90 277 12 2 6 12 J_ 21 .025 .067 .043 .083 The test for constant relative risk across year of birth strata gives a P-value of .229. Further, a likelihood ratio test suggests that these SMR's are not different (P = .392). �j. Cause Specific Comparisons The <VHi.se .sponi f \.r. death count,0, for the West Point Study Group are givon in Table Table 38 WEST POINT MORTALITY BY CAUSE Cause Count Accidents Infectious disease Malignant neoplasms Circulatory Digestive Genitourinary 111 defined 6 1 6 5 1 1 1 21 Cause specific comparisons are carried out with three causes, cancer (malignant neoplasms), other diseases, and nondisease (accidents, suicides, homicides and ill-defined), with an adjustment for year of birth by stratification on year of birth. Relative risks are calculated using the method of Mantel and Haenszel (14). These results, based on the counts in Tables 39 and 40, are shown in Table 41. Table 39 CAUSE SPECIFIC COMPARISONS RANCH HAND OFFICERS VERSUS WEST POINT Ranch Hand At Risk Dead West Point At Risk Dead Cause Birth Year Nondisease 1925-1933 1934-1940 166 117 1 M 305 153 5 1 Cancer 1925-1930 1931 1932 1933 1934 1935-1940 72 23 35 36 24 93 0 0 0 0 0 0 20 59 90 136 141 12 0 1 3 1 1 0 Other diseases 1925-1934 1935-1940 190 93 2 1 446 12 8 1 31 �Table 40 CAUSE SPECIFIC COMPARISON COMPARISON OFFICERS VERSUS WEST POINT Birth Year Cause Nondisease Comparisons Dead Number Other diseases 1 11 2 1 2 79 90 136 153 2 2 1 272 164 148 332 2 2 1 79 90 136 153 3 1 1 436 148 109 223 9 1 1 169 136 141 12 1 5 2 1 1929-1931 1932 1933 193^-1937 272 164 148 1929-1931 1932 1933 1934-1937 Cancer West Point Dead Number 1929-1932 332 1933 1934 1935-1937 2 3 1 Table 41 CAUSE SPECIFIC RELATIVE RISKS, P-VALUES 95$ CONFIDENCE INTERVALS FOR LOG RELATIVE RISK 95% Conf Interval Cause Comparison Nondisease RH vs WP Comp vs WP 1.072 0.841 (-1.504 - 1.643) (-1.354 - 1.009) .931 .775 .051 .059 Cancer RH vs WP Comp vs WP 0.690 (-1.634 - .891) .564 .089 Comp vs WP 0.474 0.779 (-3.540 - 2.047) (-2.367 - 1.867) .600 .817 .082 .056 RH vs WP Comp vs WP 0.539 0.728 (-2.191 - .954) (-1.940 - .306) .441 .702 .120 .067 Other diseases RH vs WP All causes RR for Log Rel Risk 32 P-value Power �While the Ranch Hand versus West Point cancer comparison cannot be assessed using the Mantel-Haenszel procedure, the absence of Ranch Hand cancer deaths in this analysis is of interest. This finding is consistent with the apparent but nonsignificantly decreased Ranch Hand cancer mortality noted in the Ranch Hand versus matched comparison group analysis (Chapter III). 33 �Chapter VI STATISTICAL ASPECTS 1. Purpose The purposes of this chapter are 1) to briefly describe each statistical procedure used in the preceding chapters 2) to state the underlying assumptions of each procedure and 3) discuss the validity of those assumptions in this study. The procedures used in this analysis were survival curve estimates and confidence bands, linear rank tests, relative risk estimation and standardized mortality ratios. Points 1-3 are addressed for each procedure in Sections 2 through 5. 2. Survival Curve Estimation and Confidence Bands The survival function of a homogeneous population, S(t), is defined as the probability of surviving t years. The problem is to estimate S(t) and make a confidence statement about that estimate based on randomly censored data. Randomly censored data occur in survival studies since analyses are usually carried out before all subjects have failed. In the present application, failure is defined as death and censorship occurs because most subjects are still living at the time of analysis. Other causes for censorship in this kind of epidemiological study are loss to follow-up or death from causes other than those of interest. Thus far in this study, there have been no subjects lost to follow-up, and all causes of death are of interest. The survival function is estimated here by the product limit estimate K(t), also called the Kaplan-Meier estimate (6). This estimate is derived under the assumption that, in a life testing experiment with n subjects on test, exactly k subjects, with k less than n, are observed to fail; the other n-k remaining are observed only until they are censored. The subjects are assumed drawn randomly from a homogeneous population. Censorship is assumed to be independent of failure. The Kaplan-Meier estimator is asymptotically unbiased and reduces to one minus the empirical distribution function in the absence of censoring. In the present application, the homogeneous populations are the Ranch Handers, the comparisons and various subgroups of these two groups. Death time is taken as age at death measured to the nearest month; censoring time is age" on 31 December 1982, measured to the nearest month. Survival time is age at death or age on 31 December 1982 for those subjects still living. The process n[K(t)-S(t)] converges weakly to a zero mean Gaussian process, as n tends to infinity, under random censorship when the underlying survival function S(t) and the censoring distribution are continuous on a bounded interval (27). This convergence is the theoretical basis for the confidence band algorithm (7) used in Figures 2 and 3, Chapter III and Appendices VI. �The independence of death and censorship can be assumed to hold horc since censorship (survival to December 31, 1982) is not being invoked on individuals because they appear to be at unusually high, or low, risk of death (28). Direct contact has been lost with two Ranch Handers and nine comparisons as described in Chapter II, but these are assumed to be alive, and hence censored at their age on 31 December 1982. The reason for this assumption is that the extensive death ascertainment system is believed to be thorough enough so that, had any of these subjects died, the death would have been detected. Hence, while contact has been lost, loss to follow-up for the purpose of mortality determination has not occurred (29). All other subjects still alive on 31 December 1982 are censored at their age on that date. The validity of inferences based on the estimate K(t) and its associated confidence band depends on the sample size and the observed number of deaths. The sample sizes and numbers of deaths in every stratum used in these analyses exceed the minimum requirements for these procedures (7). The survival curve estimates and confidence bands displayed in Figures 2 and 3 and Appendix VI are not adjusted for year of birth. To do so would have required stratification on year of birth, creating many small strata with associated sample size difficulties. Some year-of-birth adjusted plots in the larger occupational strata will be presented in the next report. 3. Linear Rank Procedures The hypothesis of interest in this analysis is that the actual survival distributions of the Ranch Handers and their matched comparisons are identical. The procedures of choice for testing equality of the two unknown survival distributions based on the matched and censored data in this study are the censored data extensions of the exponential scores and Wilcoxon tests, due to Prentice (8). The first of these is widely known as the logrank test. The test statistics, T, are of the form given by equation 6-23 of (28), where the summands are calculated on matched sets consisting of survival information on one Ranch Bander and his matched mortality comparisons. The statistic T, for either logrank or generalized Wilcoxon summands, is approximately standard normal under the null hypothesis (9). tions other study favor The large sample normal approximation for T will hold when all distribuare continuous and all censoring times are mutually independent of each and independent of death. These assumptions are well satisfied in this since the censorship mechanism, survival to time of analysis, does not one group over the other. In these procedures, the sampling unit is a matched set, so that these tests are adjusted for all matching variables. Prior to calculation, matched sets with Ranch Handers in the same race and job classification having the same year of birth are merged. 35 �The logrank and extended Wilcoxon tests are locally most powerful when the logarithm of the survival times are distributed as extreme value or logistic random variates, respectively. While the efficiency of these procedures peaks at these two underlying distributionsf they have been shown to be robust against departures ( ) These distributional assumptions, however, are 8. not viewed as strictly valid in this study since there is good evidence in the literature that survival time due to certain cancers and other diseases is log normally distributed (30, 31, 32, 33). A linear rank procedure of the Prentice form, whose efficiency peaks under the lognormal distributional assumption, can be constructed" (3*0, but this algorithm is not available at the present time; it will be included in the next analysis. The effect of this departure from the assumptions is considered mild. It should also be noted that these distributional assumptions cannot be checked since these match sets are small and the observations in the combined samples of all matched sets cannot be assumed to have a common distribution. Therefore, reliance must be placed on historical data to determine which linear rank procedure to use. The logrank and Wilcoxon procedures are used here because they are powerful and widely accepted in epidemiology and statistics. 4. Relative Risk Estimation Two relative risk estimators are used in this analysis, a generalization of the Ejigou-McHugh estimator for one to many matched data (12) and the Mantel-Haenszel estimator for stratified data (14). The Ejigou-McHugh estimate was chosen because it allows full adjustment for the one-to-many year-of-birth matching in this study, it is asymptotically as efficient as the maximum likelihood estimator and it is noniterative. The Mantel-Haenszel estimate was chosen because of its ease of calculation, efficiency (35), and general acceptance. It's variance is estimated according to the advice of Anderson et al. (36). Recent work suggests that the variance of the Mantel-Haenszel statistic might be better estimated by a jack-knife procedure (37); this newer method will be carried out in the next mortality report. The Ejigou-McHugh estimator in its published form is suitable only for 1 to R matched designs in which the number, R, of controls matched to each case is the same for all cases. Since the number of controls matched to each Ranch Hander is not the same for all Ranch Handers, the Ejigou-McHugh estimate and its variance was extended to a one-to-many matched design in which the number of comparisons is allowed to vary from case to case. Since this extension is unpublished it is stated in Appendix V for reference. The extended estimate and its variance reduces to the Ejigou-McHugh estimate and variance when all matched sets contain an equal number of comparisons. It is asymptotically efficient and consistent and is noniterative. The Ejigou-McHugh estimate and the Mantel-Haenszel estimate are based on the assumption that relative risk is constant across levels of the matching variable. Some indication that this assumption holds in this study when the data is grouped, by stratifying on year of birth, is furnished by likelihood ratio testing; there is no evidence in this study to suggest that relative 36 �risk is not constant across levels of the matching variables when the event of interest is death from any cause. Therefore, the Ejigou-McHugh and Mantel-Haenszel estimates are appropriate for these data. 5. Indirect Standardization With either an external or internal standard, the SMR is a good summary mortality index for comparing two or more populations, provided the product model, P.jj=ripj, holds, where PJJ is the probability of death in stratum i of population j, r^ is a set of standard stratum specific rates and PJ characterizes the mortality of population j, 1=1,2, ..., I, j=1,2, ..., J, (38, 13). If standard rates are known from some external source and if the product model holds, the best estimate of pj is proportional to the SMR. If J=2, the product model holds, and if one of the two groups is used as the standard, the SMR estimates relative risk. In any case, any SMR summary of mortality data should be preceded by analytical and graphical tests of fit of the product model. Because one of the study groups was always used as the standard in these analyses, the test of fit of the product model was, equivalently, a test of constancy of relative risk across year of birth strata. The fit of the model was verified in each analysis. Further, a likelihood ratio test for equality of population was carried out as described by Gail (13). The results of both tests are summarized by their P-values in each application. The sample sizes in every application are large enough so that chi-square approximations hold; these analyses are, therefore, valid and appropriate. The expected number of deaths in the SMR used in these analyses was calculated as In^rj, where n^j is the number of subjects in the ith stratum of the jth population. The person-years SMR was not used here for two reasons. First, its validity as an estimator of relative risk is dependent upon the fit of the proportional hazards model for which an omnibus test is not currently available. Secondly, the person-years calculation is typically carried out from entry into follow-up (5); in this study, follow-up begins at first entry to Vietnam or Southeast Asia and these entry dates are being verified at this writing. 6. Comparing Observed Life Table Data with a Known Survival Curve The procedure of Gail and Ware (17) is used in these analyses to compare Ranch Hand and comparison group survival data with published period life tables. The basic assumptions of this procedure are that death and censorship are independent competing risks and that the reference curve is a survival distribution for some external population. The test is of the form e v wnere an e are ^°j~ j }/(I j ^ ^» °j $ j observed and expected numbers of deaths in age interval j, and Vj is the variance of OJ-BJ. The statistic is not an omnibus goodness-of-fit test consistent against all alternatives to the null hypothesis that the observed sample comes from a known survival distribution. Rather, it has good power against proportional hazards alternatives or, more loosely, against alternatives for which the observed survival is better (or worse) in every interval than predicted by the known survival curve. 37 �The independence of death and censorship assumption is well satisfied in these data, as discussed in Section 2 of this chapter. The life tables used in these analyses do not, however, represent the survival distribution of any population since they are period, not cohort, life tables. The appropriateness of this procedure is, therefore, dependent upon the extent to which these period life tables approximate the survival distribution of some relevant reference population. These period tables were used because the more appropriate cohort life tables were not available at the time of analysis. �Chapter VII CONCLUSION 1. Introduction The mortality analyses described in this report have not revealed any adverse death experience in the herbicide/dioxin exposed cohort. The results of the analyses, regardless of the source of the comparison data, were consistent: at this time, there is no indication that operation Ranch Hand personnel have experienced any increased mortality or any unusual patterns of death in time or by cause. They are not dying in increased numbers, at earlier ages, or by unexpected causes. The fact that only a relatively small number of Ranch Hand deaths were available for analysis is reassuring in itself. However, the fact that adverse effects have not yet been detected does not imply that an effect will not become manifest at a future time or after covariate adjusted analyses. For this reason, further analyses are intended and mortality in the study population will be ascertained annually for the next 20 years. A summary of the statistical techniques applied to each source of comparison data is presented in Table 42. It should be noted here that these analyses have been carried out without knowledge of covariate information, such as herbicide exposure, industrial chemical exposure, or other risk factors and that these analyses were carried out at a time when approximately 96? of Ranch Handers and their matched comparison subjects were still living. The data, therefore, must be viewed as preliminary to more definitive analyses, which will be performed over the next 20 years. Table i»3 summarizes the results of the noncause specific analyses by source of the comparison data, and Table M presents the results of the cause specific analyses. 39 �Table 42 SUMMARY OF STATISTICAL PROCEDURES USED IN ANALYSIS Comparison Database Internal Comparison Group 1978 1978 DoD U.S. Life West Point White Males Tables Class of 1956 Noncause Speoifio Analyses Logrank & Wilcoxon Procedures Ejigou-McHugh Relative Risk Mantel-Haenszel Relative Risk SMR/Breslow-Day Product Model Gail-Ware Procedure + + •«• + + + + + + Cause Specific Analyses Ejigou-McHugh Relative Risk Mantel-Haenszel Relative Risk + + + Procedure usage is indicated by a "+" symbol. 40 �SUMMARY OF NONCAUSE SPECIFIC MORTALITY ANALYSES BY SOURCE OF COMPARISON DATA Internal Comparison 1978 US Group White Males^ Ranch Hand Group RH = C RH0 = C0 RHE = CE RHp = Cp RHG = CG Comparison Group RH <«US RH0 «<US RHE SUS C <«US C0 <«US CE <«us Internal Occupational Group Specific « £ < « <« P P P P P 1978 DoD West Point Life Tables1 Class of 19562 RH0 «<DoD0 RHE = DoDE CQ < RH0 - WP0 C0 = WP0 RH0 $ RHE RHp $ RHG C0 < CE valued greater value equal to value equal to value equal to value equal to than .10 or less than .10 or less than .05 or less than .01 or less than .001 RH Ranch Hand Group C Comparison Group 0 Officers E Enlisted F Flying G Ground 1 2 Validity of these comparisons is questionable (see Chapter H) Statistical inference is limited by small sample size 3 All P value symbols are based upon SMR and Gail-Ware analysis Table W SUMMARY OF CAUSE SPECIFIC ANALYSES BY SOURCE OF COMPARISON DATA RH Versus Internal Comparison No significant difference in cause specific relative risks RH Versus West Point* No significant difference in cause specific relative risks * Statistical inference is limited by small sample size �2. Internal Comparison Group Based on these early results, there appears to be no significant difference between Ranch Handers and comparisons as regards mortality. This null finding holds for both cause specific and noncause specific comparisons. One within group comparison did yield a significant difference, however. The non-Black comparison officers are living significantly longer than the non-Black comparison enlisted personnel. This may reflect the underlying health care and socioeconomic differences between these two groups. Non-Black Ranch Hand officers also appear to be living longer than non-Black Ranch Hand enlisted personnel, but this finding cannot be viewed as significant, with a P-value of .142 (Table 17). This lack of significance in the Ranch Hand analysis might be attributed to the smaller group sizes within the Ranch Hand cohort in contrast to the comparison cohort. 3. External Comparisons As outlined in the study protocol, considerable effort was expended in the selection of the study comparison group. While the chosen comparison group appeared closest to the Ranch Hand cohort except for herbicide exposure, it seemed appropriate to also contrast the Ranch Hand mortality experience to that of additional comparison groups. Three additional comparison data sets were then selected: mortality data from the West Point Class of 1956, the DoD Nondisability Retired Officer and Enlisted Life Tables for 1978, and the U.S. White Male Life Table, also for 1978. These data sets were chosen in a hierarchical fashion with the expectation that, in the absence of a herbicide effect, the Ranch Handers would have: 1) a mortality pattern comparable to the West Pointers, 2) a lower mortality than the DoD group due to the healthy worker effect, and 3) a still lower mortality than the U.S. male cohort due to healthy worker and military selection effects. These expectations were reassuringly fully realized with respect to overall mortality. Additionally, interesting officer-enlisted differentials emerged. As discussed below, these officer-enlisted differentials may have resulted from sample size effects or from covariable effects, potentially including herbicide exposure. 4. Power Considerations The power limitations of this study, specifically regarding mortality from rare conditions, such as soft tissue sarcoma, were fully acknowledged and described in the protocol (Ref 1, page 67). For example, a fatal disease with an incidence of .001 would require an approximate risk of 4 for a power of 0.8. Power calculations, while desirable for planning and study design, are also revealing at analysis. They are, however, sometimes difficult to carry out without further assumptions. The powers of the logrank and Wilcoxon tests �and the likelihood ratio tests in the SMR analyses are not calculable at this time due to the lack of appropriate methodology. The powers of the tests for cause specific mortality were calculated at the estimated relative risk. The values were low because the estimates of relative risk were close to unity and/or the data were sparse. The null findings in this report are unlikely to have been observed by chance had the true group differences been substantial. For example, if the true overall relative risk were in fact equal to 2, a crude calculation gives a probability of .0007 of observing a relative risk smaller than the observed .96*1 (Table 7). This probability is less than .001 if the true relative risk is 1.5. These findings are, therefore, very likely reflective of a near overall equivalence between Ranch Handers and their matched comparisons. Finally, these unadjusted findings do not preclude the possibility of the emergence of significant differences after adjustment for risk factors. 5. Consistency Patterns When the analysis of each external comparison data base is considered separately, the restrictions inherent in each source limit the strength of the inferences which can be made. However, when the results of all internal and external comparison data bases are considered in context, some patterns of consistency emerge. While some of these patterns may not have firm statistical underpinnings, they still may provide epidemiologic clues to the dynamics of the mortality process. The Ranch Hand officers exhibit a very consistent and predictable pattern across all analyses. As shown in Table ^43, their mortality is nearly the same as that of their most equivalent comparison groups (the matched comparison group officers and the West Point group). As the comparison groups become progressively less equivalent to the Ranch Hand group, the relative mortality of the Ranch Hand officers improves, presumably due to selection comparability (healthy worker effect, etc.). Their mortality is lower than that of their enlisted counterparts; however, this difference is not as striking as is the statistically significant comparable analysis between the matched comparison officers and the matched enlisted personnel. Unfortunately, the cross-comparison trends for the enlisted Ranch Handers are not as clearcut. Their mortality is greater,though not significantly different from their matched comparisons. The enlisted comparison group had a highly significant underrepresentation of mortality against both the DoD and US life tables, whereas the Ranch Handers are equivalent to the DoD group and only marginally better than the 1978 US White males. The consistent observation that the enlisted Ranch Handers appear to demonstrate less of a difference in relative mortality than do their matched comparisons is intriguing. This may reflect an actual increase in mortality due to herbicide exposure or some other factor, or it could be an artifact of small sample size created by the 1:5 matching or basic comparability problems as previously described. The inclusion of substantially more subjects in one group than another can have a profound effect on the significance level of a �statistical technique. Nevertheless, these observations are of interest, and will continue to be subjected to detailed analysis throughout the course of the follow-up study. This trend is consistent with self-perception of herbicide exposure held by many of the Ranch Hand group. Covariate analyses will be conducted, the herbicide exposure index will be applied to these data, and the effects of interaction will be assessed to determine whether the Ranch Hand enlisted findings are real or artifactual. The next mortality assessment will include analyses by person-year of follow-up, adjusted for age in an effort to better address the issue of latency. As the number of deaths in the study population increases with the passage of time, all of the statistical approaches outlined in the protocol (1) will be applied to the data. �Appendix I RANCH HAND II PRINCIPAL INVESTIGATORS COINVESTIGATORS, CONTRIBUTORS, AND MANAGEMENT PERSONNEL A. Principal Investigators George D. Lathrop, MD, MPH, PhD, FACPM Colonel, USAF.MC Chief, Epidemiology Division Patricia M. Moynahan, RN, MS Colonel, USAF, NC Chief, Occupational Epidemiology Section Richard A. Albanese, MD, GM-15 Chief, Biomathematical Modeling Branch Data Sciences Division William H. Wolfe, MD, MPH, FACPM Lt Colonel, USAF,MC Chief, Epidemiology Services Branch B. Coinvestigators Joel E. Michalek, PhD, GS-13 Mathematical Statistician Data Sciences Division Richard C. McNee, MS, GM-13 Chief, Advanced Analysis Branch Data Sciences Division Alton J. Rahe, MS, GS-13 Mathematical Statistician Data Sciences Division �Appendix I (Continued) C. Contributors William J. Besich, BS, GS-12 Computer Systems Analyst Data Sciences Division Vincent V. Elequin, BS, RRA, GS-11 Medical Record Librarian Occupational Epidemiology Section William E. Nixon, BS, GM-13 Computer Systems Analyst Data Sciences Division Thomas J. White, MA Senior Subject Matter Specialist Data Sciences Division i Alvin L. Young, BS, MS, PhD Major, USAF Special Assistant in Military Herbicides D. Management Personnel Project Director: Roy L. DeHart-, MD, MPH, MS, FACPM Colonel, USAF, MC Commander, USAF School of Aerospace Medicine Project Resource Manager: Melvin B. Dobbs Colonel, USAF, BSC Director, Systems Acquisition Research, Development and Acquisition Aerospace Medical Division Air Force HQ Systems Command Coordinator: Ronald D. Burnett Colonel, USAF, BSC Command Bioenvironmental Engineer Office of the Command Surgeon Air Force Surgeon General Coordinator: Robert A. Capell Major, USAF, BSC Assistant for Bioenvironmental Engineering Office of the Surgeon General 46 �Appendix II SCIENCE PANEL Advisory Committee on Special Studies Relating to the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants. Dr. G. W. Comstock Johns Hopkins Research Center Box 2067 Hagerstown MD 217^0 Dr. John Doull Professor Department of Pharmacology and Toxicology University of Kansas Medical Center Kansas City KA 66103 Dr. John A. Moore (Chair) Deputy Director National Toxicology Program P.O. Box 12233 Research Triangle Park NC 27709 Dr. Richard Monson Professor of Epidemiology Harvard School of Public Health 677 Huntington Avenue Boston MA 02115 Dr. Norton Nelson Professor and Chairman Department of Environmental Medicine New York University School of Medicine New York NY 10016 Dr. Alan Poland Associate Professor of Oncology McCardle Laboratory University of Wisconsin Madison WI 53706 Dr. Irving Selikoff Director, Environmental Sciences Laboratory Mt Sinai School of Medicine 5th Avenue and 100th Street New York NY 10029 47 �Appendix III MATCHING RESULTS IN THE MORTALITY POPULATION The matching results are described here for the mortality population consisting of 1241 Ranch Hands, their 6171 matched mortality comparisons, and the six unmatched Ranch Hands. The matching procedure is described in the Protocol (Ref. 1, pages 23~26). All study subjects were matched perfectly on job category. Three mismatches occurred on race because the recorded race designations for three study subjects were found to be incorrect at the LHA interview. These three subjects were comparisons, two were in the enlisted-other stratum (one was originally recorded as Black and was discovered to be non-Black, the other was originally recorded as non-Black and was discovered to be Black), and one was in the enlisted-flight engineer stratum (he was originally recorded as Black and was discovered to be non-Black). Matching on date of birth was carried out by first expressing date of birth in months from 1 January 1900, to the nearest month; the result is termed month-of-birth. Six discrepancies occurred in matching on month-of-birth due to erroneous months-of-birth for one Ranch Hand and one comparison. These were discovered at the LHA interview. The Ranch Hand, in the non-Black enlisted-other stratum, was discovered to be 72 months older than was recorded prior to the matching. The comparison, in the non-Black officer-pilot stratum, was found to be 15 years younger than was originally recorded. The erroneous Ranch Hand month-of-birth put all five of his matched comparisons 12 months out of range since he was originally perfectly matched to all five mortality comparisons. The erroneous comparison month-of-birth put that comparison 119 months out of range. Given the very small number of mismatches on age and race relative to the number of subjects, their effect was assumed negligible. The matching by month-of-birth, overall, and within each of the ten job and race categories within the mortality population is summarized in this Appendix. The column headed "Age Difference" lists absolute differences of months-of-birth of Ranch Hands and comparisons. The column headed "Number of Comparisons with RH younger (older)" gives, at each level of age difference, the number of comparisons within the level of age difference and older (younger) than the Ranch Hand to whom they are matched. The column headed "Total Count" gives the total numbers of comparisons having the absolute age differences with their matched Ranch Hand given in the first column; in "Total Percent", these counts are expressed as percentages of 6171. These are cumulated in the last two columns. �Appendix III MATCH SUMMARY FOR THE MORTALITY POPULATION Strata Age Difference Comparisons with RH Total Younger Older Count Cumulative Total % * Overall Officer-pilot Non-Black Officer-Pilot Black OfficerNavigator Non-Black 0 1-6 7-12 13-18 19-21 25-30 31-36 37-42 13-18 19-51 55-60 72 179 0 1-6 7-12 13-18 19-21 25-30 31-36 37-12 13-18 19-51 55-60 179 0 1-6 7-12 31-36 37-12 13-18 19-51 55 0 1-6 7-12 713 77 10 22 12 16 10 9 13 17 0 0 706 102 36 22 19 11 19 13 7 7 5 1 272 33 20 8 9 13 7 7 11 11 0 259 32 17 12 11 10 18 11 7 7 1 3 3 0 2 1 0 0 1 0 0 0 0 2 1 70 6 71 0 19 1261 1119 179 76 1 1 31 30 29 22 20 21 5 1 1261 5710 69.0 23.5 2.9 1.2 0.7 0.5 0.5 0.5 0.1 0.3 0,1 0.1 0.0 5889 5965 6009 6010 6070 6099 6121 6111 6165 6170 6171 961 531 65 37 20 20 23 25 18 18 21 1 55.2 30.5 3.7 2.1 1.1 1.1 1.3 1.1 1.0 1.0 1.2 0.1 961 1192 1557 1591 1611 1631 1657 1682 1700 1718 1739 1710 89.5 91.6 92.8 93.9 95.2 96.7 97.7 98.7 99.9 100.0 0 3 3 1 0.0 23.1 0.0 23.1 16.2 53.9 69.2 76.9 92.3 100.0 61.5 98.5 100.0 2 1 2 1 7.7 15.1 7.7 15.1 7.7 0 3 6 7 9 10 12 13 210 111 6 61.5 36.9 1.5 210 381 390 23.1 69.0 92.5 95.1 96.7 97.1 97.9 98.1 98.8 99.2 99.5 99.9 100.0 100.0 55.2 85.8 �Appendix III (Continued) MATCH SUMMARY FOR THE MORTALITY POPULATION Strata OfficerNavigator Black Number of Total Comparisons with RH Age Younger Older Count % Difference 0 1-6 7-12 13-18 19-21 25-30 31-36 Officer-Other Non-Black 0 1-6 7-12 13-18 19-21* 25 Officer-Other 13-18 1 0 2 0 0 0 0 2 1 1 1 1 38 2 1 1 0 57 8 1 0 1 2 0 Cumulative Total % 1 1 1 1 1 1 1 10.0 10.0 10.0 10.0 10.0 10.0 10.0 1 2 6 7 8 9 10 10.0 20.0 60.0 70.0 80.0 90.0 100.0 11 95 11.1 77.2 10 2 1 1 8.1 1.6 0.8 0.8 11 109 119 121 122 11.1 88.6 96.8 2 98.1 123 99.2 100.0 100.0 2 100.0 516 306 55.2 32.7 55.2 87.9 6.7 516 822 885 Black EnlistedFlight 0 1-6 Engineer Non-Black 7-12 13-18 19-21 25-30 31-36 37-12 46 EnlistedFlight Engineer Black 111 34 11 0 2 2 1 1 7 6 1 0 0 63 30 7 8 3 1 1 26 7 22 5 0 0 10 18 12 3 2 13.3 61.0 16.0 16 0 1-6 Non-Black 7-12 13-18 19-21 25-30 31-36 37-12 13-18 72 0 1-6 7-12 3.2 91,7 97.9 98.6 99.5 99.8 99.9 3 2 116 1 1 91 11 0.7 915 922 0.9 930 0.3 933 931 935 100.0 1.0 2.7 10 58 70 73 75 13.3 77.3 93.3 97.3 100.0 2382 0 1-6 7-12 19-21 55-58 EnlistedOther EnlistedOther Black 165 29 90.6 2382 7.9 0.5 0.2 0.5 0.0 0.1 0.0 0.1 0.2 2589 90.6 98.5 99.0 99.1 99.6 99.6 53.7 11.7 10 1 1 0 0 0 2 0 1 1 2 5 207 12 1 12 1 2 1 2 5 19 0 65 1 137 111 1 3 50 0.1 0.1 1.6 2601 2605 2617 2618 2620 2621 2623 2628 99.7 99.7 99.8 100.0 137 251 255 53.7 98.1 100.0 �Appendix IV YEAR OF BIRTH, OCCUPATIONAL AND RACE SPECIFIC MORTALITY Birth Ranch Hand Job Category, Race Year At Risk Dead Death Rate Officer-Pilot, Non-Black .375 1 915-19 1 920-21 1 925-29 1 930-31 1 935-39 1 910-11 1 915-19 8 31 31 113 66 60 10 3 0 0 3 3 1 Comparison At Risk Dead 1 13 11 Death Rate 23 8 5 5 .103 .081 .060 .050 .025 .011 .028 TOTAL 319 Officer-Pilot, Black 2 .027 .015 .017 .050 39 155 232 156 326 351 178 12 .031 1710 72 .011 0 1 3 2 0 0 0 0 3 1 6 0 0 0 0 0 6 0 13 0 9 35 21 13 17 163 105 67 8 3 7 3 0 0 .061 .013 .029 2 0 1 1 0 0 80 2 390 13 .033 1 1 0 0 6 1 0 0 2 0 10 0 1 0 1 3 2 1 0 0 0 0 0 0 2 3 6 11 0 0 0 1 1 0 1 0 1 930-31 1 935-39 1 910-11 1 915-19 TOTAL Officer-Navigator 1 925-29 Non-Black 1 930-31 1 935-39 1 910-11 1 915-19 TOTAL Officer-Navigator 1 930-31 Black 1 935-39 TOTAL Officer-Other, Non-Black 1 910-11 1 915-19 1 920-21 1 925-29 1 930-31 1 935-39 1 910-11 1 915-19 TOTAL 13 1 .029 .018 .025 12 .077 19 66 1 .010 1 123 0 25 51 .091 .083 .015 .021 �Appendix IV (Continued) Job Category, Race Officer-Other, Black Birth Ranch Hand Year At Risk Dead Death Rate Comparison At Risk Dead Death Rate 1940-44 TOTAL Enlisted-Fit Eng Non-Black 1 0 0 3 2 0 0 1925-29 1930-34 1935-39 1940-44 TOTAL Enlisted-Other Non-Black 1905- 9 1910-14 1915-19 1920-24 1925-29 1930-34 1935-39 1940-44 1945-49 1950-54 1 6 5 3 0 1 0 1 15 2 0 4 8 12 28 76 52 67 270 11 0 2 0 3 2 6 1 2 9 0 25 Enlisted-Other Black .333 .200 .049 .049 .041 .033 .056 935 46 .049 1 5 1 .333 10 34 16 15 2 .100 .150 .063 .133 .133 75 9 .120 2 10 48 60 140 0 .167 .500 .250 .071 .079 .019 .030 .033 376 263 340 1333 56 2 5 7 18 14 8 7 36 .200 .104 .117 .129 .037 .030 .021 .027 0 52 52 2628 97 .037 .143 35 40 35 .034 145 2 3 1 4 .057 .075 .029 .028 .038 1 0 0 1 TOTAL 2 4 3 15 10 7 5 .032 Enlisted-Fit Eng Black .0*17 .042 6 20 61 304 243 211 90 1.000 255 10 .039 .047 �Appendix V THE EXTENDED EJIGOU-McHUGH RELATIVE RISK ESTIMATOR Let R k , k=1,2, ..., K, denote the distinct numbers of comparisons matched to the cases and let nk denote the number of matched sets with exactly Rk comparisons. A matched set is defined as the case and his matched comparisons. Let n=ni+n2+ ... +nj( denote the total number of matched sets. Define Zk«i,T» k-1 .2 ..... K, i-0,1, by Zk 0 T * tne number of matched sets, among those having exactly Rk comparisons, in which the case is alive and exactly T of the R k comparisons have died, T=1,2, ..., Rk Zk,1 T * the number of matched sets, among those having exactly Rk comparisons in which the case has died and exactly T of the Rk comparisons have died, T=0,1,2, ..., Rk-1 . The extended estimate, \p, is given by K 1 Rk I zk,0,Tzk,1 ,T-1/(zk,0,T+zk,1 ,T-l) K Rk Z * TZ2k,0,T/(Rk-T+1)(Zk,0,T+Zk,1,T-l) k-1 T-1 and its variance is estimated by K Rk Z Z Zkf0>T/[i|;+(Rk-T+1)/T] k-1 T-1 Since K is finite, this estimate has the same distributional properties as the Ejigou-MoHugh estimator; it is asymptotically efficient and unbiased. The underlying assumptions used in its derivation are that the disease under study is of low incidence and that relative risk is constant over the levels of the matching variables. The Ejigou-McHugh estimate and the above extension are equivalent in asymptotic efficiency to maximum likelihood estimation (12). 53 �Appendix VI Figure 4 SURVIVAL CURVE ESTIMATE AND 95% CONFIDENCE BANDS FOR POOLED RANCH HANDERS C.9 0.3 Ci) z 0.7 - 14 - O.G - CO C'.V> - 2: C3 C.4 CT ce: 0 . 3 C.I . 0I 0 <Q 10 bO 70 RGF. Figure 5 SURVIVAL CURVE ESTIMATE AND 95% CONFIDENCE BANDS FOR POOLED COMPARISONS I 0.9 0.0 § 0«7 »—i > £ 0.6 W Q.& 2 0.4 I— o CE or. ° •3 u. 0.2 0.1 0 0 J_ _. 10 :ji"" fiC-f 54 I '"0 70 �Figure 6 SURVIVAL CURVE ESTIMATE AND'95% CONFIDENCE BANDS FOR RANCH HAND OFFICERS 0.9 O.Q 0.7 0.6 9s 0.5 •z. CJ 0 0.3 0.2 0.1 0 0 10 20 30 60 70 ROE Figure 7 SURVIVAL CURVE ESTIMATE AND 95% CONFIDENCE BANDS FOR COMPARISON OFFICERS I 0-9 o.e 0.7 0.6 z H- 0.4 0.3 0.1 0 . IK 30 60 ROE 55 70 �Figure 8 SURVIVAL CURVE ESTIMATE AND 95% CONFIDENCE BANDS FOR RANCH HAND ENLISTED PERSONNEL 1 0.9 0.8 g 0.7 oc to 0.5, z 2 Q.4 Iu S 0.3 u. 0.2 O.I 0 10 30 60 70 RGE Figure 9 SURVIVAL CURVE ESTIMATE AND 95% CONFIDENCE BANDS FOR COMPARISON ENLISTED PERSONNEL I 0.9 O.Q g 0.7 o.e cn z S 0.4 0.3 0.2 0.1 0 1— 10 no f. 56 60 70 �Figure 10 SURVIVAL CURVE ESTIMATE AND 95% CONFIDENCE BANDS FOR RANCH HAND FLYING PERSONNEL 1 0.9 0.0 0.7 > 0.6 or O.b z o £ 0.3 U_ 0.2 0.1 0 10 20 30 E>0 60 70 flGF. Figure 11 SURVIVAL CURVE ESTIMATE AND 95% CONFIDENCE BANDS FOR COMPARISON FLYING PERSONNEL 1 0.9 0.0 Z 0.7 U 0.6 W 0-b CJ 0.3 0.2 0.1 0 10 20 30 bO 57 60 70 �Figure 12 SURVIVAL CURVE ESTIMATE AND 95% CONFIDENCE BANDS FOR RANCH HAND GROUND PERSONNEL 0.9 0.9 g 0.7 £ 0.5 to 0.5 z •-• 0.4 ho £ 0.3 u_ 0.2 0.1 10 20 30 60 70 ROE Figure 13 SURVIVAL CURVE ESTIMATE AND 95% CONFIDENCE BANDS FOR COMPARISON GROUND PERSONNEL 1 0.9 0.8 Si 0.7 > £ 0.6 W 0.5 Z •-< 0.4 o £ 0.3 u_ 0.2 0.1), 0 0 10 30 40 flOE 58 £.0 70 �REFERENCES 1. Lathrop, G. D., Wolfe, W. H., Albanese, R.A. and Moynahan, P. M. Epidemiclogical investigation of health effects in Air Force personnel following exposure to herbicides: Study Protocol. SAM-TR- 82-4*1, Dec 1982. 2. Honchar, P. A., and Halperin, W. E. 2,4,5-T, trichlorophenol, and soft tissue sarcoma. Lancet Jan 31:268-269 (1981). 3. Hardell, L., and Sandstrom, A. Case-control study: soft tissue sarcomas and exposure to phenoxyacetic acids or chlorophenols . Br. J. 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Indirect standardization and multiplicative models for rates, with reference to the age adjustment of cancer incidence and relative frequency data. Journal of Chronic Diseases 28: 289-303 (1975). 61 �PROJECT RANCH HAND II AN EPIDEMIOLOGIC INVESTIGATION OF HEALTH EFFECTS IN AIR FORCE PERSONNEL FOLLOWING EXPOSURE TO HERBICIDES BASELINE MORTALITY STUDY RESULTS 30 JUNE 1983 Prepared for: The Surgeon General United States Air Force Washington, D.C. 20314 Approved for public release; distribution unlimited EPIDEMIOLOGY DIVISION DATA SCIENCES DIVISION USAF SCHOOL OF AEROSPACE MEDICINE (AFSC) BROOKS AIR FORCE BASE, TEXAS 78235 �EXECUTIVE SUMMARY Baseline Mortality Study The Ranch Hand II epidemiologic study'uses a matched cohort design in a nonconcurrent prospective setting, incorporating mortality, morbidity, and follow-up studies. The purpose of this report is to present the baseline mortality study results. , ,>••• Since 1979, a detailed population ascertainment process has enumerated a total of 1269 Ranch Hand personnel who served in Vietnam during the period of 1962-1971. As described in the protocol, this total is believed to comprise the entire exposed study population. The eligibility of each Ranch Bander was verified by a hand review of his personnel record. A comparison group was formed by identifying all individuals assigned to selected Air Force organizational units with a mission of flying cargo to, from, and In Vietnam during the same period. All Ranch Hand and comparison subjects designated as killed in action were removed from the study population. By a computerized nearest neighbor selection process, up to 10 comparison individuals were matched to each Ranch Hander by job category, race, and age to the closest month of birth. A hand record review of the matched comparison sets revealed that on the average, 8.2 comparison individuals were fully suitable for study. From each matched comparison set, five individuals were randomly selected for the mortality study, yielding a 1:5 design. Every Ranch Hander and his set of comparisons will be the subjects of annual mortality updates throughout the entire 20 years of the follow-up study so that emerging mortality patterns or disease clusters may be detected with maximal sensitivity. Each living Ranch Hander and his first and willing comparison match were selected to participate in a comprehensive physical examination and an in-home interview; the results of this study will be presented in a subsequent report in late 1983. A mortality determination on 1,247 Ranch Banders and 6,171 comparison subjects was made, sequentially using the data sources of the Air Force, Veterans Administration, Social Security Administration, Internal Revenue Service, and personal contact efforts. As of December 31, 1982, 50 Ranch Hand and 250 comparison subjects had died (certified on/before April 27, 1983). Death certificates were obtained on all 300 deceased subjects and were coded by an Air Force nosologist (ICD, 9th ED). All codings were verified by the National Center for Health Statistics. Autopsy results are currently being sought for future analyses. Statistical analyses of noncause specific death emphasized survival curve estimates, linear rank procedures, relative risk estimates, and standardized mortality ratios (SMRs). Cause specific analyses were limited to relative risk estimates because of small cell sizes. In addition to these approaches, three other data bases were contrasted to the Ranch Hand population, where possible; the 1978 US White Male Mortality experience, the 1978 Department of Defense (DoD) Nondisability Retired Life Table, and the mortality experience of the West Point Class of 1956. These additional comparison groups have substantial comparability or sample size limitations, rendering conclusions to the weakest order. Analyses with these "external" comparison groups were accomplished to crudely define the healthy worker effect and to determine if the Ranch Hand group mortality was drastically out of line with that of other military populations. �Data analysis showed that the mortality experience of the Ranch Hand group is nearly Identical to that of the comparison group. Analyses showed that officers are living" longer than enlisted personnel in both Ranch Hand and comparison groups. This difference between officers and enlisted personnel was statistically significant in the comparison group whereas it was not in the Ranch Hand cohort. A contrast of the Ranch Hand and comparison group to the 1978 DoD Life Table showed significantly less mortality for Ranch Hand officers, comparison officers and comparison enlisted men, however, there was not a statistically significant favorable mortality rate for Ranch Hand enlisted personnel. This pattern of mortality was also seen in a contrast of the Ranch Hand and comparison groups to the 1978 U.S. white male mortality experience. That is, highly favorable mortality differentials for Ranch Hand officers, comparison officers and comparison enlisted personnel were observed, but not for Ranch Hand enlisted. This trend is consistent with the self perceptions of differential herbicide exposures reported by many of the Ranch Hand subjects. The reason(s) for these observations are speculative at present, but may include the related items of sample size, socioeconomic differences, access to medical care, and health education and possible herbicide effects. Cause specific analyses were statistically nonsignificant. The Ranch Handers showed a relative paucity of overall cancer but an excess of digestive disorder deaths, both statistically nonsignificant. No soft tissue sarcoma deaths were detected in either group. Analyses of both the Ranch Hand and the comparison groups to the 1978 US White male mortality experience showed highly significant favorable findings. Most of these differences are speculatively attributed to the healthy worker effect. A contrast of the Ranch Hand and comparison groups to the 1978 DoD Life Table showed significantly less mortality for Ranch Hand officers and comparison officers and enlisted men. The West Point comparison showed nonsignificant SMRs of 0.530 and 0.778 for the Ranch Hand officers and the comparison group officers, respectively. Overall, the limitations of the statistical power calculations in most of these analyses were substantial in most analyses due to 1) the low mortality rate (4%) in the Ranch Hand and comparison groups to date, 2) the inherently small group of Ranch Handers (as described in the study protocol), and 3) the observed relative risks which approached unity in most categories. This baseline mortality report can in no way be regarded as conclusively negative because this small, young, and relatively healthy cohort may not have yet reached the latency period wherein attributable fatal disease might be expected and detected within limited power boundaries of this study. Future commitments for the annual mortality updates include detailed covariate analyses for disease risk factors, herbicide exposure, and confounding industrial chemical exposures. Further, subsequent morbidity reports will include full spectrum, disease specific analyses, e.g., cancer (fatal, ongoing, cured) in an effort to enhance study sensitivity to emerging herbicide effects, if they occur. ii �AIR FORCEHEALTH STUDY (PROJECT RANCH HAND II) AN EPIDEMIOLOGIC INVESTIGATION OF HEALTH EFFECTS IN AIR FORCE PERSONNEL FOLLOWING EXPOSURE TO HERBICIDES BASELINE MORBIDITY STUDY RESULTS 24 FEBRUARY 1984 Prepared for: The Surgeon General United States Air Force Washington, D.C. 20314 George D. Lathrop, Colonel, USAF, MC William H. Wolfe, Lieutenant Colonel, USAF, MC Richard A. Albanese, M.D., GM-15 Patricia M. Moynahan, Colonel, USAF, NC Approved for public release; distribution unlimited. .£>. USAF SCHOOL OF A E R O S P A C E MEDICINE Aerospace Medical Division (AFSC) Brooks Air Force Base, T e x a s 7 8 2 3 5 �.* EXECUTIVE SUMMARY BASELINE MORBIDITY STUDY The Ranch Hand II epidemiologic study uses a matched cohort design in a nonconcurrent prospective setting, and .incorporates mortality, morbidity, and follow-up studies. -The purpose of this report is to present the baseline morbidity study. The morbidity study design matched each living Ranch Hander (by age, Job, and race) to the first living and compliant member of a randomly selected comparison mortality set of 5 individuals, producing a 1:1 contrast. The comparison group was formed from numerous flying organizations which transported cargo to, from, and within Vietnam, but were not involved in aerial spray operations of Herbicide Orange. Of the potential study participants, 99.5$ were located. Early in the physical examination phase of the study, it was discovered that 18$ of the entire comparison group was ineligible to participate because of inappropriate selection. Thereafter, study eligibility was certified only after a hand-review of personnel records. Next-in-line compliant comparisons entered the study as replacements after fully completing the questionnaire and physical examination. Statistical analyses of these replacement individuals later showed that they differed from the original comparisons in a variety of subtle and often opposite ways. As a conservative measure to avoid possible bias by the inclusion of the replacements in the analyses, a management decision was made to base the statistical tests in this report primarily upon contrasts of the Ranch Hand group to the original comparison group. The preponderance of data was obtained from the in-home interviews and the physical examination, each conducted under contract to the Air Force by Louis Harris and Associates, Inc., New York NY, and the Kelsey-Seybold Clinic, P.A., Houston TX, respectively. All contacts with the participants were carried out with utmost professionalism and sensitivity. Other morbidity data sources included reviews of medical records, military personnel documents, and birth certificates; in-home questionnaires and telephone questionnaires of the study participant's wives, former wives and, occasionally, their next-of-kin. All aspects of the study were voluntary. As a contract requirement, data collection personnel were blind as to the exposure status of the participants. Ninety-seven percent of the Ranch Handers and 93$ of the comparisons participated in the in-home interview. For the physical examination, 87$ of the Ranch Handers and 76$ of the comparison group participated, a total of 2,272 individuals. This differential attendance at the examination may have introduced a potential participation bias that, in a military population predominantly engaged in flying duties, is multifactorial and complex. All study phases were monitored by stringent quality control standards. Statistical analyses of the data consisted primarily of log-linear models, logistic regression techniques, generalized linear models, matched covariate analyses, and Kolmogorov-Smirnov, chi-square, and t tests. The physical examination and the in-home questionnaire data were analyzed by major organ system. In terms of general health, more Ranch Handers perceived themselves to be in fair or poor health than did their comparisons. No �group differences were detected for hematocrit or percent body fat determinations. Unadjusted group differences in sedimentation rate were not observed; however, significantly more young comparisons had abnormalities in sedimentation rate than did their Ranch Hand counterparts. There were no statistically significant differences in the occurrence of malignant or benign systemic tumors between the groups. One case of soft tissue sarcoma was found in a comparison member. Significantly more nonmelanotic skin cancer was noted in the Ranch Hand group, but these - analyses have not yet considered (adjusted for) sunlight exposure, the prime etiology of these cancers. Such nonmelanotic skin cancer (predominantly basal cell carcinoma) is the most common neoplasm in the White population of the United States. Up to the statistical limits of the study there were no consistent data that showed that the Ranch Handers were developing uncommon cancers, or cancer in unusual sites, or at an unusual age. Measures of fertility and reproductive outcome showed mixed results. It is emphasized that the fertility and reproductive results are preliminary at this time as they are based largely upon subjective self reports that await full medical record and birth certificate verification. Four measures of fertility: number of childless marriages, couples with the desired number of children, the infertility index and the fertility index, showed no difference between the Ranch Hand and comparison groups. A semen specimen obtained from those willing and able to provide one showed no group differences with respect to total sperm count or percent abnormal sperm. There were no significant findings in conception outcomes for miscarriages, stillbirths, induced abortions, or live births. For live birth outcomes no differences were observed for prematurity, learning disability, or infant deaths. There was no significant disparity between groups for the classifications of severe or moderate birth defects. By parental history, however, Ranch Hand offspring showed significantly more minor birth defects (birth marks, etc). Reporte'd neonatal deaths and physical handicaps were also significantly excessive in the Ranch Hand group when contrasted to the total comparison group. All fertility and reproductive findings in the Ranch Hand group showed inconsistent relationships to the herbicide exposure index. Medical records and birth certificates are currently being chronicled for complete verification of all historical findings. A comprehensive neurological examination showed no consistent abnormalities in the cranial nerves, peripheral nerves or central nervous system function of the Ranch Handers. As expected, there was a profound influence of diabetes and alcohol in both groups upon numerous neurological tests. Detailed psychologic data were obtained on all participants at both the in-home interview and the physical examination. It is emphasized that the majority of psychological data was derived from self reported responses during interview and has not been fully assessed for the effect of differential reporting. A variety of subjective deficits (fatigue, anger, fear, anxiety, etc) were significantly more common in the high school educated Ranch Handers. Educational level significantly and consistently influenced most subjective test results. In sharp contrast, more objective performance testing by the Halstead-Reitan battery and IQ testing did not reveal any significant intergroup differences. The roles of overreporting and the Post Vietnam Stress Syndrome In these analyses have not as yet been assessed. Liver function tests and clinical history data showed mixed results. Ranch Handers had some elevated liver enzyme tests and lower cholesterol levels. More Ranch Handers were found to have hepatomegaly and verified histories of prior hepatic disease than their counterpart comparisons. Exposure to alcohol, degreasing chemicals, and industrial chemicals in general, influenced ii �the liver test results. Ranch Handers reported significantly more symptoms resembling porphyria cutanea tarda than the comparisons-, but these data have not been verified by medical record reviews nor were they substantiated by laboratory testing or by physical examination. Exposure index analyses were essentially negative. In the dermatologic evaluation, no cases of c'hloracne were diagnosed clinically or by biopsy. A thorough questionnaire analysis of acne showed that the incidence, severity, duration, and anatomic location did not differ between groups, and suggested that the historical occurrence of chloracne was highly unlikely in the Ranch Handers. Evaluation of the cardiovascular system showed equal proportions of abnormalities in blood pressures, electrocardiograms, past electrocardiograms, and heart sounds in both groups. Ranch Handers are not having premature heart attacks or generalized heart disease. However, the Ranch Handers showed significant deficits in 2 specific peripheral leg pulses and all leg pulses as a group. These puzzling findings were highly correlated with age and smoking patterns, and verified past heart disease. The assessment of the immune system by laboratory testing was compromised by excessive test variability. An independent review committee determined which test data were suitable for statistical analysis. As an unexpected finding, the test data were significantly influenced by the age and smoking history of the participant; no group differences were detected after adjustment for these factors. A hematologic test battery revealed three red cell abnormalities in the Ranch Hand group, but these were difficult to place into a clinical or epidemiologic context. Evaluation of renal, pulmonary, and endocrine functions generally disclosed small and inconsistent proportions of abnormalities between groups, and were deemed clinically unimportant. An unrefined assessment of all summed and weighted organ system abnormalities by group did not show an aggregation of multisystem disease or malfunction. Any interpretation of these study data, in whole or in part, must carefully consider the methodical steps required for a proper inference of causality. It is specifically pointed out that many group differences were largely based upon subjective data, and that a subtle effect of differential reporting is suggested but has not been fully evaluated. For objective data, group differences were generally within normal ranges and were not correlated to the herbicide exposure index, nor fell within the expected latency periods following Vietnam service. The proposed clinical end points of dioxin exposure, chloracne, soft tissue sarcoma, and porphyria cutanea tarda, were not found in the Ranch Hand group (study power limitations recognized). Overall, substantial credence is given to the objective study findings, particularly after observing the consistent duplication of the classical effects of risk factors such as age, smoking, alcohol, etc., in almost all clinical areas. Additional work with these baseline data is still required in the areas of data base refinement, statistical testing and bias analysis, exposure index refinement, establishment of the follow-up examination requirements, and collaboration with other dioxin research studies. This baseline report concludes that there is insufficient evidence to support a cause and effect relationship between herbicide exposure and adverse health in the Ranch Hand group at this time. The study has disclosed numerous medical findings, mostly of a minor or undetermined nature, that require detailed follow-up. In full context, the baseline study results should be viewed as reassuring to the Ranch Handers and their families at this time. iii �PROJECT RANCH HAND II AN EPIDEMIOLOGIC INVESTIGATION OF HEALTH EFFECTS IN AIR FORCE PERSONNEL FOLLOWING EXPOSURE TO HERBICIDES MORTALITY UPDATE -1984 10 DECEMBER 84 William H. Wolfe, Colonel, USAF, MC Joel E. Michalek, PhD Richard A. Albanese, M.D. George D. Lathrop, Colonel, USAF, MC Patricia M. Moynahan, Colonel, USAF, NC Prepared for: The Surgeon General United States Air Force Washington, D.C. 20314 EPIDEMIOLOGY DIVISION DATA SCIENCES DIVISION USAF SCHOOL OF AEROSPACE MEDICINE (AFSC) BROOKS AIR FORCE BASE, TEXAS 78235 �Project Ranch Hand IT Mortality Update - 1984 EXECUTIVE SUMMARY HAOKCR<WNI> The purpose of the Ranch Hand II Study is to determine whether those Individuals involved in the aerial spraying of herbicides in Vietnam during the'Ranch Hand operation have experienced any adverse health effects as a result of their participation in that program. The study evaluates both mortality (death) and morbidity (disease) In these Individuals 6ver a 20-year period of time after the studies were initiated. The baseline mortality study was released in June 1983 and the baseline morbidity study in February 1984. Neither study demonstrated health effects which could be conclusively attributed to herbicide or dioxln exposure. The reader is referred to reports of the studies for further details (1, 12). METHOD The present study report describes the second mortality analyses. Deaths in the 1256 Ranch Hand and 6171 comparison subjects were determined, using the data sources of the Air Force, Veterans Administration, Social Security Administration, Internal Revenue Service, and personal contacts. As of 31 December 1983, 54 Ranch Handers and 265 comparison subjects had died. Death certificates were obtained on all subjects. Autopsies were conducted on 157 of the individuals who had died. Results have been obtained for 104 of these autopsies to confirm the death certificate findings. Autopsy reports for the 53 others have been requested, but have not yet been obtained. Extensive statistical analyses were accomplished, as detailed in the report, to compare the death experience in the Ranch Hand population with the comparison group. In addition, death experience in these groups was compared to the 1978 U.S. White Male Mortality experience, the 1978 Department of Defense Nondisability Retired Life Table, the mortality experience of the West Point Class of 1956, the USAF active duty personnel, and the active U.S. Civil Service population. RESULTS As was the case in the first mortality report, the current mortality analyses did not reveal any statistically significant differences in mortality between the exposed and comparison groups. The percentages dead in each major category are summarized below. Percent Deaths Ranch Hand Comparison Rank Officers Enlisted 3.2 4.9 4.0 4.5 Occupation Flying Ground 3.6 5.1 4.7 3.9 Note: None of the above differences between the Ranch Hand and Comparison groups are statistically significant. �Ranch Hand Total Overall 4.3 Comparison 4.3 As was reported In the baseline mortality study, the Ranch Hand officers had a nonstatlstically significant though slightly lover death rate than their comparisons, Ranch Hand flyers had a nonstatlstically significant though slightly lower death rate than comparisons, and Ranch Hand ground personnel had a slightly higher but nonstatlstlcally significant death rate than the comparisons. The herbicide/dioxln exposure index described In the morbidity report was applied to the data, and no relationship between exposure and mortality experience was identified. As was also noted in the baseline mortality study, analyaes consistently demonstrated significantly better survival in the Ranch Hand officers than Ranch Hand enlisted members, as was the case with comparison officers and comparison enlisted personnel. Cause-specific analyses did not demonstrate any Increased Ranch Hand mortality for accidents, suicide, homicide, malignancy or circulatory system disease. No unusual patterns of malignancy were observed in either the Ranch Hand or comparison groups, a finding which would be expected from the small number of deaths to date. When compared to the 1978 U.S. White male population, the Ranch Rand officers, comparison officers, and comparison enlisted are living significantly longer than expected. Although Ranch Hand enlisted are also living longer, the difference is not Significant. A similar pattern was seen in analyses using the DOD retired population. All groups bad a mortality experience similar to the civil service population. As would be expected from the fact that individuals In the active duty population who develop severe chronic disease are medically retired, all groups in this study had an increased mortality when compared to the Air Fore* population currently on active duty. Both Ranch Hand and comparison officers had mortality similar to the West Point group. I i CONCLUSION AND RECOMMENDATION Continued mortality surveillance is recommended, since the study groups are still relatively young and healthy. While sufficient time may have elapsed for some clinically significant conditions to occur, additional time Is necessary for other conditions, which; nay possibly be attributable to herbicide exposure, to develop. At this time, however* there Is no evidence of increased mortality as a result of herbicide exposure in those individuals who accomplished the Ranch Hand spray operations in Vietnam. �ABSTRACT OF REPRODUCTIVE OUTCOME DRAFT REPORT, 17 December 1984 Abstract: This report was written in response to requests from the Office of Science and Technology Policy, the Chair - Agent Orange Working Group and by direction of the Air Force Deputy Surgeon General. It was intended as an "interim" analysis of the data and not as a definitive answer to the birth defects issue. Since the release of the baseline morbidity report in February 1984, birth defects and neonatal deaths reported by study participants during the baseline questionnaire have been verified by record review. This verification was accomplished by the review of birth and other medical records, birth certificates and death certificates. Since not all data can be verified for at least an additional 24 months, these interim analyses were based on the v e r i f i c a t i o n of the p o s i t i v e reports only. Verification of negative responses to the birth defect and neonatal death questions have not as yet been completed. The draft report was submitted to the Advisory Committee on Special Studies Relating to the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants. Their comments have been received and will be discussed with them in a forthcoming visit to the Ranch Hand Office. This interim assessment will then be forwarded to the OSTP through the Chair, AOWG. b-s � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 199 Folder The folder containing the original item. 5598 Series The series number of the original item. Series VIII Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Lathrop, George D. Patricia M. Moynahan Richard A. Albanese William H. Wolfe Description An account of the resource <strong>Corporate Author: </strong>Epidemiology Division, Data Sciences, Division, USAF School of Aerospace Medicine (AFSC), Brooks Air Force Base, Texas Date A point or period of time associated with an event in the lifecycle of the resource June 30 1983 Title A name given to the resource Project Ranch Hand II: An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides, Baseline Mortality Study Results ao_seriesVIII Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 059 Folder The folder containing the original item. 1577 Series The series number of the original item. Series III Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Lathrop, George D. Patricia M. Moynahan Richard A. Albanese William H. Wolfe Description An account of the resource <strong>Corporate Author: </strong>United States Air Force School of Aerospace Medicine, Aerospace Medical Division (AFSC), Brooks AFB, Texas Source A related resource from which the described resource is derived Banbury Report 18: Biological Mechanisms of Dioxin Action Date A point or period of time associated with an event in the lifecycle of the resource 1984 Title A name given to the resource An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides Subject The topic of the resource Air Force Health Study Ranch Hand crew ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/ed8c1fec7593a8ef31278d2cec0a7ecf.pdf d01b274a9f366bc3df58bc723762ccd2 PDF Text Text Item ID Number 01 576 Lathrop, George D. United States Air Force School of Aerospace Medicine ( RupOrt/ArtlClO TitiB An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides: Mortality Update-1984 Journal/Book Title Year 1984 Month/Day December 10 Color Number of Images n so Descrlpton Notes Wednesday, May 23, 2001 Page 1577 of 1608 �PROJECT RANCH HAND II AN EPIDEMIOLOGIC INVESTIGATION OF HEALTH EFFECTS IN AIR FORCE PERSONNEL FOLLOWING EXPOSURE TO HERBICIDES MORTALITY UPDATE -1984 10 DECEMBER 84 William H. Wolfe, Colonel, USAF, MC Joel E. Michalek, PhD Richard A. Albanese, M.D. George D. Lathrop, Colonel, USAF, MC Patricia M. Moynahan, Colonel, USAF, NC Prepared for: The Surgeon General United States Air Force Washington, D.C. 20314 EPIDEMIOLOGY DIVISION DATA SCIENCES DIVISION USAF SCHOOL OF AEROSPACE MEDICINE (AFSC) BROOKS AIR FORCE BASE, TEXAS 78235 �Project Ranch Hand TI Mortality Update - 1984 EXECUTIVE SUMMARY BACKGROUND The purpose of the Ranch Hand II Study is to determine whether those individuals involved in the aerial spraying of herbicides in Vietnam during the Ranch Hand operation have experienced any adverse health effects as a result of their participation in that program. The study evaluates both mortality (death) and morbidity (disease) in these individuals over a 20-year period of time after the studies were initiated. The- baseline mortality study was released in June 1983 and the baseline morbidity study in February 1984. Neither study demonstrated health effects which could be conclusively attributed to herbicide or dioxin exposure. The reader is referred to reports of the studies for further details (1, 12). METHOD The present study report describes the second mortality analyses. Deaths in the 1256 Ranch Hand and 6171 comparison subjects were determined, using the data sources of the Air Force, Veterans Administration, Social Security Administration, Internal Revenue Service, and personal contacts. As of 31 December 1983, 54 Ranch Handers and 265 comparison subjects had died. Death certificates were obtained on all subjects. Autopsies were conducted on 157 of the individuals who had died. Results have been obtained for 104 of these autopsies to confirm the death certificate findings. Autopsy reports for the 53 others have been requested, but have not yet been obtained. Extensive statistical analyses were accomplished, as detailed in the report, to compare the death experience in the Ranch Hand population with the comparison group. In addition, death experience in these groups was compared to the 1978 U.S. White Male Mortality experience, the 1978 Department of Defense Nondisability Retired Life Table, the mortality experience of the West Point Class of 1956, the USAF active duty personnel, and the active U.S. Civil Service population. RESULTS As was the case in the first mortality report, the current mortality analyses did not reveal any statistically significant differences in mortality between the exposed and comparison groups. The percentages dead in each major category are summarized below. Percent Deaths Ranch Hand Comparison Rank Officers Enlisted 3.2 4.9 4.0 4.5 Occupation F l y i n g 3 . 6 Ground 5.1 4.7 3.9 Note: None of the above differences between the Ranch Hand and Comparison groups are statistically significant. i �Ranch Hand Total Overall 4.3 Comparison 4.3 As was reported in the baseline mortality study, the Ranch Hard officers had a nonstatistically significant though slightly lower death rate than their comparisons, Ranch Hand flyers had a nonstatistical1v significant though slightly lower death rate than comparisons, and Ranch Hand ground personnel had a slightly higher but nonstatistically significant death rate than the comparisons. The herbicide/dioxin exposure index described in the morbidity report was applied to the data, and no relationship between exposure and mortality experience was identified. As was also noted in the baseline mortality study, analyses consistently demonstrated significantly better survival in the Ranch Hand officers than Ranch Hand enlisted members, as was the case with comparison officers and comparison enlisted personnel. Cause-specific analyses did not demonstrate any increased Ranch Hand mortality for accidents, suicide, homicide, malignancy or circulatory system disease. No unusual patterns of malignancy were observed in either the Ranch Hand or comparison groups, a finding which would be expected from the small number of deaths to date. When compared to the 1978 U.S. White male population, the Ranch Hand officers, comparison officers, and comparison enlisted are living significantly longer than expected. Although Ranch Hand enlisted are also living longer, the difference is not significant. A similar pattern was seen in analyses using the DOD retired population. All groups had a mortality experience similar to the civil service population. As would be expected from the fact that individuals in the active duty population who develop severe chronic disease are medically retired, all groups in this study had an increased mortality when compared to the Air Force population currently on active duty. Both Ranch Hand and comparison officers had mortality similar to the West Point group. CONCLUSION AND RECOMMENDATION Continued mortality surveillance is recommended, since the study groups are still relatively young and healthy. While sufficient time may have elapsed for some clinically significant conditions to occur, additional time is necessary for other conditions, which may possibly be attributable to herbicide exposure, to develop. At this time, however, there is no evidence of increased mortality «is a result of herbicide exposure in those individuals who accomplished the Ranch Hand spray operations in Vietnam. ii �Table of Contents Page Executive Summary i Table of Contents ill 1 . In t roduct i on 1 2. 2 Ranch Hand Versus Comparison Group Analyses 3. Within Group Analyses of Mortality 12 4. 13 Cause-Specific Analyses 5. Noncause-Speclfic Comparisons with External Population . . 20 . 6. Comparisons with the West Point Group 33 7. Further Covariate Adjustments 38 8. Future Commitments 40 9. Summary and Conclusions..... 40 References 42 Principal Investigators 43 Appendix - Mortality by Year of Birth 44 iii �Project Ranch Hand II Mortality Update - 1984 1. Introduction This report updates the findings of the baseline mortality report (1) released on June 30, 1983. The reader is referred to the baseline report for information regarding the study design, statistical procedures, the mortality determination process and previous findings. Nine newly identified Ranch Banders have been added to the data file since the baseline report. One of these, a non-Black Enlisted ground crew member, died in 1981 of circulatory disease. Summary counts of the population at risk and the number of deaths in each of the three groups are shown in Table 1. The analyses in this report are based on this data and the data in Table 4. Table 2 contains the counts of new deaths in the population since the last report. Table 3 in this report corresponds to Table 3 in the baseline report and contains summary counts and death rates by job, race and group. These counts reflect cumulative mortality as of 31 December 1983 (certified as of 8 June 1984). Table 1 Summary Counts of Death by Rank and Occupation Ranch Hand At Risk Dead Rate (%) Rank Officers Enlisted Comparison At Risk Dead Rate ( ) % 466 790 15 39 0.032 (3.2) 0.049 (4.9) 2278 3893 91 174 0.040 ( . ) 40 0.045 (4.5) Flying Ground 646 610 23 31 0.036 (3.6) 0.051 (5.1) 3163 3008 149 116 0.047 (4.7) 0.039 (3.9) Total 1256 54 0.043 (4.3) 6171 265 0.043 (4.3) Occupation Table 2 Deaths During 1983 by Rank and Occupation Ranch Hand Rank Officer , Enlisted Comparison At Risk 1983 Deaths At Risk 1983 Deaths 451 754 0 3 2190 3731 3 12 3023 2898 9 6 Occupation Flying^ Ground 624 581 At risk count does not include the newly identified Ranch Hander who died prior to 1983. 1 �Table 3 Occupational and Race Specific Mortality Ranch Hand Comparisons At Risk Dead Rate At Risk Dead Ra_te_ Race Occupation Non-Black 350 Officer-Pilot 82 Officer-Nav 25 Officer-Other Enlisted-Fit Eng 191 532 Enlisted-Other 6 Officer-Pilot 2 Officer-Nav 1 Officer-Other Enlisted-Fit Eng 15 Enlisted-Other 52 Black Total 1256 0.034 0.024 0.040 0.037 0.053 0.000 0.000 0.000 0.133 0.038 1740 390 123 935 2628 13 10 2 75 255 74 14 3 51 101 0 0 0 10 12 54 0.043 6171 265 0.043 12 2 1 7 28 0 0 0 2 2 0.043 0.036 0.024 0.055 0.038 0.000 0.000 0.000 0.133 0.047 2. Ranch Hand Versus Comparison Group Analyses. Survival contrasts were made using linear rank procedures, survival curves, relative risk estimation and standardized mortality ratios. Survival curves were estimated via the product-limit estimate of Kaplan and Meier ( ) 2 . Linear rank testing was carried out using the logrank test and Prentice's censored data extension of the Wilcoxon test ( ) All linear rank tests were carried out with 3. matched sets merged when Ranch Banders differed by less than one year relative to date of birth. Within each stratum of job and race, these merged matched sets were used as separate strata for testing purposes. The matched data relative risk procedure, due to Ejigou and McHugh (4) is applied only to the 1241 Ranch Handers with matched comparisons and the stratified relative risk or SMR estimate is applied to all 1256 Ranch Handers. �Group contrasts were made on officers, enlisted personnel, flying personnel, ground personnel and the total group. Summary counts are shown ir\ Table 4. Table 4 Summary Counts by Rank, Occupation and Group Flying Personnel Groups Ranch Hand Comparisons At Risk 440 2153 Officer Dead Rate 14 88 0.032 0.041 Enlisted At Risk Dead Rate 206 1010 9 61 0.044 0.060 At Risk 646 3163 Total Dead 23 149 Rate 0.036 0.047 Ground Personnel Groups Ranch Hand Comparisons Officer At Risk Dead Rate 26 125 1 3 0.038 0.024 At Risk 584 2883 Enlisted Dead Rate 30 113 0.051 0.039 Total At Risk Dead Rate 610 3008 31 116 0.051 0.039 Survival curves were estimated only for officers, enlisted, flying, ground personnel and all personnel in Ranch Hand and the comparison groups. There is a substantial degree of overlap between these subgroups, with 96% of both the Ranch Hand and comparison ground personnel being enlisted. The enlisted category includes both ground support and flying enlisted personnel. Survival curves for the overall Ranch Hand and comparison groups are shown in Figure 1. The curves for officers, enlisted personnel, flyers and ground personnel are shown in Figures 2 through 5. �Figure 1 Survival Curve Estimates for All Ranch Banders and All Comparisons 1 0.9 0.8 COMP I °'? i—< > 0.8 OT o.e o »-« 0.4 o u_ 0.2 0.1 10 90 30 40 BO 60 70 flGE Figure 2 Survival Curve Estimates for Ranch Hand and Comparison Officers 1 0.9 0.8 O z 0.7 0.8 CO 0.5 . z o O cr 0.3 a; u_ 0.2 _ O.I - 0 10 20 30 40 flOE A 80 60 70 �Figure 3 Survival Curve Estimates for Enlisted Ranch Banders and Comparisons 1 0.9 COMP 0.8 cb > 0.6 o: » z o «- 0.6 0.4 U cr 0.3 a: u_ 0.2 0.1 10 20 _L 40 J_ 30 60 80 70 flQE Figure 4 Survival Curve Estimates for Ranch Hand and Comparison Flyers 1 0.8 0.8 RH Cb S °' 7 > > 0.6 CO 0.6 z CD •- »-«, 0 0.4 0.2 0.1 _ 0 to 20 30 40 flOE 5 60 60 �Figure 5 Survival Curve Estimates for Ranch Hand arid Comparison Ground Personnel 1 0.9 0.8 > r> w 0.6 0.61- z o *-* 0.4 _ O 0.3 0.2 . 10 20 40 60 70 fl&E The patterns qualitatively evident in these graphs are seen quantitatively in subsequent statistical analyses. Linear rank procedures were carried out on the same four subgroups and on all personnel to assess death patterns by time. These procedures are designed so that the statistic will be positive when Ranch Handers are dying before comparison subjects and negative when comparisons are dying prior to Ranch Handers. The results are shown in Table 5 (Table 6 in the baseline report). The rank statistic used is a fair measure of group difference only when this difference occurs consistently within each tested stratum. Since the strata in these analyses were formed by date of birth, occupation and race, the rank statistic is fair only when the group difference in death times does not change with date of birth, race and occupation. As will be shown later, there is an indication that there is an effect of date of birth on relative risks in the officer subgroup. Thus, rank statistics on officers must be interpreted carefully. Further, since there is an indication that mortality contrasts change with rank and occupation, the overall logrank value and p-value, shown in Table 5 are not valid summarv statistics. �Table 5 Test Results and P-values for Noncause-Specific Survival Group Officer Enlisted Flying Ground Logrank (value) P-value (-0..682) 0.495 ( 0,640) 0.522 (-1.144) 0.253 ( 1.303) 0.192 Wilcoxon (value) P-value (-0.771) 0.441 ( 0.575) 0.565 (-1.228) 0.220 ( 1.235) 0.217 Total ( 0.076) 0.939 ( 0.009) 0.993 Table 5 suggests that ground personnel in the Ranch Hand group are dying sooner than their matched comparisons (logrank = 1.303), but the difference is not statistically significant (p=0.192). The negative values of the logrank and Wilcoxon statistics for officers (logrank = -0.682) and flying personnel (logrank « -1.144) suggest that Ranch Banders in this group may be living longer than their matched comparisons. Similar analyses on the same subgroups (officer, enlisted, flying, ground and total) were carried out on data from non-Black subjects only. The results are shown in Table 6. Table 6 Test Results and P-values for Noncause-Specific Survival Non-Black Ranch Handers and Non-Black Comparisons Group Logrank (value) P-value Wilcoxon (value) P-value Officer Enlisted Flying Ground (-0.668) ( 0.686) (-1.229) ( 1.436) 0.504 0.492 0.219 0.151 (-0.755) 0.450 ( 0.626) 0.531 (-1.305) 0.192 ( 1.360) 0.174 Total ( 0.101) 0.919 ( 0.037) 0.970 The findings in Table 6 clearly parallel those of Table 5, as would be expected from the small size of the Black cohort in this study. Relative risk estimates, the associated 95% confidence intervals, two-sided p~values for testing the null, hypothesis of relative risk equal to unity, and power for detecting a relative risk of 2 in these data are shown in Table 7. These estimates are based on a matched data algorithm and summarize the relative prevalence of death in the Ranch Hand and comparison groups. As with the rank tests, the estimated relative risks are unbiased only when the relative risks can be assumed to be constant across date of birth strata. There is indication that this assumption is not met in the officer cohort so that their estimated relative risks must be viewed with caution. On the other hand, the assumption appears to be well met in the flying, ground and enlisted subgroups so that these relative risk estimates appear to be reliable. Since there is an indication that relative risk changes with rank and occupation, the overall relative risk, 0.965, is not a valid summary statistic. 7 �Table 7 Relative Risks, 95% Confidence Intervals, P-Values and Power for Noncause-Specific Deaths to Date (1241 Ranch Handers Versus 6171 Matched Comparisons) Group Rel Risk Conf Int 1.134) 1.475) 1.052) 1.793) P-yalue Powejr 0.275 0.692 0.174 0.274 0.886 0.980 0.968 0.928 Officer Enlisted Flying Ground 0.715 1.077 0.718 1.259 (0.295, (0.679, (0.385, (0.724, Total 0.965 (0.666, 1.264) 0.823 0.998 Table 7 shows that Ranch Hand flyers are experiencing fewer deaths than their matched comparisons (relative risk = 0.718), but this group difference Is not statistically significant (p=0.174). The Ranch Hand ground personnel have experienced more deaths (relative risk = 1.259) than their matched ground comparisons, but, again, this excess is also not statistically significant (p=0.274). Year-of-birth specific mortality rates are given in Tables 8 through 12, with the corresponding standardized mortality ratios (SMR) and associated p-values (5). In each analysis, the comparison group is the internal standard. The SMR will accurately estimate the relative risks within each stratum in these analyses if the year-of-birth specific relative risks are equal. A likelihood ratio test for the hypothesis of equal year-of-birth specific relative risks was carried out for each analysis, and its p-value is denoted by PI. In addition, the hypothesis that the relative risk is unity, given that relative risk is constant across strata, was tested; its p-value is denoted by P2. The SMR and both p-values are given for each contrast. Additional post hoc analyses are presented at the end of this section to show that the hypothesis of equal year-of-birth specific relative risks may not be met in the officer and flying cohorts. Table 8 Year-Of-Birth Specific Mortality Rates (1256 Ranch Handers Versus 6171 Comparisons) (SMR = 1.008, PI = 0.258. P2 - 0.983) Ranch Hand At Risk Dead Rate 1905-1914 1915-1919 1920-1924 1925-1929 1930-1934 1935-1939 1940-1944 1945-1954 Total 5 17 48 84 305 210 210 377 2 5 3 2 17 7 5 L3 1256 54 0.400 0.294 0.063 0.024 0.056 0.033 0.024 0.034 Comparison At Risk Dead Rate 14 96 241 501 1389 1020 1096 1814 3 12 24 44 73 36 23 50 6171 265 0.214 0.125 0.100 0.088 0.053 0.035 0.021 0.028 �Table 9 Officer-Specific Mortality Rates by Year-Of-Birtb (SMR =0.797, PI = 0.236, P2 - 0.404) Birth Year Ranch Hand At Risk Dead Rate 1910-1924 1925-1934 1935-1939 1940-1944 1945-1949 41 194 95 91 _45 3 4 4 2 2 Total 466 15 Comparison At Risk Dead Rate 205 930 458 495 190 17 51 12 6 5 2278 0.073 0.021 0.042 0.022 0.044 91 0.083 0.055 0.026 0.012 0.026 Table 10 Enlisted-Specific Mortality Rates by Year-Of-Birth (SMR = 1.105, PI - 0.663. P2 = 0.590) Ranch Hand At Risk Dead Rate 1905-1914 1915-1919 1920-1924 1925-1929 1930-1934 1935-1939 1940-1944 1945-1954 4 9 16 41 154 115 119 332. 2. 2 3 2 13 3 3 11 Total 790 39 Comparison At Risk Dead Rate 12 54 80 211 749 562 601 1624 3 8 11 24 42 24 17 45 3893 0.500 0.222 0.188 0.049 0.084 0.026 0.025 0.033 174 0.250 0.148 0.138 0.114 0.056 0.043 0.028 0.028 Table 11 Flying-Specific Mortality Rates by Year-Of-Birth (SMR =0.751, PI = 0.765. P2 = 0.186) Ranch Hand At Risk Dead Rate 1910-1924 1925-1934 1935-1939 1940-1944 1945-1949 44 272. 145 121 64 4 9 6 2 2 Total 646 23 0.091 0.033 0.041 0.017 0.031 Comparison At Risk Dead Rate 220 1316 698 653 276 23 78 24 14 10 3163 149 0.105 0.059 0.034 0.021 0.036 �Table 12 Ground Specific Mortality Rates by Year-of~Birth (SMR = 1.306, PI « 0.604. P2 = 0.203) Ranch Hand 1905-1914 1915-1919 1920-1924 1925-1929 1930-1934 1935-1939 1940-1944 1945-1954 5 8 13 31 86 65 89 313 2 1 3 2 8 1 3 U_ Total 610 Comparison 0.400 0.125 0.231 0.065 0.093 0.015 0.034 0.035 31 14 51 66 151 423 322 443 JL538 3 6 7 19 20 12 9 _40 3008 0.214 0.118 0.106 0.126 0.047 0.037 0.020 0.026 116 When year-of-birth is dichotomized (1905-1934, 1935-1954) and survival status (alive, dead) is analyzed by group (Ranch Hand, comparison) and rank (officer, enlisted), a significant four-way interaction is evident (p=0.024). That is, the survival status by birth year by group relationship changes with rank. The officer and enlisted relative risks are 0.50 and 1.23 in the 1905-1934 year-of-birth stratum and 1.72 and 0.97 in the 1935-1954 birth-year stratum. There were no three-way interactions in this analysis. When rank is replaced by flying status (flying, ground) in this four factor analysis, no four-way interaction is seen (p=0.250), and no significant group by flying status by birth-year interaction (p=0.790) Is observed. Further, when the officer, enlisted, flying and ground subgroups are analyzed separately on survival status, group and birth year, there is no three-way interaction for enlisted (p=0.480), flying (p=0.265) or ground personnel (p=0.634) but there is a significant three-way interaction for the officers (p=0.027). That is, the survival status by group relationship changes with year of birth in the officer cohort. Taken together, these log-linear analyses indicate that date of birth is affecting the relative risk estimate (and thus the SMR and rank tests) in the officer category. Specifically, the overall death experience of the Ranch Hand officers appears to compare favorably with the comparisons. However, these diminished death rates appear to be found in the Ranch Hand officers born before 1935, while Ranch Hand officers with later birth dates evidence a rate equal to or exceeding that of the comparisons (as seen in Table 14). A summary Table 13. of logrank, relative risk 10 and SMR results obtained is shown in �Table 13 Noncause-Speclfic Statistical Summary Age at Death Logrank Group Value P -value -0.682 Officer 0.495 0.640 Enli sted 0.522 -1.144 Flying 0.253 Ground 0.192 1.303 0.076 Total 0.939 Ground Deaths to Date SMR Relative Risk RR P-value SMR P-value 0.715 0.275 0.797 0.404 0.692 1.077 1.105 0.590 0.718 0.174 0.751 0.186 0.274 1.306 0.203 1.259 Total 0.965 Group Officer Enlisted Flying 0.823 1.008 0.983 The data in Table 13 show reasonable consistency. The ground cohort displays excess death in the Ranch Hand group in contrast to the comparison group, but this group difference is not statistically significant. The officer cohort evidences less death in the Ranch Hand group in contrast to the comparison group, but, again, this group difference is not statistically significant. However, as discussed above and shown in Table 14, this favorable mortality experience occurs in those individuals born before 1935, while Ranch Hand officers born after 1935 have experienced the same or greater death rate than their comparisons. 11 �Table 14 Death Rates ~by Group, Rank, Occupation and Year-Of-Birth Year of Birth Ranch Hand Death Rate Comparison Death Rate Relative Risk Before 1935 Enlisted 0.030 0.060 0.50 After 0.034 0.020 1.72 1935 Before 1935 0.100 0.080 1.23 After 1935 0.030 0.031 0.97 Flying Before 1935 After 1935 0.041 0.030 0.066 0.030 0.62 1.00 Ground Before 1935 After 1935 0.112 0.032 0.078 0.026 1.44 1.23 Occupation The favorable, though not statistically significant, survival experience of Ranch Hand flying personnel, relative to the matched comparison flyers is shown in Figure 4, where the survival curves for Ranch Hand and comparison flyers are drawn on the same scale and coordinate system. In contrast, the relatively poorer, but not statistically significant, survival experience of the Ranch Hand ground personnel is illustrated in Figure 5, wherein the Ranch Hand and comparison ground personnel survival curves are drawn on the same coordinate system. 3. Within Group Analyses of Mortality Within group year-of-birth adjusted contrasts by occupation and rank via SMR's are summarized in Table 15. The corresponding SMR analyses are shown in the Appendix. Table 15 Summary of Within Group SMR Analyses Subgroups SMR PJ^ P^ Officers versus Enlisted Ranch Hand Comparison 0.483 0.663 0.204 0.811 0.031 0.003 Flying versus Ground Ranch Hand Comparison 0.548 0.926 0.376 0.607 0.052 0.782 12 �Table 15 shows that Ranch Hand officers are having significantly fewer deaths (SMR=0.483, p=0.031) than Ranch Hand enlisted personnel, after adjustment for yearof-birth. This officer versus enlisted differential is also significant and in the same direction in the comparison group (SMR=0.663, p=0.003). The table demonstrates the favorable mortality experience of Ranch Hand flyers and adverse mortality of the Ranch Hand ground personnel in that Ranch Hand flyers are experiencing significantly fewer deaths than Ranch Hand ground personnel (SMR=0.548, p=0.052). This flyer versus ground differential is not apparent in the comparison group (SMR=0.926, p=0.782). As discussed before and as displayed in Table 14, the favorable Ranch Hand officer and flyer mortality experience is confined to the group born before 1935. **• Cause-Speel fic Analyses Table 16 shows death counts by cause and subgroup (flying officer, ground officer, flying enlisted and ground enlisted). Counts are shown for all 1256 Ranch Handers and the 6171 comparisons. The distribution of new deaths in the Ranch Hand and comparison groups are presented in Table 17 and age adjusted relative risks for these data are shown in Table 18. Relative risks are calculated using a matched data algorithm, hence, only the 1241 Ranch Handers having matched comparisons are used. Of the 15 unmatched Ranch Handers, two have died; a flying officer died of an accident and a ground airman died of circulatory system disease. Since these data are sparse, relative risks are only calculated on officer, enlisted, flying and ground subgroups, as well as on all personnel combined. Three cells in Table 18 contain two p-values for the significance of the relative risk estimate. The first is calculated using a null variance of the estimated relative risk and the second, within parentheses, is calculated using the group non-null variance estimate. A null variance is defined as a variance that requires knowledge of the true value of the estimated parameter, and that value is set equal to the value specified In the null hypothesis. The question of which variance estimate to use, and hence, which p-value to report is a point of research in theoretical statistics. We have chosen to use the null variance when computing p-values because of analogies with other testing situations and because our power studies have shown the resulting test to be more powerful than the test using the general non-null estimate. Unfortunately, the non-null variance must be used in computing 95% confidence intervals for the relative risk, making the p-value and confidence interval sometimes incompatible. Whenever this kind of disparity occurs, both p-values are given. 13 �Table 16 Deaths by Cause and Subgroup G round Flying C RH C RH C RH £ RH C Accident 8 32 0 1 4 26 7 35 19 94 Suicide 0 4 1 0 ] 3 1 9 3 16 Homicide 0 0 0 0 0 1 2 3 2 4 Parasitic infection 0 2 0 0 0 0 0 2 0 4 Malignant neoplasm 0 13 0 1 1 11 5 18 Uncertain neoplasm 0 1 0 0 0 0 0 1. 0 2 Endocrine 0 1 0 0 0 0 1 0 1 1 Mental disorder 0 0 0 0 0 0 0 1 0 1 Nervous System 0 1 0 0 0 0 0 1 0 2 Circulatory System 4 27 0 0 1 14 12 34 17 75 Respiratory System 0 1 0 0 0 2 0 2 0 5 Digestive System 2 4 0 1 1 3 2 5 5 13 Genitourinary System 0 1 0 0 0 0 0 2 0 3 Congenital anomalies 0 0 0 0 0 0 0 0 0 0 111 defined 0 1 0 0 1 1 0 0 1 2 14 88 1 3 9 61 30 113 Flying Cause RH Total Ground 14 Total 6 43 54 265 �Table 17 New Deaths by Cause Comparison 1 1 1 1 Total Lung Cancer Stomach Cancer Undetermined Circulatory 4 Circulatory 2 Digestive 4 Cancer 1 Homicide 1 Parasitic Infection 1 Respiratory _7_ Suicides 15 _ 4 * The newly identified deceased Ranch Hander. 15 �Table 18 Cause-Specific Age Adjusted Relative Risks by Group (1241 Ranch Banders versus 6171 Comparisons) Statistic Accident Suicide Cause Homicide Malignancy Circulatory Digestive Officer Rel Risk Conf Int P-Value Power 0.994 (0.161, 1.827) 0.989 0.601 Enlisted Rel Risk Conf Int P-Value Power 0.844 0.833 (0.279, 1.410) (0.000, 2.081) 0.624 0.814 0.780 0.374 Flying Rel Risk Conf Ir.t P-Value Power 0.935 (0.324,1.546) 0.841 0.767 Ground Rel Risk Conf Int P-Value Power 0.803 1.111 (0.090, 1.516) (0.000, 2.814) 0.633 0.892 0.621 0.334 3.333 ( . 0 , 9.297) 000 0.099 0.246 1.235 1.633 (0.000, 2.486) (0.480, 2.786) 0.675 0.144 0.461 0.592 1.667 (0.000, 4.334) 0.505 0.291 Total Rel Risk Conf Int P-Value Power 0.937 0.937 (0.456, 1.418) (0.000, 2.094) 0.804 0.919 0.899 0.425 2.500 (0.000 , 6.743) 0.221 0.262 0.684 1.043 (0.095, 1.272) (0.459, 1.627) 0.397 0.883 0.681 0.832 1.923 ( . 0 , 3.907) 000 0.174 0.387 0.400 ( . 0 , 0.972) 000 0.221 (0.412) 0.526 2.500 ( . 0 ,6.743) 000 0.221 0.262 1.258 (0.445,2.072) 0.474 0.701 1.875 (0.000,4.363) 0.312 0.320 0.208 (0.000,0.625) 0,113(0.000) 0.515 0.714 (0.000,2.211) 0.758 0.306 0.998 (0.108,1.889) 0.997 0.565 0.385 (0.000,0.836) 0.117(0.008) 0.652 2.143 (0.000,5.041) 0.217 0.306 �Tables 16 and 18 must be Interpreted with care since the data are very sparse in some categories. The Ejigou-McIIugh relative risk estimate uses a variance weighting scheme of relative risks. The variance expression used is correct only for large aggregates of such matched sets. Since matched sets with large numbers of comparison deaths are rare, but tend to occur iri the older subject cohorts, it must be anticipated that relative risks from the older cohorts may not be properly weighted In the relative risks shown here. Most disease information resides in the categories of malignant neoplasm and circulatory system deaths. Digestive system mortality by ICD code is shown in Table 19, site-specific malignant neoplasm mortality is shown in Table 20 and the morphology of neoplasms is shown in Table 21. There was one case of soft tissue sarcoma in a comparison individual, but none in the Ranch Hand group. Table 19 Digestive System Mortality Deaths Ranch Hand Comparison TCD Code Pancreatitis (5770) Alcoholic cirrhosis (5712) Nonalcoholic cirrhosis (5715) Nonalcoholic fatty liver (5718) Chronic liver disease (5728) Alcoholic liver disease (5711) Duodenal ulcer (5325) Peptic ulcer (5334) Hepatocellular disease (573a) 2 4 3 1 2 0 1 0 _0 5 Total 1 0 3 0 0 1 0 0 _0 13 These codes were based on death certificate data; more detailed etiologic information has been requested but not yet received for the nonalcoholic cirrhosis and fatty liver deaths. 17 �Table 20 Site-Specific Malignant Neoplasm Mortality Site I CD Code Ranjch Hand Lip, oral cavity, pharynx (140-149) Digestive organs, peritoneum (150-159) Respiratory, intrathoracic (160-165) Bone, connective tissue, skin, breast (170-175) Genitourinary organs (179-189) Brain (191-192) Lymphatic and hematopoietic tissue (200-208) No site specification (199) Comparison 18 4 9 17 0 1 0 t 3 3 0 _!_ 5 J_ 6 Total 0 1 3 43 �Table 21 Morphology of Neoplasms ICD Code 9th Ed. M800 Deaths Ranch Hand Comp Nomenclature Neoplasms not otherwise specified (NOS) 0 Brain M801-804 1 Bronchus and Lung Colon Esophagus Pancreas Intestinal Tract Unspecified site Epithelial neoplasms (NOS) 0 1 8 0 Kidney 1 Nasopharynx 0 0 Pancreas M872-879 M905 M938-948 M959-963 M964 M965-966 M986 Prostate Unspecified site Colon Papillary and Squamous Cell Nasal Sinus Lip Tongue Lung Tonsil Adenomas and Adenocarcinomas Appendix Bronchus and Lung Colon Kidney Stomach Pancreas Nevi and Melanomas Skin (NOS) Mediaetinal Trunk Mesothelioma Bronchus and Lung Gliomas Frontal Lobe Brain (NOS) Lymphomas NOS and Diffuse Lymphomas (NOS) Reticulosarcoma Malignant lymphoma histiocytic, (NOS) Hodgkin's disease Hodgkin's (NOS) Myeloid Leukemias Acute Myelocytic Leukemia Total 19 0 1 1 1 1 1 0 2 0 0 0 0 0 0 0 0 0 1 1 Stomach M814-838 1 0 0 0 0 0 Bronchus and Lung Esophagus M805-808 ] 5 1 0 0 0 0 0 0 1 1 1 0 1 1 2. 1 2 1 0 0 1 0 0 0 1 0 0 0 0 1 0 2 J) JL 6 43 �-*• Noncause-Specific Comparisons with Ex t erna 1 Pgpu 1 a t i ons It is important to know not only how Ranch Handers and their matched comparisons relate to each other, but also how their mortality rates compare with other military and civilian populations in the United States. These contrasts are used in an attempt to place the study groups in perspective with the overall mortality experience of known populations. Given the selection factors Involved for entry to and retention in the military service, it is anticipated that the study groups would exhibit lower mortality than the U.S. White male population but poorer mortality than the active duty Air Force population. Similarly, they might be expected to be more equivalent to the DOD retired personnel or occupational cohorts such as the U.S. civil service. In this report, the mortality experience of Ranch Handers and their matched comparisons is compared with the expected death rates with reference to the 1978 U.S. White Male Life Table ( ) the 1978 Department of Defense 6, period life tables for nondisability retired military officer and enlisted personnel ( ) 1979 active duty Air Force officer and enlisted personnel life, tables (8) and a 7, 1974 U.S. active male civil service life table (9) and the West Point class of 1956 (10). 5 ] • In Tables 22 and 23, Ranch Hand officers and comparison group officers are contrasted to a 1978 DOD nondisability retired officer life table and in Tables 24 and 25, Ranch Hand and comparison group enlisted personnel are compared with a 1978 DOD nondisability retired enlisted life table. In each table, the column labeled "At Risk" lists the number of subjects entering each five-year age interval, the column labeled "Deaths" tabulates the number of deaths in the age intervals and the column labeled "Expected Deaths" gives the expected number of deaths in the age intervals of the study subjects if they had experienced the same death rates as those specified by the DOD table. The value of the test statistic for testing the null hypothesis of equality of the study and referenced life table is denoted by T; its two-sided p-value is denoted by P. While each table summarizes the findings with five-year age intervals for ease of presentation, one-year age intervals were used for the actual computation of the statistic T. A negative value of T means that the study cohort has lived longer than expected relative to the reference population. All contrasts are unadjusted for race since the DOD tables are not race-specific. All analyses are conditioned on survival to age 35, since the DOD tables do not begin until that age., The totals in Tables 22 through 25 do not, therefore, agree with Table 1. 20 �Table 22 Ranch Hand Officer Versus DOD Nondisability Retired Officer Life Table (T=-4.494, P<0.001) Age At Risk Deaths Expected Deaths 36-39 40-44 45-49 50-54 55-59 60-64 65-69 459 386 309 209 2 1 1 1 1 2 0 3.568 4.469 5. .021 .847 3. 2.320 1.212 0.141 71 36 5 20.578 Total Table 23 Comparison Officers Versus DOD Nondisability Retired Officer Life Table (T=-3.288, P<0.001) Age At Risk 35-39 40-44 45-49 50-54 55-59 60-64 65-69 2264 1924 1448 Deaths Expected Deaths 12 13 24 14 10 4 _0 77 988 367 170 33 Total 21.630 21.892 23.808 19.291 11.860 6.144 1.158 105.783 Table 24 Ranch Hand Enlisted Personnel Versus DOD Nondisability Retired Enlisted Life Table (T=-0.220, P=0.826) At Risk 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-71 Total 735 432 311 182 54 23 9 2 Deaths Expected Deaths 7 5 6 6 2 3 0 562 999 163 228 2.553 1.774 0.779 0.118 30 31.176 21 �Table 25 Comparison Enlisted Personnel Versus DOD Nondisability Retired Enlisted Life Table (T=-3.731, P<0.001) Age At Risk Deaths £2E£££S.(jL5£atlLs 35-39 3611 21 37.166 40-44 2117 20 29.397 45-49 50-54 55-59 60-64 65-69 70-74 1534 907 258 116 46 7 36 17 14 4 2 0 35.350 25.533 12.545 9.005 3.638 0.908 0 0.065 114 153.607 75-76 2 Total Tables 22 and 23 show highly favorable mortality experiences for Ranch Hand and comparison officers. Conditioned on survival to age 35, they are living significantly longer than expected using the DOD death rates (p<0.001 and p<0.001, respectively). Tables 24 and 25 show that Ranch Hand enlisted personnel are experiencing mortality patterns similar to the DOD retired enlisted population (p=0.826), and comparison enlisted are living significantly longer (p< 0.001) than the DOD nondisability retired enlisted population (conditioned on survival to age 35). This, together with the nonsignificant logrank value for Ranch Hand versus comparison enlisted personnel shown in Table 5 (p=0.522), suggests that the Ranch Hand versus comparison officer and enlisted contrasts change with age at death. A view of this is seen in Table 26, which shows linear rank test results, comparing Ranch Handers and comparisons conditioned on survival to age 35 (analogous to Table 5). Table 26 Test Results and P-values for Noncause-Specific Survival Conditioned on Survival to Age 35 Group Logrank (value) P-value Wilcoxon (value) P-value Officer Enlisted Flying Ground (-1.741) ( 1.379) (-1.331) ( 1.535) 0.082 0.168 0.183 0.125 (-1.879) ( 1.345) (-1.440) ( 1.491) Total (-0.033) 0.974 (-0.110) 0.913 22 0.060 0.179 0.150 0.136 �Categorical analyses reveal the interaction suggested by the Ranch Hand versus U.S. White male contrasts. These are shown in Tables 2.7 and 28 where survival status (alive, dead) is analyzed as a function of group (Ranch Hand, comparison) and rank (officer, enlisted) on deaths under 35 years of age and separately, on deaths over 35 years of age. Table 27 Death Before 35, Ranch Hand Versus Comparisons (Group By Rank By Status Interaction: P=0.043) Status Rank Officer Grout Alive Dead Total Ranch Hand 459 7 466 Comparison 2264 14 2278 Ranch Hand 781 9 790 Comparison 3833 60 Relative Risk 3893 2.44 Enlisted 0.74 Table 28 Death After 35, Ranch Hand Versus Comparisons (Group By Rank By Status Interaction: P=0.019) Status Rank Officer Group Alive Dead Total Ranch Hand 451 8 459 Comparison 2187 77 2264 Ranch Hand 705 30 735 Comparison 3497 114 361] Relative Risk 0.51 Enlisted 1.29 23 �In Table 28, the Ranch Hand versus comparison contrast in the officer category is significantly different from the corresponding contrast in the enlisted category. This suggests that, among those surviving to age 35, Ranch Hand officers are experiencing fewer deaths (relative risk =-- 0.51) than their matched comparisons while the Ranch Hand enlisted are experiencing more deaths than their matched comparisons (relative risk = 1.29). Death rates are shown in Table 29. The rate that is most apparently different is the low Ranch Hand officer death rate for those officers who survived to age 35. This low rate may parallel the favorable mortality experienced by those Ranch Hand officers born before 1935. Further analyses will attempt to clarify these patterns, with specific attention to cause of death. Table 29 Death Rates as a Function of Age at Death Death Rates Ranch Hand Officers En.listed Before Age 35 After Age 35 0.015 (N=466) 0.017 (N=459) Comparison Officers 0.006 (N=2278) 0.035 (N-2264) 0.014 (N=790) 0.041 (N=735) Enlisted 0.016 (N=3893) 0.033 (N-3611) 5.2 Comparison with Active Duty Air Force Life Tables The mortality experience of the Ranch Handers and their matched comparisons is contrasted with the total active duty 1979 Air Force life table, unadjusted for race, in Tables 30-35. Officers and enlisted personnel in the Ranch Hand and comparison cohorts are contrasted with active duty officer and enlisted Air Force life tables in Tables 32-35. Since the active duty Air Force life tables were accurate to only three significant figures, the expected deaths shown in Tables 30-35 are computed to three significant figures. In the active duty Air Force, individuals found to have major health deficits are quickly removed from the population by medical discharge or disability retirement. Hence, this external population is biased toward excellent health and favorable mortality. These contrasts are conditioned on survival to age 20 and death up to age 50. The totals in Tables 30 through 35 do not, therefore, agree with Table 1. Table 30 Ranch Handers Versus 1979 Active Duty Air Force Life Table (T-3.99, P 0.001) Age At Risk Deaths Expected Deaths 20-24 25-29 30-34 35-39 40-44 45-49 1256 1254 1247 1194 818 620 2 7 7 9 6 __7 5.04 5.06 3.7? 5.12 4.41 4.17 38 27.52 Total 24 �Table 31 Comparison Versus 1979 Active Duty Air Force (T-7.41, P<0.001) Ag£ At Risk 17-19 20-24 25-29 30-34 35-39 40-44 45-49 Deaths 6171 6169 6151 6122 5875 4041 2982 Deaths Expected 2 18 29 25 33 33 60 200 Total 18, 24, 24.8 153.20 Table 32 Ranch Hand Officers Versus 1979 Active Duty Air Force Officer Life Table (T=4.43, P<0.001) Age At Risk 25-29 30-34 35-39 40-44 45-49 Deaths 466 463 459 386 309 Expected Deaths 2.34 1.40 0.859 1.06 1.32 3 4 2 1 _L 11 Total 6.979 Table 33 Comparison Officers Versus 1979 Active Duty Air Force Officer Life Table (T=8.37, P<0.001) At Risk 25-29 30-34 35-39 40-44 45-49 Total 2278 2269 2264 1924 1448 Deaths Deaths Expected 9 5 12 13 24 11.4 6.86 4, 26 5. 15 6.25 63 33.92 25 �Table 34 Ranch Hand Enlisted Versus the 1979 Active Duty Air Force Enlisted Life Table (T=3.30, P<0.001) ASS. — M®™ 20-24 25-29 30-34 35-39 790 788 784 735 40-44 45-49 ^??J;!1JL 432 311 2. 4 3 7 Expected Deaths 3.17 3.18 2.31 3.57 5 __6 2.67 _JL-li 27 18.49 Total Table 35 Comparison Enlisted Personnel Versus the 1979 Active Duty Air Force Enlisted Life Table (T=6.42, P<0.001) Age At Risk 17-19 20-24 25-29 30-34 35-39 40-44 45-49 3893 3891 3873 3853 3611 2117 1534 Total Deaths Expected Deaths 2 18 20 20 21 20 _36 11.7 15.6 15.6 11.4 17.5 13.1 17.8 137 102.70 As expected, the central death rates for the active duty Air Force population are lower than those for the DOD nondisability retired population. In addition, it is expected that the Ranch Banders and their comparisons should He somewhere between these two reference populations, for reasons such as the healthy worker effect and the medical retirement of unfit individuals from the active force. This is, in fact, the case for Ranch Hand officers, comparison officers and comparison enlisted personnel. All three of these groups are living significantly longer than expected from the DOD life table, but are dying significantly sooner than expected relative to the active duty Air Force life tables. The exception to this pattern is seen in the Ranch Hand enlisted personnel who are experiencing mortality only equivalent to the DOD enlisted life table (p=0.826). They, like the other groups, are also having a significantly worse than expected mortality experience relative to the active duty Air Force enlisted life table (pcO.OOl). 26 �5 3 • Comparisons with the U.S.^Actiye Male Civil Service Life Table To further place the Ranch Handers and their matched comparisons in perspective, Ranch Handers, comparisons, and officer and enlisted personnel are 9 . These contrasted with the 1974 male active U.S. civil service life table ( ) contrasts are shown in Tables 36 through 41. There is no adjustment for civil service grade in these analyses. Therefore, socioeconomic factors may not be fully equivalent, especially in the analyses of the officer and enlisted subgroups. In future mortality updates, attempts will be made to account for the grade structure of the civil service population. Table 36 All Ranch Handers Versus U.S. Male Civil Service (T=0.140, P-0.889) Age At Risk 21-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-71 1256 1254 1247 1194 818 620 391 125 59 14 2 Deaths Expected Deaths JL 6.773 5.998 5.679 6.495 7.830 8.853 5,.907 3.,176 1,,758 0.463 0.054 54 52.997 2 7 7 9 6 7 7 3 5 0 Total Table 37 Comparison Versus U.S. Male Civil Service (T=-0.957, P-0.339) Age At Risk Deaths Expected Deaths 19-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-73 6169 6167 6149 6120 5873 4039 2980 1893 623 284 77 5 2 18 29 25 33 33 60 31 24 8 2 0 10.52.3 43.093 29.444 27.912 31.995 38.333 42.793 29.220 15.906 8.797 2.355 0.168 265 280.549 Total 27 �Table 38 Ranch Hand Officers Versus U.S. Male Civil Service ( — 1.728, P=0.084) T At Risk 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 466 463 459 386 309 209 71 36 5 Deaths Ex£ect«jd_De_aths 2.226 2.118 2.885 3.821 4.46] 3.239 1.886 0.917 0.099 15 Total 3 4 2 1 1 1 1 2 0 21.652 Table 39 Comparison Officers Versus U.S. Male Civil Service (Comparisons: T=-1.658, P=0.097) Age 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 Total At Risk 2278 2269 2264 1924 1448 988 367 170 33 Deaths 9 5 12 13 24 14 10 4 0 10.910 10.418 14.261 18.710 2.1.152 91 106.788 28 16.237 9.648 4.635 0.817 �Table 40 Ranch Hand Enlisted Personnel Versus U.S. Male Civil Service (1=1.661, P=0.097) A_g_e_ At Risk Deaths 21-24 25-29 790 788 2 4 30-34 784 3 3.561 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-71 735 432 311 182 54 23 9 2 7 5 6 6 2 3 0 _!_ 3.610 4.009 4.392 2.668 1.289 0.841 0.364 0.054 39 28.828 Total Expected Deaths 4.258 3.772 Table 41 Comparison Enlisted Personnel Versus U.S. Male Civil Service (T=1.528, P=0.127) Age At Risk 19-19 20-24 25-29 30-34 3891 3889 3871 3871 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-73 Total Deaths Expected Deaths 2 18 20 20 6.637 27.158 18.535 17.494 3609 21 17.733 2115 1532 905 256 114 44 5 20 36 17 14 4 2 0 19.623 21.641 12.983 6.258 4.162 1.538 0.168 174 153.930 The Ranch Banders and their matched comparisons are statistically quite close to the male civil service population. In these contrasts, the healthy worker effect is roughly equivalent although there is no adjustment for socioeconomic status. The contrasts of officers and enlisted personnel in the Ranch Hand and comparison cohorts with the male civil service reveal that the Ranch Hand and comparison 29 �officers are experiencing a slightly, but not significantly better mortality tban the civil service, with the Ranch Hand officers faring somewhat better than the comparison officers. Ranch Hand and comparison enlisted personnel are experiencing more mortality than the civil service with the Ranch Hand enlisted personnel faring slightly worse than the matched comparison personnel, but none of these observations are statistically significant. All of these findings are consistent with the linear rank testing shown in Table 5, the relative risks in Table 6 and the SMR's In Tables 8, 9, and 10. 5.4 Comparisons With the U.S. 1978 White Male Life Table Finally, the mortality experience of the non-Black Ranch Handers and their matched comparisons is contrasted with the 1978 U.S. White Male Life Table. Table 42 Non-Black Ranch Handers Versus the 1978 U.S. White Male Life Table (T=-4.828, P<0.001) Age At Risk 21-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-71 1180 1178 1172 1121 779 592 379 124 59 14 2 Total Deaths Expected Deaths 2 6 7 8 5 7 6 3 5 0 9.073 9.858 9.596 10.022 11.028 13.424 10.093 5.763 3.699 0.959 0.11.0 50 83.635 30 �Table 43 Non-Black Comparisons Versus the 1978 U.S. White Male Life Table (T=-12.286, P<0.001) At Risk 19-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-76 5816 5815 5799 5772 5537 3857 2846 1831 618 286 79 7 2 Total Deaths 1 16 27 23 31 29 53 31 22 8 2 0 0 Expected Deaths 10.325 55.444 48.592 47.336 49.594 54 . 105 64.837 49.932 28.956 18.756 5.228 0.845 0.063 430.324 243 Table 44 Non-Black Ranch Hand Officers Versus the 1978 U.S. White Male Life Table (T=-5.438, P< 0.001) Age At Risk 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 457 454 450 381 306 208 71 36 5 Total Dead Expected Deaths 3 4 2 1 1 1 1 2 0 3.819 3.735 4.620 5.585 6.981 5..633 3. .429 1.919 0.205 15 35.926 31 �Table 45 Non-Black Comparison Officers Versus the 1978 U.S. White Male Life Table (T—9.141, P<0.001) 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 9 5 12 13 24 14 10 4 0 Total 18.880 18.530 22.997 27.325 33.096 28.249 17.513 9.725 1.699 91 22.53 2244 2239 1899 1433 980 367 170 33 150.689 Table 46 Non-Black Ranch Hand Enlisted Personnel Versus the 1978 U.S. White Male Life Table (T=-1.585, P=0.113) Age At Risk 2.1-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-71 723 721 718 671 398 286 171 53 23 9 2 Total Dead Expected Deaths 2 3 3 6 4 6 5 2 3 0 1 5.556 6.039 5.861 5.402 5.443 6.443 4.460 2.334 1.779 0.754 0.110 35 44.181 32 �Table 47 Non-Black Comparison Enlisted Personnel Versus the 1978 U.S. White Male Life Table (T—6.393, P 0.001) Age At Risk Dead Expected Deaths 18-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-75 3563 3562 3546 3528 3298 1958 1413 851 251 116 46 7 2 1 16 18 18 19 16 29 17 12 4 2 0 _Q 6.325 33.938 29.713 28.806 26.597 26.780 31.741 21.683 11.443 9.031 3.529 0.845 0.063 152 230.494 Total The healthy worker effect Is an expected phenomenon In these data since Air Force veterans have been selected for active duty on the basis of health and technical ability. This effect is clearly evident in the overall contrasts shown in Tables 42. Both Ranch Banders and comparisons are seen to be living far longer than expected relative to the general U.S. White male population. The same effect is seen in both Ranch Hand and comparison officers (Table 44) and in comparison enlisted personnel In Table 47. The Ranch Hand enlisted personnel, however, are seen to be similar to the U.S. White male population (T--1.585, p=0.113); they are living longer than expected but not significantly so, In contrast to the other groups. The healthy worker effect is less evident in the Ranch Hand enlisted group, and this suggests that they are faring less well against the U.S. White male population than their matched comparisons. It is also important to note, in view of the poorer survival experience of Ranch Hand ground personnel, shown in Tables 5 and 6, that this group is closer to the U.S. White male population than the enlisted (Appendix Table 5), with an observed to expected death ratio of 0.883, based on 557 non-Black Ranch Hand ground personnel. Further, the corresponding finding for non-Black Ranch Hand enlisted ground personnel (Appendix Table 6), with an observed to expected ratio of 0.908 (based on 584 Ranch Hand enlisted ground personnel) suggests that the enlisted ground personnel may be experiencing adverse mortality that, while not significant relative to their matched comparisons, deserves close attention in fnture updates. 6. Comparisons with the West Point Study Group The mortality experience of Ranch Hand and comparison officers is also contrasted with the West Point Study Group. Although the West Point group is too small for all but very crude statistical comparisons, it does provide a useful benchmark for general mortality contrasts. 33 �The West Point Study Group consists of 474 members of the West Point Class of 1956. These men have been followed since that time for morbidity and mortality. All members of that class were, or still are* officers in the U.S. Armed Forces. The purpose of the West Point Study is to investigate the relationship between blood lipid levels and cardiovascular disease. Each study subject is physically examined biennially and blood samples are obtained for lipid and lipoproteln analyses at the USAF School of Aerospace Medicine (11). 6.1 Noncause-Specific Comparisons of Ranch Hand and Comparison Subgroups with the West Point Study Group No new deaths have occurred in the West Point (10) group since the baseline report and prior to 31 December 1983. The number of West Point deaths, therefore, remains at 36. For the purpose of these mortality comparisons, 15 of the 36 known West Point deaths occurring on or before 31 December 1983 were deleted; 9 of the 15 were killed in action, 1 was killed in 1959 in the line of duty and 5 were killed in automobile crashes prior to 1962. The rationale for these deletions is identical to that used for deaths of personnel killed In action from the Ranch Hand and comparison groups. Noncombat or accidental deaths prior to 1962 were deleted because death prior to 1962 would have precluded membership in the Ranch Hand or comparison group. In addition, one West Pointer is also a Ranch Hander and was removed from the West Point data base. That individual was alive on 31 December 1983. A summary of the remaining 21 deaths among the 458 West Point subjects used in these analyses is given in Table 48 and by age In Table 49. Table 49 lists the number of West Pointers at risk in each age group, the number alive on 31 December 1983, and the number dead. Table 48 West Point Deaths by Year-Of-Birth Year of Birth At Risk Dead 1930 1931 1932 1933 1934 1935 20 59 90 136 141 12 0 2 6 8 4 J_ Total 458 21 34 �Table 49 West Point Deaths by Age Alive 25-29 30-34 35-39 40-44 45-49 50-52 458 456 451 448 446 290 Dead 0 0 0 0 148 289 437 Total 2 5 3 2 8 _!_ 21 In this analysis, non-Black Ranch Hand and comparison officers are compared, without regard to cause of death, with the West Point Study group (all of the West Point subjects are non-Black). Non-Black Ranch Hand officers were matched, one-to-one, by year-of-birth, to West Point subjects. Due to the relatively small number of Ranch Hand officers and the limited year-of-birth range imposed by the age of the class of 1956, only 297 of the 458 West Point subjects received a matched Ranch Hander. Matched sets with West Pointers having the same year-of-birth were then merged to create six matched sets, corresponding to the six years-of-birth, 1930 through 1935. To compare West Pointers with comparison officers, 1368 non-Black comparison officers were matched to the 458 West Point officers, and these were then merged to six single-year-of-birth strata. Logrank tests were carried out on these matched data sets and the results are summarized in Table 50. In these analyses, survival time is age at death. SMR analyses, with the West Pointers being the standard, are shown in Table 51. Table 50 Non-Black Study Group Versus West Point Group Logrank P-values Contrasts P-value Ranch Hand officers versus West Point Comparison officers versus West Point 35 0.273 0.944 �Table SMR Comparison of Non-Black Ranch Hand and Comparison Officers With West Point (SMR=0.490) Ranch Hand Birth Year At Risk 1925-31 1932 1933-34 1935-40 98 35 60 107 Total Dead (SMR=1.00) West Point (SMB-0.790) Comparison Rate At Risk Dead Rate At Risk Dead Rate 0.020 0.029 0.017 0.037 500 164 257 _555. 38 7 6 JL3 0.076 0.043 0.023 0.023 79 90 2.77 12 2 6 12 _L 0.025 0.067 0.043 0.083 1476 64 458 21 300 2 1 1 4 In Table 51, the test for constant relative risk across year-of-birth strata has a p-value of 0.134, and a likelihood ratio test suggests that these groups are not different (p=0.306). The analyses shown in Tables 50 and 51 indicate that there is no significant difference between non-Black Ranch Hand and comparison officers and the West Pointers. 6.2 Cause-Specific Comparisons The cause-specific death counts for the West Point study group are given in Table 52. Table 52 West Point Mortality by Cause Deaths Cause Accidents Infectious Diseases Malignant Neoplasms Circulatory Digestive Genitourinary Ill-Defined Conditions 6 5 1 1 Total 21 Cause-specific comparisons are carried out for cancer (malignant neoplasms), other diseases, and nondiseases (accidents, suicides, homicides and ill-defined conditions), with an adjustment for year-of-birth by stratification on year-ofbirth. Relative risks are calculated using the method of Mantel and Haenszel (11). The results, based on the counts in Tables 53 and 54, are shown in Table 55. 36 �Table 53 Cause-Specific Comparisons Non-Black Ranch Hand Officers Versus West Point Ranch Hand Dead At Risk West Point Dead At Risk Cause Birth Year Mondisease 1925-1933 1934-1940 169 131 1 4 305 153 Cancer 1925-1930 1931 1932 1933 1934 1935-1940 74 24 35 36 24 107 0 0 0 0 0 0 20 59 90 136 141 12 0 1 3 1. 1 0 Other diseases 1925-1934 1935-1940 193 107 2 1 446 12 8 1 Table 54 Cause-Specific Comparisons Non-Black Comparison Officers Versus West Point Cause Birth Year Comparison At Risk Dead West Point At Risk Dead 1925-1931 1932 1933 1934-1940 500 164 148 664 18 2 1 6 79 90 136 153 1 2 2 1 Cancer 1925-1931 1932 1933 1934-1940 500 164 148 664 4 2 1 3 79 90 136 153 2 3 1 1 Other diseases 1925-1932 1933 1934 1935-1940 664 148 109 555 19 1 1 6 169 136 141 12 1 5 2 1 Nondisease 37 �Table 55 Cause-Specific Relative Risks, P-values and 95% Confidence Intervals for Relative Risk 95% Conf Int Rvalue Cause Comparison Re1 Risk Nondisease RH vs WP Comp vs WP 1.250 1.192 (0.257, (0.361, 6.072) 3.939) 0.782 0.774 Cancer RH vs WP Corap vs WP 0.551 (0.156, 1.949) 0.355 Other diseases RH vs WP Comp vs WP 0.446 0.951 (0.027, (0.131, 7.278) 6.916) 0.571 0.961 All causes RH vs WP Comp vs WP 0.475 0.882 (0.198, (0.189, 2.279) 4.100) 0.352 0.872 The Ranch Hand versus West Point cancer comparison cannot be assessed using the Mantel-Haenszel procedure due to the lack of cancer deaths in the Ranch Hand officer group. The overall and cause specific equivalence of these study groups and the West Pointers suggest that these analyses do not contribute enough to this study to warrant yearly reporting. 7' Further Covariate Adjustments Some of the contrasts shown in previous sections in this report are further analyzed here using information about the Vietnam experience for Ranch Handers and comparisons. These analyses are motivated by the need for clarification of previous contrasts and should be viewed as preliminary to more complete analyses which will be presented in future reports. The information used here consists of (1) tour length and (2) a measure of cumulative exposure to dioxin. Tour length is defined as the cumulative time, in months, spent on assignment to Ranch Hand units by a Ranch Hander and to C-130 cargo units in SEA by a comparison. Cumulative exposure to dioxin, termed the "exposure index," is defined in the baseline morbidity report (12) and is proportional to the dioxin content of the herbicides being sprayed and inversely proportional to the number of persons sharing the workload with the subject to whom it is applied. Ranch Hand Tour^Length The effect of tour length on mortality will be investigated in detail in future reports. In this report, some descriptive statistics on tour length are presented, and tour length is used as a factor in some exposure analyses. Table 56 shows the 5, 50 and 95 percentiles of tour length in months for flying and ground personnel, and officers and enlisted personnel in Ranch Handers and the comparisons. 38 �Table 56 Tour Length Percentlies (In Months) for Ranch Handers and Comparisons Flying Status Percentiles 50% 95% Sample Size Flying Ground 13 13 19 16 439 26 Enlisted Flying Ground 4 5 12 13 22 19 206 582 Officer Flying Ground 12 11 20 17 48 44 2939 152 Enlisted Comparison 5 5 Flying Ground 10 10 20 19 52 48 1412 3767 In general, the comparisons had longer tour lengths than Ranch Handers. This is the result of longer tours of duty at noncombat zone bases (comparisons) relative to combat area bases (Ranch Hand). 7. 2 Ranch Hand Exposure Analysejs The effect, of exposure on mortality was assessed on the 1230 Ranch Handers having exposure information in a log-linear analysis based on survival (dead, alive), rank (officer, enlisted), year-of-birth (1905-1934, 1935-1954) and exposure (light, medium, heavy). These data are shown in Table 57. Table 57 Ranch Hand Mortality Adjusted for Year-Of-Birth, Rank and Exposure Exposure Rank Light Officer Enlisted Medium Officer Enlisted Heavy Officer Enlisted Birth Year 1905-1934 1935-1954 1905-1934 1935-1954 1905-1934 1935-1954 1905-1934 1935-1954 1905-1934 1935-1954 1905-1934 1935-1954 Survival Status Alive Total Dead 62 80 62 173 80 66 55 274 78 60 81 106 2 3 8 6 2 2 9 5 3 2 5 6 39 64 83 70 179 82 68 64 279 81 62 86 112 Death Rate 0.031 0.036 0.114 0.034 0.024 0.029 0.141 0.018 0.037 0.032 0.058 0.054 �There is no four-way Interaction in these data (p=0.304), there is no three-wav interaction involving survival and exposure and the two-way survival by exposure interaction is not significant (p=0,691). The survival hy year-of-birth by rank interaction is marginally significant (p~0.0627) and the year-of-blrth hv r«nk by exposure interaction is very significant (p 0.001). Both of these observations are expected from previous analyses of these data. Tn summary, survival is not affected by exposure, with or without adjustment for rank and year-of-birtb. A restriction of survival, exposure and adjusted for birth year a restriction to deaths new findings. the analysis to officers shows no relationship between birth year (p-0.967) or between survival and exposure (p=0.907) or unadjusted for birth year (p=0.905). Finally, after 35 years of age in non-Black Ranch Handera yields no A restriction of the analysis to enlisted personnel shows a significant survival by exposure by birth year interaction (p=0.044), indicating that the survival by exposure relationship within the 1905-1934 birth year cohort is significantly different from that of the 1935-1954 cohort. Classic dose-response patterns are not seen here so that a herbicide effect cannot be reliably inferred at this time. Future work will attempt to evaluate mortality patterns as a function of occupational subgroup in the ground cohort. This effort will require simulation studies and additional interviews to delineate differential exposure between occupational subgroups. Flight line duties and herbicide contact will be ascertained objectively along with additional medical risk factors, occupational exposures and socioeconomic factors. These analyses will be increasingly meaningful as the population ages and mortality rates permit use of more incisive statistical tools. Finally, joint morbidity-mortality analyses, adjusting for relevant covariates will be carried out. Future research will be directed at the development of statistical procedures which take the repeated testing aspect of these updates into account. The feasibility of using comparison data from the entire 1:8 design will also be studied. 9, u m m r v ^ Conclusion Evaluation of summary counts of death by rank and occupation did not reveal any statistically significant differences between the Ranch Hand and comparison groups. Other mortality analyses described in this report have revealed some differences in death experience between the herbici.de/dioxin exposed group, their matched comparisons and other external comparison groups. Overall mortality of the Ranch Rand group is nearly Identical to that of the comparison group, being 4.3%. Ranch Hand officers born between 1905 and 1935 have experienced fewer deaths than comparison officers born during the same era. On the other hand, Ranch Hand officers born after 1935 have experienced more death s than their comparisons. Although these differences within birth year strata are not statistically significant, this change in the group by survival status relationship with birth year is statistically significant (p=0.0?7). Additionally, Ranch Hand officers experienced fewer deaths after ape .35 years than did comparison officers, while �Panch Hand officers experienced more deaths before age 35 years than did comparisons. Further research will investigate whether there is any association between birth year and age of death and mortality patterns in these officer cohorts. At this time, Ranch Hand ground and enlisted personnel have experienced more mortality than their comparisons, but these differences are not statistically significant. Preliminary analyses using exposure indices have indicated no association between herbicide exposure in either the officer, enlisted, flying or ground Ranch Hand subgroups. Both Ranch Hand and comparison officers have experienced less mortality than Ranch Hand or comparison enlisted personnel. Ranch Hand flying personnel have experienced less mortality than Ranch Hand ground personnel, while comparison flying and ground personnel have experienced similar mortality patterns. Examining causes of death, Ranch Hand officer and flying groups have experienced fewer deaths from cardiovascular disease and cancer than have the comparisons, but this difference is not statistically significant. No apparent specific disease excesses were noted in the Ranch Hand ground or enlisted groups relative to their comparisons. All Ranch Hand cohorts are elevated in the category of digestive system deaths, but this difference is not statistically significant. There was a single case of soft tissue sarcoma in the comparison group and no cases occurred in the Ranch Banders. The Ranch Hand and comparison groups have been contrasted with five comparison groups. Ranch Hand and comparison officers are experiencing significantly less mortality than U.S. White males and DOD retired officers. Comparison enlisted personnel are similarly experiencing significantly less mortality than U.S. White males and DOD retired enlisted. Ranch Hand enlisted personnel have experienced a mortality rate not statistically distinguishable from U.S. White males or DOD retired enlisted personnel. The Ranch Hand and comparison groups taken together have experienced a mortality pattern not statistically different from civil service employees. However, all Ranch Hand and comparison groups are experiencing significantly more mortality than the active duty Air Force, as would be expected by active duty Air Force health qualification standards. Finally, no significant differences between Ranch Hand or comparison officer death rates and those of West Point officers from the class of 1956 were detected. In conclusion, summary counts of death by rank and occupation did not reveal any statistically significant differences between the Ranch Hand and comparison groups. However, Ranch Hand officers born between 1905 and 1935 have experienced favorable mortality relative to their comparisons while the converse is true for officers born after 1935. Analogous patterns are seen in officers conditioned on age at death. Although Ranch Hand ground personnel have experienced unfavorable mortality relative to comparisons irrespective of date of birth or age at death, this difference is not statistically significant. Exposure index analyses indicate that these mortality rate differences cannot be attributed to herbicide exposure at this time. These analyses have identified several findings of interest, which will be further evaluated In future mortality updates. 41 �References 1. Lathrop, G. D., Moynahan, P. M., Albanese, R. A., Wolfe, W. H. (1983). An Epidemiologlc Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides: Baseline M o r t a l i t y Study Results. (NTIS Order Number: AD-A130 793) 2. Kaplan, E. L. and Meier, P. (1958). Nonparametric estimation from incomplete observation. JoujJ1^L_2l _?nJr Amer1can. Statist teal Association 53:457-481. "~ ~ 3. Prentice, R. L, (1978). Linear rank tests with right censorc-ci data. Biometrika 65:167-179. 4. Ejigou, A. and McHugh, R. (1981). Relative risk estimation under multiple matching. Biometrika 68:85-91. 5. Gail, M. (1978). The analysis of heterogeneity for indirect standardized mortality ratios. Jovrnal._of _the_ RojaJ^_S£aJtJ_sjtjk:jil Society, A, 141:224-234. 6. Vital Statistics of the United States, 1978 Vol II - Section 5, Life Tables; US Dept of Health and Human Services, DHHS Publication No (PHS) 81-1104; Hyattsville, Maryland; 1980. 7. Evaluation of the Military Retirement System FY 1980. Office of the Actuary, Defense Manpower Data Center, 300 North Washington Street, Alexandria, Virginia 22314. 8. Servicemen's and Veterans Group Life Insurance Programs, Sixteenth Annual Report, Year Ending June 30, 1981. VA Regional Office and Insurance Center, Philadelphia, PA 19101; 1981. 9. Board of Actuaries of the Civil Service Retirement System, Fifty Seventh Annual Report. US Government Printing Offices; 1980. 10. Clark, I)., Allen, M. and Wilson, F. (1967). Longitudinal study of serum lipids - twelve year report. American Journal of Nutrition 20:743-752. 11. Mantel, N. and Haenszel, W. (1959). retrospective studies of disease. Institute 22:719-748. 12. Statistical aspects of data from Journal of the National Cancer Lathrop, G. D., Wolfe, W. H., Albanese, R. A., Moynahan, P. M. (1984). An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides: Baseline Morbidity Study Results. (NTIS Order Number: AD-A138 340) 42 �PRINCIPAL INVESTIGATORS George I). Lathrop, MD, MPH, PhD, FACPM Colonel, USAF, MC Chief, Epidemiology Division Will!am H. Wolfe, MD, MPH, FACPM Colonel, USAF, MC Chief, Epidemiology Division Richard A. Albanese, MD, GM-15 Chief, Momathematical Modeling Branch Data Sciences Division Patricia M. Moynahan, BSN, MS Colonel, USAF, NC Chief, Occupational Epidemiology Section Epidemiology Division Joel E. Michalek, PhD, GS-13 Mathematical Statistician Data Sciences Division Retired 1 October 1984 �Appendix Table 1 Ranch Hand Officers Versus Ranch Hand Enlisted Mortality by Year-Of-Birth (SMR - 0.483, PI = 0.204, P2 = 0.(M1) Birth Year Ranch Hand Officers At Risk Dead Rate 1905-1924 1925-1934 1935-1939 1940-1944 1945-1954 41 194 95 91 45 3 4 4 2 2 Total 466 15 Ranch Hard Enlisted At Risk Dead Rate 29 195 115 119 332 7 15 3 3 11 790 0.073 0.021 0.042 0.022 0.044 0.241 0.077 0.026 0.02.5 0.033 39 Appendix Table 2 Comparison Officers Versus Comparison Enlisted Mortality by Year-Of-Birth (SMR = 0.663, PI = 0.81.1, P2 = 0.003) Birth Year 1905-1919 1920-1924 192.5-1929 1930-1934 1935-1939 1940-1944 1945-1954 Total Officers At Risk Dead Rate 44 161 290 640 458 495 190 4 13 20 31 12 6 5 2278 At Risk Enlisted Dead 66 80 2.11 749 562 601 1624 11 11 24 42 24 17 45 3893 91 0.091 0.081 0.069 0.048 0.026 0.012 0.026 Rate 174 0.167 0.138 0.114 0.056 0.043 0.028 0.028 Appendix Table 3 Ranch Hand Flying Personnel Versus Ranch Hand Ground Personnel Mortality by Year-Of-Birth (SMR - 0.548, PI - 0.376, P2 = 0.052) Birth Year At Risk Flyers Dead 1905-1924 1925-1934 1935-1939 1940-1944 1945-1954 44 272 145 121 64 4 9 6 2 2 Total 646 2.3 0.091 0.033 0.041 0.017 0.031 44 Ground Dead Rate 26 117 65 89 313 6 10 1 3 11 0.231 0.085 0.015 0.034 0.035 610 Rate 31 At Risk �Appendix Table 4 Comparison Flying Versus Comparison Ground Personnel Mortality by Year-Of-Blrth Within Comparison Group (SMR - 0.926, PI - 0.607, P2 - 0.782) At Risk Flyers Dead 6 17 25 53 24 14 10 1905-1919 1920-1924 1925-1929 1930-1934 1935-1939 1940-1944 1945-1954 Total 3163 Rate Ground At Risk Dead 0.021 65 66 151 423 322 443 0.036 1538 9 7 19 20 12 9 40 3008 Rate 116 0.133 0.097 0.071 0.055 0.034 149 0.138 0.106 0.126 0.047 0.037 0.020 0.026 Appendix Table 5 Non«-Black Ranch Hand Ground Personnel Versus the 1978 U.S. White Male Life Table ( - -0.728, P - 0.466) T Age At Risk Dead 21^24 25^29 30*3^ 35*39 40*44 45>-49 50A-54 55*59 60«64 65*69 70*-71 557 555 552 504 255 179 117 45 22 10 2 2 3 4 4 3 4 3 2 3 0 J_ Total 29 45 Expected Deaths 3.236 32.824 �Appendix Table 6 Non~Black Ranch Hand Enlisted Ground Personnel Versus the 1978 U.S. White Male Life Table (T - ^0.549, P - 0.583) Age At Risk Dead Expected Deaths 21*2»» 25*29 30-31 35^-39 40M4 15-M9 50»5H 55"59 60^61 6S--69 70K71 Total 532 530 527 180 235 169 110 ^1 21 9 2 2 3 3 1 3 4 3 2 3 0 J_ 28 1.085 4.137 *».281 3.^92 3.193 3.927 2.991 1.881 1.671* 0.75^ 0.110 30.828 46 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 059 Folder The folder containing the original item. 1576 Series The series number of the original item. Series III Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Lathrop, George D. Patricia M. Moynahan Richard A. Albanese William H. Wolfe Joel E. Michalek Description An account of the resource <strong>Corporate Author: </strong>United States Air Force School of Aerospace Medicine (AFSC), Epidemiology Division and Data Sciences Division, Brooks AFB, Texas Date A point or period of time associated with an event in the lifecycle of the resource December 10 1984 Title A name given to the resource An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides: Mortality Update - 1984 Subject The topic of the resource Air Force Health Study ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/5d9cf1d1d4bbd644387fc1c0fc067587.pdf e6a4c318a390c44a4b2e0659f5f9e40b PDF Text Text Item ID Number °1573 Author Lathrop, George D. Corporate Author United States Air Force School of Aerospace Medicine, Report/Article HUB ^n Epldemiologlc Investigation of Health Effects In Air Force Personnel Following Exposure to Herbicides: Baseline Morbidity Study Results Journal/Book Title Year 1984 Month/Day February 24 Color Number of Images D 362 Descriptor! Notes Wednesday, May 23, 2001 Page 1574 of 1608 �AIR FORCE HEALTH STUDY (PROJECT RANCH HAND II) AN EPIDEMIOLOGIC INVESTIGATION OF HEALTH EFFECTS IN AIR FORCE PERSONNEL FOLLOWING EXPOSURE TO HERBICIDES BASELINE MORBIDITY STUDY RESULTS 24 FEBRUARY 1984 Prepared for: The Surgeon General United States Air Force Washington, D.C. 20314 George D. Lathrop, Colonel, USAF, MC William H. Wolfe, Lieutenant Colonel, USAF, MC Richard A. Albanese, M.D., GM-15 Patricia M. Moynahan, Colonel, USAF, NC Approved for public release; distribution unlimited. USAF SCHOOL OF AEROSPACE MEDICINE A e r o s p a c e Medical Division (AFSC) Brooks Air Force Base, T e x a s 7 8 2 3 5 �UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PAGE (When Data Entered) REPORT DOCUMENTATION PAGE 1. REPORT NUMBER 2. GOVT ACCESSION NO 4. TITLE (and Subtitle) 7l READ INSTRUCTIONS BEFORE COMPLETING FORM 3. RECIPIENT'S CATALOG NUMBER 5. TYPE OF REPORT & PERIOD C O V E R E D An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Baseline Morbidity Study Results . ., fteo'r^D. Lathrop, Colonel, USAF, MC William H. Wolfe, Lt Colonel, USAF, MC Richard A. Albanese, MD, GM-15 Patricia M. Moynahan, Colonel, USAF, NC Interim 1979-1982 6. P E R F O R M I N G ORG. REPORT N U M B E R 8. CONTRACT OR G R A N T NUMBER(» 10. PROGRAM ELEMENT. PROJECT, TASK A R E A & WORK UNIT NUMBERS 9. P E R F O R M I N G O R G A N I Z A T I O N N A M E AND ADDRESS USAF School of Aerospace Medicine (EK) Aerospace Medical Division (AFSC) Brooks Air Force Base, Texas 78235 12. REPORT D A T E 11. CONTROLLING OFFICE NAME AND ADDRESS February 1984 The Surgeon General United States Air Force Washington, D.C. 20311* 13. N U M B E R OF P A G E S T4. MONITORING AGENCY NAME 4 ADDRESS^/ different from Controlling Office) 15. SECURITY CLASS, (of this report) Unclassified 15«. DECLASSIFICATION/DOWNGRADING SCHEDULE 16. DISTRIBUTION STATEMENT (of this Report) Approved for public release; distribution unlimited. 17. DISTRIBUTION STATEMENT (of the abstract entered in Block 20, It different from Report) 18. SUPPLEMENTARY NOTES 19. KEY WORDS (Continue on reverse aide It necessary and identity by block number) Dioxin Ranch Hand Air Force Health Study Epidemiologic Investigation Phenoxy Herbicides Herbicide Orange Morbidity 20. ABSTRACT (Continue on reverse aide It necessary and Identify by block number) In 1979 the United States Air Force (USAF) made the commitment to Congress and to the White House to conduct an epidemiologic study of the possible health effects from chemical exposure in Air Force personnel who conducted aerial herbicide dissemination missions in Vietnam (Operation RANCH HAND). The purpose of this epidemiologic investigation is to determine whether long-term health effects exist and can be attributed to occupational exposure to herbicides. This study uses a matched cohort design in a nonconcurrent prospective setting, incorporating mortality, morbidity, and follow-up studies. This DO , ™NRM73 1473 UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PAGE (When Data Entered) �UNCLASSIFIED SECURITY CLASSIFICATION OF THlS PAGfefWhen Data Entered) report presents the results of health Information on 2706 Ranch Handera and comparison individuals obtained by questionnaire and 2269 Ranch Handers and comparison individuals undergoing an extensive physical examination. This baseline report concludes that there is insufficient evidence to support a cause and effect relationship between herbicide exposure and adverse health in the Ranch Hand group at this time. The study has disclosed numerous medical findings, mostly of a minor or undetermined nature, that require detailed follow-up. In full context, the baseline study results should be viewed as reassuring to the Ranch Handers and to their families at this time. UNCLASSIFIED SECURITY CLASSIFICATION OF THIS �EXECUTIVE SUMMARY BASELINE MORBIDITY STUDY The Ranch Hand II epidemiologic study uses a matched cohort design in a nonconcurrent prospective setting, and incorporates mortality, morbidity, and follow-up studies. The purpose of this report is to present the baseline morbidity study. The morbidity study design matched each living Ranch Hander (by age, job, and race) to the first living and compliant member of a randomly selected comparison mortality set of 5 individuals, producing a 1:1 contrast. The comparison group was formed from numerous flying organizations which transported cargo to, from, and within Vietnam, but were not involved in aerial spray operations of Herbicide Orange. Of the potential study participants, 99.5$ were located.. Early in the physical examination phase of the study, it was discovered that 1856 of the entire comparison group was ineligible to participate because of inappropriate selection. Thereafter, study eligibility was certified only after a hand-review of personnel records. Next-in-line compliant comparisons entered the study as replacements after fully completing the questionnaire and physical examination. Statistical analyses of these replacement individuals later showed that they differed from the original comparisons in a variety of subtle and often opposite ways. As a conservative measure to avoid possible bias by the inclusion of the replacements in the analyses, a management decision was made to base the statistical tests in this report primarily upon contrasts of the Ranch Hand group to the original comparison group. The preponderance of data was obtained from the in-home interviews and the physical examination, each conducted under contract to the Air Force by Louis Harris and Associates, Inc., New York NY, and the Kelsey-Seybold Clinic, P.A., Houston TX, respectively. All contacts with the participants were carried out with utmost professionalism and sensitivity. Other morbidity data sources included reviews of medical records, military personnel documents, and birth certificates; in-home questionnaires and telephone questionnaires of the study participant's wives, former wives and, occasionally, their next-of-kin. All aspects of the study were voluntary. As a contract requirement, data collection personnel were blind as to the exposure status of the participants. Ninety-seven percent of the Ranch Handers and 93% of the comparisons participated in the in-home interview. For the physical examination, 87% of the Ranch Handers and 76$ of the comparison group participated, a total of 2,272 individuals. This differential attendance at the examination may have introduced a potential participation bias that, in a military population predominantly engaged in flying duties, is multifactorial and complex. All study phases were monitored by stringent quality control standards. Statistical analyses of the data consisted primarily of log-linear models, logistic regression techniques, generalized linear models, matched covariate analyses, and Kolmogorov-Smirnov, chi-square, and t tests. The physical examination and the in-home questionnaire data were analyzed by major organ system. In terms of general health, more Ranch Handers perceived themselves to be in fair or poor health than did their comparisons. No �group difference^ were detected for hewatocrit or percent body fat determinations. Unadjusted group differences in sedimentation rate were not observed; however, significantly more young comparisons had abnormalities in sedimentation rate than did their Ranch Hand counterparts, There were no statistically significant differences in the occurrence of malignant or benign systemic tumors between the groups. One cage of soft tissue sarcoma was found in a comparison member, Significantly more nqnmelanQtic gkin cancer was noted in the Ranch Hand group, but these analyses have not yet considered (adjusted for) sunlight exposure, the prime etiology of these cancers. Such nonmelanotic skin cancer (predominantly basal cell carcinoma) is the most common neoplasm in the White population of the United States, Up to the statistical limits of the study there were no consistent data that showed that the Ranch Handers were developing uncqmmpn cancers, or> cancer in unusual sites, or at an unusual age. Measures of fertility and reproductive outcome showed mixed results. It is emphasized that the fertility and reproductive results are preliminary at this time as they are based largely upon subjective self reports that await full medical record and bir^h certificate verification. Four measures of fertility: number of childless marriages, couples with the desired number of children, the infertility index and the fertility index, showed no difference between the Ranch Hand and comparison groups, A semen specimen obtained from those willing and able to provide one showed no group differences with respect to total sperm count or percent abnormal sperm. There were no significant findings in conception outcomes for miscarriages, stillbirths, induced abortions, or live births. For live birth pytcpmps no differences ..were observed for prematurity, learning disability, or infant deaths. There, was no significant disparity between groups for the classificat.ions; of severe or moderate birth defects. By parental history, however, Ranch Hand offspring showed significantly more minor birth defects (birth marks, etc). Reported neonatal deaths and physical handicaps were also significantly excessive in the Ranch Hand group when contrasted to the tot.al comparison group. All fertility and reproductive findings in the Ranch Hand: group showed inconsistent relationships to the herbicide exposure index. Medical records and birth, certificates are currently being chronicled for cpmplete verification of all historical findings. A comprehensive neurological examination showed: no consistent abnormalities in the cranial nerves, peripheral nerves or central nervous system function of the Ranch Handers. As expected, there was a profound influence of diabetes and alcohol in both groups upon numerous neurological tests. Detailed psychologic data were obtained on all participants at both the in-home interview and the physical examination. It is emphasized that, the majority of psychological data was derived from self reported responses during interview and has not been fully assessed for the effect of differential reporting. A variety of subjective deficits (fatigue, anger, fear, anxiety, etc) were Significantly more common in the high school educated Ranch Handers,. Educational level, significantly and consistently influenced rapst subjective test results. In sharp contrast, more objective performance testing by the Halstead-Reitan. battery and IQ testing did not reveal any significant iritergroup differences.. The roles of overreporting and the Post Vietnam; §tres,s Syndrome in these, analyses have not as yet been assessed. Li.ver function tests and clinical history data showed mixed results. Ranch. Handers had. some elevated liver enzyme tests, and lower cholesterol levels. More Ranch Handers were found to have hepatomegaly and verified histories of prior hepatic disease, than their counterpart comparisons. Exposure to alcohol, degreasing chemicals, and industrial chemicals in general, influenced ii �the liver test results. Ranch Handers reported significantly more symptoms resembling porphyria cutanea tarda than the comparisons, but these data have not been verified by medical record reviews nor were they substantiated by laboratory testing or by physical examination. Exposure index analyses were essentially negative. In the dermatologic evaluation, no cases of chloracne were diagnosed clinically or by biopsy. A thorough questionnaire analysis of acne showed that the incidence, severity, duration, and anatomic location did not differ between groups, and suggested that the historical occurrence of chloracne was highly unlikely in the Ranch Handers. Evaluation of the cardiovascular system showed equal proportions of abnormalities in blood pressures, electrocardiograms, past electrocardiograms, and heart sounds in both groups. Ranch Handers are not having premature heart attacks or generalized heart disease. However, the Ranch Handers showed significant deficits in 2 specific peripheral leg pulses and all leg pulses as a group. These puzzling findings were highly correlated with age and smoking patterns, and verified past heart disease. The assessment of the immune system by laboratory testing was compromised by excessive test variability. An independent review committee determined which test data were suitable for statistical analysis. As an unexpected finding, the test data were significantly influenced by the age and smoking history of the participant; no group differences were detected after adjustment for these factors. A hematologic test battery revealed.three red cell abnormalities in the Ranch Hand group, but these were difficult to place into a clinical or epidemiologic context. Evaluation of renal, pulmonary, and endocrine functions generally disclosed small and inconsistent proportions of abnormalities between groups, and were deemed clinically unimportant. An unrefined assessment of all summed and weighted organ system abnormalities by group did not show an aggregation of multisystem disease or malfunction. Any interpretation of these study data, in whole or in part, must carefully consider the methodical steps required for a proper inference of causality. It is specifically pointed out that many group differences were largely based upon subjective data, and that a subtle effect of differential reporting is suggested but has not been fully evaluated. For objective data, group differences were generally within normal ranges and were not correlated to the herbicide exposure index, nor fell within the expected latency periods following Vietnam service. The proposed clinical end points of dioxin exposure, chloracne, soft tissue sarcoma, and porphyria cutanea tarda, were not found in the Ranch Hand group (study power limitations recognized). Overall, substantial credence is given to the objective study findings, particularly after observing the consistent duplication of the classical effects of risk factors such as age, smoking, alcohol, etc., in almost all clinical areas. Additional work with these baseline data is still required in the areas of data base refinement, statistical testing and bias analysis, exposure index refinement, establishment of the follow-up examination requirements, and collaboration with other dioxin research studies. This baseline report concludes that there is insufficient evidence to support a cause and effect relationship between herbicide exposure and adverse health in the Ranch Hand group at this time. The study has disclosed numerous medical findings, mostly of a minor or undetermined nature, that require detailed follow-up. In full context, the baseline study results should be viewed as reassuring to the Ranch Handers and their families at this time. iii �PREFACE In October 1978, the United States Air Force (USAF) Surgeon General made the commitment to the Congress and to the White House to conduct an epidemiologic study of the possible adverse health effects arising from the herbicide exposure of Air Force personnel who conducted aerial dissemination missions in Vietnam (Operation Ranch Hand). The purpose of this epidemiologic investigation is to determine whether long-term adverse health effects exist, and whether they can be attributed to occupational exposure to herbicides and their contaminants. The study protocol for this effort incorporates a matched cohort design placed in a nonconcurrent prospective setting. The study approach includes mortality, morbidity, and follow-up elements linked tightly in time in order to produce the most data in the shortest time. The study addresses the question: Have there been, are there currently, or will there be any adverse health effects among former Ranch Hand personnel caused by repeated occupational exposure to 2,1,5-Trichlorophenoxyacetic acid (2,4,5,-T) containing herbicides and the contaminant, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)? At the request of the Principal Investigators (see Appendix I) the study protocol was extensively and independently reviewed. The review agencies included: The University of Texas School of Public Health, Houston TX; the USAF Scientific Advisory Board; the Armed Forces Epidemiological Board; and the National Research Council of the National Academy of Sciences. In 1980, the Science Panel of the Agent Orange Working Group was created as an additional peer review agency. This group, redesignated as the Advisory Committee on Special Studies Relating to the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants, has consented to the oversight responsibility of the Ranch Hand study and continues to monitor the conduct of this epidemiologic investigation (see Appendix II). The Air Force Health Study (Ranch Hand II) protocol emphasizes the suboptimal statistical power of the mortality study. The mortality study was motivated by the desire to use a full spectrum epidemiologic approach to the herbicide question. Additionally, the investigators were scientifically obliged to pursue the mortality study because of previous and emerging studies (some with small sample sizes) which suggested the possibility of a soft tissue sarcoma end point (Honchar, 1981; Hardell, 1979; Erikson, 1979). Within the inherent sample size limitation Of the Ranch Hand population, detection of such a rare condition will be missed unless there is marked case clustering and correspondingly high relative risks. Also, because of sample size limitations as well as the myriad of proposed clinical end points, a case-control design was not entertained. In the morbidity phase of the study, the investigators have attempted to enhance statistical power and analytic sensitivity where possible by using (1) precise matching procedures with a replacement strategy to maintain statistical power while averting a loss-to-study bias, (2) exacting quality control procedures, (3) mortality-morbidity linkages, (4) a lengthy follow-up study, (5) state-of-the-art statistical methodology, (6) continuously distributed physical examination variables, and (7) data collection focused on verifiable end points. iv �The mortality analyses have not revealed any adverse death experience in the herbicide/dioxin exposed cohort. The results of the analyses were consistent: at this time, there is no indication that Ranch Hand personnel have experienced any increased mortality or any unusual patterns of death in time or by cause. They are not dying in increased numbers, at earlier ages, or by unexpected causes. The fact that only a relatively small number of Ranch Hand, deaths were available for analysis is reassuring in itself. However^ the fact that adverse effects have not yet been detected does not imply that an effect will not become manifest at a future time or after covariate-adjusted analyses. For this reason, further analyses are intended and mortality in the ' study population will be ascertained annually for the next 20 years. The morbidity portion of the study was conducted in two phases; an in-home, face-to-face interview, and a comprehensive physical and psychological examination. Both phases were conducted by civilian organizations under contract to the Air Force, using materials and procedures prescribed by the contract. One thousand, one hundred seventy four (97?) of the Ranch Hand group and 1,156 (93?) of the initially selected comparison group participated in the questionnaire. An additional 376 comparison subjects were interviewed as replacement subjects, bringing the total number of comparison participants to 1f532. Two thousand, seven hundred eight current and former wives of the study participants were interviewed. One thousand forty five (87?) of the Ranch Hand group participated in the physical examination, and 936 (76?) of the initially selected comparison subjects participated. Two hundred eighty-eight replacement subjects also participated in the examination process, giving a total of 2,269 participants, resulting in 1,024 matched pairs for analysis. The first chapter of this report is devoted to a discussion of the background of the study and the next seven chapters present a summary of the methodology used in gathering, analyzing, and interpreting the data. The results and discussion of these analyses, organized by organ system and/or disease end point, are contained in the remaining chapters. This report assumes that readers are familiar with statistical and epidemiologic techniques. It also assumes that the reader has a familiarity with the herbicide/dioxin issue and a detailed knowledge of the protocol of the Air Force study, the baseline questionnaire, and the baseline mortality results. In the interest of brevity, the reader is referred to the protocol published as US Air Force School of Aerospace Medicine Technical Report 82-44, the baseline questionnaires published as US Air Force School Aerospace Medicine Technical Report 82-42, and the Baseline Mortality Study Results, 30 June 1983. These reports are available from the National Technical Information Service, 5285 Port Royal Road, Springfield, Virginia 22161. �ACKNOWLEDGMENTS The Principal Investigators gratefully acknowledge the outstanding support given to this project by: The Ranch Hand Association and its elected officers, for sustained encouragement of the study, assistance in population ascertainment, and camaraderie and patriotism which contributed to unparalleled participation rates. Our peer review groups, the University of Texas, School of Public Health, the Air Force Scientific Advisory Board, the Armed Forces Epidemiological Board, the National Research Council, and our Advisory Committee for their scientific contributions which have facilitated the conduct of this study and enhanced public credibility. The Air Force Research Management Structure at the Aerospace Medical Division, Brooks AFB TX; 33°3<i Contracting Squadron, Air Training Command, Randolph AFB TX; Office of the Command Surgeon, Air Force Systems Command, Andrews AFB MD; and the Air Force Surgeon General's Office, Boiling AFB DC, for program advocacy and provision of resources. The over 100 professionals, consultants, technicians, military and civilian, whose dedication and hard work over the past five years have made this report possible. vi �TABLE OF CONTENTS Executive Summary Preface Acknowledgments Table of Contents I II Ill IV V VI VII VIII IX X XI XII XIII XIV XV XVI XVII XVIII XIX Background and Study Design Population Questionnaire Methodology Physical Examination Methodology Study Selection and Participation Bias Quality Control Procedures Statistical Methods Exposure Index Development General Physical Health Malignancy . Fertility and Reproductive Outcomes Neurological Assessment Psychological Assessment Evaluation of Hepatic Status. Dermatologic Evaluation Evaluation of Other Organ Systems 1. Cardiovascular Evaluation 2. Immunology 3. Hematological Variables 1*. Pulmonary Function and Disease. 5. Renal Disease and Function 6. Endocrine Function Individual Health Assessment. Future Commitments Interpretation of Study Results and Conclusions.. •••••• References Appendixes I II III IV V VI Principal Investigators and Key Personnel Advisory Committee on Special Studies Relating to the Possible Long-term Health Effects of Phenoxy Herbicides and Contaminants Contract Management Kelsey-Seybold Normal Value Report Blood Chemistry Definition of Birth Defects, Learning Disabilities, and Physical, Mental or Motor Impairments Physical Examination Forms �VII VIII IX X XI XII 1 XIII XIV XV XVI XVII XVIII XIX XX Examination Parameters and Abnormality Weights Used in Assessing Individual Health Total Mortality and Morbidity Study Site Specific Malignant Neoplasms General Health Analyses Using Data From All Comparisons Fertility and Reproductive Analyses; Ranch Handers versus All Comparisons Introductory Letters Occupational Category and Race of the Fully Compliant Population in Percent and Counts Self-Reported Reasons for Noncompliance to Questionnaire Self-Reported Reasons for Noncompliance to Physical Examination Coefficient of Variation for Tri-Level Controls Specific Rules for Entry Into the Morbidity Study Percent Compliance by Flying Code and Military Status of the Ranch Hand and Comparison Population Non-Black Officers Relative Risks (RR) and Mean Shifts (Y) for Selected Clinical End Points Spouse and Participant Reported Birth Defects Not Meeting Study Criteria Observed Cancer Versus SEER Data Expected in 117^ Partially Compliant Ranch Handers and 956 Original Comparisons �Chapter I BACKGROUND In January 1962, President John F. Kennedy approved a program to aerially disseminate herbicides in the Republic of Vietnam (RVN). This program, code named Ranch Hand, was conducted in support of tactical military operations and had 2 missions: defoliation and crop destruction. During the 9-year duration of the operation, approximately 19 million gallons of herbicides were sprayed on an estimated 10-20$ of South Vietnam (Young, 1978; Buckingham, 1982). Of the 6 herbicides used, Herbicide Orange was the primary defoliant, and approximately 11 million gallons were dispersed. Because of the controversial nature of the mission and enemy propaganda which raised political sensitivity to chemical warfare charges, the Ranch Hand operation was subjected to intense scrutiny from the start. Initial concerns were focused on the military, political, and ecological ramifications of the spray operations (Buckingham, 1982). Since 1977, the issue has shifted to a health concern. Numerous U.S. military personnel from all services have claimed exposure to herbicides, particularly Herbicide Orange and its dioxin contaminant, during their duty in the RVN. These possible exposures, coupled with claims of attributable adverse health, have resulted in class action litigation and substantial controversy within the Government, Veterans' groups, the scientific community, and the public. The U.S. Air Force Medical Service expressed its concern for the health of Air Force personnel exposed to herbicides in October 1978, when the Deputy Surgeon General, Major General Garth M. Dettinger, told the U.S. House of Representatives' Veterans Affairs Committee that the USAF would evaluate the health of Ranch Hand personnel. An epidemiologic study design was prepared by the USAF School of Aerospace Medicine to meet this commitment. Following extensive peer review, a final study protocol was published, (Lathrop, Wolfe, Albanese, Moynahan, 1982) and the epidemiologic study was initiated. Since 1978, numerous governmental agencies, universities, and industrial firms have planned or launched additional animal and human studies. An immediate scientific issue was identified in these studies, specifically, the characteristics of the RVN exposure. Succinctly, these questions are: (1) Who was exposed to which herbicide? (2) By what means can these individuals be accurately identified for study? (3) How much, or to what degree, were they exposed (route of administration, influence of personal hygiene measure, etc.)? These areas merit careful consideration because the process of population or exposure estimation may generate substantial misclassification errors that would call for inordinate sample sizes in a contemplated study. Government and civilian scientists and the Congress have recently inquired of the Air Force Health Study as to whether it might clarify the exposure controversy in ground personnel. The answer is a qualified yes. The dose-response principle suggests that if the Ranch Hand population was more exposed to herbicides and dioxin than ground personnel, then the Ranch Handers should manifest stronger and/or earlier indications of adverse health, if they have occurred or will occur in the future. This principle is constrained by statistical power but, as noted in Chapter VII, the Ranch Hand 1-1 �morbidity study has substantial power in some clinical areas. The fact is that the average Ranch Hander was substantially exposed to the herbicides and dioxin (relative to other military personnel in RVN) on almost a daily occupational basis. Exposure calculations have estimated that an average Ranch Hander in his tour received, at a minimum, 1000 times more exposure to Herbicide Orange than would an average unclothed man, standing in an open field directly beneath a spraying aircraft. Unfortunately, the relative degree of Ranch Hand exposure vis-a-vis ground personnel has been consistently undervalued, and even reversed by various advocacy groups and the media. It is our firm belief that the Ranch Hand population is the most herbicideexposed military cohort to have served in the RVN. The fact of the unequivocal exposure in a totally ascertained population, when matched to an equally clear-cut nonexposed cohort, provides as ideal an epidemiologic setting as possible from a wartime environment. Findings of adverse health, or lack thereof, in the Ranch Hand group should serve as a significant epidemiologic pointer to the health effects issue in exposed ground personnel. STUDY DESIGN This study uses a matched cohort design in a nonconcurrent prospective setting, incorporating mortality, morbidity, and follow-up studies. A detailed population ascertainment process has identified 1269 Ranch Hand personnel who served in the RVN during the period 1962-1971. A comparison group was formed by identifying all individuals assigned to selected Air Force organizational units with a mission of flying cargo to, from, and in the RVN during the same period. Complete details on the selection of the comparison population are cited in the study protocol. By a computerized nearest neighbor selection process, up to 10 comparison individuals were matched to each Ranch Hander by job category, race, and age to the closest month of birth. An average of 8.2 comparison individuals for each Ranch Hander were determined by record review to be fully suitable for study. From each matched comparison set, 5 individuals were randomly selected for the mortality study (1:5 design). Results of the Mortality Study were released to the public on 30 June 1983. Each living Ranch Hander and the first living member of his comparison set were selected to participate in a morbidity study consisting of an in-home interview and a comprehensive physical examination. Data collection for both the questionnaire and physical examination was accomplished by contract. The follow-up study consists of mortality and morbidity components. Every Ranch Hander and his set of comparisons will be the subjects of annual mortality updates for the next 20 years, so that any emerging mortality patterns or disease clusters may be detected with maximal sensitivity. In addition, follow-up questionnaires and physical examinations will be offered to all participants in subsequent years 3, 5, 10, 15, and 20, in order to bracket the latency periods associated with possible attributable disease. 1-2 �Chapter II POPULATION The exposed population, termed "Ranch Hand", was defined as those individuals who were formally assigned to the USAF organizations responsible for the aerial dissemination of herbicides and insecticides in the Republic of Vietnam from 1962 through 1971. These individuals were identified from historical data sources (morning reports, military personnel records, and historical computer tapes) at the National Personnel Records Center (NPRC), St. Louis, Missouri and the USAF Human Resources Laboratory, Brooks Air Force Base, Texas. A total of 126*1 Ranch Hand personnel were identified through this initial process. The comparison population was defined as those individuals who were assigned to a variety of cargo-mission organizations throughout Southeast Asia during the same time period. Cargo-mission aircrew members and support personnel were selected because of sufficient population size, similar training and military background experiences, and psychological similarities to the Ranch Hand group. The comparison population was not occupationally exposed to herbicides or insecticides in the Republic of Vietnam. Identification of this population (2*1,971 individuals) was completed using the same historical data sources as were used to identify the Ranch Hand population. 1. Original Match Before matching the Ranch Hand and comparison populations, all individuals killed in action (KIA) were removed from the data base. The rationale for their removal is the assumption that combat death in the Ranch Hand group was independent of herbicide exposure. Twenty-two Ranch Handers were identified as KIA. KIA's were also removed from the comparison group for comparability purposes. The remaining Ranch Hand population was matched to the comparison population with an iterative nearest-neighbor computer program (Lathrop, Wolfe, Albanese, Moynahan, 1982). This procedure attempted to match 10 comparison individuals with each Ranch Hander to the closest month of birth* race (Black versus non-Black), and occupational code (1-officer—pilot, 2-officer—navigator, 3-officer—nonflying, H-enlisted—flyer, and 5-enlisted—ground). Table II-1 presents the total number of study participants by occupation code, and race. �Table II-1 DISTRIBUTION OF THE INITIALLY MATCHED STUDY POPULATION BY OCCUPATION AND RACE Number Occupation Code Ranch Hand Comparisons Non-Black 1 2 3 4 5 3318 780 250 1871 5277 Officer-Pilot Officer-Navigator Officer-Nonflying Enlisted-Flyer Enlisted-Ground Subtotal 1167 11,496 Black 1 2 3 4 5 6 2 1 15 51 Officer-Pilot Off icer-Navigator Of ficer-Nonflying Enlisted-Flyer Enlisted-Ground Subtotal 75 1242 TOTAL The total Ranch Hand population consists of 37% officers and 63$ enlisted personnel. Seventy-seven percent of the total Ranch Hand officer population are pilots, 17$ navigators, and 6% other officers; 26$ of the total Ranch Hand enlisted population are flight engineers and 74$ are enlisted nonflying personnel. Following the match, the majority of Ranch Handers had 10 comparisons. The exceptions were the non-Black pilots who had a mean of only 9.5 comparisons per exposed individual due to the extreme ages of several individuals, and the Black pilots and other Black officers who had means of 2.7 and 5.0 comparisons, respectively. Six percent of the exposed population was found to be Black and88$ of this population was enlisted. Of these enlisted personnel 77$ were occupational code 5, Enlisted - Other. All subjects are males. The mean age of the study subjects is approximately 45 years. 2. Ineligibility In December 1981, the USAF Principal Investigators were advised by the questionnaire contractor that several comparison subjects had reported no experience in Southeast Asia, suggesting that inappropriate selection of some comparison subjects had occurred. Manual review of the comparison populations II-2 �military personnel records revealed that 18$ of the 12,193 comparison individuals in the original match were indeed ineligible for study. The inadvertent inclusion of several non-Southeast Asia military organizations had resulted in the selection of these inappropriate individuals. The percent loss to the total 1:1.0 matched comparison population due to ineligibility by occupation code, race, and average age is presented in Table II-2. Table II-2 PERCENT INELIGIBLE BY OCCUPATION CODE AND RACE, WITH AVERAGE AGE OF INELIGIBLES BY OCCUPATION CODE Race Non-Black Black Total Percent Loss and Occupation Code Counts of Ineligible Comparisons 4 2 TOTAL 1 5 3 (12$) 414 (12$) 90 (34$) 84 (12$) 230 (24$) 1254 (18$) 2072 (13$) 2 (5$) 1 (60$) 3 (10$) 15 (23$) 115 (20$) 136 (12$) 416 (11$) 91 (34$) 87 (12$) 245 (24$) 1369 (18$) 2208 Average Age in 48 Years (as of Nov 83) 48 46 48 42 44 Table II-2 shows that of the 18$ loss to the total matched population 18$ occurred in the non-Black and 20$ occurred in the Black population subsets. Thirty-four percent of all participants in occupation code 3 (nonflying officer) and 24$ in occupation code 5 (nonflying enlisted) were lost due to ineligibility. The losses from occupation code 5 clearly exceed the losses in the other 4 categories. The nonflying enlisted individuals were on average the youngest (42 years) while the flying officer and flying enlisted categories were on average the oldest (48 years). A full log-linear analysis (see chapter VII) with all three matching variables included simultaneously was not performed because of the many small cell counts involved. A log-linear model fitted to the three-way frequency table based on eligibility, occupation code, and race, revealed a significant association of eligibility with occupation code (P<.001, adjusted), but not with race (P=.41, adjusted). Because the comparison ineligibility problem was identified after the morbidity study questionnaire and physical examination contracts had been implemented, the ineligible comparisons were removed from the matched cohort and the remaining comparison matrix was collapsed to fill the vacancies created by these removals. This process is characterized in Figure II-1. II-3 �Figure II-1 REMOVAL OF THE INELIGIBLE COMPARISONS AND THE SHIFT LEFT RANCH HAND RH . COMPARISONS X X" ! . V f r2 C X* 4-t. V" X ^ > This figure shows a hypothetical Ranch Hander (RH) and his 10 comparison subjects (CT-CIQ). The C^, C^ and C7 were found to be ineligible and removed. All remaining eligibles were then shifted to the left, i.e., C2 became C-|, Cij became C2, etc. Following the removal of all ineligible subjects, the study was reduced to a 1:8 design. The ineligible selection, the shift left and the subsequent comparison population reduction was presented to the Advisory Committee in 1982. This group felt that the impact of group ineligibility on the study design was negligible; however, subsequent analysis demonstrated a potential impact on inferential reliability (See Chapter V, Compliance and Bias). Statistical considerations required that the shifted population be flagged and analyzed independently of the original comparisons. The data in this report have been primarily analyzed using the original comparisons in an attempt to best describe potential herbicide effects. Wherever possible, analyses using the entire comparison population are also included. During the conduct of the initial morbidity study 5 additional Ranch Handers were identified through personnel record sources and Veterans Administration Education Benefits and Financial Records. These 5 individuals had not been identified earlier because the majority of their military personnel records had been destroyed in a fire at the NPRC in St. Louis. Three of these 5 were newly discovered Ranch Handers and 2 were comparisons who were subsequently identified as Ranch Handers. Ten additional Ranch Handers were identified following the completion of the morbidity study. These individuals will be included in the follow-up study. No attempt was made to select comparisons for these new Ranch Handers. During the removal of ineligible subjects, 1 Ranch Hander, a Black officer pilot, lost his only comparison and remains unmatched, giving a total of 16 unmatched Ranch Handers, of which 6 are in this study. At the time of morbidity study implementation there were 1,211 Ranch Handers matched to 1,026 original and 212 shifted comparisons. Three eligible shifted comparisons were deleted following data collection. The comparison population (C-j) eligible for data collection for the baseline morbidity effort is presented in Table JI-3 by occupation group and nature of the comparison group, i.e., original or shifted. II-lJ �Table II-3 COMPARISON POPULATION ELIGIBLE FOR THE MORBIDITY STUDY BY. OCCUPATION CODE AND NATURE OF COMPARISON GROUP I.E., Occupation Code ORIGINAL OR SHIFTED (C-|) Original Comparisons (0) Shifted Comparisons (S) Total Non-Black 1 2 3 307 72 13 169 Subtotal 6 12 18 122 966 199 1165 5 2 1 15 0 0 0 0 13 5 2 1 15 50 60 13 73 1026 212 1238 Black 1 2 3 Subtotal TOTAL Sixty-four percent of the shifted comparison population is in occupation code 5 (Enlisted-ground). All Black shifted comparisons are in this group, as well. The study protocol estimated that 39? of the entire Ranch Hand population would complete the physical examination portion of the morbidity study. This initial estimate of compliance was based on an estimate of the influences of status (military active duty, military retired, separated and flying) on the individual who could not be guaranteed confidentiality of medical findings. Status also influenced locatability. Active duty and military retired personnel are located through military data sources, while separated individuals must be located through civilian sources. The status and the flying category of the Ranch Hand and comparison population are presented in Tables II-4 and II-5. II-5 �Table II-4 STATUS OF THE RANCH HAND AND MATCHED MORBIDITY COMPARISON POPULATION (C<\) Status Comparison Original Shifted Ranch Hand Active Duty Retired From Military Separated TOTAL 185 576 442 157 510 359 27 85 100 1203* 1026 Total 212 1238 *39 Ranch Hands were deceased at the initiation of the morbidity study. Table II-4 demonstrates that 4856 of the population is retired from the military; 15% remain on active duty; and 37% are separated. Those individuals currently holding military or civilian flying certificates are presented in Table II-5. Table II-5 COUNTS OF THE INDIVIDUALS HOLDING MILITARY AND CIVILIAN FLYING CERTIFICATES, THE RANCH HAND AND MATCHED COMPARISON POPULATION (Cj) Status Original Ranch Hand Military Flying Federal Aviation Admin Certificate TOTAL Comparison Shifted Total 82 128 78 128 12 16 90 144 210 206 28 234 This table shows that 17/6 (210/1203) of the Ranch Handers and 19$ (234/1238) of the total C-\ population presently have military aviation codes or Federal Aviation Administration (FAA) certificates that define active participation in aviation. Twenty percent (206/1026) of the original and ^3% (28/212) of the shifted comparison population hold FAA certificates. 3. Study ^Selection The study protocol defines the morbidity population as all living Ranch Handers and their first randomly selected, alive and compliant comparison. The selection procedure for the questionnaire and physical examination is presented in Figure II-2. II-6 . �Figure II-2 SELECTION PROCEDURE FOR THE QUESTIONNAIRE, PHYSICAL EXAMINATION, AND FOLLOW UP STUDY COMPARISON INDIVIDUALS (RANDOMLY ORDERED) RANDOMLY SELECTED MORTALITY CONTROLS MATCHED RANCH HAND I I I II 1 _. * t « ** t f DEAD — UNWILLING * VOLUNTEER * * REPLACEMENT CANDIDATES In this example, the first randomly ordered comparison was found to be dead. The second was contacted but unwilling to participate, and the third vol-^ unteered to participate in the morbidity study. This process resulted in a third comparison subset, the replacement population. As shown in Figure II-2, this population resulted from the refusal of the original and shifted comparisons to participate in the morbidity study. The study protocol required that the replacement comparisons be matched to the noncompliant individuals on health perception and that they be treated separately in the statistical analyses. In actuality, they were not matched on health perception but were the first volunteers in the randomly ordered mortality sets following original comparison refusals. Because the health perception of the replacement was not matched to the original, comparison subject data analyses and inferences based on these analyses will only be reported for the original and total comparison populations. In this design, deceased Ranch Handers cannot be replaced for physical exam, while deceased comparisons can be replaced due to the one-many matching. This disparity could lead to inferential bias if cause-specific death rates differ in the two groups. Thus far, these rates are not significantly different. II-7 �This epidemiologic study was designed as a matched cohort design. There were 1211 Ranch Handers matched to comparisons by age, race and occupational category at the initiation of the morbidity study. The matched comparison population consisted of 1026 original and 212 shifted comparisons. Three ineligible shifted comparisons; were deleted following data collection. The shifted group resulted from inappropriate selection, removal, and shifting left of the comparison population. Additionally there were 16 Ranch Handers who could not be matched, Ninety-four percent (1171/1247) of the study population is non-Black. The average age of the population is 45 years and 15$ (185/1203) remain on active dutyT Eighteen percent (210/1203) of the Ranch Handers and 19% (234/1238) of the total comparison group have either military flying duties or FAA certificates that denote active participation in, aviation. ,,There were 39 known deceased Ranch Handers. As a study requirement, all morbidity study comparisons were alive at the initiation of the morbidity effort. In summary, 1208 living Ranch Handers and 1238 original and shifted comparisons were entered into the morbidity study. II-8 �Chapter III QUESTIONNAIRE METHODOLOGY 1. Introduction The purpose of the extensive questionnaire was to collect data that could be analyzed for the subjective presence of adverse health effects that might be related to herbicide exposure. The study protocol required that all living exposed subjects and their primary comparisons be offered a comprehensive personal and family health questionnaire administered in the subject's home by a civilian contractor experienced in survey research. The personal nature of the information, peer review recommendations, and the study protocol called for face-to-face interviewing techniques (Herman, 1977; Fry, 1958). In addition to the study participants, the contractor was also required to interview the participant's current and former wives, as well as the first order next-of-kin of deceased individuals to obtain complete morbidity data. Whenever individuals, their spouses, or next-of-kin would not consent to participate in a face-to-face interview, attempts were made to collect the information by telephone (Colombotos, 1969). For the individual who absolutely refused to participate in this data collection process an abbreviated or noncompliant telephone interview format was designed and its use was attempted (Simon, 1971*). This chapter discusses the development and the implementation of the questionnaires used in the study. 2. Questionnaire Development The data collection instruments for the morbidity study were developed and implemented by three separate contracts. The first of, these, awarded to Research Statistics, Inc of Houston, Texas in 1979, developed a statement of work (SOW) which described, in survey research terms, the questionnaire requirements to support the effort. This SOW was used as the basis for the questionnaire development contract which was later awarded to the National Opinion Research Center (NORC) of New York, New York. The questionnaire instruments were developed by NORC in cooperation with the Principal Investigators and included questions concerning a broad range of health effects. The choice of specific effects included in the instruments was based on scientific studies of humans and animals exposed to phenoxy herbicides and dioxins. Hypothetical health effects based on studies in biochemical and biological systems were also included. In addition, veterans' complaints and the public's perception of the health effects of these chemicals were also considered. Questions were designed to allow the maximum degree of data verification by physical examination and medical and personnel record reviews. At the suggestion of NORC, portions of previously field-tested questionnaires were incorporated in the study instruments to maximize the validity of the questionnaires. The sources of the field-tested questionnaires are presented in Table III-1. �Table III-1 SOURCES OF QUESTIONNAIRE ITEMS Section of USAF Health Study Questionnaire Field Tested Questionnaires Marital History The Lives of Women in American Society (Institute of Human Reproductive Studies; Columbia University School of Public Health, Denise B. Kandel) Pregnancy outcomes The Lives of Women in American Society Conception difficulty National Survey of Family Growth Cycle, (National Center for Health Statistics; Vital and Health Statistics, Series 2, #76 January 1978 William F. Pratt) Education General Social Survey (National Opinion Research Corporation, Roper Public Opinion Research Center, University of Conneticut 1981, James A. Davis) Occupation General Social Survey Health outcomes Procedures and Questionnaires of the National Medical Care Utilization and Expenditure Survey (National Center for Health Statistics; Series A, Methodological Report #1, 1980 Robert R. Fuchsberg) Smoking, drugs Drug Abuse Reporting Program (Institute of Behavioral Research, Texas Christian University, 1976 Saul B. Sells) Drinking Drug Abuse Reporting Program Erosion of cognitive abilities Drug Use Vietnam Veteran 11972; Resurvey of Vietnam Veterans 197 * (Washington University. Department of Psychiatry Lee I. Robbins; Special Action Office Monograph, Series A #1, April 1973) Aggression Stressful Life Events and Their Contexts (Rutgers University Press 1981; Barbara Snell and Bruce T. Dohrenwend) Isolation Young Adults Survey, New York State Drug Study (Columbia University School of Public Health. Longitudinal Research on Drug Use 1978, Denise B. Kandel Fatigue Young Adults Survey Social Desirability response set Health Insurance Study 1975-1982 (Rand Corporation; Santa Monica, CA Dec 1979 John E. Ware, Jr.) III-2 �Anxiety Health Insurance Study Depressive episode Diagnostic Interview schedule (Dr. Lee Robbins, Washington University, St. Louis, MO) Panic disorder Diagnostic Interview Schedule An acceptability pretest of the developed questionnaires was conducted in May 1981. Twenty study subject, 18 spouse, and 2 next-of-kin interviews were completed. Following minor modifications, these instruments became the final questionnaires for the implementation contract. They were not publicly released prior to implementation. 3. Questionnaire Implementation; Contract Award and Administration Louis Harris and Associates, Inc (LHA) was competitively awarded a 9-month implementation contract in September 1981. The purpose of this contract was to collect baseline data on the study population through the use of the developed questionnaires. The specific elements of each questionnaire are presented in Table III-2. Table III-2 ELEMENTS OF THE QUESTIONNAIRES Type Questionnaire Elements Study Subject Demographic, educational, occupational, medical, compliance, toxic exposures,and reproductive experience Spouse (present and former) Comprehensive reproductive history Next-of-kin Modification of study subject questionnaire Noncompliant (Telephone) Perception of health, use of prescribed medication, medical conditions, work absenteeism, income and reasons for noncompliance LHA first reviewed the questionnaire and reformated the instruments from a horizontal to a longitudinal format to better suit their interviewing style. The contractor's management personnel selected interviewers, scheduled training programs, and defined procedures to be used in the conduct of the contract. Ninety interviewers were selected and trained in a series of 11 training sessions held throughout the United States and Europe. All training sessions were taught by either the LHA Vice-President for Research Services, or the Project Director. All LHA interviewers (84 women and 6 men) had a minimum of 1 year prior experience in interviewing, with at least 1 experience with health data collection. Race matching of interviewers and respondents was accomplished in III-3 �the majority of cases in order to enhance rapport and accuracy of data (Hyman, 195*0. Interviewer bias was additionally limited through a review of the interviewer* s military experience and background. Several potential interviewers were excluded because they were spouses of USAF personnel or personally knew some of the study participants. The LHA staff was not informed of the exposure status of any individual in this study before or after the completion of the contract. LHA interviewers reported to the Project Director in the New York office on a weekly basis. The first two interviews of each interviewer were critiqued by this staff prior to allowing further interviewing. Additionally, the USAF received weekly reports from the Project Director on all aspects of the contract. An interactive relationship between the USAF and LHA staff was essential throughout this contract. In addition to data collection, LHA also contracted to locate the study population, obtain signed medical release forms, assess the intent of the subject to participate in the physical examination phase of the morbidity study, and to attempt to convert those individuals who absolutely refused all data collection attempts. 4. Questionnaire Implementation; .....Location Initial contact with the Ranch Hand and the original comparison population occurred in November 1981. At this time each potential participant was sent certified introductory letters and a fact sheet. These letters were signed by the Secretary of the USAF and the USAF Surgeon General. They defined participation as voluntary and explained the limited confidentiality of positive medical findings diagnosed during the physical examination portion of the Morbidity study. Examples of these materials are presented in Appendix XI. LHA followed the USAF letters with their own introductory letters. The assigned interviewer then contacted the potential study participant by phone for scheduling the in-person questionnaire. Initial contact with the shifted population was also completed by this series of letters and telephone contact. Letter mailing and identification of this group to LHA was completed by April 1982. Initial contact with the replacement comparison group occurred by letter followed by LHA phone contact until the final questionnaire administration contract extension, i.e. November 1982. From November 1982 all initial contact with replacement comparisons was by the USAF by telephone. For this small group, questionnaire administration was scheduled by the USAF interviewers in conjunction with the physical examination. Introductory USAF letters were sent after the replacement comparison agreed to complete the physical examination. LHA letters were, of course, not sent to this population. Therefore, within the replacement subset of comparison participants there are individuals whose interview was completed by the USAF at the physical examination site and not in their home. Table III-3 presents the algorithm developed for locating study participants during the questionnaire administration contract. �TaMalll-3 ALGORITHM OF THE LOCATION PROCESS OF LHA AND USAF DURING THE QUESTIONNAIRE ADMINISTRATION CONTRACT LHA Location Process Location •«—[ USAF Location Process TOTAL POPULATION USAF CERTIFIED LETTER nontocation Location-4- LHA LETTER USAF RECORD SEARCHES: FAMILY CONTACTS nontocttion Location nontocation POSTAL SEARCH nontocation location-4- INTERNAL REVENUE SERVICE (1980 DATA BASE) LOCAL PHONE DIRECTORY SEARCH nontocation nontocation Location • VETERANS ADMINISTRATION FACILITY USE DATA BASE MOTOR VEHICLE REGISTRY SEARCH y nonlocatton nontocation REMAINS UNLOCATABLE Location GEOGRAPHIC SEARCH nontocation Location • REMAINS UNLOCATABLE COMPARISON REPLACEMENTS This algorithm demonstrates the multiple sources used to locate study participants. This process was completed for all study subjects forwarded to LHA (Ranch Hand; original, shifted, and replacement comparisons). For a small number of replacement comparisons (23) not forwarded to LHA because of contract termination, the majority of the USAF location process was completed while the LHA process was not completed. Replacements for the original and shifted nonlocatable comparisons were not identified to LHA until the location algorithm was complete. 5. Questionnaire Implementation; Data Collection Once the study participant was located, an individual LHA interviewer was assigned. The interviewer initially contacted the participants by phone or by telegram -if his phone number was unlisted. The participant was informed of the length of the interview (average 1.5 hrs; range 30 minutes to 3 hours) and scheduled the in-home questionnaire at his convenience. Whenever possible, interviews of current spouse were scheduled for the same day and followed the study participants interview. These interviews were conducted privately in Order to obtain independent reproductive histories. If the participant refused to participate in the interview, his name was forwarded to the central office III-5 �and conversion attempts were made by the LHA central office. Noncompliant telephone questionnaires were administered to the refusals by the central office. The telephone administration system was implemented in April 1981. At the time of the in-persbn questionnaire, all participants read and signed a privacy act statement and completed a Life Events Chart. This chart acted as a recall guide to the chronology of events discussed in the questionnaire. Interviewers were required to ask questions exactly as written, were not allowed to interpret questions, or inject personal commentary, nor were they allowed to skip between sections of the questionnaire. They were also instructed to probe "don't know" answers at least once. At the conclusion of the interview, medical record release forms were signed for those physicians and medical facilities reported in the questionnaire, and the study participant was also asked whether or not he would agree to participate in a physical examination. The respondent was also asked to give the' current name and address for each former spouse listed in the questionnaire, so that spouse interviews could be scheduled and conducted with these individuals. Medical permission forms for medical record data of spouses and children were inadvertently omitted at the time of interview. A system to obtain these data was initiated following the USAF receipt of questionnaires. Due to high and favorable participation rates, patient flow and logistic difficulties in both the questionnaire and physical examination portions of the morbidity study, it was necessary to extend the LHA contract through November 1982 and the examination contract to 15 December 1982. Because the contracts did not overlap experienced USAF interviewers were required to complete questionnaire administration to participants at the physical examination site. 6. Questionnaire Implementation:^Data^Processing All completed interviews were sent to the LHA central office following initial field editing by the responsible interviewer. Each completed questionnaire was repeatedly edited by the LHA Project Director's staff. To ensure that every question was answered, participants were recontacted to provide missing data. This staff also coordinated and supervised the coding, keypunching and key verification of all completed interviews as they were translated to computer tape. Classifications and coding schemes used included the International Classification of Diseases, 9th Revision, Bureau of Labor Statistics, Standard Industrial Classification, and specific USAF codes for job and aircraft designation. LHA reported that it took an average of 2 hours to fully edit and code each interview. All keypunching was 10056 verified. Discrepancies were reconciled by review of the hard copy interview. A set of data cleaning programs was developed by the LHA data processing staff to locate and identify errors and inconsistencies in the data set on tape. These programs were reviewed and approved by USAF data processing personnel. In addition, the USAF developed additional programs to further cleanse the data. In neither case were programs used that would force data to meet inner consistency checks. The objective of data editing was to ensure that the final data set accurately represented the respondent's information. A total of 6 data tapes were delivered to the USAF from LHA. A copy of the data tapes was sent directly from LHA III-6 �to the Advisory Committee on Special Studies Relating to the Possible Long-term Health Effects of Phenoxy Herbicides and Contaminants. The data tapes were delivered at least 3 months later than the original contract established dates. 7. USAF Data Process! ng The questionnaire data collected during contract extensions and at the physical examination site were edited but not keypunched. These data were delivered in hard copy to the USAF. The USAF coded, verified, keypunched and entered the data on computer tape. Because of late data delivery and the volume of unkeypunched data, systematic review and comparison of all (LHA and USAF) hard copy questionnaires to the data tapes was not accomplished as planned. A comparison of 25 hard-copy questionnaires to data entered on the tapes was accomplished by USAF data processing personnel. The findings of this keypunch review are presented in Chapter VI, Quality Control Procedures. Morbidity coding was reviewed; however, because of incorrect and missing morbidity codes the USAF receded all reported medical conditions. Additionally, the LHA data tapes did not include all data collected by the interviewer in the supplemental recording book. These data were required to form the link between the parents, their children, and all medical provider data (the basis of medical verification procedures). The USAF therefore developed systems and hired personnel to support the entry of these data in preparation for analyses. 8. Summary Questionnaire methodology includes the development and implementation of multiple questionnaire instruments through civilian contractors. The NORC developed and LHA administered the instruments. Both contractors worked closely with the USAF. These close interactions resulted in the participation shown in Table Table SUMMARY OF QUESTIONNAIRE PARTICIPATION Type Questionnaire Ranch Hand - Study Subject Counts of Participants Comparison Original Shifted Replaced Air Force TOTAL 1171 956 200 346 30 1208 - Spouse (Current & Former) - Telephone 10 Noncompliant 962 200 333 5 1500 34 8 7 20 69 1532 Medical record release forms were obtained by the contractor during data collection. These permission forms are the basis of the medical record verification program presently in process for data collected by questionnaire. Data delivery to the USAF from the contractor was delayed. Medical coding was reaccomplished and data linkage systems were developed by the USAF to make the most efficient use of the data collected. III-7 �Chapter IV PHYSICAL EXAMINATION METHODOLOGY .Subsequent to the administration of the questionnaire, a voluntary comprehensive physical examination was offered to all individuals in both the exposed and comparison groups. The primary prerequisite for entry into the examination phase of the study was the completion of the baseline questionnaire. In the event that the initially selected comparison chose not to participate in both the questionnaire and the physical examination, a replacement was selected from among the other comparisons in the matched set, as depicted in Chapter II, Figure 11-1. The two and one-half day examination was conducted in Houston, Texas by the Kelsey-Seybold Clinic, P.A. At the time of evaluation, an extensive physical examination, medical history with a review of systems, and indepth laboratory analyses were conducted. A concise Examiner's Handbook in the Air Force Health Study Protocol placed strong emphasis on quality assurance and was used to minimize variability and insure comparability of data over the 12-month duration of the physical examination contract. Strict compliance with this document was required. Physical examinations were performed at the earliest practical time following the completion of the questionnaire, since close sequencing would limit the development of major symptoms or diseases in the interval between the questionnaire and the examination. Physical examinations were performed at a single location and all contractor personnel evaluated the participants without knowledge of their exposure status. The number of examiners and the turnover of staff membersiwas kept to a minimum to limit between-examiner variability. A more detailed discussion of the physical examination quality control program is contained in Chapter VI. All laboratory tests were subjected to rigid quality control, and laboratory and physical examination data were measured on a continuous scale whenever possible to improve statistical power in the analysis. An Air Force physician was present at the examination site throughout the duration of the contract to act as a liaison between the subjects, the contractor and the Air Force, and to insure that the examination protocol was scrupulously followed. Although the on-site monitors closely observed each examiner and technician, the monitors remained unobtrusive during the examinations, and were not permitted to confirm, criticize or otherwise influence the examiners' findings. The components of the physical examination were specifically selected to address those medical end points known or suspected to be caused by phenoxy herbicides and dioxin (Crow, 1970; Kimbrough, 1980). The question of whether significant chronic effects are produced in humans is a controversial issue (Homberger et al, 1979; Reggiani, 1980; Wolfe and Lathrop, 1983). Reviews of physical chemistry data, animal toxicity data, human exposure case reports, and epidemiologic studies have been relatively unsuccessful in identifying specific and objective medical end points for the chronic effects of exposure (Jirasek et al, 1973; Jirasek et al, 1974; Poland, 1979; Young, 1978). The list of known IV-1 �or suspected acute and subacute effects following TCDD exposure is extensive, and many of the end points are highly subjective and extremely difficult to evaluate (Oliver, 1975; Poland et al, 1979). While chloracne appears to be a consistent, chronic effect of moderate to heavy exposure, the implication of this condition on long-term health is unknown (Young et al, 1978). At best, a list of potential organ systems which should be carefully evaluated can be developed. Ideally, one would like to have a sensitive and specific examination or laboratory procedure to detect the effects of these chemicals in human tissues. Unfortunately, there is a lack of clearly defined end points in the scientific literature, and, other than chloracne, distinct clinical syndromes or unique effects indicative of chronic illness have not been identified. The signs and symptoms currently attributed to exposure are confounded by age and other causes, and the effect, if present, may be lost in common symptoms from other causes of disease (in contrast to conditions such as diethyl-stilbestrolinduced vaginal adeno-carcinoma and angiosarcoma of the liver caused by vinyl chloride exposure). In the absence of sensitive and specific indicators of exposure, a comprehensive examination format was developed around these target organ systems listed in Table IV-1. The complexity and the length of the evaluation and the invasiveness of each examination procedure were all key factors in the final choice of the examination components since all of these factors have a significant impact on the compliance behavior of the individuals considering participation in the study. Table IV-1 TARGET ORGAN SYSTEMS/CONDITIONS Dermatologic Hepatic Neoplastic Neurological/Psychiatric Endocrine/Reproductive Immunologic Hemopoietic A general summary of the major components of the examination is presented in Table IV-2, and examples of the examination forms are included in Appendix VI. The laboratory procedures conducted on each subject are listed in Table IV-3. For each participant 20 cc of serum, 100 cc of urine, and all remaining semen were aliquoted and stored at ~70°C for future analyses. When technology developments identify additional analytic procedures which will IV-2 �assess the health effects of phenoxy herbicides and dioxin, these specimens will then be tested. The slides used in the 10,000 white blood cell differential and the semen analysis were also preserved. Table IV-2 RANCH HAND II PHYSICAL EXAMINATION General Physical Examination (Internist) Neurological Examination (Neurologist) Dermatological Examination (Dermatologist) Electrocardiogram (Resting, H-Hour Fasting) Pulmonary Function Study (1 Second Forced Expiratory Volume, Vital Capacity) , Chest X-ray (Ulnar, Peroneal, Sural) Nerve Conduction Velocities Psychological Evaluation Minnesota Multiphasic Personality Inventory (MMPI) Cornell Wechsler Memory Scale I Wechsler Adult Intelligence Scale (WAIS) Wide Range Achievement Test (WRAT) Halstead-Reitan Neuropsychological Battery (Internist) (PhD Psychologist) Patient Outbriefing and Discussion of Individual Results IV-3 �Table IV~3 LABORATORY PROCEDURES Chemistry Panel: Blood Urea Nitrogen (BUN) Creatinine Cholesterol High-Density Lipoprotein Triglyceride Serum Oiutamic Oxaloacetic Transaminase (SCOT) Serum Giutamic Pyruvic Transaminase (SGPT) Gamma Glutyrl Transpeptidase (GGTP) Lactic Dehydrogenase (LDH) Creatine Phosphokinase (CPK) Blood Alcohol Total Bilirubin Direct Bilirubin Alkaline Phosphatase Glucose i } Fasting and 2 Hour Cdrtisol Hormone Assay: Leutenizing Hormone (LH) Triiodothyronine (T3) Follicle Stimulating Hormone Total Thyroxine (T4) (FSH) Free Thyroxine Index (FTI) Testosterone Hematology Panel: Erythrocyte Sedimentation Rate Prothrombin Time Serological Test for Syphilis (RPR) White Blood Cell Count (with 10,000 cell differential) Red Blood Cell Count Hemoglobin Hematocrit Red Cell Indices Platelet Count Urinalysis 2JJ-Hour Urine: Volume Delta Amino Levulinic Acid Coproporphyrins Uroporphyrins Porphobilinogen Creatinine Semen Analysis: Volume Count Abnormal Forms Hepatitis B Testing: Surface Antigen Antibody to Surface Antigen Core Antibody �Under special circumstances, additional laboratory procedures were carried out on selected participants. Those individuals with a history of having fathered children with birth defects had' blood drawn for a determination of karyotype. The serum of participants with a medical history or review of systems indicating the possibility of an immune system deficiency was evaluated by immunoelectrophoresis. Antinuclear antibody determinations were performed on individuals with a history suggestive of connective tissue disorders. In addition, all individuals with a past history of hepatitis were tested for antibody to hepatitis A virus. After 20 April 1982, all participants whose study identification number ended in either 1, 3» 6 or 9 were selected for special immunologic testing. Blood from these individuals was drawn and sent to a subcontractor for the evaluation of B and T cell counts, enumeration of T cell subpopulations, and studies of B and T cell function following mitogen stimulation. In all, 592 randomly selected subjects took part in this portion of the evaluation. Since human sensitivity and compassion could seriously enhance participation in the follow-up phases of the study, every opportunity was taken by the contractor and the Air force to make the experience enjoyable, relaxing and rapport building. Study participants were housed in a comfortable motel, and transportation, meals and a modest stipend were provided. Family members were encouraged to accompany the participants, but at no expense to the government. Any emergency medical care required by the participants during their stay, in Houston was provided by the contractor and paid for by USAF. Additionally, any diagnostic procedures necessary to clarify potentially lifethreatening conditions were also performed (computerized tomography, cardiology consultation, etc.). Detailed in-briefings were provided to ail participants (and optionally to accompanying family members), in order to explain the background and nature of the study as well as the routine medical requirements for the fasting status laboratory procedures. During waiting periods between examination phases, participants were encouraged to become acquainted with other participants and ask any questions they had about the examination, its rationale or the Air Force Health Study. The normal tension associated with psychological testing was relieved by frequent breaks. Any individual problems were quietly and diplomatically managed by the contracting staff and the site monitor. Over 95% of the participants expressed praise for the quality and thoroughness of the examination and pledged to return to the next examination. Subjects arrived in Houston on either a Sunday or a Tuesday afternoon. A 1-hour briefing was given to each group of participants by the Air Force monitor and a Kelsey-Seybold physician. During this briefing, the purpose of the study and a detailed explanation of the examination content and schedule were discussed. The next 2 days (Monday/Tuesday or Wednesday/Thursday) were spent in the examination. Upon arrival at the clinic on the first morning, all participants were met by two Kelsey-Seybold staff members: the Patient Coordinator and the Program Director. After the day's events were explained, medical history and other forms were completed and blood specimens were drawn. All participants on active flying status with the Department of Defense or FAA had their blood drawn while reclining. Others had the option of sitting or lying. IV-5 �All fasting blood specimens were obtained following a minimum of seven hours without alcohol, food or cigarettes. Participants were requested to consume a 250-gram carbohydrate diet for the 3 days prior to their arrival to prepare for the fasting and 2-hour postprandial glucose testing. All alcoholic beverages were to be avoided as well. Compliance with these requirements and the 21* hour urine collection was determined. Breakfast followed the blood draw and postprandial specimens were then obtained at appropriate times. One-half of each group underwent physical examination on the first day while the other half were in psychological testing. On the second day, the schedule was reversed. During the final half-day, each participant received detailed briefings from a PhD psychologist and one of two Internal Medicine specialists. During these briefings, the results of all portions of the physical examination performed at the Kelsey-Seybold Clinic were discussed with the subject, any questions he had were answered, and suggestions for medical treatment or follow-up were made when indicated. If immediate follow-up was indicated, direct contact with the participant's personal physician was made, and appropriate treatment was arranged. The results of those laboratory procedures performed at subcontracting laboratories and the results of the MMPI were not discussed. Payment of expense vouchers and the provision stipend checks were delayed until after the completion of the debriefing to encourage attendance at these sessions. IV-6 �Chapter V STUDY SELECTION AND PARTICIPATION BIAS 1. Introduction The main emphasis in the design and conduct of any epidemiologic study is comparability of the groups under study (Monson, 1980), and the strength of epidemiologic inference is directly associated with group comparability. In this study, Ranch Hand and comparison group comparability was assured by design since strict criteria were used to define the exposed (Ranch Hand) and thf nonexposed (comparison) cohorts and since replacement comparisons were to be matched to original comparisons by perception of health. The cohorts were matched on the variables of age, race, and occupation group to minimize confounding and assure comparability in these variables. Within the nonexposed cohort, however, 4 subgroups resulted from the original match, the removal of ineligibles, replacement for noncompliance, the termination of the questionnaire and physical examination contracts, and the lack of data to match replacements to original comparisons. These groups are: original comparisons (0), shifted comparisons (S), replacement comparisons (R), and those replacement comparisons questioned by experienced Air Force interviewers (A). Because of logistic limitations, scheduling opportunities differed somewhat for each of these groups. Since compliance with this study was voluntary, the occurrence of differing scheduling options could have resulted in inadvertent selection bias (Cook and Campbell, 1979). The purpose of this chapter is to present the factors known to influence study participation, describe and analyze the responses of the Ranch Hand and the comparison groups to the opportunity to participate and to assess the potential bias of differential compliance. The analytic, and inferential implications of self-selection and potential participation bias will also be discussed. Participation is described in terms of location and compliance. A total of 1208 Ranch Hands and 1669 comparisons were the potential participants in this morbidity study. 2* Factors Known to Influence Study Participation The study protocol estimated that 65% of the Ranch Handers would participate in the questionnaire and that 6Q% of these subjects would also participate in the physical examination. One major reason for these low estimates was the recognition of the negative influence of employment in flying occupations on compliance to physical examination. This negative influence was reinforced _in the press and the subsequent advice of the Airline Pilots Association to their members not to participate in this study. This difficulty was anticipated by the principal investigators and is discussed in section VIII of the study protocol. Table V-1 presents a list of factors that could affect study participation. Those components of each factor that are considered in the study protocol for data collection are identified with an asterisk. V-1 �Table V-1 FACTORS POTENTIALLY AFFECTING STUDY PARTICIPATION Factors Components Health Bias *Self perception Current Use Long Term Care Abortion Pattern *Absenteeism *Current Medications Fertility History Current Family Health Familial History Severity of Past Disease Pending Retirement Bias Death Logistic Factors *Time Away From Family *Time Away From Job Distance to Exam Site *Income *Active Pilot (FAA) Other Factors Flying Status (USAF) Officer/Enlisted Age Race Current Status: AD/Sep Stipend Employment Status Dissatisfaction with Military "Operational Factors" Manner of Study Contact Scheduling Window Interviewer Bias Publicity Bias Motivational Bias Compensation Bias The factors and the outlined components of each factor suggest the complexity of the compliance/noncompliance decision made by each study participant, Ranch Hander or comparison. The importance assigned to each component by the individuals in the Ranch Hand and comparison groups is most likely not equivalent. The Ranch Hand group was actively encouraged by the Ranch Hand Association to participate while no such organization exists for the comparison group. V-2 �3- Location Mailing addresses, fpp e@ch study subject were determined through multiple military and civilian sourpes. Study subject location was initially identified by a certified mailing to these addresses/. Current mailing addresses could not be identified for the nQnlpc§tabJe population. Two-tenths percent of the Ranch Hand and 0.5? p? the total comparison group were nonlocatable. This, is well above the 99? location r§te estimated in the stu^y protocol. Table V~2 presents the counts pf the. Ipcated/npnlpcated population by Ranch Hand and type of comparison. Table V-2 COUNTS AND PERCENT OF LOCATABJ,E/NQN-L.OCATABLE ALIVE. STUD! SUBJECTS BY RANCH HAND AND 'NATURE OF THE COMPARISON GROUP Comparison Ranch Ha.nd Locate 1206 (99.8$) NonLocate 2 (0.2?) 1208 Original Shifted Replacements* Total 1023 (99.7$) 212 (10056) 425 (98.6?) 1660 (99.5?) 3 (0.3?) 6 (1.130 9 (0.5?) 1026 212 431 1669 *Includes those indiyiduia.ls interviewed by USAF interviewers (A). The two unlocated Ranch Hajnd individuals were separated from the military, and both had been nqnflying enlisted personnel when on active duty. One was Black and the other was npn-Black;. Three of the 9 unbeatable comparisons were in the originally selected cohort. These 3 individuals were separated from the military, enlisted when on active duty (1 was a flying enlisted while the other 2 were nonflying enlisted) and all were non-Black. The locate algorithm was not completed on the replaced comparison "cannot-locate" population. Five of these 6 individuals were non-Black, The, Black individual was?, separated and had served in an enlisted nonflying capacity. One other separated nonflying enlisted individual was non-Black.. The remaining 4 replaced npnlocated comparisons were non-Black pilots. Two pf these;, were separated, 1 was on reserve status and the other was retired. Overall, nonlocation did npt impact data collection in this study. The 11 npnlocataple subjects are assumed, to be alive and location will be attempted fpr the fpilpw.-up phases of the study. The replacement comparison group nonlocatable rate of 1.4? is of borderline significance when contrasted with th,e rajbe in the originally selected group (P = 0.06). This test was performed pn the proportions using the normal approximation to the binominal, this difference., was a, result pf the termination of the questionnaire contract prior to completion pf the exajnijia.tion process. The names of 3 P? the 6 replacement individuals we,re npt sent to the questionnaire contractor while the 3 others were sent only 1 month prior to contract termination. The V-3 �replacement strategy as de.signed in the study protocol could not be implemented due to termination of the questionnaire contract prior to the completion of the physical examination contract. 4. Study Participation; Compliance Study participation was characterized as being either fully compliant ( FC) (completed the physical examination and the questionnaire); partially compliant (PC) .(completed only the questionnaire) or noncompliant (NC) (refused the physical examination and the in-home questionnaire). Within the noncompliant group are those who completed an abbreviated telephone questionnaire. Figure V-1 shows that of the 1206 locatable Ranch Handers alive at the initiation of the morbidity study, 1045 were fully compliant to the physical examination and an additional 129 completed the questionnaire but refused the physical examination. Ten of the 32 noncompliant Ranch Handers completed the telephone questionnaire. Figure V-1 RANCH HAND PARTICIPATION Original Population n ,1264 .. . ,1 Matched Population n=1242 22 Added Population to Morbidity Study ' \ Living? n=1247 / \ N Deceased n=39 ° Potential Morbidity Study Participants n=1208 ' % * f Is Study Participant Locatable? n=1208 J \ No Non-locat.!* / 1 / Complied with ^ < Questionnaire \ n=1174 TUT /'Complied Witlr, / Physical v \ Examination / \ n=1045 / \ ——,.-- ---• TT Fully Compliant n =1045 No Partially Compliant n=129 �Figure V-2 describes the compliance patterns for the original, shifted and replaced comparison population. Of the 1023 locatable eligible original comparisons, 773 were fully compliant, 183 were partially compliant and 67 were noncompliant. Thirty-four of the noncompliant individuals completed the short telephone questionnaire. FHure V-2 COMPARISON POPULATION PARTICIPATION P /ait . . "° Took \ \ __ /No s LCan't Locate 3 Noncompkant n«67 y 7io" J ^ PartiaNy Compliant n--183 IBS Fully Compliant n=773 1 Completed Telephone n=8 Partialy Phy$ic81 J n=3? _._ No \ t FuNy Compliant n*163 ... . .... ... V fteplacements-for-ineligible Shifted Comparisons V-5 NoncOfflp) •nt n=49 48* 1 Completed Telephone n=27 Yes / Took A "* > \ Physical /"" Yes \ Original Comparisons / Took \ N \ < Questionnaire >~~ Yes »\ V n-137 t t n- 302 j i iMWMM —[canl Locate 6 | — ' -_i» ml29 Replacemerit Compairinn n-431 , j j.- ai _._-_. ^e--.* _ / Took '» rWoconipiini "*" n»12 No\ / Tetephone n«34 ;. Yes y> > p Contact End Omitted 17 1 Shifted »on + 2 Lociti / * i 102 No ( Y«. / \n» 1 / p • 1*\ \" V- Mtital Matched Compailioni .••1241 ^ Yes FuNy Compliant 1 1 t Partialy 1 CompKant t 75* n«88 4 * Number differencenext replacement stopped because prior comparisnn compked after refusing 1 V Replacements-for-NoncdmpNant comparisons �Data collected by the noncompliant telephone instrument was delivered to the United States Air Force in written format following the implementation of the replacement strategy. The telephone questionnaire was not administered to the noncompliant replacement candidates prior to selection for the study, and therefore, the data necessary to match the original and replacement comparisons by similar perception of health status was hot available (Lathrop, 1982). The next living individuals in the designated matched sets were selected as replacements. The data collected in the noncompliant instrument will be discussed in future publications. Figures V-1 and V-2 are summarized in Table V-3, in which Ranch Hand and comparison participation is presented. Table V-3 FULL, PARTIAL, NONCOMPLIANCE OF THE RANCH HAND AND COMPARISON POPULATION BY NATURE OF THE COMPARISON GROUP, i.e., ORIGINAL (0), SHIFTED (S), REPLACED (R), AIR FORCE INTERVIEWERS (A) lp_ RH Fully Compliant (FC) Partially Compliant (PC) NonCompliant (NC) TOTALS 773 183 67 1206 1023 :S Comparisons _A I 258 163 88 37 49 H 212** 395 Total r» 1224 308 128 30 1660 3P *4 individuals were interviewed at the Physical Examination site by USAF interviewers. **3 Additional shifted comparisons were removed due to ineligibility identified following data collection. V-6 �The mean age of the population by compliance, group is presented In Table V-4, Table V-4 MEAN AGE OF THE RANCH HAND ANP COMPARISON POPULATION BY NATURE OF THE COMPARISON GROUP (0, S, R) AND TYPE OF COMPLIANCE (NC, PC, FC) Type Compliance Comparison Mean Age S 0 Ranch Hand Mean Age Non-Black 41 43 44 41 42 45 39 39 43 40 41 41 39 39 41 NC PC FC 39 43 42 35 39 42 34 38 40 Black NC PC FC ^Includes those individuals interviewed by USAF interviewers U). Table V-4 indicates that the nonoompliant group is on the average younger than either the partially or fully compliant in both Black and non-Black strata. The compliant population i? further described by race in Table V-5. This data is abstracted from Appendix XII, Occupational Category and Race of the Fully Compliant Population in Percent and Counts. Table V-5 PERCENT FULLY COMPLIANT OFFICER/ENLISTED CATEGORIES BY RACE RANCH HAND AND COMPARISONS (0, S, R) Comparison ' Shifted Replacements Ranch Hand Original Non-Black Officers Enlisted 35* 88* 73* 77% 78* 77* 61* 74* Black Officers Enlisted 67% 90% 88% 75% * # 69* 62* No individuals in this category. V-7 �This table suggests that Ranch Hand enlisted personnel complied at higher rates than officers and that Ranch Hand non-Black officers complied more than Black officers. The number of Black participants is very small and is therefore not included in the following analyses but is included in Appendix XII. Appendix XVII was used to construct the data in Table V-6. Flying status is presented as flying/nonflying which includes both military and civilian information. Military status is categorized as active duty, retired, and separated/reserve. Table V-6 PERCENT FULLY COMPLIANT OFFICERS BY FLYING STATUS AND MILITARY CATEGORY (NON-BLACK ONLY) Ranch Hand n=372 NonFlylng Flying Comparison Original Shifted Replacements n=46 n=283 n-113 NonNonNonFlying Flying Flying Flying Flying Flying Active Duty (A) 77.8 96.3 58.9 76.2 87.5 75.0 57.9 88.9 Retired (R) 86.0 93-5 86.0 86.5 100.0 96.0 83.3 77.1 Separated/ Reserve (SV) 51.9 87.0 39.3 62.9 37.5 61.5 32.4 63.0 The flying separated/reserve category in this data set complied less than any other strata (P<0.01), and flying status contributed significantly to the compliance decision (P<0.01). As illustrated in Table V-6, a complex set of interactions was involved in compliance. A log-linear model which was fitted to the three-way frequency table based on flying/military status, compliance, and group membership, revealed a three-way interaction (P=.07) in these data, rendering interpretations based on simpler models misleading. Since age and race are also related to flying/military status, tests of association between these factors and compliance need to be studied in the context of the many interactions present. These more complex relationships will be explored in future reports. V-8 �A summary of compliance is presented in Table V~7. Table V-7 PERCENT OF THE STUDY POPULATION COMPLYING TO THE QUESTIONNAIRE AND PHYSICAL EXAMINATION Ranch Hand Questionnaire 97% (1174/1206) Physical Examination 87% (1045/1206) Original Comparison Shifted Replacements 92% (956/1023) 94* (200/212) 88% (376/425) 76$ (773/1023) 77% (163/212) 68% (288/425) Ranch Hand personnel participated in the questionnaire at a rate higher than all comparison groups. This participation was 32% greater than the original protocol estimate of Ranch Hand compliance. Differential compliance to questionnaire did occur in the comparison groups with the original and shifted group complying 5% more than the replaced comparison group (unadjusted; P=0.003)« Table V-7 shows that differential compliance also occurred between the Ranch Hand and the original comparison group in their compliance to physical examination (unadjusted; P<0.001) as well as within the comparison groups with the original and shifted comparison groups complying 8-9% more than the replaced group (unadjusted; P<0.001). 5. Noncompliance The reasons given by study participants for noncompliance were compared. Appendixes XIII and XIV display all reasons given. These data were collected in a nonstandard manner by Louis Harris and Associates, the Kelsey-Seybold Clinic, and USAF personnel. The responses were then allocated to the categories presented in the appendix. They describe that the majority of the reasons given for noncompliance were "no time-no interest" and passive refusal. Table V-8 shows the percent of refusals in the Ranch Hand and comparison groups implying these disinterest reasons. V-9 �Table V-8 PERCENT OF REFUSALS CATEGORIZED AS REFUSALS FOR REASONS OF DISINTEREST Comparison Shifted Ranch Hand Questionnaire Physical Examination Original 86% 67$ 91$ 49$ 50% 58% 54$ 58% Replacements These data indicate that the noncompliant replacement comparisons were passive refusals less often than were the other comparison groups. The percent refusals due to job commitment and confidentiality are described in Table V-9. Table V-9 PERCENT OF QUESTIONNAIRE REFUSALS CATEGORIZED AS JOB COMMITMENT AND CONFIDENTIALITY Original Ranch Hand Job Commitment Confidentiality/ Active Duty TOTAL Comparison Shifted Replacements 3% - 24$ 5% IM - 24$ 5% 17$ - 48$ Forty-eight percent of the replaced population stated that they refused to participate in the questionnaire because of a job commitment or the issue of confidentiality. 6. Scheduling Opportunity The names of the Ranch Hand and original comparison groups were provided to the questionnaire contractor in November 1981. The contractor was given the shifted comparison population in April 1982 and the replacement population continued to be identified to the contractor through 15 Nov 1982. Physical examination scheduling was contingent upon completion of the questionnaire. Therefore, while the Ranch Handers and the original comparisons had 1 year to schedule and complete the study, the shifted comparisons had a maximum of 9 months, and the replacement comparisons were afforded a more limited scheduling opportunity. V-10 �Figure V-3 PERCENT COMPLETED PHYSICAL BY CALENDAR DATE JAN FEB MAR RANCH HAND ALL CONTROLS — APR MAY ORIGINAL KIN V-11 JUL AUG SEP OCT NOV DEC �Figure V- PERCENT COMPLETED PHYSICAL BY CALENDAR DATE 100 80 ^A 60 40 X r X 20 X JAN FEB ALL CONTROLS X MAR APR MAY JUN SHIFTED JUL AUG SEP OCT NOV DEC REPLACEMENTS Figures V-3 and V-1! show the cumulative percent of the Ranch Hand and comparison groups (original, shifted and replacement) completing the physical examination by time. Figure•V-3 shows the similar time pattern of the Ranch Hand and original comparison group completing the physical examination. Figure V-ty shows that the shifted and replacement comparison groups were restricted in scheduling by the nature of the implementation of the design and contract time limitations. The overall comparison group cumulative completion of physical examination by calendar date is shown on both Figure V-3 and V-4. Fifty percent of the Ranch Hands and the original comparisons had completed their physical in May 1982, 50$'of the shifted group had completed in July 1982, while 50% of the replaced group did not complete until October 1982. V-12 �7. Bias Assessment of Replacement Comparisons From the above discussions and that in Chapters II and III, 2 questions are forthcoming which are of interest to inferential reliability. First, "Are the shifted and replaced comparisons valid for use without special statistical treatment?" Secondly, "What is the bias, if any, associated with the differential compliance to the physical examination?" The following sections deal with these 2 questions in turn. 8. Evaluation of the Replacement Comparison Participants^ Since the replacements used in the study, whether S, R or A, were simply the next individual in the randomized match set involved, the appropriate test for replacement bias is the test for 0, S, R or A group differences while conditioning on the variables of age, occupation and race. Specifically, if S, R and A are unbiased groups they should appear to be random samples drawn from the same population as yielded the original (0) set, after adjustment for matching variables. Tests of replacements against original comparisons were accomplished in accordance with procedures set out in the Study Protocol. Following the proto^col, replacements for comparisons were tested first in terms of 3 primary variables to be ascertained oh all participants: (a) subjective health assessment, (b) current utilization of long-term health care, and (c) recent work absenteeism pattern. Statistical testing of these 3 primary variables and•of additional questionnaire and physical examination variables was done in a prespecified manner. First, group A was tested against group R to determine if these groups could be combined. If R and A could be combined, the R + A group was tested against group S to determine if these groups could be combined. If R + A and S groups could be combined, 0 was tested against R + A + S. All testing was done at the 0.05 level. If the test for combination was not met at any stage, appropriate subtesting was performed. When the dependent variable was categorical, testing was performed with log-linear models adjusting by occupational category and age, with age dichotomized as less than 40 years and greater than or equal to 1)0 years providing groups of roughly equal sizes across occupational categories. When the dependent variable was continuous, analysis was performed with a general linear models program adjusting for occupational category and age as with the log-linear models. All of this testing was done to ascertain whether the S, R and A groups could be viewed as drawn from the same population as yielded the 0 group. Thus, the problem is one of hypothesis testing. Careful estimation of the magnitude or directionality of effects noted was not attempted. However, the reader can evaluate magnitude by reviewing data presented in the following paragraphs. In reporting their health status, participants were allowed to use the categories: "excellent," "good," "fair" and "poor." Because of small sample sizes, the "fair" and "poor" responses were combined in the analysis of the data. Table V-10 provides a view of the data, collapsed across occupational V-.13 �categories and age. No statistically significant differences between the S, R and" A groups were found in either the partially compliant or fully compliant groups. However, when taken together, the fully compliant S, R and A groups appeared statistically different from the fully compliant original comparisons (P < 0.001). Additionally, the fully compliant 0 and S groups were found to be statistically different (P = 0.01), as were the fully compliant 0 and R groups (P - 0.0045). No statistically significant differences were noted among those individuals who took the questionnaire only. Table V-10 SELF-ASSESSMENT OF HEALTH STATUS (NON-BLACK PARTICIPANTS ONLY) Participants Who Took Questionnaire Only Fair or Poor Status •* Excellent Good Group •*• N Participants Who Took Questionnaire & Physical Examination Fair or Excellent Good Poor N 0 50.935 34.7$ 14.5$ 173 38.0$ 48.0$ 14.0$ 727 S 61.8* 26.5$ 11.8$ 34 36.4$ 40.3$ 23.4$ 154 R 51.3$ 10.5$ 76 49.6$ 34.3$ 16.1$ 242 A _ 38.2$ _ _ 0 46.7$ 43.3$ 10.0$ 30 36.4$ 11.0$ 118 38.4$ 41.4$ 20.2$ 976 Ranch Hand 0 S R A 52.556 - Original Comparison » Shifted Comparison - Replacement Comparison = Air Force Interviewed Comparison Use of long-term health care was assessed by inquiring about regular use of medications for heart, kidney, thyroid, renal and other disease states. No statistically significant differences were found between the 0, S, R and A groups regarding regular use of medications. Table V-11 provides a view of the data collapsed across occupational categories and age. V-14 �Table V-11 MEDICATION USE (NON-BLACK PARTICIPANTS ONLY) Group Participants Who Took Questionnaire Only (PC) Percent with Chronic Medication Use N Participants Who Took Questionnaire and Physical Examination (FC) Percent with N Chronic Medication Use 0 23.6$ 174 28.3$ 728 S 14.755 34 27.9$ 154 R 19,7$ 76 30.2$ 242 A - 0 16.7$ 30 118 29.4$ 979 Ranch Hand 0 S R A 14.4$ * Original Comparison - Shifted Comparison * Replacement Comparison - Air Force Interviewed Comparison Work absenteeism was assessed by a consideration of reported time loss from work during the 6 months prior to interview. No statistically significant differences were noted between the 0, S, R and A group on this parameter (relevant data provided in Table V-12). V-15 �Table V-12 WORK LOSS (NON-BLACK PARTICIPANTS ONLY) Group 0 s R A Ranch Hand 0 S R A Participants Who Took Questionnaire Only (PC) Percent with Work Loss N 16.8* 14.7* 12.0$ 18.81 Participants Who Took Questionnaire and Physical Examination (FC) Percent with Work Loss N 20.556 707 21.1* 18.6$ 152 237 23.356 20.356 173 34 75 0 112 30 955 » Original Comparison - Shifted Comparison - Replacement Comparison - Air Force Interviewed Comparison Thus, for the 3 basic variables emphasized for test by the study protocol, the replacement comparisons (S+R+A) were found to be statistically significantly dissimilar from the originals on 1 variable, self-assessment of health. To more fully assess replacement-original differences, 9 additional variables from the questionnaire were examined: (1) household income, (2) participant education (high school or less, greater than high school), (3) participant anger scale, (4) participant psychoneurological erosion scale, (5) participant anxiety scale, (6) participant depression, (7) reported liver ailments, (8) spouse miscarriage rate, and (9) occurrence of acne. The fully compliant nonBlack replacements (S+R+A) were observed to be statistically significantly different from the fully compliant original comparison participants as regards education (P = 0.04), anxiety level (P =0.02), and psychoneurological erosion (P = 0.02). With respect to education 48.856 of the fully compliant replacement comparisons report more than a high school education, while 43.756 of the original comparisons report more than a high school education. Original fully compliant comparisons reported more moderate to severe anxiety than did the replacements (56.9/6 versus 55.656 respectively). Reported psychoneurological erosion addresses difficulties with mental tasks such as arithmetic work. The replacement comparisons reported erosion more commonly (37.256) than did the original comparisons (30.256). These measures of psychological status were not validated as truly measuring their intended end points and they are not necessarily statistically independent of one another, nonetheless, a picture of differences between the comparisons subsets is evident. Thus, of 12 variables drawn from the questionnaire, 4 variables (reported health status, education, anxiety level and psychoneurological erosion) distinguish the replacement comparisons(S+R+A) from the original comparisons testing V-16 �at the 0.05 level. The differences observed are not only statistically significant but may also reflect clinically meaningful differences if the self-reporting is accurate. Analyses of bias have also been conducted using physical examination data end points to obtain a firmer evaluation, and these analyses are described in the following paragraphs. Five laboratory variables have also been examined for evidence of differences among the comparison groups: white blood cell count (WBC), hemoglobin concentration (HGB), total bilirubin (TBIL), serum glutamic oxalic transaminase (SCOT) and lactic dehydrogenase (LDH). This testing is summarized in Table V-13- The analyses were performed with a general linear models program, operating on WBC and HGB in natural units and TBIL, SCOT and LDH in logarithmic units. It is clear from Table TM3 that there is definite indication of comparison group differences. Table V-13 SUMMARY OF BIAS ASSESSMENTS OF REPLACEMENT COMPARISONS USING LABORATORY MEASURES (NON-BLACK PARTICIPANTS ONLY) Clinical Variable WBC HGB TBIL SGOT LDH Adjusted Mean For Original (0) Comparisons Adjusted Mean For All Replacements (S+R+A) P Value F<j>r Mean Differential 7 .78 15 .9 0 ,609 32 ,7 141.2 0.027 0.522 0.063 0.498 0.265 7.24 16.0 0.577 33.1 142.0 Lastly, 13 clinical variables from the physical examination itself were evaluated for 0, S, R, A comparison group differences. As summarized in Table V-14, statistically significant differences were found. V-17 �Table V-14 SUMMARY OF BIAS ASSESSMENTS OF REPLACEMENT COMPARISONS USING MEASURES FROM THE PHYSICAL EXAMINATION *1. Systolic Blood Pressure No differences detected *2. Diastolic Blood Pressure No differences detected *3. Posterior Tibial Pulse rS 1 statistically different from R + A 0 statistically different from R + A *4. Dorsalls Pedis Pulse No differences detected rS 1 statistically different from R + A 0 statistically different from R + A *5. EKG rS statistically different from R + A 0 not different from R + S + A 6. Vibration Sense 1 7. Tremor rs 1 statistically different from R + A 0 statistically different from S 8. Nerve conduction velocity above the elbow No differences detected 9. Nerve conduction velocity below the elbow No differences detected 10. Peroneal nerve conduction velocity No differences detected 11. Full Scale Intelligence Quotient No differences detected rS 1 statistically different from R + A 0 statistically different from R + A 12. MMPI Scale D No differences detected 13. MMPI Scale L *Black participants removed. Taken together the analyses described above imply very strongly that the S, R and A comparison groups are not random samples drawn from the same population as the original comparisons ( ) Since the comparison group differences are 0. not observed in all variables studied, a possible approach is to perform a prior test of significance (PTS) to test for appropriateness of replacement use, followed when possible by a Ranch Hand-all comparison test. This use of a PTS has been discussed with appreciable detail in the statistical literature (Bozivich et al, 1956; Bancroft, 1964; Kale and Bancroft, 1967; Arnold, 1970; Cohen, 197*0. Recommendations in this literature suggest a preliminary test for combination using an alpha level of 0.25> followed by a test of differences at an alpha level of 0.05. Calculations of study power with and without V-18 �the PTS have indicated that, given the sample sizes in this study, the PTS only provides partial protection against inferential bias. This result can be understood by reference to Figure V-5 where 2 power curves are given. Figure V~5 POWER CURVES FOR ALTERNATIVE ANALYTICAL METHODS Figure V~5. Curve 1: Power curve for Ranch Hand-original comparison tests on means. Curve 2: Power curve for Ranch Hand-comparison tests on means assuming replacement comparisons are unbiased. F is the symbol for ratios of Ranch Hand-comparison means. The lower power, curve (curve #1) is for a test of difference between the Ranch Hand group (N=1045) and the original comparisons (N=773)« The upper curve (curve #2) is for the same test of difference but between the Ranch Hand group and all comparisons (N-1224) assuming that the replacements are unbiased. These curves are drawn for a hypothetical clinical variable with ratio of standard deviation to mean being 0.200. The variable F is the ratio of the exposed mean to the comparison mean. The slight displacement of the 2 curves in the vertical direction (power) is easily negated by small degrees of bias in the replacement comparisons. V-19 �The Study Protocol reflects a strong concern for a variety of biases that may be operating in this study. The effect of the potential bias, by using the shifted and replacement members of the comparison group, was not uniformly viewed by the Principal Investigators. Because of time constraints, the Science Panel was not convened to address this complex issue. Instead, a management decision was made to base the primary clinical analyses upon a contrast of the Ranch Hand group and members of the original comparison group. For completeness of data descriptions, some chapters additionally contain analyses founded upon the entire comparison group. 9. Noncompliance Bias The data in the previous section suggest that a degree of self-selection did occur in association with compliance to the physical examination, indicating that the group who came to physical examination may be biased from the original sample. Since this report emphasizes analysis of data from fully compliant participants, selection biases associated with physical examination compliance are of importance. Table V<-15 displays differences between fully and partially compliant study participants. Table V-15 DIFFERENCES BETWEEN FULLY COMPLIANT (TOOK QUESTIONNAIRE AND PHYSICAL EXAMINATION) AND PARTIALLY COMPLIANT (TOOK QUESTIONNAIRE) STUDY PARTICIPANTS: P VALUES FOR TEST OF NO DIFFERENCE Ranch Hand Fully Compliant Original Comparison Fully Compliant Versus Par t i al 1 y_ Compl i ant _ Versus . Health Status Medication Use Work Loss Household Income Education Anger Anxiety Erosion Depression Liver Ailments Miscarriages Acne 0.006 <0.001 0.79 0.32 0.66 <0.001 0.020 <0.001 0.007 0.76 0.97 0.37 , 0.001 0.23 0.30 0.86 0.39 0.01 0.61 0.002 0.36 0.64 0.077 0.75 Eighty-seven percent of the Ranch Hand group were compliant to the physical examination while 76% of the original eligible comparisons attended. Let RRObS be the observed relative risk calculated from the physical examination data and RR be the actual relative risk of the originally drawn groups. Direct algebraic considerations provide the relationship V-20 �0.13 Ye + 0.8? RR - ———^—,_,-— 0.24 Yc + 0.76 RRQbs Equation #1 In this equation, Ye is the ratio of the prevalence of the finding in the Ranch Hand group noncompliant to physical examination, to the prevalence in Ranch Hand individuals who were examined; the term Yc is the same ratio for the comparison group. In other words, the values Ye and Yc are within-group noncompliant-to-compliant relative risks. The values of Ye and Yc are in fact not known so that RR can in fact not be known with exactness. Were RR0bS • 1.00 and were the finding ra,te 0.100 in the fully compliant comparison group, Ye and Yc could both range from zero to 10, indicating that RR could take values from 0.28 to 2.86. Thus, noncomplianee to the physical examination is a serious concern in the attempt to properly infer herbicide effects from group differences noted at physical examination. It is possible to develop an indication of the magnitude of the withingroup relative risks Ye and Yc using data from the questionnaire. From Table V-15, it is clear that in several instances (roughly 50%') the fully compliant replacements are not statistically different from the partially compliant or, approximately, Ye =* rc = 1.0. In these cases, an observed relative risk, RI *obs» is at least approximately equal to the actual relative risk, RR of the original sample. On the other hand, using the health status data, Ye is estimated to be 0.54 while Yc is 1.0*4 for .the categories "fair-poor" health, indicating (using Equation #1) that RR = 0.93 RRObs- Tnis result implies the possibility that the use of physical examination data can overestimate a relative risk by 7%.. On the other hand, for the erosion scale Ye is 0.52, while i c is 0.63, providing RR = 1.03 RRObs» vhich implies the possibility that the physi: cal examination could underestimate relative risk by 3%> These calculations of Ye and Yc use questionnaire data, and thus, the results are indications only of bias in the physical examination, due to the extrapolation from 1 data set to another. Nevertheless, the results do indicate a range of bias which is much smaller than the range obtained when no assumptions about Ye and YC are made. It is difficult to conceive of a partially compliant rate or proportion as being different from a fully compliant rate or proportion by more than a factor of 2. Thus it may be assumed that 0.5 ^ Ye $ 2.0 0.5 •$ Yc < 2.0 under this assumption 0.75 RR0bs S RR ^ 1.28 RRObs V-21 �An inequality such as the one above should be applied to each study result reported here to reflect the possible effect of selection bias. If the above inequality is used, the smallest observed relative risk that can be considered actually larger than 1 is 1.33 (=0.75~1) and the largest observed relative risk that can be considered actually smaller than 1 is 0.78 (=1.28~1). Or, as a simpler rule of thumb, full sample relative risks may be assumed to be within ±30% of observed relative risks. Of course, this measure of uncertainty due to noneompliance must be added to the uncertainty due to finite sample sizes, and to other sources of possible inferential error. It is not feasible to numerically evaluate the degree of bias in physical examination measurements of continuously distributed variables such as blood pressure, hemoglobin concentration or pulmonary volumes, using questionnaire data, as no analogous values were obtained from the questionnaire. An equation similar to Equation #1 holds for the ratio of group mean values for a continuous variable, namely: 0.13 Ye1 + 0.87 RAT RAT = obs Equation #2 0.24 Yc1 +0.76 In this equation, RATobs is the ratio of the Ranch Hand fully compliant mean to the comparison fully compliant mean, RAT is the ratio of the means of the complete original samples, Ye1 is the ratio of the partially compliant mean to the fully compliant mean in the Ranch Hand set and Y,J is the same ratio for the comparison participants. Estimates of Ye1 and Yc' are not available; however, it is difficult to conceive of a partially compliant mean as different from a fully compliant mean in the same group by more than 20$; whence, we assume: 0.80 ^ Ye1 S 1.20 0.80 S YC1 < 1.20 Under this assumption 0.93 RATobg < RAT ^ 1.08 RATObs that is, full sample ratios are anticipated to be within ±8% of observed sample ratios of means. The potential error in sample mean ratios portrayed above must be considered by the reader in the interpretation of mean shift data presented in this report. V-22 �10. Summary and Conclusion The comparison group in this study is divisible into 3 subgroups: original comparisons, shifted comparisons and replacements. Due to study implementation and contractual constraints, the shifted and replaced comparison groups were scheduled differently from the original comparison group for the study questionnaire and physical examination. The original comparisons were handled in a manner essentially identical to that of the Ranch Handers. Analysis has shown that replacements differ from original comparisons on compliance to questionnaire and physical examination; however, shifted comparisons are not statistically significantly different from originals on these parameters. Both shifted and replacement comparisons have been found to be statistically significantly different from the original comparisons on a variety of questionnaire and physical examination measures. This source of potential bias is completely avoided in this report through the primary use of the original comparisons in hypothesis testing. Differential compliance to the physical examination occurred with 87/6 of the Ranch Handers and 76% of the comparisons attending. This fact raises the concern for a second bias which cannot be avoided, and it could be a result of media and Ranch Hand Association support for this study. It is suggested, however, that this bias is not large. Worst-case estimates imply that observed relative risks are displaced from correct relative risks by no more than 30$ by noncompliance effects, and observed mean ratios are displaced by no more than 8%. V-23 �Chapter VI QUALITY CONTROL PROCEDURES Quality control aspects of the Air Force Health Study have been of major importance since the inception of the study design. The focus of quality control concerns has been 1) to ensure the highest quality and validity of this study, 2) to reduce variability and bias in all data, 3) to validate all statistical methods and enhance statistical power wherever possible, and 4) to protect government resources. The purpose of this chapter is to present a categorical overview of the quality control procedures and to present representative data, where appropriate. 1 • Prestudy Considerations The Study Protocol was formulated and refined in 1979-1980, during which time it underwent H independent peer reviews and a final review and approval by the Science Panel of the Agent Orange Working Group. Knowledge gained from visits to national and international herbicide dioxin experts was also instrumental in refining the Protocol. Initial contract management aspects were handled on a scientific business basis. The Principal Investigators developed comprehensive statements of work with specific evaluation criteria. All contract proposals were evaluated without reviewer knowledge of the proposer and then scored independently on their scientific and business merits. Contracts were awarded on the basis of scientific and medical quality; price considerations were secondary. Fixed-price competitive contracts were written where feasible. During the conduct of the contracts, numerous scientific and business meetings were held with the contractors in an attempt to ensure quality and timeliness of the data. Scientific concerns continued as the primary emphasis throughout the periods of contract performance. The population ascertainment process for both the Ranch Hand and comparison groups has continued for over 4 years. Extensive computer searches and a hand review of all available military personnel records have assured an almost conr plete and comparable identification mechanism. In addition, individual responses to the Ranch Hand Reunion Association and wide media coverage of the Agent Orange issue have greatly assisted both the ascertainment and addressupdate processes. A few potential study participants whose records were burned in the National Personnel Record Center remain uncategorized at this time. Both populations were subjected to a rigorous systematic location process (see Chapter III), resulting in a location efficiency of 99.556; this achievement has eliminated population selection bias and has afforded each individual a maximum opportunity to participate in the study. The computer technique to match each Ranch Hander to a comparison individual by job category, race, and age to the closest birth month was exceptionally rewarding, as about 70% of the matches were exact to birth month and year, as well as to job and race. Such precision has enhanced the analytic flexibility of the statistical techniques cited in this report. VI-1 �2. Questionnaire Data The quality of questionnaire data was enhanced by 2 distinct mechanisms: 1) all questionnaire instruments were designed by nationally recognized survey research organization; and 2) the instruments were administered in an in-home setting by another outstanding survey research firm. A minimum number of highly qualified interviewers were used to reduce data variability, and the interviewers were blind to the exposure status of the respondent. In addition, the interviewers were specially trained and then race matched to the study participants, where possible. Spouse fertility data was obtained independently of the male interview but within the same interview setting. The data collection verification process was conducted sequentially. The Louis Harris Associates Incorported (LHA) field interviewer completed a questionnaire thoroughness edit, followed by a Central Office thoroughness check and appropriate editing. Participants were recontacted by phone, when necessary. LHA trained the United States Air Force interviewers and project staff to complete the identical sequential process. A double blind key punch system was used for both the LHA and USAF collected questionnaire data. Range checks identified outliers, and discrepancies were resolved. The contractor randomly validated completed interviews by phone; however, these interviews have not been analyzed for this report. An early USAF sampling review of the data revealed key punch error rates in specific sections of the questionnaire that ranged from 0 - ].H%. The USAF systematic review and receding of all medical areas included in this report have reduced these error rates. Further, subsequent to the questionnaire, each participant's military personnel record was hand reviewed, in order to provide exact data in the time and location of military assignments. These data have been used in this report in lieu of the memory-dependent military duty information obtained by the questionnaire. Most study-participant questionnaire data were designed to be crossreferenced to review-of-systems data and physical examination findings. A no^ table exception, fertility birth defect data, will be validated by birth certificate or medical records, if retrievable. Female response data were used in all fertility/birth defect analyses, when available. In instances of multiple marriages and offspring, unexpected difficulty was often encountered in assigning a child to the correct spouse pair. Such discordant results were resolved by a hand review and computer input of the questionnaire .data. Thereafter, this system supported all offspring data for analyses herein. Next-of-kin interview data will be verified by cross reference to the deceased's medical records. No attempt was made to validate the abbreviated noncompliant questionnaire because of the individuals expressed disinterest in the study. 3» Physical Examination Data The bulk of scientific data of most concern to the public and veterans will stem from the physical examinations in this study. Consequently, great emphasis has been placed upon quality control of the physical examination and laboratory procedures. VI-2 �All examinations were conducted at a single site by a contract medical organization of unquestioned reputation. The contractor was required to provide board certified physicians for the examination. Dermatologists were required to attend a 1-day intensive training session on the diagnosis of chloracne. A minimum number of physicians and paramedical staff was used to reduce data variability. The credentials of each physician and senior psychol'ogist were submitted to the Air Force for approval. The contractor fulfilled the commitment to maintain a stable work force throughout the contract, best exemplified by the facts that (1) approximately 90% of the general physical examinations were conducted by one internist, (2) all electromyographic tests were performed by one technician using a single constantly calibrated machine, and (3) 90% of the final diagnostic assessments were made by 2 internists (master diagnosticians). All medical examiners were required to adhere strictly to the physical examination specifications as cited in the Study Protocol and were not permitted to evaluate a participant outside of his medical specialty area. Thus, each examiner was blind to examination findings outside his area of expertise, as well as to the exposure status of each participant. An Air Force physician, serving as an om-site physician monitor, conducted frequent inspections of all aspects of the physical, psychological, and laboratory examinations to ensure contract compliance and to approve further diagnos^ tic workups for those participants exhibiting serious medical findings. Further, the Air Force monitor was periodically supplemented by Air Force consultant physicians in the areas of internal medicine, cardiology, dermatology, psychiatry, psychology, immunology, and laboratory medicine. For study participants crossing 2 or more time zones, 1 to *» additional rest days were provided before the examination, in order to standardize psychological and laboratory parameters. All examination data were provided to the diagnostician who confirmed significant positive findings and formulated a diagnosis, if one was warranted. The diagnostician then carefully debriefed the participant and recommended follow-up medical action, if indicated. Electrocardiograms (ECG's) on all participants were sent to the Clinical Sciences Division, USAF School of Aerospace Medicine for cross-reference to the USAF ECG Repository. All data from the examination was collated and checked for completeness; this process was rechecked prior to submission to the data processors. Computer entry of all data was made by a single key-to-disk entry with hard copy verification; visual range checks were accomplished prior to transmittal. The Air Force data processors conducted a small sampling from the data set and detected sectional error rates ranging from 0.2 - 1.3$, with 6 of the 7 sectional rates ranging from 0.2 - Q.H%. Plausible ranges were established for most variables and all data outside this range were verified against the hard copy of the examination. All discordant transcription errors were corrected; otherwise, the data were accepted as correct. Inconsistent dates were corrected, where possible. All data sets or subsets were checked for reasonability and, in many cases, the information was verified by the hard copy of the examination. 1. Laboratory Procedures Because the thrust of the physical examination was to cast as wide a clinical net as possible, the importance and number of laboratory tests were substantially increased over an ordinary diagnostic or screening examination. Thus, all contract and subcontract laboratories were required to be licensed VI-3 �and certified by the College of American Pathologists or by the Centers for Disease Control under the Clinical laboratory Improvement Act of 1977. For the laboratory battery of 36 tests, each responsible contract or subcontract laboratory was required to maintain quality control data for audit. The bulk of nonradioassay procedures was accomplished at the contract clinic; a DuPont Automated Chemical Analyzer III (ACA) and Hemalogs 890 and D90 Automated Counters performed the majority of tests. For the ACA, reagents of the same lot number were used throughout the study period. Stringent research grade coefficients of variation (CV's) were required for most assays (see Appendix XV), often necessitating repeat runs to meet these standards. Where available for specific assays, trilevel controls were run at intervals of every 10th specimen, and 1 specimen set of every 15th was run in duplicate. These results were used to generate cumulative sum quality control charts to determine if test systems drifted significantly out of control over time since the CV's are relatively insensitive to trends over time. Of the 14 assays with CV requirement standards, 7 were significantly (P <.05) out of standard at 1 or more levels, On-site visits and detailed power calculations with respect to detecting differences between means showed that these variances would not substantially or biologically alter group comparisons or conclusions. Adjustment of study participant clinical values for drift and other variations in laboratory control levels was considered, but was determined unnecessary. This decision was made by evaluating participant and laboratory quality control values for High-Density Lipoprotein (HDL). Deviations were computed from each overall tri-level mean and these were substra.cted from each participant's value. The distributions with and without adjustment were then contrasted. The results are tabulated below: Table VI-1 HDL VALUES ON 2227 PARTICIPANTS (mg/100 ml) Qrig_lnalmValue Mean Standard Deviation 46.18 12.61 Adjusted Value 46.12 12.72 No increase in HDL precision is noted. In fact, a small increase in the standard deviation was found, clearly indicating that adjustment would not improve the ability to detect group differences. Immunologic assessments were performed by subcontract on 592 participants. Participants were randomly selected (terminal digit of their random study number) midway through the physical examination contract. The subcontractor was blind as to the exposure status and group membership of each individual. The functional capacity of lymphocytes to respond to mitogens or antigens and the number of T and B lymphocytes were measured in isolated peripheral blood. An Immunologic Peer Review Group (see Appendix I) was convened on-site to review technical procedures and to develop analytic strategies. This panel determined VI-4 �that 56 of the 592 samples were not processed due to technical errors in specimen handling. The procedure used for isolation of purified mononuclear cells was substandard. This resulted in cell populations which were depleted of adherent mononuclear cells and contaminated with polymorphonuclear leukocytes and red cells. Differential counts on purified cells were not accomplished so that the actual number of nomonuclear cells used for each assay was not determined. A number of the lymphocyte function assays had excessive variation, manifested by a coefficient of variation (CV) greater than 1556, as reflected in Table VI-2. Table VI-2 PERCENT OF GROUPED LYMPHOCYTE FUNCTION ASSAYS EXCEEDING A CV OF 15$ Functional Test Concanavallin A Phytohemagglutinin Tetanus Toxoid Pokeweed Antigen Percent 15.8 20.3 75.7 10.2 Although CV's were excessive, these variations appeared to be randomly distributed since there were no observed trends over time and there were no differences in error distribution between groups. Only 11 duplicate specimens were received (1 per 50 specimens). Intraspecimen reproducibility was impaired and several split samples varied by more than 50$. Similarly, intraspecimen reproducibility was reduced and represented sporadically within the data set. Further, 54/432 specimens (12.555 of the total) had a ratio of concanavallin A to phytohemagglutinin less than 0.30, indicating mitogen dysfunction rather than failure of lymphocytes to respond to mitogen. The low levels of stimulation observed in many tetanus toxoid-stimulated cultures additionally suggested that caution should be used in the interpretation of the functional results. Accordingly, the Immunology Peer Review Group recommended that the lymphocyte function data not be used clinically to determine the immune status of an individual participant. Further, the panel recommended that the functional data set be used only to evaluate differences, if any, between the Ranch Hand and comparison groups. The T and B lymphocyte enumeration studies demonstrated acceptable reproducibility and acceptable daily and long-term variations between the total T lymphocyte (T^) and the sum of lymphocyte subsets (Tij and T0). Criteria for exclusion of T and B lymphocyte data were (1) samples exhibiting greater than a 30% background fluorescence (11 samples or 2$), and (2) samples with a Tg or TH proportion of less than 10$ (7 samples or 1.3$). Although differential counts were not performed initially on the Ficoll-hypoque separated cells, sufficient paraformaldehyde-stored cells were available after conclusion of the contract to permit a 250 cell differential count on 525 of the 592 specimens. VI-5 �This count permitted the calculation of absolute T and B lymphocyte numbers. After application of acceptibility criteria, cell count data were available on 1*90 specimens. 5. In-Hpuse Data Col1 ec tion and _Statistical,Analysis The complexity and time constraints of this study have made it impractical to hire a series of contractors and expect them to accomplish integrated and timely work. Thus, the Air Force investigators and technical staff have assumed major roles in the areas of population ascertainment and location, verification of eligibility in the study, medical recbrd and personnel record validations, determination of replacements, examination scheduling, medical coding, repository formation, and statistical analyses. Where at all possible, in-house actions have been documented by coding schemes, decision rules, user manuals, and computer audit trails. It is our desire to submit duplicate unedited copies of all contractor data tapes to the Advisory Committee for storage and any possible later use. The data repository task has been monumental. All medical coding has been accomplished in duplicate with resolution of disputes. All in-house gathered data have been subjected to 100/f echo and consistency checking. Subsamples have been obtained to develop quality control error rates. Backup hard copies have been created for all data bases in the event of computer loss or malfunction. The statistical approach to this study consists of a preset state-of-theart framework. The statistical strategy was detailed before the data were reviewed or the group membership codes broken. Both external peer review and internal reviews (conducted by civilian consultants) have validated our approaches. Computer software have been extensively validated by using mock data sets. Vl-6 �Chapter VII STATISTICAL METHODS 1. Statistical Study Design Study data fall naturally into 3 classes: data addressing symptoms, as reported by the subject at questionnaire or in the medical history; data addressing medical signs, determined at physical examination or by review of medical records; and data addressing mortality. A fully expressed or overt herbicide effect would be characterized by increased mortality and more signs and symptoms in the Ranch Hand group as contrasted with the comparison group. These effects should increase with increasing exposure to herbicide. As defined in the study protocol, a subclinical herbicide effect should not be associated with increases in mortality or symptom reporting, but should be found as increases in abnormal findings on physical examination of exposed personnel. These abnormal findings should be more common in the subset of individuals most highly exposed. Symptom reporting is subjective by definition and, thus, subject to influences that could significantly impair proper inference. For example, a stoic and/or highly patriotic individual might unconsciously or consciously suppress the expression of symptoms. Similarly, anxiety associated with middle or older age could prompt elaboration of symptoms. Association of increased symptom reporting with increasing herbicide exposure is suggestive of a true herbicide effect but is not strongly confirmatory as exposed personnel are at least partially aware of the degree of their exposure and could be suppressing or elaborating symptoms in terms of their perceived exposure. The study design permits a specific check on the possibilities of overreporting or underreporting of symptoms. The technique involves contrasting the incidence of physical findings when symptoms are present, between the Ranch Hand and comparison groups. The policy followed in this report is that, if there are no group differences in the sign to symptom ratio, underreporting or overreporting is considered unlikely. If there are group differences in the sign to symptom relationship, underreporting or overreporting is possible, but medically, a real group difference may still exist. Overreporting can be assessed by contrasting reported illness with the results of the physical examination and by medical record reviews. However, this assessment is much more difficult for reported psychological symptoms, since a record of hospitalization, the most reliable indicator of verified illness, occurs only in the most severe forms of psychological illness. 2« The Need forAdjustment Procedures When samples are drawn from a very large or potentially infinite population of individuals, 2 samples of equal size rarely display the same number of diseased individuals. Thus, when comparing 2 groups of individuals, one must ascertain whether the differences are or are not compatible with differences VII-1 �due to random sampling. Two groups of individuals are said to be statistically significantly different when the differences between the groups cannot be accounted for by random sampling or chance mechanisms. If 2 groups are statistically significantly different and 1 of the groups has experienced a specific exposure, this is suggestive that the exposure and the disease may be causally related. However, great care must be exerted in this setting since other unevaluated factors may be the true cause of the observed group differences, and group difference is only 1 element in the causal chain. Adjustment procedures are those statistical procedures which allow objective treatment of intervening variables which can distort the true herbicide effect, if one is, in fact, present. Failure to deal with an important intervening variable can either, induce a false effect or obscure a bona fide effect. Statistical procedures for ascertaining statistical significance and for adjustment used in this report are briefly outlined in a subsequent section of this chapter. The presence of intervening variables occurs either because the sampling procedure used was not completely random or because, by chance, widely different cohorts have been drawn. Matching is a statistical procedure which can partially protect against intervening variables. In this study, the exposed and comparison cohorts were matched on age, race and military occupational category. Intervening variables are also called covariables, risk factors, or subr stitution variables, depending on the literature consulted. There currently exists no objective method for ascertaining that all relevant intervening variables have been accounted for. When all known intervening variables have been examined, there is some degree of comfort that observed relationships are correct. Small sample sizes can, however, markedly inhibit study of intervening variables. A type of intervening variable that is of special interest is the confounding variable (Kleinbaum et al, 1981; Anderson et al, 1980). A confounding variable is an intervening variable that is associated both with the disease under consideration and the exposure categories being used in the study. Failure to adjust for the confounding variable means that the estimated exposuredisease association may be biased. Nonconfounding intervening variables, on the other hand, affect the precision of estimated exposure-disease associations. In the context of intervening variables or covariables, the concept of interactions is important (Kleinbaum et al, 1982). Interaction occurs when the statistical distribution of a random variable (such as a relative risk, or the difference between group sample means) is a function of a second variable (such as age or weight). The study of interactions in a data set is important for it may lead to the discovery of subpopulations at increased or decreased risk from the population taken as a whole. Confounding and interaction can occur together or separately. VII-2 �The use of 1 or more measures of exposure (exposure indices) is an extremely useful addition to the study of group differences. Supplementing the analysis of group differences, the use of exposure indices looks within the exposed group to determine whether the more highly exposed individuals tend to exhibit more disease or abnormalities. The use of exposure indices provides a potentially tighter assessment of herbicide exposure. However, by working with the Ranch Hand group, primarily, sample size limitations also impact this technique. Also, use of exposure indices does not obviate the need to be concerned with confounding and other intervening variables. The construction of exposure indices for the Ranch Hand II study is described in another section of this report. 3. Overview of Specific Statistical Methods In this report, log-linear models have been used when the dependent variable under consideration was categorical or made categorical. Covariables that are intrinsically continuous were stratified for use as adjusting variables in the analysis. Most of the analyses presented in this report are unpaired analyses and, thus, do not fully exploit the paired design of the study. Prior to performing a paired analysis that collapses over matching variables, it is important to determine that the matching variables do not interact with the exposure variable in affecting the dependent variable. The tests presented in this report include these assessments of interaction and, thus, are the early stage of a full paired analysis, as well as being useful for inference in their own right. When unpaired analyses are performed on paired data, there is a consequent loss of test power and less of a chance of detecting a herbicide effect, if one exists. However, an unpaired analysis can actually be more powerful than a paired analysis if study noncompliance or other causes of missing data have resulted in large numbers of broken pairs (Bishop, et al, 1975). The software package used to perform the log-linear analyses in this report is BMD-P4F. In all analyses, the hierarchical modeling procedure was used which starts by examining all covariates and collapses across covariates only when relevant interactions are noted to be null. Whenever the dependent variable was a continuous variable and the covariables were a mixture of categorical and continuously distributed values, regression, multiple regression and/or general linear models were used (e.g., GLM of the Statistical Analysis System). In these analyses in the report, the covariables were always entered as linear terms only. Also, .unless otherwise noted, all group-by-covariate terms (interaction terms) were used in all models. When group comparisons were made without adjusting for intervening variables, simple parametric tests were used, such as the statistic assuming underlying normal distributions. When it was judged that parametric assumptions were not reasonable, the hypothesis of no difference between Ranch Hand and comparison distributions was tested by the Kolmogorov-Smirnov Two-Sample Test (Gibbons, 1971). VII-3 �In this study, a very large amount of data has been collected on each par>ticipant. In this report more than 190 dependent variables were tested. Testing at the 0.05 level means that in 5 out of 100 instances where there has actually been no association, an association will be falsely inferred. The picture is more complex in this report, since as with many epidemiologic studies, measures are not independent but are highly associated. Those variables thought to be most associated with one another have been grouped into clinical categories and these are used for reporting; e.g., general health, psychology, neurology, etc. However, it cannot be assumed that the clinical categories are completely independent from one another. Within each clinical category, whenever possible, summary indices have been developed to provide an overall view of participant status and lessen the likelihood of false inference. Another important concept which protects against false attribution of herbicide effect is careful consideration of the pattern of statistically significant results. If a herbicide effect is being falsely inferred, it might be in a direction opposite to that expected from prior reports. On the other hand, if a test is found significant with a high degree of confidence, its credibility must be considerably enhanced. The inverse of falsely attributing a herbicide effect is the problem of failing to detect an effect when one actually exists. This involves the questions of study power. Power is addressed at length in the study protocol but an overview is provided in this chapter. Under the condition of equal Ranch Hand and comparison group sizes, and assuming unpaired analyses, Table VII-1 provides the approximate sample sizes needed to detect specific relative risks with approximate probability 0.80 (<* = 0.05). The present study is able to detect (with probability 0.80) those relative risks enclosed below the heavy line drawn through the table. Study power for continuous variables is shown in Table VI1-2. The mean shift refers to the displacement of the Ranch Hand mean relative to the control. The variables considered are normally distributed; and unpaired testing is assumed in the table. The present study has approximately an 80$ chance of detecting mean shifts below the heavy line drawn through the table. One thousand forty-five Ranch Handers complied to the physical examination in this study. With this size group, disease states with a cumulative incidence in the group of 1/500 or less have a 1058 chance or greater of no cases at all being encountered. More detail on this point is given in Table VII-3 where the probability or seeing no cases at all is provided for other cumulative incidence values. Another view of study power can be obtained through use of the P values reported in this volume. These observed probabilities permit a direct evaluation of study power against the alternative hypothesis defined by the observed statistic. For example, in categorical tables, the chi-square statistic can be inferred from the cited P value. This observed chi-square statistic can be used as the alternative hypothesis to the null hypothesis of statistical independence. Taking the observed chi-squared statistic as the noncentrality parameter in the appropriate chi-squared distribution, a calculation of study power against the observed effect is possible (Johnson and Kotz, 1970). Table VII-ij �VII-4 provides a short summary of P-value power relationships. Using Table VII-1, if a P-value of 0.10 is reported from a 2X3 table categorical analysis, it may be inferred that study power against the observed effect was H7% (using the two degrees of freedom column in the table). This implies that, if the groups are really as different as they appear from the data, this difference would be detected as statistically significant 4? times out of 100 hypothetical repetitions of this study. Table VII-i| can also be used to approximately assess the power of linear model analyses. The test statistic in these analyses is an F distribution associated with Y} and Y2 degrees of freedom. The degrees of freedom, Yg associated with dependent variable mean squared error is usually quite large in this study. Thus the FCYi.Yg) distribution can be usually well approximated by a X2(Yi) distribution. The degree of freedom, YI , will be 1 when equality between 2 variables such as slopes or group means is under test, and will be the number 2 when equality between 3 variables is under test, as in the trilevel exposure index case. VII-5 �Table VlI-1 NEEDED SAMPLE SIZES 10 fiETECf EXPOStJRE EFFECTS IN TWO SAMPLE TESTING ASSUMING EQUAL SAMPLE SIZES* DATE Of DISEASE IN CONTROL POP = P CONTROL MULTIPL[ESMCtCft IN EXPOS!ED GROUP •RELATI I/ERISK 1.25 1.50., 1 10000 1 ,408,64? 388,536 1 5000 704,244 194,244 2.00 3.00 4.00 5,00 6.00 7.00 8.00 9.00 10.00 114,381 36,618 19,623 12,843 9,339 7,244 5,869 4,905 4,196 57,182 18,306 9,809 6,420 4,668 3,621 3,656 1,958 1,281 1 931 722 585 489 418 1,824 1 977 1 '" 464 639 360 291 243 208 2,933 2,451 2,097 1 ioob" 1 140,722 500 70,282 19,331 5,703 13,930 3,838 1,127 359 6,886 1,895 555 176 38,810 11,423 1 TOO r 192 125 90 70 56 47 40 94 61 44 34 27 22 19 1 50 *This study has unequal sample sizes; therefore these tabled values are underestimates. VII-6 �Table VII-2 NEEDED SAMPLE SIZES TO DETECT EXPOSURE EFFECTS IN TWO SAMPLE TESTING ASSUMING EQUAL SAMPLE SIZES* *This study has unequal sample sizes; therefore underestimates. these tabled values are Table VII-3 PROBABILITY OF ZERO CASES AS A FUNCTION OF CUMULATIVE INCIDENCE Probability of Finding Zero Cases in a Group of 1045 Participants Piease Prevalence .901 .811 .593 .351 .123 .005 1/10,000 1/5,000 1/2,000 1/1,000 1/500 1/200 VII-7 �Table VII-4 STUDY POWER AGAINST OBSERVED EFFECTS OBSERVED PROBABILITY (P- VALUE) DEGREES OF FREEDOM .001 .01 .05 .908 .730 .500 .924 .780 .583 .938 .816 .642 .948 .845 .689 .10 .25 ,376 .210 .470 .300 .536 .367 .590 .425 Study power can be severely influenced by the analytical or statistical method brought .to. bear on the data. For example, in an evaluation of blood pressure, very small differences in group mean blood pressure can be detected using parametric or nonparametrlo testing of measures of location; however, if group differences in hypertension prevalence are analyzed, a lesser or no group difference might be found using categorical .statistical methods such as loglinear models. In general, there is less power to detect a group difference in specific medical diagnoses of a disease state with categorical procedures, than with the underlying continuous variable. However, even in the absence of statistically significant differences in disease rates, group differences in means and variances are still indicative of differences in disease rates that might be detected if sample sizes were larger. Because of these considerations, analyses in this report of continuous variables and the associated normal-abnormal categories are both provided wherever possible. 4. Verification By Medical Records and Interpretive Precision This report contains a retrospective morbidity element since both the questionnaire and physical examination inquire about illnesses or medical conditions that may have occurred in the participant prior to this study. These reports of illness are currently being verified by medical record. The study plan additionally includes verification of negative responses. In this report, some reported conditions have been verified by medical record but no verification of negative responses is currently available. This correction of false positives improves the hypothesis testing only if the false negative rate can be assumed negligible, perhaps a reasonable assumption in a military population. If the false negative rate is not negligible, significant bias and loss of precision remains in the hypothesis test. VII-8 �Chapter VIII EXPOSURE INDEX DEVELOPMENT A potential link of clinical end points with herbicide exposure can be tested within the Ranch Hand cohort by using a measure of exposure (exposure index). In general one would search for increasing indications of illness at higher levels of exposure. However, exceptions to this assumption of a consistently increasing dose-response curve are possible through a variety of biomedical mechanisms. The exposure index used in this report relates to the TCDD-containing herbicides: Herbicide Orange, Herbicide Purple, Herbicide Pink and Herbicide Green. Archived samples of Herbicide Purple suggest that the material had a mean TCDD concentration of approximately 33 ppm and that Herbicide Orange had a mean concentration of 2 ppm. Herbicides Pink and Green contained twice the TCDD of Herbicide Purple and therefore have been estimated to contain TCDD at a concentration of approximately 66 ppm. The index used TCDD ! in this report is written below: Gallons of TCDDContaining Herbicide Ej - {weighting} x Sprayed in the RVN Factor Theater During the Ith Subject's Tour 1 x Number of Airmen with Subject's Duties in the Vietnam Theater during the ith Subject's Tour The TCDD Weighting Factor is 24.0 or 1.0, depending on whether the material sprayed was sprayed before or after 1 July 1965. The weighting factor of 1 is used for the period after 1 July 1965, as the HERBS TAPE and other documentation (Young et al, 1978) show only Herbicide Orange being disseminated by Air Force-flown, fixed-wing aircraft at that time. Prior to 1 July 1965, procurement records and dissemination information show that a combination of Green, Pink and Purple was procured and sprayed by Air Force individuals in Vietnam. Using available data (Young et al, 1978) on gallons of Green, Pink and Purple procured and sprayed, a mean of 48.0 ppm was established for the time period prior to 1 July 1965. Dividing by 2 to normalize to Herbicide Orange, the weighting factor becomes 24.0 (i.e., 48/2 = 24/1). The dates of each subject's tour(s) in the Republic of Vietnam were determined by a manual review of military records. The HERBS TAPE was used along with Contemporary Historical Evaluation and Combat Operations (CHECO) Reports and quarterly operations reports to construct a table of gallons of TCDD-containing herbicide sprayed for each month during the operation. These data are shown in Table VIII-1. For Herbicide Orange missions actual gallons are shown; while for Herbicides Purple, Pink and Green the factor of 24.0 is already VIII-1 �Included making these effective Herbicide Orange or equivalent Herbicide Orange gallons (TCDD at 2 ppm). the CHECO Reports and quarterly operations reports were used in addition to the HERBS TAPE, as the HERBS TAPE currently available does not list all pre-1965 spray missions. Again, only fixed^wing spray missions are compiled in Table VIII-1, as Ranch Hand personnel were not involved with helicopter and other spraying (e.g., backpack). Also provided in Table VIII-1 are Ranch Hand manning in each occupational category by month, as derived from a review of military records. A computer program was written to address this table with each subject's tour dates to the nearest month, to calculate his exposure index in effective or equivalent Herbicide Orange gallons. The exposure index reflects the effective number of gallons of Herbicide Orange to which the airman was potentially exposed, where exposure to the higher TCDD-containing herbicides (Purple, Pink, Green) has been properly weighted to place them on the same footing as Herbicide Orange. As seen by examining the above index definition, the index developed should correlate with the individual's exposure but cannot be an exact measure of actual exposure or body burden. The index is an estimate only, since TCDD concentration is known to have varied across herbicide lots, and since the index does not reflect exceptional exposures such as aircraft hits by enemy fire or dumps (these events are essentially assumed equally distributed). Additionally, the index reflects potential exposure only and does not address specific and determining details of the actual contact. While the index certainly contains errors when applied to judge the exposure of a specific individual, in,studying groups of Individuals epidemiologically, as in this report, these individual errors are expected to balance out or statistically cancel to a great extent, providing some degree of useful inference. The numeric exposure index calculated by the procedure described above was subsequently categorized into 3 levels (Low, Medium, High) for use in statistical analyses; and, this categorization was accomplished in a different manner for each Ranch Hand occupational category in order to optimize study capability to detect a herbicide effect. Details of the exposure categorization are as follows. The study design called for 5 occupational categories: (a) officer-pilot, (b) officer-navigator, (c) officer^other, (d) enlisted-flying, and (e) enlisted-ground. For all exposure index analyses presented in this report, only 3 occupational categories are employed. Specifically all officers were combined into 1 class titled "officer". This combination was accomplished since navigators and pilots were exposed in the same manner, and since individuals in the "officer-other" category were administrators whose exposure was considered effectively zero. Additionally, in the enlisted-ground group, all administrative personnel were assigned a zero exposure value. Under these basic rules, the categorizations shown in Table VIII-2 were developed. A very balanced membership in each occupational category has been provided for each exposure level, optimizing statistical ability to detect a herbicide effect if one exists. VIII-2 �HERBICIDE ORANGE EQUIVALENT GALLONS AND RANCH HAND MANNING BY MONTH Gal Ions Sprayed 10/61 11/61 12/61 01/62 02/62 03/62 04/62 05/62 06/62 07/62 08/62 09/62 10/62 11/62 12/62 01/63 02/63 03/63 04/63 05/63 06/63 07/63 08/63 09/63 10/63 11/63 12/63 01/64 02/64 03/64 04/64 05/64 06/64 07/64 08/64 09/64 10/64 11/64 12/64 01/65 02/65 03/65 04/65 05/65 06/65 07/65 08/65 09/65 10/65 11/65 12/65 01/66 02/66 03/66 04/66 05/66 06/66 07/66 08/66 09/66 10/66 11/66 0 0 0 191426 324216 191426 0 0 0 0 0 334126 334126 0 90879 0 0 0 0 0 174024 259150 0 0 339588 377172 942630 121454 363758 755312 56799 152271 612709 282789 777669 1413945 1413945 1413945 1413945 1296116 1437510 730538 659841 1767431 0 942630 26500 44650 78850 106900 148525 152450 129150 135600 141050 183900 191830 112300 192050 213970 122040 164800 Pilot (Occ 1) 0 5 9 14 14 15 16 15 12 13 11 12 9 10 8 9 7 12 12 10 10 11 8 10 7 6 5 7 5 8 9 10 7 9 9 8 9 11 10 11 12 13 14 15 16 19 19 22 23 24 23 21 22 21 22 21 20 21 26 28 34 41 Navigator (Occ 2) 0 1 2 2 2 2 2 3 2 2 2 2 1 0 0 0 Other Officer (Occ 3) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 2 3 3 3 3 3 3 3 4 5 4 3 4 4 4 4 4 4 6 5 6 6 4 5 6 6 8 8 9 8 8 Flying Enlisted (Occ 4) Other Enlisted (Occ 5) 0 6 7 7 7 7 6 6 5 5 5 5 5 5 4 5 5 5 5 5 4 8 8 9 9 10 6 7 7 5 6 5 5 6 5 4 4 4 6 6 6 6 6 6 7 7 7 6 6 10 11 0 14 20 23 23 20 14 13 7 4 5 6 6 5 5 4 4 6 6 7 7 6 4 4 6 6 6 5 4 4 2 2 2 3 3 2 2 1 1 1 1 1 2 2 4 3 3 3 6 12 12 16 26 32 37 38 41 45 46 62 85 104 to 2 2 2 2 2 2 2 3 4 VIII-3 10 10 10 9 10 9 11 12 16 18 �HERBICIDE ORANGE EQUIVALENT GALLONS AND RANCH HAND MANNING BY MONTH Ga11ons Sprayed 12/66 01/67 02/67 03/67 04/67 05/67 06/67 07/67 08/67 09/67 10/67 11/67 12/67 01/68 02/68 03/68 04/68 05/68 06/68 07/68 08/68 09/68 10/68 11/68 12/68 01/69 02/69 03/69 04/69 05/69 06/69 07/69 08/69 09/69 10/69 11/69 12/69 01/70 02/70 03/70 04/70 05/70 06/70 07/70 08/70 09/70 10/70 11/70 12/70 01/71 02/71 03/71 04/71 05/71 06/71 07/71 08/71 09/71 10/71 212100 202360 363830 285400 208300 251320 335860 253884 162895 298615 265335 372425 383605 333595 27450 48200 307740 336300 226325 258100 289160 216300 72250 189100 218750 264450 197450 356500 339800 353800 383533 287425 299100 206800 181000 205100 276900 186350 152100 153730 45700 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Pilot (Occ 1) 45 49 59 51 50 53 55 51 63 60 55 55 58 54 65 69 72 75 77 84 91 89 89 101 94 98 91 90 94 93 88 91 85 83 83 90 76 66 58 59 54 51 47 44 40 40 34 30 25 23 23 23 23 23 28 29 29 29 29 Navigator jOcc 2) 9 9 13 13 14 15 13 15 13 18 19 17 18 19 19 20 20 18 18 19 18 22 20 17 17 19 18 17 20 19 19 16 16 15 17 16 16 15 15 13 13 14 14 11 9 7 6 5 4 4 4 4 4 4 4 4 4 4 4 Other Officer (Occ 3) 5 5 5 4 4 4 3 3 4 5 5 6 6 6 6 5 6 6 6 7 9 8 8 7 8 7 5 5 6 6 7 6 6 6 6 6 5 5 5 5 5 5 3 2 Flying Enlisted (Occ 4) 28 28 28 28 33 34 36 37 32 33 36 33 34 33 35 34 36 32 37 42 45 44 49 53 51 51 51 53 54 54 57 55 55 61 61 60 52 54 41 39 37 29 18 16 14 13 14 15 13 14 14 14 14 14 14 14 14 14 14 Other Enlisted (Occ 5) 123 123 116 114 108 101 105 163 160 161 149 145 129 127 141 160 161 160 164 187 192 147 155 153 154 154 166 172 161 151 155 152 155 142 122 118 114 116 122 125 109 94 84 74 63 43 37 35 30 28 28 28 28 28 28 28 28 28 28 �Table VIII-2 EXPOSURE INDEX CATEGORIZATION Exposure Category Effective Herbicide Orange Gallons Corresponding to Exposure Category Number of Ranch Hand Participants in Exposure Category Officer Low Med High S 35,000 35,000 - 70,000 > 70,000 140 150 151 Enlisted-Flying Low Med High £50,000 50,000 *- 85,000 > 85,000 67 70 66 Enlisted-Ground Low Med High £ 20,000 20,000 i 27,000 > 27,000 185 186 207 Occupational Group VIIIr-5 �Chapter IX GENERAL PHYSICAL HEALTH Five general variables were used in the analyses of the general health status of the study participants. The individual's self-perception of health was obtained during questionnaire administration and reflects a personal and subjective evaluation of health. It is susceptible to varying degrees of bias, both conscious and subconscious. The physician's assessment of the presence of distress is a crude objective measure of general health status and is less biased. This assessment was made on initial observation by the examiner, prior to any direct examination. Thus, patients who appeared ill or in distress on this initial observation were generally quite ill. The examining physician also reported his assessment of the concordance between the subject's apparent age and his chronological age. Two other variables, percent body fat and the erythrocyte sedimentation rate, were also evaluated. There were 1045 Ranch Hand and 773 originally selected comparison participants included in the analyses in this chapter. Slight variations in these numbers occur occasionally due to missing data. Similar analyses were conducted using all compliant comparisons, regardless of replacement status. The results of these additional analyses were essentially no different from the results of the analyses with the originally selected comparisons presented in this chapter. Appendix IX contains representative results of these additional analyses. The relative risks and confidence intervals for the dependent variables analyzed in this chapter are included in Appendix XVIII. 1. Subjective Assessments The results of a log-linear analysis of the self-perception of health in the Ranch Hand and comparison groups with three covariates (age, race and occupational category) are discussed in this section and are shown in Table IX-1. Table IX-1 SELF-PERCEPTION OF HEALTH BY GROUP AND AGE .Age _<40 >i»0 Perception Ranch Hand Number Percent Comparisons Number Percent P value Excellent Good Fair/Poor 129 173 72 (31.5) (46.3) (20.9) 91 120 25 (38.6) (50.8) (10.6) P-.017* Excellent Good Fair/Poor 254 256 139 (39.1) (39.4) (21.il) 203 239 83 (38.7) (45.5) (15.8) P-.025** *Relative risk £40 - 1.82; 95% Confidence Interval (1.18 to 2.10) **Relative risk >40 = 1.35; 95? Confidence Interval (1.05 to 1.76) IX-1 �This analysis demonstrates a statistically significant difference between the two groups, with the Ranch Banders perceiving their health to be poorer than the comparisons. No significant three-factor interaction effects associated with self-perception and group were observed. However, age had a statistically significant association with health perception (P < 0.001) and with group membership (P -• 0.02), thus indicating confounding by age. Race was found to have no association with either group membership or perception of health (P values of 0.94 and 0.87, respectively). The examiner's initial assessment of the appearance of ill health or distress also paralleled the participants' self-perceptions, with more Ranch Handers appearing to be ill than comparison subjects. Although these illappearing individuals accounted for less than 1% of each group, there was borderline statistical significance as shown in Table IX-2. Table IX-2 EXAMINER'S ASSESSMENT OF ILLNESS OR DISTRESS BY GROUP Examiner's Assessment 111 Well Ranch Hand Numberv Percent 8 1,033 ( 0.8) (99.2) Comparison Number Percgnt 1 769 ( 0.1) (99.9) P - 0.056 This measure is somewhat more objective than the participant's selfperception of health but is nevertheless influenced by the participant's emotional status, and bias can thus still be a factor in this result. The participants' self-perception of health appeared to be worse than the examiner's assessment in both groups; however, as demonstrated in Table IX-3, the pattern of discordance does not differ between the two groups. When the examiner's estimates of the participant's apparent ages were contrasted to their chronological ages, 976 (93. W of the Ranch Handers and 737 (95.6$) of the comparisons were observed to appear as old as they actually were. Fifty-one (4.950 of the Ranch Handers and 19 (2.5%} of the comparisons appeared to be younger than their actual age while 18 (1.7?) and 15 (2.0?) respectively appeared to be older. This observation was statistically significant (P* 0.029) and demonstrated a tendency for the Ranch Handers to appear somewhat younger than their actual ages. IX-2 �Table IX-3 . ., • DISCORDANT SELF-PERCEPTIONS OF HEALTH Better than Examiner Ranch Hand Comparison Worse than Examiner 2 0 205 109 2. Objective Assessments Percent body fat and erythrocyte sedimentation rate were albo analyzed in the setting of general health status. While these measures are not indicative of specific diseases, they do indirectly reflect the general state of health. Body fat percentages were calculated from height (inches) and weight (Ibs) measurements (Hodgdon, 1983) using the formula. % Body Fat = (weight/height2) (1015.724) - (17.28460). Data were missing or unmeasurable (greater than 100$) for 7 participants (3 comparison and 4 Ranch Handera), and these individuals were excluded from the analysis. The distribution of these data is shown in Table IX-4 and Figure IX-1, where the percentage of participants falling in each grouping and the cumulative percentages are displayed. Figure IX-1 PERCENT BODY FAT DISTRIBUTION 34 x RH CUMULATIVE * COMP CUMULATIVE PERCENT BODY FAT | RANCH HANGERS (COMPARISONS IX-3 �The percent of body fat appeared to be reasonably normal in its distribution. No significant differences were detected between the variances (P = 0.34) or the means (P =• 0.67) of the two groups. Table IX-4 DESCRIPTIVE STATISTICS - PERCENT BODY FAT Number of Subjects Mean Std Dev 1,041 770 21.12 21.22 5.36 5.19 Ranch Hand Comparison In an effort to assess the extremes of obesity and leanness in the two groups of participants, individuals below 10$ or over 25? body fat were considered to be lean or obese, respectively. The distribution of subjects in three weight categories is shown in Table IX-5. Chi-square procedures revealed no significant differences between the Ranch Hand and comparison groups (P«0.89). Table IX-5 DISTRIBUTION OF BODY FAT PERCENT Lean <W%) Normal (10-25$) Number Percent Number Percent Ranch Hand Comparison 13 7 (1) (1) 824 607 (79) (79) Obese (>25) Number Percent 207 157 (20) (20) Total 1044 771 P= 0.89 The percent body fat and group membership relationship was further evaluated by covariance analysis using age, race and occupational category as covariates. Age and percent body fat were associated (P = 0.02), but this association was not affected by group membership; that is, there was no three-way interaction (P = 0.17). None of the sources of variation associated with race were found to be significant. Percent body fat was significantly different between the three occupational categories (P => 0.04), but this association was the same in both Ranch Hand and comparison groups. IX-4 �Sedimentation rate values presented a right skewed distribution for both groups. Table IX-6 presents the percentile values for each group. A two-sample Kolmogorov-Smirnov test revealed no significant differences in the two unadjusted distributions (P - 0.99). The normal range of sedimentation rate for males is less than or equal to 12 mm and only 5% of each group exceeded normal. Table IX-6 PERCENTILE DISTRIBUTION OF SEDIMENTATION RATE RESULTS 5* 25* JJ2* 75%. 95% Ranch Hand 0 1 2 4 12 Comparison 0 1 2 4 13 . Kolmogorov-Smirnov; P = 0.99 A multifactor log linear analysis of sedimentation rate by group membership, age (£40, >40), hematocrit «42, 42-52, or >52%) and the examiner's assessment of illness or distress was performed. The interaction of sedimentation rate, group membership, and age was significant (P = 0.002) as shown in Table IX-7. Ranch Handers 40-years of age or less had significantly fewer sedimentation rate abnormalities than did their comparisons, while no group difference was noted in individuals over the age of 40. Table IX-7 SEDIMENTATION RATE, AGE AND GROUP MEMBERSHIP Group Sedimentation Rate Abnormal Normal Number Percent Number Percent P Value £ 40 Ranch Hand Comparison 2 10 (0.5) (4.2) 372 227 (99.5) (95.8) 0.001 > 40 Ranch Hand Comparison 39 29 (5.8) (5.4) 628 504 (94.2) (94.6) 0.764 IX-5 �The sedimentation rate was found to have a significant association with hematocrit, the appearance of illness or distress, and percent ttody fat. Table IX-8 displays these data. Since these variables were unassociated with group membership, combined data for both groups are used. Table IX-8 SEDIMENTATION RATE HEMATOCRIT/DISTRESS/BODY FAT ASSOCIATIONS Sedimentation Rate Normal Abnormal Number (Percent) Number (Percent) P Value 13 66 1 < 42$ 42-52* > 52% Hematocrit 102 (11.3) ( 4.0) 1598 ( 3-D 31 (88.7) (96.0) (96.9) <0.001 2 78 (22.2) ( 4.3) 7 1724 (87.8) (95.7) 0.009 3 59 19 (15.0) ( 4.1) ( 5.2) 17 1372 348 (85.0) (95.9) (94.8) 0.049 Appearance of Illness or Distress 111 Well % Body Fat < 10 10-25 > 25 These findings are consistent since an increasing sedimentation rate, abnormal body weight, decreasing hematocrit, and an ill appearance are all traditional indicators of illness, and therefore should be related. The relationships between self-perception of health, sedimentation rate, and age were also explored. These significant relationships are shown in Table IX-9. IX-6 �Table IX-9 SELF-PERCEPTION OF HEALTH, AGE/SEDIMENTATION RATE ASSOCIATIONS Self-Perception of Health Excellent Good Fair/Poor P Value Sedimentation Rate Abnormal Normal 18 671 35 765 28 294 <0.001 S 40 > 40 224 465 294 506 97 225 0.06 Age These relationships were independent of group membership and are not unusual since illness generally increases with advancing age. 3. Herbici de Exposure Analysis The exposure index was applied to the variables in the general health analysis to determine whether a dose-response effect could be identified. As described in Chapter VIII, the index is expressed in equivalent-galIons of dioxin-containing herbicide potentially encountered by each individual during his Ranch Hand tour of duty. Three categories of exposure were used: low, medium, and high. The cutoff values for these categories were chosen so that statistical power could be maximized in the analyses. The interrelationship between a Ranch Hander's self-perception of health and exposure is shown in Table IX-10. Three occupational groupings were analyzed: officers, flying enlisted, and enlisted ground personnel. Nonflying officers were included in the analysis and were assigned to the low exposure category. Their jobs were primarily administrative in nature and involved relatively lower levels of exposure than the flying officers. IX-7 �Table IX-10 HEALTH PERCEPTION IN RANCH HANDERS BY OCCUPATIONAL GROUP AND EXPOSURE CATEGORY Counts Within Exposure Category Low Med High Occupational Group Perception Officer N = 361 Excellent Good Fair/Poor 65 Enlisted, flying N - 183 Enlisted, ground N - 472 P Value 68 42 .13 0.72 11 65 15 18 Excellent Good Fair/Poor 18 29 12 18 24 16 23 29 14 0.84 Excellent Good Fair/Poor 43 59 48 41 95 42 41 67 36 0.13 Total: 1016 These analyses revealed no significant association between exposure and perception of health. The P value of 0.13 among the enlisted ground personnel is of interest, but consistent trends are not seen in the data. Similarly, exposure was found to have no significant association with the examiner's assessment of distress or ill health. The occupational category analysis is shown in Table IX-11. Statistical testing of these data was not conducted due to the small number of individuals judged to be ill by the examining physician. IX-8 �Table IX-11 EXAMINER'S ASSESSMENT OF HEALTH JN RANCH HANDERS BY OCCUPATIONAL GROUP AND EXPOSURE CATEGORY Counts Within Exposure Category; Low Med High Illness or Distress Occupational Group Officer 111 Well 0 111 1 127 1 124 Enlisted, flying 111 Well 0 59 0 59 1 65 Enlisted, ground 111 Well 2 149 0 178 3 142 Similarly, the associations between exposure and apparent age and exposure and body fat were evaluated. These data are presented in Tables IX-12 and IX-13. Table IX-12 APPARENT AGE OF RANCH HANDERS BY OCCUPATIONAL GROUP AND EXPOSURE CATEGORY Occupational Group Counts Within Exposure Category Low Med High Apparent Age P Value Officer Younger Same Older 7 103 1 10 117 1 8 116 1 Younger Same Older 1 57 1 5 54 0 2 64 0 0.22 Younger Same Older 5 142 4 6 169 4 6 136 6 0.88 0.99 Enlisted-flying Enlisted-ground IX-9 �Table IX-13 PERCENT BODY FAT BY OCCUPATIONAL GROUP AND EXPOSURE CATEGORY Occupational Group Counts Within Exposure Category Low Med High % Body Fat P Value Officer 0 91 20 225% 1 103 21 0.57 1 52 6 0 51 15 0.34 2 14 35 10-25? 1 97 30 1 48 10 £10$ 136 39 3 115 30 0.95 Enlisted-flying 10-15$ Enlisted-ground 10-25$ £25$ It is evident from these data that levels of exposure had no relationship to the examiner's assessment of apparent age and percent body fat regardless of occupational category. 4. Summary Overall, the analyses of the general physical health of the study participants revealed classical associations between clinical measures of ill health such as sedimentation rate, obesity/leanness, age, hematocrit, self-perception and the appearance of distress. Statistically significant group differences between the Ranch Hand and Comparison groups were limited to the subjective measures of self-perception of health and the examiner's assessment of illness or distress. The Ranch Handers, as a group, perceived themselves to be in poorer health than did the comparison group. Similarly, the examiner felt that more Ranch Handers appeared ill than did the comparisons. However, ill appearing individuals accounted for less than 1$ of both groups. The analysis of these variables against the exposure index did not reveal any dose-response effects. Overall, the available evidence does not support the presence of such an herbicide effect operating at this time. IX-10 �Chapter X MALIGNANCY 1. Introduction Of all the health effects being attributed to dioxin, cancer is one of the most feared in the minds of the veteran groups, the media and the general public. Dioxin has been identified as a carcinogen or cocarcinogen in some strains of rats and mice (Toth, et al, 1979; Kociba et al, 1978, 1979; Kouri, 1978); however, its carcinogenic effects in humans are unclear. Epidemiologic studies of carcinogenic effects in humans have been generally limited to investigations of phenoxy herbicide exposure among soft-tissue sarcoma patients in Sweden (Hardell and Sandstrom 1979; Axelson, 1977) and studies among industrial groups involved in the production of trichlorophenol and 2,4, 5^T (Zack, 1980; Honchar, 1981). These studies have been contradictory and the issue is still being debated in scientific as well as public forums. The clarification of this important issue is a major focus of the Air Force Health Study. Questions concerning a history of cancer or tumor were asked during both the in-person questionnaire and the physical examination. Question 36a of the study subject questionnaire concerned cancer alone while other areas of the questionnaire focused on tumors or other major medical conditions. In addition, the physical examination subjectively identified additional participants with a history of cancer in the past medical history and objectively identified participants with evidence of prior or newly diagnosed cancer. Figure X-1 shows the algorithm used for data collection for cancer in the study population, as well as those reported cancers that were entered into the cancer verification process. In this algorithm 114 individuals (65 Ranch Handers and 49 comparisons responded "yes" to question 36a, 10 other individuals (3 Ranch Handers and 7 comparisons) responded yes to other questionnaire questions concerning tumors or other major conditions, while 92 additional individuals (50 Ranch Handers and 42 comparisons) reported or were diagnosed as having cancer or tumors during the physical examination. A total of 22 reported cancers occurred prior to the individual's Southeast Asia tour of duty, and these cancers were removed from all analyses. A total of 194 individuals reporting cancer were entered into the verification process (105 Ranch Handers and 89 comparisons). Cancer verification was completed by review of the individual's medical records and available pathology reports. Although cancers reported by all participants were entered into the validation process, only the data from the Ranch Hand group and the subset of originally selected comparisons who completed physical examination were fully analyzed statistically. The rationale X-1 �X-1 ALGORITHM OF COUNTS ON REPORTED CANCERS BY SOURCE OF DATA 1 Responded "Yes" to question 36a iiovo you ovor had cancer?" RH OC 32 55 scj RC.J Total 49 Data 1 Additional "Yes" Physical Examination Subjoctivo and/or objactivo report of cancer OCJfi SCJ2 RC to other Questions 1 scjj RCJJ Total_7 Totals RH 118 OCJSJ SCJ2 RCJ1 TotalJ|§ Removed from Analysis RH-Ranch Hand OC=Ori|inal Comparison SC -Shifted Comparison RC "Replaced Comparison RVN-Republic of Vietnam Tour Cancer occurred before qualifying RVN/SEA tour RH OC_g 13 SC 2 RC_J Total_9 Entered into cancer verification process for this restriction of the database is discussed in Chapter V, Study Selection and Participation Bias. Verification records were obtained with permission forms signed by the participants at the time the questionnaire was administered. The verification process was supported with a limited access computer software program. All reported cancers were classified as to behavior, type and morphology. In addition, cancers were classified as being skin or systemic due to the differing natures of these disease processes. The findings of the verification process are presented in Table X-1. X-2 �Table X~1 SUMMARY OF CANCER VERIFICATION PROCESS Location Behavior of Cancer Skin Malignant Ranch Hand . . ;':. .. 0 Comparison* S R Total 15 7 5 27 Benign 35,. 17 14 3 1 18 Diagnosis not supported 13 6 4 1 11 13 3 3 0 6 No record of treatment at facility as reported 1 0 0 1 Medical record not available 0_ J_ J_ _2 39 18 8 65 Differential Diagnosis at physical examination; individual declined follow-up TOTAL Systemic 79 Malignant 10 2* 2 14 Benign 8 10 0 0 10 Not supported 4 0 0 0 0 p_ p_ 0_ _Q_ 20 2 Medical record not available TOTAL 26 2 24 *Includes 1 Ranch Bander and 1 comparison who expired following interview 0 - Original S - Shifted R - Replacement X-3 �2. Skin Cancer Seventy-five percent (79/105) of all Ranch Hand and 73% (65/89) of all comparison-reported and verified neoplasms were cancer of the skin. Forty-four percent (35/79) of the Ranch Hand reported skin cancers were verified as malignant while H2% (27/65) of the reported total comparison skin cancers were verified as malignant (P - 0.74). All individuals with malignant skin cancer were non-Black. The occurrence of verified skin cancer in those participants who completed the questionnaire (regardless of their compliance to physical examination) was significantly higher in the Ranch Hand group when compared to the total comparison group (P-0.03) or to the subset of original comparisons (P=0.04). Table X-2 shows the distribution of verified malignant skin cancers by cell type. Table X-2 VERIFIED MALIGNANT SKIN CANCERS BY CELL TYPE; REPORTED BY FULLY AND PARTIALLY COMPLIANT PARTICIPANTS Comparisons Ranch Handera* 0 S R Total 31 11 5 5 21 Melanoma 3 1 1 0 2 Squamous Cell 1 3 0 0 3 0 J_ 0 1 15 7 5 Cell Type Basal Cell Fibrosarcoma TOTAL 35 ' 27 *1 Ranch Hander experienced 2 skin cancers, 1 melanoma and 1 squamous cell. He has been counted only once and placed under melanoma in this table. 0 = Original S - Shifted R - Replacement Nonmelanoma cancer accounts for 91$ (32/35) of the Ranch Hand and 93$ (25/27) of the comparison group skin cancers. This difference is not statistically significant (P =0.87). These findings are consistent with reported data that nonmelanoma cancer of the skin is the most common malignant neoplasm in the white population of the United States (Schottenfeld and Fraumeni, 1982). The distribution of these verified skin cancers by anatomic site is presented in Table X-3. X-4 �Table X-3 COUNTS OF SKIN CANCER BY ANATOMIC SITE Melanoma Nonmelanoma skin cancer RH Face, head and neck Comparison O S R Total 26 12* 5** 3 RH Comparison 0 S R Total 20 1 0, 0 0 0 Upper extremities 1 1 1 0 2 0 1 0 0 1 Trunk 5+ 1 0 2 3 2 0 1 0 1 Lower extremities 0 0 0 0 0__ 0 0 0 0 0 32 a 6 5 3 1 1 0 2 TOTAL 25 +Includes 1 Squamous cell *Includes 3 squamous cell **Includes 1 fibrosarcoma RH 0 S R - Ranch Hand » Original - Shifted - Replacement Nonmelanoma skin cancers arose on the face, head and neck in 81$ (26/32) of the Ranch Handers and in 80% (20/25) of all comparisons (P - 0.91). This distribution and the cell types of skin cancers is consistent with recently published information on the epidemiology of skin cancer (Schottenfeld and Fraumeni 1982). The occupational category of those individuals with verified skin cancer are presented in Table X**1*. The counts of these individuals with cancer are relatively small and all occupational categories contribute to the Ranch Hand increase. Followup reports will contain additional analyses of these data with detailed considerations of sample size and age in each of the occupational strata. Table X-4 COUNTS OF THE FACE, HEAD, AND NECK DISTRIBUTION OF NONMELANOMA SKIN CANER; RANCH HAND VERSUS TOTAL COMPARISONS Occupational Code Officers Flying Enlisted Nonflying Enlisted Ranch Hand Cases Rate/100 16 3 3.7 1.5 1.3 26 Total Comparisons Cases Rate/100 11 1 8i •I • ••! !! 20 X-5 1.9 O.H �While medical literature implicates ultraviolet radiation from the sun as the dominant risk factor in the development of nonmelanomic skin cancer (Scott et al 1974), it was not possible to fully evaluate the effects of sun exposure in the initial phase of this study. Information required for this analysis will be obtained in the follow-up phases of the effort. 3. Systemic Cancer A total of 50 systemic cancers (26 Ranch Handers and 24 comparisons) were reported and entered into the verification process (Table X-1). Of these, 14 Ranch Handers and 14 comparisons (10 Originals, 2 Shifted, and 2 Replacements) were verified as having had malignant systemic neoplasms. All individuals with systemic malignancy are non-Black.The site specific classification of these neoplasms is presented in Table X-5. Table X-5 MORBIDITY SITE SPECIFIC VERIFIED SYSTEMIC MALIGNANT NEOPLASMS Ranch Hand Site; ICD Code (9th Ed) 0 Comparison S R Total Lip, oral cavity, pharynx (140-149) 4 2 0 0 2 Digestive organ, peritoneum (150-159) - 4 0 1 5 Respiratory, intrathoracic (160-165) 3* 1 1* 0 2 Genitourinary organ (179-189) 6 2 1 0 3 Other & unspecified sites (190-199) 1 1 0 0 1 Lymphatic & hematopoietic tissue (200-208) - 0 0 1 1 14 10 2 2 14 Bone, connective tissue, skin, breast (170-175) TOTAL *Includes 1 Ranch Hander and 1 comparison who expired following interview 0 = Original S = Shifted R - Replaced Four Ranch Handers and 2 original comparisons were found to have had neoplasms of the lip, oral cavity and pharynx, and all of these individuals reported a history of cigarette and/or cigar smoking. X-6 �Six Ranch Handers and 3 comparisons were found to have had malignancies of the genitourinary organs. The (? Ranch Hand cancers included 1 prostate, 2 testicular, 2 bladder and 1 kidney neoplasm while the 3 comparison cancers included 1 of the prostate and 2 of the bladder. Both cases of testicular cancer were of a germ-cell morphology (one embryonal and one seminoma). Unadjusted statistical testing revealed no significant difference in total genitourinary cancer in the two groups (P = 0,42). Peak incidence rates of testicular cancer in the general population occur between the ages of 35 and 55, and bladder cancer has a peak age of onset between 50 and 70 years. All Ranch Hand bladder cancers, occurred prior to age 50 and all verified comparison genitourinary cancer occurred at age 55 or later. The Ranch Hand testicular cancers occurred at 35 and 38 years of age. These are observational data, and are based on very small sample size. Five comparisons were, found to have had verified malignancies of the digestive organs. There were no Ranch Hand cancers of this organ system. These cancers included 1 of the appendix, 1 of the pancreas, and 3 colon cancers. The annual incid.ence rate for colon cancer increases dramatically with increasing age after the age of 30. The ages at the onset of the colon cancers in the comparison group were 35, ^3, and 50 years. The occurence of gentourinary, oropharyngeal and digestive cancers in the study population was compared to the experience of the Surveil.lanc.e, Epidemiology and End Results program (SEER). Based on these tumor registry data, there is a 30% probability of observing two or more testicular cancer in the Ranch Hand group, and a 29$ probability of two or more bladder cancers. Similar contrasts revealed only a 3% chance of observing the 4 oropharyngeal cancers and a 2% chance of seeing a total absence of digestive cancers i,n the Ranch Hand group. The probabilities of finding the observed numbers of these malignancies in the comparison group were 32$ or greater.. Table X-6 shows the known morbidity and mortality of the Ranch Handers and comparisons from cancer to date. Appendix VIII shows the site specific distribution of bpth the morbidity and mortality study cancers. The mortality sections of these tables include only the first cohort of the comparison population from the Baseline Mortality Study (Lathrop, 1983). X-7 �Table X-6 TOTAL MORTALITY AND MORBIDITY STUDY MORPHOLOGY OF SYSTEMIC NEOPLASM ICD-0 CODES MORTALITY NOMENCLATURE RANCH HAND MORBIDITY* COMPARISON RANCH HAND COMPARISON 0 M800 Neoplasm not otherwise specified (NOS) Bronchus and Lung Intestinal Tract s H 0 0 1 1 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 1 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 M801-804 Epithelial neoplasms Appendix Bladder Bronchus and Lung Kidney Lip Nasopharynx Tongue Unspecified site Vocal Cord 0 0 0 0 1 0 1 0 1 0 0 M805-808 Papillary and Squamous Cell Lip Lung 0 0 0 0 2 1 2 0 0 0 M812-813 Transitional Cell Papillomas and Carcinomas Bladder 0 0 2 0 1 0 M814-838 Andenomas and Adenocarci nomas Bronchus and Lung Colon Kidney Prostate Pancreas 0 0 0 0 0 1 0 0 0 0 1 1 0 0 2 0 1 1 0 0 0 0 0 0 0 0 M850-854 Ductal, lobular, and medullary neoplasms Thyroid 0 0 0 1 0 0 M872-879 Nevi and melanomas Mediastinal 1 0 0 0 0 0 Mesothelioma Bronchus and Lung 0 1 0 0 0 0 Germ cell neoplasms Testicle 0 0 2 0 0 0 0 1 1 0 0 0 M905 M906-909 M938-948 Gliomas Frontal Lobe 1 0 0 1 0 1 1 0 1 X-8 0 1 �Table X-6 (Cont) TOTAL MORTALITY AND MORBIDITY STUDY MORPHOLOGY OF SYSTEMIC NEOPLASM ICD-0 CODES RANCH HAND M965-966 Hodgkins disease Hodgkins (NOS) M986 MORBIDITY* MORTALITY NOMENCLATURE COMPARISON RANCH HAND COMPARISON 0 s R 0 0 Myeloid Leukemias Acute myelocytic leukemia 0 0 0 1 0 0 ~r T 0 = Original S •- Shifted R * Replaced *Two morbidity study participants (1 Ranch Hand, 1 comparison) expired following interview. They are included in the mortality column of this Table because of their date of death. ^ • Covarlate JVn^alysis Group Membership The previous sections of this chapter contained descriptions of the cancer data on the occurrence of skin cancer and systemic cancer in the Ranch Hand and originally selected comparison groups. Except where noted, the remaining analyses in this chapter are based on the Ranch Hand and comparison population that had verified cancer and had completed the physical examination. Covariates used in these analyses included smoking habits and exposure to asbestos, industrial chemicals (yes, no), insecticides (yes, no), degreasing chemicals (yes, no), and nontnedical x-ray sources (yes, no). The results of the basic two-factor analysis are shown in Table X-7. X-9 �Table X-7 VERIFIED CANCER AND GROUP MEMBERSHIP Original Comparisons (N-773) Skin Cancer Yes No Ranch Hand (N~1045) 11 762 \ 35 1010 / \ 25 1169 / P = 0.07 13 1032 / \ 11 1183 / P = 0.46 P - <0.01 Systemic Cancer Yes No 8 765 \ P = 0.68 Total Comparisons* (N=1194) ' . * ^j * This total does not include the 30 participants interviewed by USAF interviewers. The group differences in skin cancer are statistically significant, in the original subset that completed physical examination, (P = < 0.01) and borderline in the total comparisons (P = 0.07), with an excess in the Ranch Hand group. The relative odds of skin cancer in the Ranch Handers are 2.35 and are 1.20 for systemic cancer, with confidence intervals of 1.16 to 4.;90, and 0.47 to 3.15 respectively. These broad intervals are due to the small numbers of cancers available for analysis. The analysis of skin cancer in the Ranch Handers and the original comparisons was repeated with months of agricultural/forestry/fisheries work as a covariable. Seventy-one (6.855) of the Ranch Handers and 66 (8.555) of the original comparisons had worked in these occupations; however, these statistical adjustments did not alter the significant difference between the groups. The P value after adjustment remained 0.01. These analyses are as yet incomplete since they have not accounted for the relationship between skin cancer and geographic area of residence or exposure to other potential skin carinogens. Geographic area of current residence in a mobile military population may not discriminate differences in ultraviolet radiation exposure. An attempt to collect data that will support analyses for geographic and ethnic background will be made at the time of the first follow-up examination. Three-factor analytic techniques were used to account for the possible confounding effects of the covariables listed above. Exposure to industrial chemicals, degreasing chemicals and smoking habits were not different in the Ranch Hand and comparison groups. The analyses of systemic cancer demonstrated an association between cancer and smoking which approached statistical significance (P » 0.07). However, there were no significant differences or suggestive trends between the groups for systemic cancer. X-10 �Significant group differential in exposure to x-ray (P <0.001), insecticides (P <0.001), and asbestos (P = 0.05) were also identified. More comparisons than Ranch Handers were exposed to asbestos and x-ray but more Ranch Handers had previously been exposed to insecticides, many during their tours of duty in RVN. Three-way interactions between variables were significant only for the systemic cancer by group by insecticide analysis (P - 0.01) and suggestive for the systemic cancer by asbestos by group analysis (P =0.16). The results of these analyses are displayed in Table X-8. Table X-8 RESULTS OF THREE-FACTOR LOG-LINEAR ANALYSES OF SYSTEMIC CANCER, GROUP MEMBERSHIP AND CHEMICAL EXPOSURE (P VALUES) Exposure rroup by Cancer Statistical Relationship Group by Cancer by Cancer by Exposure Exposure Exposure by Group Asbestos 0.72 0.04 0.33 0.16 Degreasing Chemicals 0.68 0.33 0.71 0.23 Industrial Chemicals 0.71 0.25 0.34 0.84 Insecticides 0.72 <0.001 0.89 0.01 Smoking 0.50 0.46 0.07 0.53 X-Ray 0.63 <0.001 0.46 0.86 X-11 �Table X-9 RESULTS OF THREE-FACTOR LOG-LINEAR ANALYSES OF SKIN CANCER, GROUP MEMBERSHIP AND EXPOSURE (P VALUES) Exposure Analysis Group by Cancer Group by Exposure Cancer by Exposure Asbestos 0.009 0.04 0.24 0.11 Degreasing Chemicals 0.009 0.37 0.20 0.47 Industrial Chemicals 0.009 0.30 0.03 0.58 Insecticides 0.02 <0.001 0.19 0.79 I Smoking 0.01 0.44 0.70 0.22 X-Ray 0.008 <0.001 0.86 0.51 Cancer by Exposure by Group As shown in Table X-9, analyses of skin cancers demonstrated a significant difference between the Ranch Hand and the original comparison group that completed physical examination. These data again demonstrate the, significant group differential in skin cancer. Even after covariate adjustment (asbestos, industrial chemicals, smoking, x-ray, insecticide and degreasing chemical exposure) the significant group difference in the occurrence of skin cancer remained. Significant between group differentials were noted for x-ray and, asbestos exposure, as previously seen in the systemic cancer analyses. A significant association between skin cancer and exposure to industrial chemicals. #as found (P - 0.03). Associations between the occurrence of skin cancer and exposure to degreasing chemicals and insecticides are also of interest, with g|H68estive P values of 0.20 and 0.19 respectively. 5« Exposure Index Analyses The group difference in cancer occurrence was further evaluated using the exposure index, divided into low, medium, and high degrees of exposure. These analyses used only data gathered on the Ranch Hand group. Table X-10 contains the data and results from the basic two-factor analysis (herbicide exposure versus cancer). X-12 �Table X-10 HERBICIDE EXPOSURE VERSUS CANCER Occupational Group Systemic Cancer Yes Jlo Exposure Level Skin Cancer Yes jto Flying Officers 1 1 3 Low Medium High 110 127 122 P - 0.48 7 5 8 104 123 117 P - 0.62 Flying Enlisted 0 2 1 Low Medium High 59 57 65 P = 0.35 3 1 0 56 58 66 P « 0.14 Ground Enlisted 2 .3 0 Low Medium High P - 0.31 149 176 148 2 5 4 149 174 144 P * 0.63 These analyses did not reveal a dose-response effect between herbicide exposure and the occurrence of either skin or systemic cancer in the Ranch Hand group; however, the number of cancers within each exposure level are very small. A "suggestive" negative association between herbicide exposure and skin cancer was noted among the enlisted flying group (P -• 0.14) with decreasing occurrence of cancer with increasing exposure; however, cell sizes were quite small. Three-factor analysis suggested the presence of interactive effects from insecticide and x-ray exposure, in the flying officers for systemic cancer, and industrial chemicals, degreasing chemicals, and insecticides among the enlisted ground personnel for skin cancer. The results of these analyses are Shown in Tables X-11, and X-12, X-13, X-14, and X-15. X-13 �Table X-11 THREE-FACTOR ANALYSIS: EXPOSURE, SYSTEMIC CANCER, AND INSECTICIDE EXPOSURE AMONG FLYING OFFICERS* Insecticide Exposure Yes Herbicide Exposure Systemic Cancer Yes N_o 1 1 0 low medium high 74 79 72 P = 0.62 No 0 0 3 low medium high 36 48 50 P =0.09 * Three-way interaction P value - 0.10 These data demonstrate confounding by insecticide exposure, with a borderline association between systemic cancer and herbicide (P » 0.09) in the noninsecticide-exposed group of officers. However, the validity of statistical testing in this instance is compromised due to the extremely small number of cases in the analysis. Similarly, this effect is seen with x-ray exposure (Table X-12). Tables X-13, X-14 and X-15 present the data for the herbicide exposure, cancer, industrial chemical, degreasing chemical and insecticide three-factor analyses for enlisted personnel. Confounding is again seen. X-14 �Table X-12 THREE-FACTOR ANALYSES: HERBICIDE EXPOSURE, SYSTEMIC CANCER, AND X-RAY EXPOSURE AMONG FLYING OFFICERS X-ray Exposure Herbicide Exposure Yes Systemic Cancer Yes N£ 1 1 0 low medium high 23 23 33 P - 0.49 No low medium high 0 0 3 87 104 89 P = 0.04 * Three-way interaction P value - 0.04 Table X-13 THREE-FACTOR ANALYSIS: HERBICIDE EXPOSURE, SKIN CANCER, AND INDUSTRIAL CHEMICALS EXPOSURE AMONG ENLISTED GROUND PERSONNEL* Industrial Exposure Yes Herbicide Exposure Skin Cancer Yes 14o 0 1 3 low medium high 79 96 73 P - 0.12 No 2 4 1 low medium high 70 78 71 P « 0.45 * Three-way interaction P value - 0.10 X-15 �Table X-14 THREE-FACTOR ANALYSIS: HERBICIDE EXPOSURE, SKIN CANCER, AND DECREASING CHEMICAL EXPOSURE AMONG ENLISTED FLYING PERSONNEL* Degreasing Chemical Exposure Skin Cancer Yes No Herbicide Exposure low medium high Yes 3 0 0 41 51 0.04 low medium high No 0 1 0 16 17 15 P = 0.42 * Three-way interaction P value - 0.17 Table X-15 THREE-FACTOR ANALYSIS: HERBICIDE EXPOSURE, SKIN CANCER AND INSECTICIDE EXPOSURE AMONG ENLISTED FLYING PERSONNEL* Insecticide Exposure Yes Herbicide Exposure Skin Cancer Yes No low medium high 3 0 0 30 36 41 0.03 No low medium high 0 1 0 26 22 25 P - 0.32 * Three-way interaction P value =0.13 While these data show some confounding for exposure to x-ray, insecticides, industrial chemicals and degreasing chemicals, stratified analysis reveals no evidence of a dose-related effect for exposure to the herbicides used by the USAF in the RVN and the occurrence of cancer. The validity of the statistical X-16 �testing in the exposure index analyses is compromised by the extremely small numbers of cancers available for analysis. Therefore, any Inferences based on these data must be made with caution. 6. Summary The analysis of these data revealed significantly more skin cancer in the Ranch Hand group than in the subset of original comparisons who completed physical examination. This finding was of borderline significance in all original comparisons and in the total comparison population; however, these data are not fully corrected for exposure to the sun and other skin carcinogens. There were no significant group differences for the occurrence of systemic cancer. A small increase in oropharyngeal cancers and a total absence of digestive cancers were observed in the Ranch Hand group. The exposure index analyses did not demonstrate a dose-response effect for either skin or systemic cancer. Of interest was a borderline significant association between systemic cancer and smoking in both groups, demonstrating the sensitivity of the analyses to the effects of this known carcinogen. X-17 �Chapter XI FERTILITY AND REPRODUCTIVE OUTCOMES 1. .Introduction The potential effects of Herbicide Orange exposure on reproduction, fertility., or the incidence of birth defects are highly emotional issues among Vietnam veterans and have received wide media coverage. Animal fertility studies in various species have shown variations in 2,4-D; 2,11,5-T and TCDD toxicity relative to age, dosage levels and routes of administration. TCDD exposed male mice when mated with unexposed females exhibited no abnormalities in mating behavior, fertility, sperm concentration, sperm motility, survival of offspring, or neonatal development (Lamb, 1980). Conversely, administering Herbicide Orange directly to pregnant mice resulted in three fetal effects: cleft palate, decrease in fetal weight, and fetal mortality (Courtney, 1970). The Australian Birth Defects Study of veterans serving in Vietnam showed no asspciation between birth defects of children from veterans and their Vietnam experience (Case Control Study, Australia 1983). Reports from the Seveso, Italy accident, where 220,000 people were potentially exposed to TCDD in 1976, have shown that the incidence of congenital malformations and abortions in exposed women was below expected values for the region. Of 31* aborted fetuses examined for defects, no fetal malformations were attributed to exposure to TCDD. Additionally, developmental abnormalities in children have not been exhibited (Regianni, 1980). A reproductive study of the wives of DOW Chemical Company workers exposed to 2,4,5-T/TCDD found no differences in fertility patterns, fetal wastage, or birth defects (Townsend and Badner, 1981). In 1979 the Administrator of Environmental Protection Agency declared an emergency suspension of 2,4,5,-T based on the Alsea, Oregon study finding of an increased incidence of spontaneous abortion .in 3 Oregon areas sprayed with the herbicides. This study's findings prepared by the Epidemiologic Studies Program, Human Effects Monitoring Branch, Benefits and Field Studies Division, Office of Pesticide Programs, Office of Toxic Substances, and The Environmental Protection Agency remain controversial. Data concerning fertility and reproductive events in this study were collected during the questionnaire and physical examination. Questions regarding reproduction, fertility/infertility, and offspring history were asked of study participants both in the in-home questionnaire and at the physical examination. In addition to the data collected from male respondents, questionnaires focusing on reproductive history were administered to all available spouses and partners. The data from the reconciliation of subject and spouse questionnaire responses constitute the data base described in this report. This reconciliation was based primarily on spouse data and study participant data only when spouse data was not collected. Analyses for this chapter are based on nonverified subjective questionnaire reporting. Analyses for this chapter are based on nonverified subjective questionnaire reporting. This report also contains data on children with defects and not defects per se. When a child was reported to have multiple birth abnormalities the most serious was analyzed. Sperm counts, and sperm abnormalities from the physical examination are also XI-1 �analyzed. Verification of reported fertility events is presently ongoing and the analyses presented here are based on interim unverified data. Seven thousand' three hundred ninety-nine conceptions are analyzed in this chapter. These represent 3293 Ranch Handers' or their spouses' reported conceptions and 4106 total comparison group or their spouses' reported conceptions. Comparison conceptions include 2669 original and 1437 shifted and replaced comparisons. The Ranch Hand and original comparisons' conceptions were analyzed considering 5 covariates: mother's smoking and drinking during each conception; mother's age; father's age; and the time of conception, i.e, before or after the father's military tour in Southeast Asia. Log-linear models were used to analyze the reproductive events of interest: miscarriages, still births, induced abortions, infant and neonatal deaths, and total numbers of live births. Live births were further analyzed for reported birth defects, learning disabilities and physical handicaps. Analyzed birth defects were those reported within a comprehensive range of ICD codes. Other reported birth defects included a broad range of pediatric conditions perceived by the parents as birth defects. Birth defects meeting ICD definition are further classified as to the severity of the defect. Fertility and reproductive outcomes were not analyzed by race for this report. These data will be presented in subsequent reports. Questionnaire collection of fertility and reproductive information was linked to reproductive events that occurred while the participant was married, living with a partner, or reported in the questionnaire as other pregnancies. Fertility and reproductive events were keyed to the specific relationship in order to reconcile the information with similar data collected from all available spouses and partners. Figure XI-1 presents an algorithm for the development of the fertility data base. XI-2 �Figure XI-1 ALGORITHM FOR THE DEVELOPMENT OF FERTILITY /REPRODUCTION DATA BASE otal Study Participant Total Spouse Reportet Reported Conceptions Conceptions 7204 6333 1 \ \ , \ v _ '.„,, .,„_ ,,._,_ ^ » Study Participant * Spouse Reported \ -—— __ Non-Live Birth Reported Live Births 6047 ^ Spouse Reported 1025 1 Non-live Births ""'""sso a'* i 1157 Respondent Data Base \ 1 Updated by Spouse x [ \ Merged Live Births 6085 i \ Twins and Triplets —•——— Counted as Single t Event .._l""~'l'" Live 6040 \ \ No Spouse Inf orma tion Response ""SriT" ,. , , -,- J<w ' i i L Non-Live 1359 1 1 Total Conceptions 7399 Of the 7204 total respondent reported conceptions shown in Figure XI-I 604? (84$) were reported as live births and 1157 (16$) were reported as nonlive births. The spouses reported 6333 total conceptions. These are shown in the upper right portion of the figure. Of the total conceptions reported by spouses as attributable to the male respondent, 5308 (84$) were reported as live births and 1025 (16$) were reported as nonlive births. Figure XI-1 shows that the spouse-reported births were matched to the respondent reported live births and 38 children were added to the respondent data base. Six thousand eighty-five live births were thus identified. The first born of multiple births were maintained in the data base and the remaining children were deleted yielding 6040 live births. Three hundred thirty-four nonlive births were added to the nonlive birth study subject file as a result of the match of the male respondent and spouse files. Seven thousand three hundred ninety-nine total conceptions are contained in the merge of the live and nonlive birth files. Xl-3 �The data in Figure XI~1 are based on unverified data. The data in the fertility file has not been fully cleansed of keypunch, editing or other potential sources of errors. The study participant data collection stressed natural children; but, inadvertently, data collection resulted in information on multi^ple adopted, step and natural children. Additionally, there was no data link between spouse, male respondent and children. Following receipt of data, a USAF computer system was created to define this link, but precise definition of total conceptions, live births and nonlive births must await verification by receipt of birth certificates and medical records. This processing is presently ongoing and will be finalized in future reports. Of the 7399 conceptions analyzed in this report 3293 were reported by Ranch Handers or their spouses and 4106 were reported by the total comparison group or their spouses. Comparison conception included 2669 in the subset of originally selected comparison individuals and 1^37 in the group of shifted and replacement comparisons. 2. Fertility/Infertility Data on the number of conceptions, number of marriages, duration of marital and nonmarital relationships, and the number of couples with the desired number of children were gathered during the in-home questionnaire. Three reproductive indices were derived from these data; the Infertility Index (number of childless marriages per total number of marriages), the Married Fertility Index (number of conceptions per years of marriage) and the Total Fertility Index (number of conceptions per years together). The Total Fertility Index includes time spent in nonmarital relationships. The data on fertility/infertility outcomes are presented in Table XI-1. XI- H �Table Xt-1 FERTILITY/INFERTILITY OUTCOMES FOR QUESTIONNAIRE COMPLIANT INDIVIDUALS Group PC P value; RH versus Originals All Variable RH AC Number of participants 1174 956 Number of Marriages 1456 1167 1860 Number of conceptions 3292 2668 4106 Number of participants with conceptions 1043 856 1359 1531 • Mean number of conceptions per participant 2.80 2.79 2.68 Mean number of marriages 1.24 1.22 1.21 - Number of childless marriages Infertility index Number of couples with children, having the desired number of children 385 283 0.264 0.243 708 560 - 448 0.241 891 0.32 0.23 0.67 0.73 Married fertility index 0.165 0.155 0.158 >0.25 >0.25 Total fertility index 0.163 0.154 0.157 >0.25 >0.25 RH = Ranch Hand OC = Original Comparisons AC = All Comparisons Although the crude numbers of conceptions and childless marriages differ between the Ranch Hand and comparison groups, the mean number of conceptions per participant and the proportion of marriages without children are not different. The percentages of couples with children who had the desired number of children, are not significantly different. Two hundred eighty-three of the 1045 Ranch Handers (27.1$) and 211 of the 733 originally selected comparisons (27.3$) attending the physical examination had vasectomies (P = 0.92). Seven hundred fifty-eight of the Ranch Handers (72.5$) and 561 of the comparisons (76.5$) submitted semen specimens. Of those participants willing and able to provide semen specimens, 186 Ranch XI-5 �Handers and 140 comparisons had vasectomies and/or orchiectomies (N = 6) and were therefore excluded from the statistical analysis of sperm counts. Six of these participants with a history of vasectomy were found to have sperm in their specimen and they were informed of these findings. The semen specimens from the remaining 993 participants were analyzed by general linear model techniques, using continuous variables of sperm count and the percentage of each participant's sperm which had abnormal morphology. The means, standard deviations and median values for the sperm counts and percent of sperm with abnormal morphology are displayed in Table XI-2. These analyses were adjusted for age and exposure to industrial chemicals, and revealed no significant group differences in sperm counts (adjusted P = 0.77), or in the percentage of abnormal sperm morphology (adjusted P = 0.71). Twenty-seven Ranch Handers and 19 comparisons had abnormal sperm morphology out of 560 and 409 analyzed specimens, respectively. Unprotected exposure to industrial chemicals (ever, never) had no significant effect in these analyses. However, age had a significant effect on sperm count (P = 0.0001), with sperm count increasing with age. The relevance of this observation is unclear since the counts may be biased somewhat by the differential compliance observed with increasing age. Compliance differed significantly with age (P < 0.001) but not by group (P = 0.78). This in sperm count increase was the same in both the Ranch Hand and comparison groups, with a slope of 1.69 in the Ranch Hand/original analysis, and 1.85 in the Ranch Hand/all analysis. These slopes were significantly different from zero (P = 0.0001). There was no significant association between age and abnormal sperm morphology (adjusted P = 0.57). The distribution of sperm counts in the two groups is presented in Figure XI-2, and the distribution of abnormal sperm morphology percentage is displayed in Figure XI~3. The patterns of compliance to semen specimen collection is shown in Figure XI-4. Table XI-2 DESCRIPTIVE STATISTICS OF SPERM VARIABLES BY GROUP Standard Deviation Mean P value Median Count (in million/ml) Original Comparisons Ranch Hand All Comparisons 111 .864 108.833 102.782 111.469 111.025 108.475 80 86 78 \ / \ 0.77 0.99 Percent Abnormal Sperm Original Comparisons Ranch Hand All Comparisons 9.614 9.705 9.643 5.182 5.525 5.946 XI-6 9 9 8 0.71 0.79 �Figure XI-2 DISTRIBUTION OF SPERM COUNTS BY GROUP 20-59 60-119 120-179 180-239 SPERM COUNT IN MILLION/ML XI-7 239 RANCH HAND COMPARISON �Figure XI-3 DISTRIBUTION OF ABNORMAL SPERM BY GROUP 0-4 5-9 10-14 15-19 20-24 PERCENT ABNORMAL FORMS XI-8 24 RANCH HAND COMPARISON �Figure XI- SEMEN SPECIMEN COMPLIANCE BY AGE AND GROUP 100 40 20 =35 35-39 40-44 45-49 AGE 50-54 x RANCH HAND * COMPARISON 3. Conception Outcomes In the evaluation of the outcomes of pregnancies fathered by study participants, analyses were conducted on all reported pregnancies in which the date of conception was known, and repeated on a subset of those in which information on maternal age, maternal smoking, and drinking habits was available from spouse questionnaires (complete data subset). There were an additional 95 conceptions in which data were too incomplete for analysis, and thus were deleted from the data base. There is no difference in the pattern of missing data between groups, as shown in Table XI-3. XI-9 the two �Table XI-3 COMPLETENESS OF CONCEPTION INFORMATION Group Complete Data Partial Data Incomplete Data Original Comparisons 2278 3t8'(13.0$) 42(1.6$) Ranch Hand All Comparisons 2781 (84.5$) 459 (13.9?) 3435 (83.75?) 599 (14.6$) (5W 8. \ 53 (1.6$) ( 72 (1.8$) / P Values • °'64 The occurrence of miscarriage was determined for each conception in which a date was reported. Similarly, outcomes of induced abortion, stillbirth and live birth were also determined. Adjustments for maternal factors of age (< 35, S 35), smoking (yes, no) and alcohol use (yes, no) and paternal age « 35, £ 35) could not be performed on these pregnancies with partial data, and no analysis was possible on those with incomplete data. In the covariate adjusted analyses, the primary statistical relationship of interest is the complex relationship between group outcome and time. Use of the pre-SEA conception experiences allows the Ranch Hand pre-SEA conceptions to serve as a standard for comparison with post-SEA conceptions. This is of special importance since 63-2$ of the Ranch Hand and 63.6$ of the comparison conceptions were pre-SEA events. Table XI-4 presents the data and the results of the analysis of these outcomes. Similar analyses using data from the entire comparison group are presented in Appendix X. The results of these additional analyses were essentially the same as those in Table XI-4. XI-10 �Table XI-4 ANALYSES OF CONCEPTION OUTCOMES, UNADJUSTED FOR MATERNAL COVARIABLES (COMPLETE AND PARTIAL DATA SUBSETS); RANCH HANDERS VERSUS ORIGINAL COMPARISON Yes Post-SEA Pre-SEA (50 No Yes No 190 (15.9) 130 (13.6) 1001 825 Miscarriage Ranch Hand Comparison (0) 295 (14.4) 205 (12.3) 1754 1467 0.06 0.13 Stillbirth Ranch Hand Comparison (0) 13 (0.6) 13 (0.8) 2036 1659 16 (1.3) 8 (0.8) 1175 947 P = 0 .27 0.60 Induced Abortion Ranch Hand Comparison (0) 13 14 (0.6) (0.8) 2036 1658 62 65 (5.2) (6.8) 1129 890 0.12 0.47 Live Birth Ranch Hand Comparison (0) 1723 (84.1) 1435 (85.8) 326 237 917 744 (77.0) (77.9) 274 211 0.62 0.15 These data demonstrate a borderline significant group difference in miscarriage (P = 0.06) prior to Southeast Asia duty and a suggestion of a difference (P = 0.13) post-SEA. However, inferences based on these analyses, unadjusted for key factors affecting pregnancy outcome, are of questionable value. Therefore, those conceptions in which full covariate information was known, were analyzed in greater detail. The data reflecting outcomes for both pre- and post-SEA conceptions are shown in Table XI-5, and the results of the adjusted analyses are displayed in Table XI-6. XI-11 �Table XI-5 CONCEPTION OUTCOMES (COMPLETE DATA SUBSET) BY GROUP MEMBERSHIP AND TIME; RANCH HANDERS VERSUS ORIGINAL COMPARISONS Yes Pre-SEA (%) Post-SEA (*) Yes No No Miscarriage Ranch Hand Comparison 239 172 (13.7) (11.9) 156 (15.0) 104- (12.5) 1505 1276 883 726 P = 0.12 P = 0.13 Stillbirth Ranch Hand Comparison 9 8 (0.5) (0.6) 12 8 1735 1140 P = 0.89 (1.2) (1.0) 1027 822 P - 0.69 Induced Abortion Ranch Hand Comparison 8 7 (0.5) (0.5) (3.6) (4.0) 37 33 1736 1441 1002 797 P = 0.61 P - 0.92 Live Birth Ranch Hand Comparison 1487 1258 (85.3) (86.9) 257 190 . 833 682 P = 0.19 (80.2) (82.2) P = 0.27 Table XI-6 RESULTS OF THE ANALYSIS OF CONCEPTION OUTCOMES; RANCH HANDERS VERSUS ORIGINAL COMPARISONS P value Relationship Miscarriage by Group by Pre/Post-SEA 0.76 Stillbirth by Group by Pre/Post-SEA 1.00 Induced Abortion by Group by Pre/Post-SEA 0.89 Live Birth by Group by Pre/Post-SEA 0.94 XI-12 206 148 �Although a group difference of 15/S versus 12.555 in post-SEA miscarriage is observed (P * 0.12), both groups had similar post-SEA conception outcomes relative to their own pre-SEA baseline experiences (P = 0.76). Ranch Hand miscarriages increased from 13-7? pre.-SEA to 15.054 post-SEA while comparison miscarriages increased from 11.9$ to 12.5%. Thus, while more Ranch Hand conceptions resulted in miscarriages than the comparisons, they started from a higher level before their herbicide exposures occurred, and in the overall analyses, there was no significant difference. These rates of miscarriage are comparable to estimates of 10-2055 for the general US population (Last, 1980). The rate of stillbirths in the US population is 0.98?, again comparable to the observed rates in this study. Similar analyses were conducted using data from all comparison individuals, and the results of these procedures were similar to those presented in Table XI-6. The data and analytic results of these additional analyses are shown in Appendix X. The effect of increasing maternal age was evident in all of these measures, with highly significant increases in miscarriage and induced abortion and decreases in live births associated with increasing age (P £ 0.01). The increase in induced abortions in both groups is unexplained, but is most likely the result of the altered legal status of induced abortion and its increased social acceptance. Exposure index analyses were performed in each of the three occupational categories (Officers; Enlisted, Flying; and Enlisted, Ground). The degree of exposure in each of these categories was stratified as low, medium or high (see Chapter VIII). Since the stratification by occupational category and exposure level and patterns of missing covariate data resulted in smaller groups, analyses had to be conducted using each covariate separately. A single analysis using all covariates would have resulted in unacceptably small cell sizes for meaningful analysis. The number of conception outcomes by occupational category available for each covariate analysis are presented in Table XI-7, and results of each covariate analysis are shown in Table XI"--8. XI-13 �Table XI-? NUMBER AND RESULT OF CONCEPTION OUTCOMES FOR EACH COVARIATE ANALYSIS BY OCCUPATIONAL CATEGORY Parameter Covariable Officers Yes No Category Enlisted Flying Yes No Enlisted Ground Yes No 102 102 122 122 Miscarriage Maternal Maternal Maternal Paternal Smoking Alcohol Age Age 34 34 44 44 225 225 241 250 19 19 22 22 100 100 119 119 Stillbirth Maternal Maternal Maternal Paternal Smoking Alcohol Age Age 2 2 3 4 257 257 282 290 2 2 2 2 117 117 139 139 Maternal Maternal Maternal Paternal Smoking Alcohol Age Age 17 17 18 24 242 242 267 270 6 6 9 9 113 113 132 132 14 14 23 29 630 630 707 710 Maternal Maternal Maternal Paternal Smoking Alcohol Age Age 205 205 219 219 54 54 66 75 92 92 108 108 27 27 33 33 521 521 576 576 123 Induced Abortion Live Birth XI-14 7 7' 8 9 542 542 608 617 637 637 722 730 123 154 163 �Table XI-8 RESULTS OF THE CONCEPTION/EXPOSURE INDEX ANALYSES Parameter Occupational Category Outcome/Exposure P Value, Adjusted for; Maternal Paternal Smoking Alcohol Age Age 0.04 0.30 0.54 0.04 0.26 0.50 0.07 0.19* 0.62 0.06 0.20 0.51 Officers Enlisted, Flying Enlisted, Ground 0.12 0.12 0.04* <0 .01 * 0.25 0.25 0.48 0.43* Officers Enlisted, Flying Enlisted, Ground 0.27 0.60 0.24 0.24 0.55* 0.23 0.57* 0.37* 0.29 0.59* 0.45 0.43 Miscarriage Officers Enlisted, Flying Enlisted, Ground Stillbirth Officers Enlisted, Flying Enlisted, Ground Induced Abortion Live Birth * Three-way covariate interaction is present. - Data too sparse for valid statistical analysis The only statistically significant findings observed are for miscarriage and for induced abortion among officers. Consistent patterns of increasing adverse outcomes of pregnancy with increasing herbicide exposure are not evident for other outcomes. In all four covariable analyses in the officer group, there was a significant association between miscarriage and exposure level (low, medium and high). 4. Live Birth Outcomes Those conceptions resulting in a live birth were further analyzed to determine the frequency of adverse events in those infants and children. As in the assessment of conceptions, unadjusted analyses were conducted on all reported live births in which a date of conception was known or could be estimated from the known date of birth. Analyses were repeated on those live births for which information on maternal age, maternal smoking, and maternal use of alcohol were available. Table XI-9 presents the distribution of live births within the subsets with complete and partial data. The difference in the proportion of the groups with only partial data are not statistically significant. Those births with inadequate data are omitted. XI-15 �Table XI-9 COMPLETENESS OF LIVE BIRTH DATA Complete Data Partial Data Total Original Comparisons 1940 (89.0$) 239 (11.0$) 2179 \ i Ranch Hand 2320 (87.8$) 320 (12.2$) All Comparisons 2922 (87.2$) 429 (12.8$) 2640 ( ) 3351 P Values \) • £ \ 0.43 Based on in-home questionnaire responses and respondent definitions of gestational age, there were no differences in the occurrence of prematurity, and postmaturity in the Ranch Hand and comparisons groups (PO.85). Further analyses of the incidence of prematurity based on objective criteria of birth weight will be conducted after birth certificate verification. Information concerning learning disabilities, physical handicaps, birth defects and the occurrence of neonatal and infant death was collected for each live birth. The information was obtained as a "yes" response primarily from the spouse questionnaire. Study subject responses were used when spouse data were unavailable. Data collection questions included: "Did (child) have any birth defects?"; "Does/Did (child) have a diagnosed learning disability?"; and "Does/Did (child) have any physical, mental, or motor impairments?" Yes responses to all 3 questions had been coded by the USAF from the ICD-9-CM based on the mother's or father's statement concerning the kind of birth defect, learning disability or physical, mental or motor impairment. For each defect reported for each child, the interviewer had the opportunity to document 3 statements within the question regarding the kind of birth or developmental problem. Therefore, each yes response had in some cases 3 ICD~9'-CH codes. A computer program was written to select defined birth defects, learning disabilities and physical, mental and motor impairments. For the child with multiple reported birth defects, he/she was counted only once for analysis. For children with multiple reported birth defects the most serious condition was analyzed. This report contains data on children with reported defects and not all reported defects; analyses of total reported defects will occur in a future report. A thorough review of the birth defect codes including key punch and code verification was accomplished prior to analysis of the merged data file. This review was not accomplished for reported learning disabilities or physical, mental and motor impairments, neonatal or infant death. The comprehensive definition of those reported defects within the definition for this report are presented in Appendix V. Reported birth defects not within the acceptable definition are presented in Appendix XIX. Counts of the total-reported and within-definition birth defects are presented in Table XI-10. Fifty-nine percent of the Ranch Hand and 64$ of the total comparison reported defects were within the acceptable defined range of birth defect. XI-16 �Table XI-10 COUNT AND PERCENT OF TOTAL REPORTED WITHIN-DEFINITION BIRTH DEFECTS Within Definition Total Reported Original Comparison Ranch Hand All Comparisons 218 292 137 172 212 ( W 6 334 P Values 0.37 0.24 The 5-6/6 difference in the perception of conditions which constitute a birth defect is not statistically significant. However, differential reporting of birth defects is of concern because media attention to hypothesized effects from exposure to the herbicide may affect parental reporting. In addition literature suggests the possibility that parents could perceive post-SEA births as "vulnerable" children (McCormick, 1982). Because of the above factors, all reported defects within range were categorized as severe, moderate, and limited (those of minor medical consequence) birth defects. This approach is based on a recent study (Christianson, 1981) which demonstrated that the incidence of reported congenital anomalies increased as children aged. Living children with reported defect average 23 years of age at the present time, with an age range of 2 through 39 years, and therefore, many years of parental observation have elapsed. The definition used for the collapsing of data into this system are as follows: Severe: Conditions which are life threatening or produce severe handicaps (e.g., physical, mental, motor). Moderate: Conditions which are not life threatening and handicaps which with medical care will not interfere with the individual's overall health or socio-economic progress. Limited: All conditions which without medical care would not interfere with the individual's health or socio-economic progress. Those reported birth defects without type of defect data were included in the limited category. Responses to birth defects which were unclear, incomplete or could be classified into more than one category were classified in the highest category applicable to the condition. Table XI-11 summarizes the reported birth defects categorized by level of severity system. XI-17 �Table XI-11 SUMMARY OF CHILDREN REPORTED WITH BIRTH DEFECTS BY LEVEL OF SEVERITY (SEVERE, MODERATE, LIMITED) RANCH HAND AND COMPARISON, PRE AND POST SEA TOUR Nature of Reported Defect Original Comparisons Counts % Ranch Hand Counts % Total Comparisons CountsT PRE-SEA Severe Moderate Limited 51 32 56. 35, 8 Ha., i •" 50 27 10 57 31 12 62 40 20 51 33 16 TOTAL 90 100 87 100 122 100 34 34 Ji 40 40 20 86 100 POST-SEA Severe Moderate Limited 32 22 26 TOTAL 80 18 20 10 100 48 37.5 111.5 21 100 TOTAL (PRE AND POST-SEA) Severe Moderate Limited TOTAL 83 54 33 49 32 19 68 47 20 50 35 15 96 74 38 46 36 18 170 100 135 100 208 100 This table shows that overall, 19% of the Ranch Hand, 15/t of the original and 18>6 of the total comparison group reported birth defects were classified as "limited." Ranch Handers reported &% limited pre-SEA and 32.5? post-SEA. Original comparisons reported '\2% pre^SEA and 2156 post-SEA and total comparisons reported 161 and 20%, respectively. These observations will be analyzed more fully in subsequent reports. Table XI-12 presents the analysis of the live birth outcomes for the partial and complete data subsets unadjusted for maternal factors of smoking, age and alcohol use. XI-18 �Table XI-12 ANALYSES OF LIVE BIRTH OUTCOMES, UNADJUSTED FOR MATERNAL COVARIABLES (COMPLETE AND PARTIAL DATA SUBSETS); RANCH HANDERS VERSUS ORIGINAL COMPARISONS Yes Pre~SEA (%) No Yes 1662 1373 77 51 Post-SEA (%) No Learning Disability Ranch Hand Comparison 61 62 (3.5) (4.3) P «= 0.26 (8.4) (6.9) 840 693 P = 0.24 Physical Handicaps Ranch Hand Comparison 144 112 (8.3) (7.4) 1579 1323 132 85 P = 0.57 (14.4) (11.4) 785 659 P = 0.07 Infant Death Ranch Hand Comparison 8 3 (0.5) (0.2) 1715 1432 4 (0.4) 3 (0.4) P = 0.23 913 741 P - 0.92 Birth Defects Ranch Hand Comparison 90 87 (5.2) (6.1) 1633 1348 80 48 P = 0.31 (8.7) (6.5) 837 696 P - 0.08 Neonatal Death Ranch Hand Comparison 25 17 (1,5) (1.2) P = 0.51 1698 1418 14 3 (1.5) (0.4) 903 741 P = 0.02 Live birth outcomes were not statistically different in the 2 groups prior to the participants tour of military duty in SEA. However, 3 of the 5 measures of outcomes after SEA duty demonstrated borderline or statistically significant differences between the Ranch Hand and comparison groups. The significant findings in neonatal deaths (P = 0.02), and the borderline significant XI-19 �finding for birth defects (P = 0.08) and physical handicaps (P = 0.07) were not adjusted for the effects of key covariables. Therefore, the data from those live births with full covariate information (complete data subset) concerning the maternal covariables were analyzed. Table XI-13 displays the pre-SEA and post-SEA data from this subset of births. Table XI-13 LIVE BIRTH OUTCOMES (COMPLETE DATA SUBSET); RANCH HANDERS VERSUS ORIGINAL COMPARISONS Parameter Pre-SEA (50 Post-SEA (50 No 75 47 (9.0) (6.9) 758 635 126 77 (15.1) (11.3) 707 605 No Yes 57 (3.8) 57 (4.5) 1430 1201 (9.0) (8.2) 1353 1155 Yes Learning Disability RH Comp Physical Handicap RH Comp Infant Death RH Comp 7 (0.5) 2 (0.2) 1480 1256 Birth Defects* RH Comp 78 (5.2) 80 (6.4) 1409 1178 76 44 Neonatal Death RH Comp 20 (1.3) 17 (1.4) 1467 1241 14 (1.7) 3 (0.4) 134 103 3 (0.4) 1 (0.1) (9.1) (6.5) 830 681 757 638 819 679 *Analysis includes 2 Ranch Hand birth defects which were double counted. Log-linear analyses, simultaneously considering all covariates (maternal age, maternal smoking, and maternal alcohol use, and paternal age) were accomplished. Table XI-14 confirmed the differences in birth defects initially seen in the unadjusted analyses of post-SEA live births. This finding was statistically significant (P = 0.04) after adjusted analysis. Suggestive associations were noted in learning disabilities (P = 0.19) and in neonatal deaths (P = 0.20). Incidence rates of neonatal death and infant death in the general US population are estimated to be 0.9958 and 1.4$, respectively (Last, 1980). The incidence rate of major birth defects in the general population is estimated to be 3-~5%, but varies, depending upon the criteria used to define the "defects." XI- 20 �Table XI-14 RESULTS OF THE ANALYSIS OF LIVE BIRTH OUTCOMES; RANCH HANDERS VERSUS ORIGINAL COMPARISONS Relationship P Value Learning Disability by Group by Pre/Post SEA Physical Handicap by Group by Pre/Post SEA 0.19 0.1(5 Infant Death by Group by Pre/Post SEA 0.81 Birth Defects by Group by Pre/Post SEA 0.04 Neonatal Death by Group by Pre/Post SEA 0.20 The distribution of reported post-SEA birth defects is presented in Table XI-15. This table clarifies the reported birth anomalies by level of medical consequence. Twelve congenital anomalies of the skin (ICD code 757) are present in the Ranch Hand data. This category of skin anomalies is quite broad, and includes simple birth marks, pigmentary changes, and more serious conditions. Reanalysis of the data concerning birth defects among live births in which full covariate data were available was accomplished with skin anomalies deleted. The birth anomalies included in the ICD category 757 are generally of minor medical consequences and their removal from analysis can be expected to provide a clearer understanding of group differences in birth defects of major health significance. This analysis revealed no significant group difference between Ranch Hand and comparison group live births for the remaining nonskin birth anomalies (P = 0.14). However, this weak association is still of interest. All reported birth defects are presently being validated by medical record reviews. Significant associations were noted (P < 0.05) between maternal smoking during pregnancy and learning disabilities, physical handicaps, infant deaths and birth defects. Maternal alcohol use during pregnancy was also associated with physical handicaps (P < 0.001). Future analyses of the birth defect data will also make use of the severity level classification. Live birth analyses using data from all of the comparisons were also conducted, and are contained in Appendix X. These analyses identified significant group differences in physical handicaps, birth defects and neonatal deaths. However, the influences of increased sample size and potential replacement group bias (differential reporting) have not been taken into consideration in these analyses. XI-21 �Table XI-15 COUNTS OF ANALYZED PQST-RVN BIRTH DEFECTS REPORTED BY RANCH HANDERS AND ORIGINAL COMPARISONS BY ICD CODE, LEVEL OF SEVERITY, AND AS STATED BY PARENT ICD-9-CM Codes 228 Ranch Harid Level of Severity S M L 1 Nomenclature Reported by Spouse/Study Subject Original Comparisons Level of Severity S M L 1 Blood tuner en nose Henagioma on left portion of head and face 1* 52* Micrcgnathia 5531 Umbilical hernia 711 1* 1* Spina bifida Open spine (severe case of Spina bifida) 712 1* 1* 1 Spinal cord and brain not connected Brain damage 1 713 744 1 Deaf in left ear (nerve underdeveloped) Malformed ear Bump en ear Missing small part of right earlobe 2 1 745 1 1* Septal defects Double cutlet right ventricle Heart murmur Foramen ovale was not totally closed 1 746 1 1 1 A congenital heart Heart valve Heart SV node, two nodes in heart Heart condition Blue baby 1 * 747 '3 1 748 Slightly, eye coordination 2* 1 Patent ductus Varicose vein in right groin Underdeveloped lungs, Premature Spot on lung XI-22 1 2 1 1 1 �Table XI-15 (Cont) COUNTS OF ANALYZED POST-RVN BIRTH DEFECTS REPORTED BY RANCH HANDERS AND ORIGINAL COMPARISONS BY ICD CODE, LEVEL OF SEVERITY, AND AS STATED BY PARENT ICD-9-CM Codes 749 Ranch Hand Level of Severity S M L 1* Cleft lip Cleft palate 2 Pyloric stenosis Skin growing across his esophagus Large bubble or abscess on throat TE fistula Tongue tied 2 1 750 751 Nomenclature Reported by Spouse/Study Subject Original Comparisons Level of Severity S M L 1 1 Couldn't eat her food Uhdescended testicle Hypospadia Opening for urinating lower than normal Vagina fused, had operation 752 3 1 753 Defective kidney Malformation of right kidney Infantile polycystic kidney disease 754 Talipes Club foot Dislocated hips Leg bowed in at birth required cast and then braces Chest cavity deformity Ankle bones deformed Foot turned in Toes turned in 2 2 Left hand had no fingers, has thumb Crooked femur bone Possible hip or feet or both developed later Deformed feet Two toes joined together Hip and foot defect, wore a brace Extra finger and toe 1 1 755 1- XI-23 3 1 2 1 2 1 �Table XI-15 (Cont) COUNTS OF ANALYZED PQST-RVN BOTH DEFECTS REPORTED BY RANCH HANDERS AND ORIGINAL COMPARISONS BY ICD CODE, LEVEL OF SEVERITY, AND AS STATED BY PARENT ICD-9-CM Codes Ranch Hand Level of Severity S M L 1 Nomenclature Reported by Spouse/Study Subject Original Comparisons Level of Severity S M L 3 1 Leg turned in, wore a cast for 3 months Bones from knees to ankles grew inward Webbed finger on hand Delta phalanges of index fingers Crooked foot or legs Leg problem, knees hurt as infant 1 Unusually tiny head Premature fusion of sagittal sutures Skull slightly deformed Bone deformity Small neck muscles from being in breach position Feet curved in at birth 1 1 1 5 1 1 Ichthyosis No finger or toe nails Skin pigmentation Skin discoloration Yellow color, disappeared in a week Birthmarks Two nipples on breast Skin tags Down's Syndrome 3 1 1 756 1 1 1 757 1 2 758 2 TOTAL 3D 18 26 = 74 1 1 1 1 1 19 19 *Child deceased. Table XI-15 relates the ICD codes to the level of severity to the reported statement of the spouse or study participant. Of the 7** post<-RVN Ranch Hand reported birth defects, 30 are of a severe and 18 of a moderate level of severity. Counts of reported birth defects pre-RVN and post-RNV by occupational category are presented in Table XI-16. Inspection of this table shows that the increase in reported birth defects postf-RVN are predominately from personnel in �the Ranch Hand and total comparison enlisted ground occupational category. However, these data have not yet been adjusted by the number of live births in each occupational category. Table XI-16 COUNTS OF REPORTED BIRTH DEFECTS PRE- AND POST-SEA BY OCCUPATIONAL CATEGORY (OFFICER, ENLISTED-FLYING, ENLISTED-GROUND) Occupational Category Officer Enlisted Flying Enlisted Ground TOTAL Ranch Hand Pre-SEA Post-SEA Counts Counts Original Comparisons PrerSEA Posfr-SEA Counts Counts Total Comparisons Pre-SEA Post-SEA Counts Counts 44 15 40 16 52 22 13 12 15 5 21 10 21_ _49 25 23 40 45 78 76 80 44 113 77 Exposure analyses were performed using the covariates of maternal age, maternal smoking, maternal alcohol use, and paternal age. Each covariable was analyzed separately. The number and result of live birth outcomes by occupational category available for each covariate analysis are presented in Table XI-17 and the results of each covariate analysis are shown in Table XI-18. XI-25 �Table XI-17 NUMBER AND RESULT OF LIVE BIRTH OUTCOMES FOR EACH COVARIATE ANALYSIS BY OCCUPATIONAL CATEGORY Parameter Learning Disability Covariable Officers Yes No Category Enlisted Flying No Yes Enlisted Ground Yes No Maternal Maternal Maternal Paternal Smoking Alcohol Age Age 15 15 16 16 190 190 203 203 8 8 8 8 84 84 100 100 52 52 53 53 469 469 523 523 Maternal Maternal Maternal Paternal Smoking Alcohol Age Age 26 26 26 26 179 179 193 193 12 12 13 13 80 80 95 95 81 81 86 86 440 440 490 490 Maternal Maternal Maternal Paternal Smoking Alcohol Age Age 1 1 1 1 204 204 218 218 1 1 1 1 91 91 107 107 2 2 3 3 519 519 573 573 Birth Defects Maternal Maternal Maternal Paternal Smoking Alcohol Age Age 12 12 12 12 193 193 207 207 11 11 12 12 81 81 96 96 50 50 53 53 471 471 523 523 Smoking Alcohol Age Age 3 3 3 3 202 202 216 216 4 4 4 4 88 88 104 104 6 6 6 6 515 515 570 570 Physical Handicap Infant Death Neonatal Death Maternal Maternal Maternal Paternal XI-26 �Table XI-18 RESULTS OF THE LIVE BIRTH/EXPOSURE INDEX ANALYSES Outcome/Exposure P Value, Adjusted for; Maternal Paternal Smoking Alcohol Age Age Parameter Occupational Category Learning Disability Officers Enlisted, Flying Enlisted, Ground 0.47 0.46 0.31 0.31* 0.92 0.94 0.89 0.85 Physical Handicap Officers Enlisted, Flying Enlisted, Ground 0.07 0.89 0.78 0.07 0.69 0.79* 0.06 0.47 0.76* 0.05 0.56 0.79 Infant Death Officers Enlisted, Flying Enlisted, Ground Birth Defects Officers Enlisted, Flying Enlisted, Ground 0.02 0.03 0.39 0.02 0.06 0.35 0.02 0.03 0.46 0.02 0.03 0.41 Neonatal Death Officers Enlisted, Flying Enlisted, Ground - Data too sparse for valid statistical analysis. * Significant three-factor interaction is present. These results demonstrate consistency across all covariates for each of the live birth outcomes; however, as noted in Table XI-18, the data are sparse in many instances, especially for officer and enlisted flying personnel. Birth defects are found to have a statistically significant association with herbicide exposure level in the officer and enlisted flying groups. However, there is not a consistent increase in defects with increasing exposure in the officer category. In the enlisted flying group the adverse outcome did increase consistently with increasing exposure. The pattern in the officer group demonstrated a two-fold rise in the medium level but the highest exposure group had the lowest proportion of children with defects (1.2$). Physical handicaps in children of officers demonstrated borderline significance. 5. Summary A summary of the findings of the fertility and reproductive analyses are displayed in Table XI<-19. XI-27 �Table XI-19 SUMMARY OF FERTILITY AND REPRODUCTIVE ANALYSES Parameter Infertility Sperm Count Sperm Abnormality Unadjusted 0 A NS P Values Exposure Analyses by Occupational Group Adjusted Enlisted Enlisted 0 A Officers Flying Ground NS NS NS NS NS NS NS NS NS NS NS NS NS Conception Outcomes Miscarriage Stillbirth Induced Abortion Live Birth 0.13 NS 0.12 NS 0.15 0.10 NS NS 0.04 0.19 NS 0.12 NS NS NS NS NS 0.05 NS NS NS 0.02 0.03 NS Live Birth Outcomes Prematurity Learning Disability Physical Handicap Infant Death Birth Defects Defects Excluding Skin Anomalies Neonatal Death NS NS 0.07 NS 0.08 0.05 <0.01 NS 0.04 0.19 NS NS 0.04 0.12 0.02 NS 0.02 0.02 <0.01 0.14 0.20 0.07 0.03 NS = Nonsignificant 0 = Original Comparisons A = All Comparisons The analyses in this chapter did not reveal any significant differences in fertility/infertility and sperm counts between the Ranch Hand and either comparison group. Conception outcomes of miscarriage, stillbirth, induced abortion and live births also were not found to differ significantly. Analyses unadjusted for known risk factors of pre-SEA conception history, maternal age, maternal smoking, and maternal alcohol use, and paternal age revealed a suggestive association for increases in miscarriage after the father's SEA service in the Ranch Hand group. However, this association and a borderline increase in post-SEA induced abortion in the original comparison group were not evident after consideration of these other risk factors. Analyses of these conception outcomes with the herbicide exposure index also did not reveal any evidence of herbicide effects. A statistically significant association between increasing herbicide exposure and miscarriage was identified in the officer group but this XI-28 �effect was not observed in the other occupational categories. Borderline significance was noted in officers for stillbirth and induced abortion, but these findings did not increase in occurrence with increasing exposure. Significant differences were reflected in the analyses of live birth outcomes. These differences were observed for birth defects after the analyses were adjusted for parental covariates. There appeared to be a clustering of birth anomalies of the skin in children of the Ranch Handers. There were no significant group differences for other birth defects, but a suggestive association remained (P = 0.1*0 after reanalysis with the skin anomalies excluded. Suggestive group differences between the Ranch Handers and original comparisons were also observed after adjusted analysis for learning disability and neonatal death. Exposure analysis identified several findings of statistical and borderline significance; however, the patterns were not consistent across occupational strata. Overall, birth defects demonstrated statistical significance in the adjusted intergroup analysis, and 2 of the 3 occupational group exposure analyses. A larger number of live birth outcome differences were observed in analyses comparing the Ranch Handers to the total comparison group; however, it is unclear whether these differences are true group differences, or are due to changes in sample size or replacement bias (differential reporting). The value of these analyses in making inferences is therefore limited at this time. The findings in this chapter do require further evaluation of the possible link between herbicide/dioxin exposure and birth defects. The analyses have relied heavily on unverified spouse reports, and the effect of differential reporting of conception and birth outcomes in pregnancies and in children who the parent might perceive as "special" or "vulnerable" has not been evaluated. This evaluation will be conducted using birth certificates and medical records so that an analysis of verified fertility/reproductive data can be included in the report of the first follow-up physical examination. XI-29 �Chapter XII NEUROLOGICAL ASSESSMENT 1. Introduction Neurological abnormalities have long been recognized as acute toxic effects following the exposure of humans to phenoxy herbicides and dioxin (Goldstein, 1959; Wallis, 1970; Berkley, 1963; Boeri, 1978). Signs and symptoms, such as hyporeflexia, a decrease in nerve conduction velocity, general muscular weakness and decreased sensation in the extremities have been noted. One study documented demyelination as a result of 2,4-D exposure (Dudley, 1972). While these effects have only been demonstrated acutely following heavy exposures, complaints of peripheral neuropathy are prominent among Vietnam veterans who have participated in the Veterans Administration Agent Orange Registry Program. Twelve percent of the 110,000 patients in the Registry had complaints compatible with symptoms of peripheral neuropathy. The recognized acute neurotoxicity of these chemicals and the prevalence of neurological complaints among veterans were primary factors in the decision to place a major emphasis on the neurological evaluation of participants in this study. During the administration of the questionnaire, each subject was asked to provide information on any major health conditions he may have experienced. All reported neurological conditions were coded using the ICD-9~CM and group analysis of the distribution of the conditions was performed. As revealed in Table XII-1, there were no statistically significant differences in reported neurological diseases between the Ranch Hand and comparison groups. Table XII-1 DISTRIBUTION OF REPORTED NEUROLOGICAL DISEASES BY GROUP MEMBERSHIP Disease Category Original Comparisons Ranch Hand 2 2 7 15 Inflammatory Diseases Hereditary and Degenerative Diseases Peripheral Disorders Disorders of the Eye Disorders of the Ear and Mastoid All Comparisons 3 1 7 3 3 11 21 21 23 P = 0.73 XII-1 0.69 �There were 1045 Ranch Handers, and 773 originally selected comparisons included in the analyses in this chapter. Where analyses were accomplished using the total comparison group, the data from 1194 comparisons were used. Some variation in numbers did occur due to missing data. In the analyses of the data obtained from the neurological evaluation, only those participants with a negative serological test for syphilis were included since chronic neurological disease can result from inadequately treated syphilis (5 Ranch Handers and no comparisons were found to have positive serological tests for syphilis.) In addition, data from 15 individuals found to have edema of the extremities on physical examination (8 Ranch Handers and 7 comparisons) were deleted from the analyses of the peripheral sensory nerve evaluation and nerve conduction velocities since edema can interfere with these clinical evaluations. Several covariables were considered in the analysis. The use of alcohol (dichotomized to ever/never); years of unprotected exposure to industrial chemicals (yes, no), insecticides (yes, no), and degreasing chemicals (yes, no); and 2-hour postprandial glucose levels equal to or greater than 120 mg/dl were used as covariates. 2. Cranial Nerve Status The functional integrity of all 12 cranial nerves was assessed during the neurological examination. The specific cranial nerves and the examination parameters used in their evaluation are listed in Table XII-2. XII-2 �Table XII-2 CRANIAL NERVE EVALUATION Cranial Nerve Parameter I Sense of smell Olfactory II Optic Visual fields Oculomotor Pupillary reaction to light Ocular movement IV Trochlear Ocular movement V Trigeminal Facial sensation Corneal reflex Clenching jaw III VI Abducens Ocular movement VII Facial Smile Palpebral fissure VIII Acoustic Balance (Romberg Sign) IX, Glossopharyngeal X Gag reflex Vagus Speech Tongue position XI Spinal Accessory Palate and uvula movement Neck movement XII Neck range of motion Hypoglossal Analysis of the examination data revealed no statistically significant differences in cranial nerve function between the Ranch Hand and comparison groups. No significant three-way interactions between the examination parameters, group membership and the covariables of glucose and alcohol were noted. These results are summarized in Table XII-3. Data from the entire comparison group are also presented. XII-3 �Table XII-3 ANALYSIS OF CRANIAL NERVE FUNCTION Cranial Nerve Parameter I Smell, left Smell, right II Group RH OC AC RH OC AC # Normal P Values; Ranch Hand Versus Original All # Abnormal Comparisons Comparisons 19 12 19 759 1172 1027 760 1171 0.67 0.68 17 11 17 1025 0.73 0.70 0.91* 0.87* Visual fields, RH OC left 1037 AC 1186 3 2 3 Visual fields, RH right OC 1038 768 1186 2 3 4 0.43* 0.51* 1031 763 1180 8 4 6 0.52 0.43 655 486 7*6 349 265 423 0.82 0.49 1035 769 1190 7 4 4 0.68 0.26 OC AC RH OC AC 1038 770 1191 4 3 3 0.99* 0,58* Corneal reflex RH 1043 772 1193 2 1 1 0.75* 0.49* OC AC RH OC AC 1042 773 1194 1 0 0 AC III Light reaction RH OC AC III-IV, Ocular movement RH OC VI AC V Sensation, left RH Sensation, right Jaw clench 768 _ XI I-4 _ �Table XII-3 (Cont'd) ANALYSIS OP CRANIAL NERVE FUNCTION Cranial Nerve Parameter Grour # Normal P Values; Ranch Hand versus Original All # Abnormal Comparisons Comparisons Smile RH OC AC 1035 767 1186 4 2 4 Palpebral fissure RH OC AC 986 731 1131 VIII Balance RH OC AC IX Gag reflex Speech VII 0.65* 0.85* 59 42 63 0.84 0.70 833 625 813 207 148 228 0.69 0.26 RH OC AC 1030 760 1180 15 13 14 0.67 0.58 RH OC AC 1041 770 1190 0 1 RH OC AC 879 662 1085 4 2 Palate and RH uvula movement OC AC 1042 771 1192 3 1 1 RH OC AC 1004 748 1158 41 Tongue in midline XI XI, XII Neck range of motion *P RH OC AC - 0.26* 3 0.63* 0.51* 0.48* 0.26* 0.44 0.24 3 25 36 values are of limited validity due to small cell sizes in these analyses = Ranch Hand = Originally selected comparison = All comparisons = Cells containing zeros; P values not valid XI I-5 �The 18 neurological parameters listed in Table XII-3 were again analyzed with regard to occupational group and exposure level. The exposure index, stratified into 3 occupational groupings and 3 levels of exposure, was applied to these cranial nerve data. These results are summarized in Table XI1-4. Fully adequate cell sizes were obtained in only 13 instances. In these analyses, in which no individuals in either group had abnormalities, statistical testing for significance was invalid, and P values are not given. Table XII-4 CRANIAL NERVE FUNCTION VERSUS EXPOSURE LEVEL WITH EACH OCCUPATIONAL CATEGORY Cranial Nerve Parameter I Smell, left 0/F E/F E/G 0.79 0.67 0.16 Smell, right 0/F E/F E/G 0.01 0.84 0.31 Visual fields, left 0/F E/F E/G 0.05 O.HO 0.41 Visual fields, right 0/F E/F E/G 0.06 0.40 0.11 Light reaction 0/F E/F E/G 0.32* II III Occupational Category P Value 0.28 III, IV, VI Ocular movement 0/F E/F E/G 0.21* 0.33* 0.47* V Sensation, left 0/F E/F E/G 0.32 0.12 0.72 Sensation, right 0/F E/F E/G 0.64 0.34 0.35 Corneal reflex 0/F E/F E/G 0.55 XII-6 �Table XII-4 (Cont'd) CRANIAL NERVE FUNCTION VERSUS EXPOSURE LEVEL WITH EACH OCCUPATIONAL CATEGORY Cranial Nerve Parameter Occupational Category Jaw clench 0/F E/F E/G 0 .64 0/F E/F E/G 0 .64 0 .57 Palpebral fissure 0/F E/F E/G 0 .97* 0 .14 0 .12* VIII Balance 0/F E/F E/G 0 .89* 0 .25* 0 .44* IX Gag reflex 0/F E/F E/G 0 .99 0 .84 0 .20 Speech 0/F E/F E/G 0 .38 0.34 0 .11 Tongue in midline 0/F E/F E/G 0 .07* 0 .30* 0 .40* Palate and uvula movement 0/F E/F E/G 0 .64 0/F E/F E/G 0 .67* 0 .78 0.46 VII XI XI, XII Smile Neck range of motion 0/F = Officer, flying E/F = Enlisted, flying * = Cell sizes of 5 or less i- » Cells containing zeros; P values not valid XII-7 P Value - - .0 .43 E/G = Enlisted, ground �3. Peripheral Nerve Status The variables used in the assessment of peripheral nerve function were analyzed with the covariates of 2-hour postprandial glucose in excess of 120 mg/6, history of alcohol use and unprotected exposure to industrial chemicals, insecticides and degreasing chemicals. There were statistical interactions between group membership (Ranch Hand and comparison) and insecticide exposure, and between insecticide exposure and the other covariables. Since these relationships have no impact on the primary question being addressed by this study, further statistical analyses of these interactions will not be undertaken at this time. Analysis of the data pertaining to the peripheral nervous system is summarized in Table XII-5. Data from the entire comparison group are also presented. With the exception of a borderline association between group and Babinski reflex in the originals and a significant association in the entire comparison group, these analyses did not demonstrate statistically significant differences in neurological functions between the 2 groups. Matched pair analyses were performed on the Babinski reflex and the vibration sense data, using the Breslow matched logistic regression technique. A P value of 0.18 was found for the Babinski reflex and a nonsignificant P value of O.1!? was found for vibration sense. Significant interactions were, however, detected between postprandial glucose levels and several of the examination parameters. The association between abnormal glucose metabolism and peripheral neurological disease is well recognized (Scientific American, 1983) and its demonstration in this study reflects a degree of confidence in the quality of the neurological data collection process. These glucose by neurological disease associations are shown in Table XII-6. A positive history of alcohol use had borderline significance with pin prick (P = 0.07). In this analysis, a continuing effect of abnormal glucose is seen for vibration (P = 0.0005), patellar reflex (P = 0.03), Achilles reflex (P = 0.04), and light touch (P = 0.03). Alcohol use also had a borderline significant effect on pin prick (P = 0.07). XII-8 �Table XI1-5 ANALYSIS OF THE PERIPHERAL NERVOUS SYSTEM Parameter Group # Normal P value; Ranch Hand versus All Original # Abnormal Comparisons Comparisons Pin prick RH OC AC 934 691 930 97 73 101 0.94 0.76 Light touch RH OC AC 958 707 953 73 57 78 0.78 0.67 Muscle Status (strength, bulk) RH OC AC 1003 745 1009 37 28 32 0.94 0.62 Vibration RH OC AC 954 698 941 78 67 91 0.38 0.30 Patellar Reflex RH OC AC 1034 766 1003 4 5 5 0.45 0.74 Achilles Reflex RH OC AC 995 746 1005 39 26 35 0.62 0.62 Biceps Reflex RH OC AC 1030 767 1032 8 H 8 0.53 1.00 Babinski Reflex RH OC AC 1024 770 1039 9 2 2 0.10 0.03 RH = Ranch Hand OC = Original comparisons AC = All comparisons XII-9 �Table XII-6 POSTPRANDIAL GLUCOSE ABNORMALITIES VERSUS NEUROLOGICAL FINDINGS (RANCH HANDERS VERSUS ORIGINAL COMPARISONS) Parameter Examination Status Glucose Status # Normal # Abnormal P Value Light Touch Normal Abnormal 1406 100 259 30 0.03 Vibration Normal Abnormal 1402 106 250 39 0.0005 Patellar Reflex Normal Abnormal 1514 5 286 4 0.03 Achilles Reflex Normal Abnormal 1463 48 273 17 0.04 Pin prick Normal Abnormal 1369 137 256 33 0.23 The data from the Ranch Hand group were also analyzed against the exposure index. As shown in Table XII-7, there were no three-way interactions between occupational group, herbicide exposure and the neurological parameters evaluated. No statistically significant results were found in the analysis of exposure versus examination parameters. Borderline associations were noted for vibration in the enlisted flying group (P = 0.10) and for Babinski Reflex in the enlisted ground personnel (P == 0.09). The relevance of these findings, in the face of the other negative results, is unclear at this time. There were no distinct patterns of increasing abnormality with increasing exposure. Table XII-7. PERIPHERAL NEUROPATHY BY EXPOSURE ANALYSES: SUMMARY OF P VALUES Occupational Group Parameter Pin prick Light Touch Muscle Status Vibration Patellar Reflex Achilles Reflex Biceps Reflex Babinski Reflex Officer Enlisted Flying Enlisted Ground 0.78 0.40 0.43 0.94 0.50 0.35 0.49 0.57 0.99 0.83 0.96 0.10 0.57 0.53 0.57 0.53 0.47 0.81 0.65 0.96 1.00 0.60 0.91 0.09 XII-10 �4. Evaluation of Central Functioning A brief evaluation of central nervous system coordination processes was accomplished, focusing on the presence of muscle tremor, finger-to-nose coordination, gait and balance as assessed by the modified Romberg Sign. These analyses are shown in Table XII--8. As in the analysis of the peripheral nerves, there were no significant interactions of these findings with chemical exposures or group membership; however, abnormal glucose metabolism was associated with abnormal balance (P = 0.0002) and the presence of tremor (P = 0.00*1). Alcohol also had a significant effect on the presence of tremor (P = 0.05) and a borderline effect on balance (P = 0.09). Breslow matched pair analysis of the tremor and coordination data revealed nonsignificant P values of 0.21 and 0.31 respectively. Table XII-8 ANALYSIS OF CENTRAL FUNCTION P values; Ranch Hand versus Original All # Normal # Abnormal Comparisons Comparisons Parameter Tremor RH OC AC 985 742 995 55 31 46 0.19 0.36 Coordination RH OC AC 992 7^3 998 48 30 43 0.44 0.59 Romberg Sign RH OC AC 833 625 813 207 148 228 0.64 0.26 Gait RH OC AC 24 14 22 0.47 0.76 758 1018 RH = Ranch Hand OC = Original comparisons AC = All comparisons Exposure analysis was performed on these parameters as well. Three-factor analysis of parameter by exposure level by occupational group again demonstrated no significant interactions. In these analyses, the herbicide exposure/coordination analysis yielded a suggestive association (P = 0.10). Again, there was a statistically significant association between an abnormal Romberg Sign and abnormal glucose metabolism (P = 0.002). Two-way analysis results are shown in Table XII-9. XII-11 �Table XII-9 HERBICIDE EXPOSURE VERSUS ABNORMALITY OF CENTRAL FUNCTIONING SUMMARY OF P VALUES Parameter Tremor Coordination Romberg Sign Gait Officers P Values Enlisted Flying 0.50 0.07 0.89 0.54 0.76 0.16 0.25 0.38 Enlisted Ground 0.20 0.63 0.44 0.11 5. Nerve Conduction Velocity Nerve conduction was evaluated using a continuous measurement and analyzed using a general linear model technique for maximal statistical power. Velocities were measured from 2 locations in the ulnar nerve and from 1 P°s~ ition in the peroneal nerve. Covariables in these analyses included history of alcohol use (measured in drink-years), abnormalities in postprandial glucose levels (equal to or greater than 120 mg/dl), and unprotected exposure to industrial chemicals, insecticides and degreasing chemicals. No associations between the chemical exposures and conduction velocities were identified on covariate analysis; however, highly statistically significant associations were noted in both the Ranch Hand and comparison groups between alcohol use and glucose and conduction velocity. This association held for both measurements of the ulnar nerve (P ts 0.01) with the velocity decreasing as the drink-years of alcohol increased. Glucose was found to be associated with conduction velocity in the peroneal nerve (P = 0.002) and both ulnar velocities (P = 0.001) with velocity decreasing as glucose level increased. These analyses did not demonstrate any significant intergroup differences in velocities in either nerve. The unadjusted and adjusted means and their respective P values are presented in Table XII-10. Similar analyses, using data from the entire comparison group, were performed with similar means and results. Table XII-10 NERVE CONDUCTION VELOCITY (M/SEC) AND GROUP MEMBERSHIP Nerve Ulnar (above the elbow) Group (N) Unadjusted Mean P Value Adjusted Mean P Value R (1035) C (769) 55.88 56.15 0.30 55.89 56.12 0.38 Ulnar R (1042) (below the elbow) C (771) 60.50 60.73 0.39 60.52 60.71 0.48 Peroneal 48.22 48.14 0.74 48.23 48.93 0.66 R (1041) C (769) XII-12 �Herbicide exposure analyses were performed using the covariates of occupational group serum glucose and history of alcohol use. These results are shown in Table XII-11. Table XII-11 ADJUSTED MEAN NERVE CONDUCTION VELOCITY (M/SEC) AND EXPOSURE Nerve Low Exposure Med-High High P Value Officers Ulnar (above elbow) 55.77 55.66 55.97 0.90 Ulnar (below elbow) 60.54 60.60 61.10 0.70 Peroneal 47.69 47.76 47.87 0.96 Ulnar (above elbow) 54.54 55.72 55.35 0.53 Ulnar (below elbow) 58.31 60.68 60.83 0.03 Peroneal 48.22 48.28 48.29 0.99 Ulnar (above elbow) 55.53 56.60 56.33 0.24 Ulnar (below elbow) 59.96 60.74 60.69 0.96 Peroneal 48.34 48.31 49.00 0.14 Enlisted Flying Enlisted Ground These exposure analyses have not demonstrated any consistent trends in conduction velocity and increasing exposure either within or between occupational categories. A single significant result (P = 0.03) was found in the distal ulnar nerve velocity in flying enlisted personnel, but there was no corresponding finding in the same nerve when measured over a larger distance above the elbow (P = 0.53). The borderline significance in the peroneal nerve velocity of ground enlisted personnel (P = 0.14) was not evident in the other occupational categories. Again, significant associations with glucose were noted, with P values falling between 0.06 and-0.005. XIl-13 �6. Summary As summarized in Table XII-12, detailed analyses of the neurological examination data pertaining to the status of the cranial nerves, peripheral nerves and central functioning were performed. Table XII-12 SUMMARY OF NEUROLOGICAL STATUS Parameter Group Analyses JP Values) Exposure Off Enl Fly Enl Gnd Cranial Nerves 1 2 3 4 0.01 0.05 NS NS NS NS NS NS 0.16 0.11 NS NS 5 NS NS 0.12 NS 6 7 • NS NS NS NS NS NS NS NS NS 0.14 NS 0.12 8 9 10 11 12 NS NS NS NS NS NS NS 0.07 NS NS NS NS NS NS NS NS NS 0.11 NS NS NS NS NS NS NS NS NS 0.10 NS NS NS NS NS NS NS NS NS NS NS 0.10 NS NS NS NS NS NS NS NS NS NS NS 0.09 0.19 NS NS NS NS 0.07 NS NS NS 0.16 NS NS NS NS NS 0.11 NS NS NS NS 0.03 NS NS NS 0.14 Peripheral Nerves Pin Prick Light Touch Muscle Status Vibration Patellar Reflex Achilles Reflex Biceps Reflex Babinski Reflex Control Function Tremor Coordination Romberg Gait Conduction Velocity Proximal Ulnar Distal Ulnar Peroneal NS NS NS NS = Nonsignificant XII-14 �With the exception of a borderline increase in the proportion of Ranch Handers with a positive Babinski reflex, there were no significant differences detected between the Ranch Hand and comparison groups with respect to neurological parameters. The Babinski reflex, however, did not show a significant relationship to past herbicide exposure. There were no consistent findings of increasing abnormality with increasing herbicide (dioxin) exposure. The relative risks and confidence intervals for the dependent variables - analyzed in this chapter are included in Appendix XVIII. Thus, it appears at this time, that there are no neurological abnormalities in the Ranch Hand group that can be attributed to herbicide exposure in Vietnam. The evaluation of neurological status among the participants in this study has demonstrated the ability to identify classical interactions between abnormal glucose metabolism and alcohol use and evidence of neurological abnormalities. These findings lend confidence to the validity of the negative findings of a chronic herbicide (dioxin) effect on the neurological system. XII-15 �Chapter XIII PSYCHOLOGICAL ASSESSMENT Since 1961 , psychological abnormalities have been ascribed to acute phenoxy herbicide exposure (Bauer, 1961). Subsequently, a wide range of psychological symptoms, including anxiety, depression, emotional instability, and asthenia have been reported following exposure (Monarca and di Vito, 1961; Kramer, 1974; Poland et al, 1971). Since many Vietnam veterans have expressed concern that their exposure to the defoliants during the war caused them to experience psychological and behavioral problems, the psychological functioning of the study participants was assessed in both the questionnaire and physical examination phases of the study. Overall, the responses of 1045 Ranch Handers, 1230 comparisons, and a subset of 773 originally selected comparisons were analyzed. Slight variations in these numbers occurred in some analyses due to missing data. Except where indicated, all analyses reported in this chapter used the data from the subset of originally selected comparisons. Each participant was asked whether he had ever experienced psychological illness. Additionally, six specific psychological dimensions were explored in detail in the questionnaire: depression, anxiety, erosion of skills, social isolation, fatigue, and aggressive or impulsive behavior. The questions used were selected from an extensive test battery, previously developed and validated (Robbins, 1982). More standardized measurements of psychological performance were obtained during the physical examination by the use of several standardized tests. The Cornell Index, the Minnesota Multiphasic Personality Inventory (MMPI), the HalsteadReitan Battery and the Wechsler Adult Intelligence Scale (WAIS) were the primary testing instruments. Throughout much of this chapter, educational level (high school versus college) and rank (officer versus enlisted status) received special attention in all analyses. These variables are widely recognized as having major influences on psychological testing performance (Dalstrom, 1960) and their importance in the setting of the Air Force Health Study was very apparent. Dependent variables were stratified by education and rank, and in log-linear techniques, they were used as covariables. Table XIII-1 displays the education and rank distributions of the Ranch Hand and original comparison groups. Table XIII-1 EDUCATION AND RANK DISTRIBUTION OF RANCH HAND AND ORIGINAL COMPARISON GROUPS Ranch Hand High School College Officers Enlisted Original Comparisons High School College 54 (14.3?) 324 (85.7?) 53 (18.2?) 239 (81.8?) 521 (80.8?) 124 (19.2?) 377 (79.4?) 98 (20.6?) XIII-1 �Regardless of statistical technique or procedure, the analytic results of all psychological testing from the high school group closely mirrored those of the enlisted group, and college results matched those of the officer group, since, in general, the attainment of a college degree is a prerequisite for commissioning as an officer. However, 121! of the Ranch Hand enlisted and 98 of the original comparison enlisted personnel have college degrees as well. The similarities between these groups are graphically demonstrated in Figure XIII-1, where full scale IQ scores are compared. Since the variables of rank and education had identical impact on the analyses of psychological data, only the data from the educational analyses will be presented. The results of the rank analyses parallel those of education, and their presentation in this report would not further clarify the herbicide/dioxin issue. Figure XIII-1 COMPARISON OF EDUCATIONAL ACHIEVEMENT AND RANK FULL SCALE 10 (RANCH HAND) FULL SCALE 10 (COMPARISON) 71 7M4 I OFFICERS FULL SCALE 10 (RANCH HAND) <70 7014 IS-11S 116-140 IQ SCORE H-111 11H40 »140 IOSCME FULL SCALE IQ (COMPARISON) »140 CD <70 BleH SCHO l ° XIII-2 7044 (5-115 10 SCORE 116-149 »14t O HKH SCHOOL �1. Analysis of Questionnaire Data a. Past History of Emotional or Psychological Illness Detailed information concerning reported emotional or psychological illnesses was sought and, wherever possible, these illnesses were coded to the ICD-9-CM, 1980 edition. The unadjusted chi-square analyses of these data are presented in Table XIII-2. It is evident from these analyses that there were no statistically significant differences in the type of reported psychological illnesses between the Ranch Hand and either the entire comparison group or the subset of original comparison individuals. Table XIII-2 DISTRIBUTION OF REPORTED PSYCHOLOGICAL ILLNESS BY TYPE OF ILLNESS Type of Illness Original Comparisons Ranch Hand Entire Group Comparison Psychoses i» 6 4 Alcohol Dependence 2 5 7 Anxiety H 9 5 Other Neuroses 6 16 9 \ / \ / \ / \ / P = 0.91 P = 0.59 b. Psychological Indices A further comparison of the responses to the psychological subsections of the questionnaire was performed. Responses to the questions addressing each psychological dimension were combined in an index equal to the number of positive responses for each dimension. Group differences in the distribution of questionnaire responses were tested by the Kolmogorov-Smirnov two-sample test, and the results are tabulated in Table XIII-3 and XHI-il. The isolation Index was analyzed in .a discrete fashion, adjusted for educational level. The data for this index are presented in Table XIII-5. When the responses to the isolation scale are dichotomized as equal or greater than 14 or less than 1*1, a relative risk of 1.97 is seen, with a 95% confidence interval of 1.11 to 3.58. The number of individuals analyzed in the depression index is reduced, since this is primarily an index of severity, and those individuals not reporting depression were excluded from the analysis. XIII-3 �Table XIII-3 QUESTIONNAIRE PSYCHOLOGICAL INDICES (HIGH SCHOOL EDUCATION) Standard Deviation Kolmogorov Smirnov P Value Group N Mean Score Fatigue Ranch Hand Comparison 573 430 15.33 13.64 6.24 5.52 < 0.001 Anger Ranch Hand Comparison 573 430 11.27 9.99 4.74 3.64 0.002 Erosion Ranch Hand Comparison 572 429 22.34 20.00 7.90 6.70 < 0.001 Anxiety Ranch Hand Comparison 555 419 24.62 21.91 8.67 7.73 < 0.001 Depression (Severity) Ranch Hand Comparison 141 60 5.79 5.30 3.15 2.85 0.89 Index Table XIII-4 QUESTIONNAIRE PSYCHOLOGICAL (COLLEGE EDUCATION) INDICES Group N Fatigue Ranch Hand Comparison 447 335 12.79 12.83 4.55 4.45 0.88 Anger Ranch Hand Comparison 447 335 9.55 9.46 3.09 3.08 0.71 Erosion Ranch Hand Comparison 448 336 20.12 19.90 5.80 5.54 0.94 Anxiety Ranch Hand Comparison 437 328 21.23 20.51 6.74 5.96 0.63 Depression (Severity) Ranch Hand Comparison 60 39 5.22 4.46 2.80 2.11 Index *Data too sparse for valid analysis XIII-4 Standard Deviation Kolmogorov Smirnov P Value Mean Score * �When an unadjusted analysis of reported depression (yes, no) was performed, there was a statistically significant group difference (P=0.002) with the Ranch Handers reporting more depression then the comparisons. This is not necessarily inconsistent with the analysis of severity (P=0.89). Table XIII-5 ISOLATION INDEX, ADJUSTED FOR EDUCATION Index Score Group S5 6-7 8-9 10-11 12-13 £14 Total Ranch Hand 16 81 535 269 91 48 1040 Comparison 3 75 425 200 49 18 770 0.002 The questionnaire responses to the questions concerning fatigue, anger, erosion, anxiety, and depression were analyzed with the exposure index, using a general linear model. When Blacks and non-Blacks were combined, the anger index was observed to be suggestively associated with exposure (P = 0.13) in officers but not in either of the enlisted occupational strata. All other exposure analyses had P values in excess of 0.40. Educational level is a major influence on responses to the psychological assessment portion of the questionnaire. The responses to these questions did not differ between college educated Ranch Handers and comparisons, but all indices except depression did differ significantly in the high school educated participants. These variables were all subjectively measured, and the specific subsets of questions were not validated. It is unclear from these data whether these differences reflect a herbicide effect unique to the largely high school educated enlisted group or an educationally related response to a highly emotional public issue. This difference may also be a reflection of postVietnam stress in the frontline Ranch Hand personnel in contrast to the reduced stress in the comparison group stationed in support areas of SEA. 2- Physical Examination Parameters During the physical examination, the Cornell Index, the Minnesota Multiphasic Personality Inventory (MMPI), the Halstead^Reitan Battery and the Wechsler Adult Intelligence Scales were used to assess psychologic functioning. Again, results were comparable whether using rank or educational attainment as stratification variables, and only the educational analyses are presented. XIII-5 �a. Cornell Index The Cornell Index is a subjective 10 to 15 minute self-administered inventory of neuropsychiatric symptoms and complaints. It has been standardized and is a widely used testing instrument. Grading of the responses to the Cornell results in an overall index and separate indices for each of the ten subelements of the instrument. A total index score of 8 or less is considered to be normal. The overall index scores for the Ranch Hand and comparison groups were contrasted using the Kolmogorov-Smirnov technique after stratification for educational level (Table XIII-6). High school educated participants demonstrated a highly significant group differential (P <0.001) but the index scores in the college, groups were not different. Table XIII-6 ANALYSIS OF CORNELL INDEX BY GROUP (KOLMOGOROV-SMIRNOV TWO-SAMPLE TEST) Educational Level Mean Score Group Standard Deviation P Value High School Ranch Hand Comparison 9.21 6.44 10.35 7.79 < 0.001 College Ranch Hand Comparison 3.66 3.44 5.13 4.58 0.59 The subelement scores were analyzed by log-linear techniques using 6 categories of response. These results are displayed in Table XIII-7( and the results of a similar analysis, using data from all available comparisons, are included as well. These results were all adjusted for educational level, since education was found to affect test scores in a highly significant manner (P <0.0001). Categorical analysis of the subelements revealed significant group differences between the Ranch Handers and the original comparisons in all areas except depression and the neurocirculatory system (NCS). This finding in depression on the Cornell Index is inconsistent with the significant observation noted in the responses to the in-home questionnaire, and may reflect the presence of differential reporting. The NCS scores were suggestive of group differences with a P value of 0.12. Analysis of the entire comparison group revealed similar findings. XIII-6 �Table XIII-7 CATEGORICAL ANALYSIS OF GROUP DIFFERENCES IN THE CORNELL INDEX (ADJUSTED FOR EDUCATION)* P Value: Ranch Hand Versus Original Comparisons All Comparisons Parameter Fear and Inadequacy Depression Nervousness and Anxiety Neurocirculatory System Startle Psychosomatic Hypochondria Gastrointestinal System Sensitivity Troublesomeness 0.02 0.39 0.002 0.12 0.004 0.002 0.05 0.01 0.08 0.06 0.06 0.16 0.009 0.14 0.04 0.002 0.12 0.01 0.29 0.06 * All of these parameters were significantly affected by education level (P <0.0001) Analysis of the Ranch Hand group's overall Cornell Index by degree of exposure was performed, using log-linear techniques. The Cornell Index was compared with exposure level (low, medium, and high) and education (high school and college) after stratification for occupation. In each occupational category, the index was clearly influenced by educational level but not by degree of herbicide exposure. Table XIII-8 contains the results of these analyses. Table XIII-8 EXPOSURE ANALYSIS OF THE CORNELL INDEX (ADJUSTED FOR EDUCATIONAL LEVEL) Occupational Category P Value Cornell Versus Exposure Cornell Versus Education Officer 0.91 0.09 Enlisted, flying 0.53 0.05 Enlisted, ground 0.26 0.04 Analysis of the overall Cornell Index identified significant group differences among high school-educated individuals (P <0.001), with the Ranch Handers having a significantly higher mean (abnormal) score. However, this XIII-7 �finding was not observed among the college educated individuals. Log-linear analyses of the Ranch Handers and original comparisons, adjusted for education, revealed significant differences in 6 of the 10 subscales of the index (P £ 0.05) and borderline or suggestive findings in three others (P S 0.12). Despite these group differences, education adjusted exposure analysis of the overall Cornell Index did not identify any association between level of exposure and Cornell Index. b. Minnesota Multiphasic Personality Inventory (MMPI) The MMPI, a standardized set of 566 subjective self-administered questions concerning various aspects of behavior and personality, was completed by 1023 Ranch Handers, 76? original comparisons, and 1194 total comparisons. Scoring was performed by machine, using the standard criteria for normality of 30-70. The comparison of the distributional characteristics of the responses to each of the subelements of the MMPI are shown in Tables XIII-9 and XI11-10. The effect of educational level on psychological scores is again seen, with more suggestive and/or significant differences between groups appearing in the high school stratum. The validity scale was not different between Ranch Handers and comparisons in either educational stratum; however, the high school comparisons exhibited a greater degree of denial (K scale) than the high school Ranch Handers. Depression (P = 0.16), paranoia (P = 0.19) and hysteria scales (P = 0.12) were suggestive of group differences in the high school stratum and significant differences were noted in the masculinity/femininity, hypochondria, mania/hypomania, and social introversion scales, with comparisons faring better than the Ranch Handers. The college stratum demonstrated borderline significance in the masculinity/femininity scale (P = 0.09) and a significant difference (P = 0.04) in social introversion. The masculinity/femininity scale is heavily influenced by the range of interests held by the participants. As individuals increase their education and broaden their interests beyond traditional "male" activities, the score tends to rise (Lachar, 1974). This is demonstrated by the means of 57.87 to 59.15 in the college stratum and means of 54.85 to 55.94 in the high school group. The consistent finding of significance in social introversion, with the Ranch Handers being more inwardly directed, is striking, but its clinical relevance is unclear. The percent of the Ranch Handers and comparisons exhibiting abnormal MMPI scores (greater than 70 or less than 30) are shown in Table XIIIH1 for those scales with suggestive or significant findings. The increased score on the denial (K) scale of the MMPI for the enlisted comparison group may be an indication of a relative differential in reporting between the two groups. When considered in the light of an increased enlisted Ranch Hand hypochondria scale on both the Cornell Index and the MMPI, overreporting in the Ranch Hand group is indicated. XIII-8 �Table XIII-9 ANALYSIS OF MMPI TESTING IN HIGH SCHOOL-EDUCATED PARTICIPANTS (RANCH HAND N - 575; COMPARISON N = 430) Parameter Validity Group Ranch Hand Comparison Defensiveness (L Scale) Ranch Hand Comparison Ranch Hand Comparison Ranch Hand Comparison Ranch Hand Comparison Ranch Hand Comparison Consistency (F Scale) Denial (K Scale) Hypochondria Depression Hysteria Mean Score 1 .85 1.73 51.99 52.03 51.95 50.65 53.95 55.63 59.74 57.22 60.47 58.39 60.12 58.90 56.38 55.89 55.94 54.85 51.72 50.68 Ranch Hand Comparison Ranch Hand Comparison Ranch Hand Comparison Ranch Hand Comparison Ranch Band Comparison Ranch Hand Comparison 57.53 55.97 Ranch Hand Comparison 56.03 54.49 Ranch Hand Comparison Comparisons greater than Ranch Hand 52.31 50.80 Psychopathic/Deviate Masculini ty/Feminini ty Paranoia Psychasthenia (Anxiety) Schizophrenia Mania/Hypomania Social Introversion XIII-9 57.27 55.59 Standard Deviation 4.54 4.07 7.84 8.15 9.29 7.16 8.86 8.12 13-36 10.95 13.98 11.96 KolmogorovSmirnov P Value 0.99 0.98 0.44 0.03* 0.05 0.16 9.96 8.23 11.00 10.52 0.12 8.32 8.94 0.01 8.66 8.33 12.23 10.07 13.42 9.71 10.36 10.31 10.38 9.50 0.19 0.86 0.47 0.45 0.01 0.006 �Table XIII-10 ANALYSIS OF MMPI TESTING IN COLLEGE-EDUCATED PARTICIPANTS (RANCH HAND N - 448; COMPARISON N = 337) Group Mean Score Standard Deviation KolmogorovSmirnov P Value Validity Ranch Hand Comparison 1.48 1.95 4.14 4.49 0.47 Defensiveness (L Scale) Ranch Hand Comparison 50.26 50.33 7.68 7.29 0.99 Consistency (F Scale) Ranch Hand Comparison 18.74 48.44 5.84 5.36 0.99 Denial (K Scale) Ranch Hand Comparison 58.46 58.41 7.53 7.64 0.99 Hypochondria Ranch Hand Comparison 55.42 54.65 9.34 8.45 0.96 Depression Ranch Hand Comparison 55.34 54.57 10.77 9.98 0.99 Hysteria Ranch Hand Comparison 59.75 59.32 7.38 7.01 0.98 Psychopathic/Deviate Ranch Hand Comparison 55.21 55.66 9.33 8.90 0.68 Masculinity/Femininity Ranch Hand Comparison 59.15 57.87 8.72 8.98 0.09 Paranoia Ranch Hand Comparison 53.62 53-26 6.96 6.64 0.63 Psychasthenia (Anxiety) Ranch Hand Comparison 53.62 54.18 8.04 8.36 0.84 Schizophrenia Ranch Hand Comparison 54.70 54.89 7.94 7.88 0.79 Mania/Hypomania Ranch Hand Comparison 55.22 54.05 9.55 10.03 0.51 Social Introversion Ranch Hand Comparison 46.83 47.50 8.67 7.98 0.04 Parameter XIII-10 �Table XIII-11 MMPI ABNORMALITY BY GROUP Level MMPI Scale Denial Ranch Hand Comparison 0.0 0.0 1.7 3.7 Ranch Hand Comparison 0.0 0.0 18.1 10.9 Depression Ranch Hand Comparison 0.2 0.0 18.1 12.2 Hysteria Ranch Hand Comparison 0.0 0.0 14.1 7.9 Masculinity/ Femininity Ranch Hand Comparison 0.0 0.0 4.5 5.6 Paranoia Ranch Hand Comparison 0.0 0.0 2.4 Mania/Hypomania Ranch Hand Comparison 0.3 0.2 8.5 8.6 Social Introversion Ranch Hand Comparison 0.0 0.0 6.8' 4.9 Masculinity/ Femininity Ranch Hand Comparison 0.0 0.0 11 .6 11.0 Social Introversion College % Below 30 Hypochondria High School Grout».. • . . Ranch Hand Comparison 0.0 0.3 1.6 1.8 . —, % Above 70 1.9 Log-linear analysis of the MMPI data, using dichotomous (normal/abnormal) responses was also conducted (Table XIII-12). Educational level was again found to exert a highly significant influence in all scales, with P values all less than 0.01. XIII-11 �Table XIII-12 LOG-LINEAR ANALYSIS OF THE MMPI SCALES BY GROUP (ADJUSTED FOR EDUCATION) P Value of Group Difference Scale Hypochondria Depression Hysteria Psychopathic/Deviate Masculinity/Femininity Paranoia < 0.001 0.02 0.002 0.39 0.84 0.26 Psychasthenia Schizophrenia Mania/Hypomania Social Introversion 0.21 0.007 0.52 0.32 Several of these analyses appear to be inconsistent with the results of the Kolmogorov-Stnirnov testing, making inference more difficult. Most of the statistically significant group differences found in the distributional analyses were in the high school group, but the log-linear analysis revealed highly significant group differences (P = 0.02) between the Ranch Hand and comparison groups after adjustment for education. Matched pair analyses, using the original comparison subset, were conducted on the hysteria, hypochondria, and masculinity/femininity scales, with respective P values of 0.02, 0.02, and 0.66. These results mirror those of the log-linear analysis in Table XIIIH2. The initial group analyses of the MMPI were performed without consideration for the variable of race. A repeat analysis of MMPI scores was also conducted for the 63 Ranch Handers and 45 originally selected comparisons, who were Black. The results of this analysis are presented in Table XIII-13. Wherever the sample size permitted, the analyses were adjusted for education; however, sparseness of data prevented adjustment in the analysis of the psychasthenia, schizophrenia, and masculinity/femininity scales and prevented any analysis for the paranoia and social introversion scales. The borderline significant finding in the schizophrenia scale (P = 0.07) is somewhat parallel to the significant P value for schizophrenia (P = 0.007) in Table XIII-12. These findings do not suggest that the factor of race is at all responsible for the overall differences in MMPI scores between the Ranch Hand and comparison groups. XIII-12 �Table XIII-13 MMPI ANALYSIS AMONG BLACK PARTICIPANTS Adjusted for Education, Scale P Value of Group Difference Hypochondria Depression Hysteria Psychopathic/Deviate Mania/Hypomania Yes Yes Yes Yes Yes 0.15 0.91 0.31 0.73 0.70 Psychasthenia Schizophrenia Masculinity/Femininity No No No 0.20 0.07 0.31 Paranoia Social Introversion N/A N/A Exposure analysis of the Ranch Hand group, using log"-linear techniques revealed a mixed pattern of significant, borderline and suggestive findings. These results are summarized in Table XIII-14. Education remains a significant factor, but consistency across occupational groups is not evident, since stratification by occupational group mirrored stratification by education. Table XIII-15 displays the exposure index data, and the percentage of abnormal MMPI scale results, for the exposure analyses with P values of concern. Only the hysteria scale in the officers attending college and the psychopathic deviate scale in both high school and college officers showed consistent increases in abnormality with increasing exposure. However, the number of abnormal scores in all of these scales was quite low and inferential accuracy is compromised. Table XIII-14 P VALUES OF THE MMPI/EXPOSURE ANALYSES (ADJUSTED FOR EDUCATION) P Value Parameter Hypochondria Depression Hysteria Psychopathic Deviate Masculini ty/Feminini ty Paranoia Psychasthenia Schizophrenia Mania/Hypomania Social Introversion Parameter Versus Exposure Enlisted Officer FlyingGround 0.21 0.70 0.21** 0.001* 0.09 1.00 0.89 0.09 0.32 0.39 : 0.97 0.11 0.76 1.00 0.81 0.64 0.05 0.12 0.13 0.33 0.02 0.16 0.0005 0.15 0.09 0.53 0.48 0.73 0.29 0.78 *Significant confounding by education present **Signifleant three-way interaction present XIII-13 P Value Parameter Versus Education Enlisted Officer Flying Ground 0.18 0.46 0.34 0.17 0.28 0.72 0.29 0.43 0.86 0.77 0.10 0.12 0.62 0.20 0.04 0.83 0.56 0.50 0.81 0.93 0.03 0.27 0.04 0.16 0.005 0.20 0.07 0,03 0.41 0.02 �TabU) XI 1 1 - 1 5 DOSE RESPONSE PATTERNS Exposure Leve I Number Normal Number AbnormaI (*) En I Isted Ground Low Med i um High 110 153 119 38 25 29 (57) 2.* (14.0*) (19.6*) En I isted Flying Low Med i um High 48 41 55 10 18 11 (17.2*) (30.5*) (16.7) En Iisted Ground Low Medium High 111 148 119 37 30 29 (25.0*) (16.9*) (19.6*) Officers (High School) Low MedIum High 10 14 24 0 5 0 (0*) (26.3*) (0*) Officers (College) Low Medium High 97 104 91 3 5 9 (.* 30) (.* 46) (9.1*) En 11sted Ground Low Med i um High 115 163 132 33 15 16 (22.3*) (.* 84) (10.8*) Officers (High School) Low Med i um High 10 19 23 0 0 1 (0*) (0*) (.* 42) Officers (College) Low Medium High 100 102 90 0 7 10 (0*) (.* 64) (10*) En Itsted Ground Low Medium High 127 164 131 21 14 17 (14.2*) (.* 79) (11.5*) Low Med i um High 105 113 111 5 15 13 (4.5*) (11.7*) (10.5*) En I Isted Ground Low Med i um High 135 172 136 13 6 12 (.* 88) (.* 34) (8.1*) Psychasthenia Enlisted Flying Low Med t um High 54 48 62 4 11 4 (.* 69) (1.9*) (6.1*) Schizophrenia Officers Low Med i um High 108 119 121 2 9 3 (1.8*) (.* 70) (2.4*) Enlisted Flying Low Med i um High 55 49 59 3 10 7 (.* 52) (16.9*) (10.6*) En IIsted Flying Low Medium High 53 50 63 6 9 3 (10.2*) (15.3*) (.* 48) Parameter Group Hypochondria Depression Hysteria* Psychopath Ic/DevI ate* Masculinity/Femininity Officers Mania/Hypomanla *Data are presented by educational level when the education/exposure Interactions are statistically significant. XIII-14 �Analysis of the MMPI data from the Ranch Hand and original comparison groups revealed significant group differences in the hypochondria, depression and hysteria scales (P S 0.02), after adjustment for education. Stratified analysis based on level of education revealed statistically significant group differences for the hypochondria and masculinity/femininity scales (P £ 0.05). However, there were no statistically significant group differences among college-educated individuals, and only in the masculinity/femininity scale was borderline significance reached (P - 0.09). Exposure analyses did not reveal any consistent patterns of statistical significance between occupational categories, level of exposure and MMPI scores. c - Haistead-Reitan The Haistead-Reitan Neuropsychological Test Battery was administered to each participant to assess the functional integrity of the central nervous system. An impairment index for each participant was calculated based upon the scores of the category, tactual performance, speech^sounds, Seashore rhythm, and finger-tapping portions of the battery. The impairment index ranged from zero to seven, based on the number of sub tests in which the participant scored abnormally. Impairment was declared if the index equalled or exceeded three. Larger numbers of participants were deleted from these analyses; since seven distinct tests contributed to the impairment index. The absence of any one made calculation of the index impossible. Analysis of dicotomous variables (normal/abnormal), adjusted for education, revealed no overall group differences (P = 0.74). A categorical analysis, unadjusted for educational level, was performed. The data and the results of the unadjusted analyses of the Ranch Hand group, the entire comparison group and the subset of original participants are presented in Table XIII-16. Table XIII-16 UNADJUSTED HALSTEAD-REITAN SCORES BY GROUP Impairment Index Original Comparisons N - 559 0 1 2 3 4 5 or more Ranch Hand N - 771 85 162 66.5%* 125 77 60 50 \ / x2 - 3.18 P = 0.67 * Cumulative % for Impairment Index 0,1,2 XIIIr-15 All Comparisons N - 883 124 226 141 66.5%* 248 194 134 85 81 163 126 68 64 \ / 2 » 1.35 X P = 0.93 66.0%* �Analyses adjusted for education were carried out on the Ranch Handers and the original subset of comparisons (Table XIIIH?). Education was again seen to be a significant factor (P < 0.0001). Table XIII-17 HALSTEAD-REITAN ANALYSIS BY GROUP AND EDUCATION Educational Level High School College Degree of Impairment 4 2 5 or Greater 1 3 Ranch Hand 54 56 45 108 88 80 Comparison 29 69 69 49 38 37 Ranch Hand 8 79 118 75 46 14 Comparison 56 28 22 13 93 56 P Value, adjusted for education - 0.57 0 An exposure index analysis was also accomplished on the data from the Ranch Hand group. As shown in Table XIII<~18, educational level was a significant covariable in the officer and enlisted flying groups, but there were no significant relationships between herbicide exposure and Halstead-Reitan performance. Table XIII-18 HALSTEAD-REITAN IMPAIRMENT AND EXPOSURE Occupational Group Adjusted P Values Halstead-Reitan Halstead-Reitan Versus Education Versus Exposure Officers 0.88 0.002 Enlisted Flying 0.44 0.05 Enlisted Ground 0.82 0.62 d. Wechsler Adult Intelligence Scale (WAIS) WAIS testing was completed on 1022 Ranch Handers and 733 original comparison individuals. The test was administered and scored in the standard manner by certified clinical psychologists and psychological technicians. As noted previously, intelligence scores (IQ) by rank were equivalent to IQ scores by education. The distributions of verbal, performance and full-scale IQ scores, by educational level and group, are shown in Figure XIII-2. XIII-16 �Figure XIII-2 FREQUENCY DISTRIBUTION IQ SCORES BY EDUCATIONAL LEVEL AND GROUP VERBAL 10 (COLLEGE) VERBAL M - (HMD WHCOL) PERFORMANCE ID (COLLEGE) PERFORMANCE 10 (HtflH SCHOOL) flU. SCALE Nt(COLLEGE) RU KALE M (MM SCHOOL) The IQ scores demonstrated consistent patterns within each educational stratum. A slight increase in the proportion of both Ranch Hand and comparison college graduates, with performance IQ's between 85 and 115, was noted. These distributions were tested for group differences by the Kolmogorov-Smirnov procedure. Suggestive but nonsignificant differences were noted for performance and full-scale IQ's in the high school stratum, but no differences were found among the college^educated group. These data are shown in Table XIII-19. XIII-17 �Table XIII-19 DISTRIBUTIONAL ANALYSIS OF IQ SCORE:, Group Mean Score Standard Deviation High School Ranch Hand Comparison 110.61 101.73 10.65 11.34 0.39 College Ranch Hand Comparison 117.00 116.84 12.97 13.73 0.73 High School Ranch Hand Comparison 102.40 104.14 11.38 11 .86 0.14 College Ranch Hand Comparison 113.70 112.37 12.62 13.33 0.50 High School Ranch Hand Comparison 101.18 102.74 10.71 11.32 0.15 College Ranch Hand Comparison 117.30 116.59 12.96 13.82 0.37 Scale Education Verbal Performance Full Scale P Value The distributions were observed to identify outliers, and the percentage of participants with scores in the abnormal range (below 85) was determined. These results are shown in Table XIII-20. Table XIII-20 ABNORMAL IQ SCORE BY GROUP AND EDUCATIONAL LEVEL College Grout Verbal Ranch Hand Comparison 3.7 3.3 9.8 13-7 Ranch Hand Comparison ,5.4 3.7 14,3 18.8 Full High School Scale Performance Educational Level Ranch Hand Comparison 4.0 3.5 10.6 15.1 Verbal Ranch Hand Comparison 0.9 0.3 58.8 54.1 Performance Ranch Hand Comparison 1.1 1.8 43.9 41.1 Full Ranch Hand Comparison 0.7 0.3 61.1 56.2 XIII-18 % Below 85 % Above 115 �Analysis of the WAIS testing scores of the Ranch Hand group, by level of herbicide exposure, revealed no consistent differences in IQ scores. The P values derived from these analyses are presented in Table XIII-21 and show only one statistically significant association (P = 0.0^). Table XIII-21 RESULTS OF IQ SCORES BY EXPOSURE ANALYSIS Occupational Group P Value Officers Enlisted Flying Enlisted Ground 0.99 0.31* 0.82 Performance Officers Enlisted Flying Enlisted Ground 0.99 O.OH 0.18 Full Scale Officers Enlisted Flying Enlisted Ground 0.99 0.23 0.25 2. Summary In this chapter, a large number of variables were analyzed using several techniques and multiple assessments. Consistent differences between high school-educated Ranch Handers and high school-educated original comparisons are seen throughout these analyses. With the exception of a single statistically significant result for social introversion (P = 0.04), these group differences are not apparent in the college educated stratum. Unstratified but educationally adjusted analyses of the MMPI scores did, however, reveal group differences which were more like those of the high school stratum. Exposure analyses did not reveal any patterns suggesting any association between psychological testing results and level of herbicide exposure. The relative risks, confidence intervals, and shifts in means for the dependent variables analyzed in this chapter are included in Appendix XVIII. Xlll-19 �Table XIII-22 PSYCHOLOGICAL ANALYSIS SUMMARY (RANCH HAND VERSUS ORIGINAL COMPARISON GROUP) Analytic Strategy (P Values) Adjusted for Education Parameter Questionnaire Indices Fatigue Anger Erosion Anxiety Isolation Depression (Severity) Stratified Analysis High School College <0.001 0.002 <0.001 <0.001 Exposure Analysis Off Enl Fly Enl Gnd NS* NS NS NS 0.002 0.89 Cornell Index NS NS NS NS NS 0 .11 NS NS NS NS NS NS 0 .05 0 .12 0 .13 NS 0.02 0.16 0.001 0.15 0.09 NS NS NS NS NS NS NS NS NS NS NS 0 .04 NS NS NS 0.18 NS <0.001 Fear and Inadequacy Depression Nervousness and Anxiety Neurocirculatory Startle Psychosomatic Hypochondria Gastrointestinal Sensitivity Troublesomeness NS NS 0.05 0.16 0.12 NS 0.01 NS NS NS NS 0.09 NS NS NS NS 0.006 0.04 0.02 NS 0.002 0.12 0.004 0.002 0.05 0.01 0.08 0.06 MMPI Hypochondria Depression Hysteria Psychopathic Deviate Masculinity/Femininity Paranoia Psychasthenia Schizophrenia Mania/Hypomania Social Introversion Halstead-Reitan <0.001 0.02 0.002 NS NS NS NS 0.007 NS NS 0.01 0.19 NS NS NS 0.001 0.09 NS NS 0.09 NS • IQ Scores Verbal Performance Full Scale NS 0.14 0.15 *Nonsignificant; P > 0.20 XI11-20 NS NS NS �The results of the analyses of the psychological data are summarized in Table XIII-22, and demonstrate a greater degree of statistically significant group differences in the more subjective measurements (questionnaire and Cornell Index) than are observed in the more objective assessments (HalsteadReitan and WAIS). The effect of differential reporting in this evaluation is as yet difficult to assess. However, the high school-educated Ranch Handers did have higher scores on the hypochondria scale of the MMPI and the psychosomatic portion of the Cornell Index than did the appropriate comparisons. Addi"tionally, the high school-educated comparisons scored higher on the MMPI K Scale (denial). These findings suggest that differential reporting may be influencing the analytic results of the in-home questionnaire and the Cornell Index. There may also be a differential response to the intense media interest in the herbicide/dioxin issue between the high school and college strata in this study. The role of "Post Vietnam Stress" in these findings is also unclear at this time. Further clarification of these factors and their impact must await analysis of the data from the follow-up phase of the study. Based on the psychological data collected during the initial in-home questionnaire and physical examination, there is no convincing evidence suggesting the presence of an adverse effect on emotional health caused by herbicide exposure. XIII-21 �Chapter XIV. EVALUATION OF HEPATIC STATUS 1. Introduction A very broad spectrum of hepatic phenomena has been reported in association with acute, subacute and chronic administration of TCDD to animals. Significant response differences between species occur, however. Serum enzyme changes (SCOT, SGPT, GGPT, LDH) have not been prominent, although SGPT levels were elevated in at least 1 study (Schantz et al, 1979). Elevated alkaline phosphatase levels have been observed with increased direct bilirubin levels (Kociba et al, 1976). Decreased serum cholesterol levels have also been noted after sublethal exposures (Schantz et al, 1979). TCDD interferes with hemoglobin metabolism affecting delta-aminolevulinic acid synthetase activity (Goldstein et al, 1973) and possibly other enzyme activities, providing, at sufficient doses, signs and symptoms of porphyria. Motivated by the literature reports of hepatotoxicity, signs and symptoms of hepatic dysfunction were sought in the participants in this study. In this qhapter, enzyme levels, bilirubin levels and lipid values are presented, along with determinations reflecting porphyrin metabolism. Clinical history data are also analyzed, along with hepatomegaly determined at physical examination. 2. Bipphemical DeterminatIons a. Analyses Overview In this section 9 biochemical determinations are studied: SCOT, SGPT, GGPT, alkaline phosphatase (Alk. Phos.), total bilirubin (T. Bill), direct bilirubin (D. Bili), lactic dehydrogenase (LDH), cholesterol (Choi) and triglycerides (Trig). These 9 variables are listed in Table XIV~1, along with the normal-abnormal ranges used in the reported statistical analyses. These ranges were adapted from Kelsey-Seybold laboratory normal ranges. In the analyses of these 9 variables, adjustments were made for 4 covariates: current alcohol ingestion (ALC), days of exposure to industrial chemicals (1C), days of exposure to degreasing chemicals (DC), and presence or absence of antibody to hepatitis B surface antigen (anti-HBsAg). The current alcohol use covariate was taken from the personal medical history administered at the time of the physical examination and is in units of average drinks per day (see Appendix VI, page 2). Current alcohol ingestion was selected as an adjusting variable over the drink years measure developed from the questionnaire, since preliminary testing indicated it correlated better with hepatic endpoints. The industrial chemical and degreasing chemical exposures were derived from the in^home questionnaire (total unprotected exposure). XIV-1 �The data analyzed were from the entire Ranch Hand cohort compliant to the physical examination (N = 1045) and the original comparisons compliant to the physical examination (N = 773). Ten Ranch Handers and 2 comparisons were removed from the analysis because of body temperature of 100°F or more, and the effect of fever on hepatic variables. Individuals whose blood contained hepatitis B surface antigen (HBgAg) were also removed from the analysis (8 Ranch Handers and 7 comparisons). b. Group Analyses Three sets of analyses were run: (1) Continuous-continuous analyses (CC): In these evaluations both the dependent variables and adjusting covariates, except anti-HBsAg which is dichotomous, were used as continuous variables in an analysis of covariance. (2) Continuous-discrete analyses (CD): In these analyses all 4 covariates were used as dichotomous variables while the dependent variables were maintained as continuous. (3) Discrete-discrete analyses (DD): All variables were analyzed in dichotomous form using the log-linear model for discrete data. In all 3 analysis settings, group-by~covariate interactions were examined. In addition, the continuous-continuous and continuous-discrete analyses models were fit without interaction terms to provide discussion of appropriate tests when dependent variable relationships with the covariates are the same in both groups. In the continuous-continuous and continuous-discrete analyses the dependent variable was normalized by using a logarithmic (base 10) transformation. Table XIV-1 NORMAL - ABNORMAL LEVELS OF NINE BIOCHEMICAL DETERMINATIONS REFLECTING HEPATIC FUNCTION Determination 1. 2. 3. 4. 5. 6. 7. 8. 9. SGOT SGPT GGPT Alkaline Phosphatase Total Bilirubin Direct Bilirubin Lactic Dehydrogenase Cholesterol Triglycerides Normal < 41 :£ 45 £ 85 < 9.7 S 1.2 SS 0.36 S200 <240' 5150 XIV-2 Abnormal > 41 > 45 > 85 > 9.7 > 1 .2 > 0.36 >200 >240 >150 �Table XIV-2 provides unadjusted means, adjusted means, and percent abnormality by groups for the 9 hepatic-related variables. A summary of the 3 classes of analyses is provided in Table XIV-3. The results in this table provide P values for Ranch Hand-comparison group differences. Table XIV-2 UNADJUSTED MEANS, ADJUSTED MEANS AND PERCENT ABNORMALITY FOR NINE LIVER-RELATED VARIABLES Variable SCOT Group RH Unadjusted Means 33-0 33.1 Adjusted Means 33-0 33.1 Percent Abnormality 13-9 1*1.8 SGPT RH COM 20.3 20.5 20.3 20.5 7.8 8.6 GGPT RH 40.2 40.1 10.8 COM 39.3 39.3 10.3 Alk. Phos. RH COM 7.68 7.53 7.69 7.52 T. Bill RH COM 0.57 0.58 0.57 0.58 D. Bili RH COM 0.23 0.24 0.23 0.24 29.0 29.7 LDH RH COM 142.1 141.7 142.1 141.7 1.7 2.1 RH 212.2 212.2 26.0 COM 216.6 216.6 27.7 RH 121.8 121.9 34.7 COM 124.3 124.1 36.1 CHOL TRIG *COM denotes original fully compliant comparisons. XIV-3 17.3 16.9 1 .8 2.0 �Table XIV-3 SUMMARY OF RESULTS UNMATCHED ANALYSES OF N I N E BIOCHEMICAL V A R I A B L E S REFLECTING P V a l u e s for Models w i t h Interaction P V a l u e s for models without Interaction Gp X ALC Gp X anti HB^Ag Gp X 1C Gp X DC .032 - - - .805 <.001 .867 <.001 - anti HBsAg .052 - .663 <.001 .662 .003 - VAR ANAL SCOT CC CD DD .127 <.001 .278 <.001 .578 <.001 -* - - - CC CD DD .736 <.001 .309 .005 .592 - - CC CD DD .731 <.001 .050 <.001 .782 <.001 - - .6 06 - ALK PHOS CC CD DD .405 .142 .734 - _- _- .0 09 _ .010 _ - _ _ TOT BILI CC CD DD .113 .0 66 .800 _ 0 .014 _. _6 3 _ .001 .100 _ - _ - _ - - CC CD DD .494 .371 .869 .0 04 .091 - - - CC CD DD .063 .024 .526 .090 SGPT GGPT DIR BILI LDH CHOL TRIG J3p_ ALC 1C _ .001 - DC .032 - .027 .6 09 - - - - Gp .483 <.001 .421 <.001 _ DC anti HB«;Ag — — « _ _ _ - _ .078 - .0 09 .011 .001 .071 .066 .423 .400 .0 09 - .011 <. 001. 095 .9 09 .770 .755 .0 03 .025 - - _ .037 - .836 .711 - - .022 <.001 .031 .020 - .601 .616 _ .016 - .023 - - _ - _ .011 _ - - - - .8 06 - CC CD DD .062 <.001 .079 .216 .014 .466 .053 - - - - CC CD D D .911 .284 .589 - - -- - - 1C .140 .115 - _ - - ALC _ _ - - L I V E R FUNCTION - _ - .061 - - - - * - denotes P > 0.050 for main effects, P > 0.100 for Interation effects In Tables XIV-2 and XIV-3, there is a very slight indication of overall group differences in the GGPT with the Ranch Hand mean greater than the comparison mean and a P value of 0.050 in the CD analysis with interaction terms. However, when interaction terms are not considered, P = 0.^21. This may indicate some interaction effects even though they were not detected as statistically significant. Additionally, no difference is detected in the CC or DD XIV-4 �analyses. A stronger indication of overall group difference is seen with LDH; however, it is interesting to note that while the Ranch Hand mean LDH is greater than the comparison mean, the Ranch Hand percent abnormal LDH is less than that of the comparison group. The Ranch Hand cholesterol mean is lower than that of ,the comparison group and the result appears unlikely to have occurred by chance (P value of 0.062 in the full model CC analysis; P values of 0.022 and 0.031 in the CC and CD analyses respectively not using interaction terms). These group differences in GGPT, LDH and CHOL are all small. Further group specific differences are noted in interaction effects with covariables. Ranch Hand SCOT levels are correlated more highly with alcohol ingestion than are comparison SCOT levels. The Ranch Hand SCOT - alcohol regression slope is 0.0178 logarithmic units per drink per day, while the comparison SCOT - alcohol slope is 0.0113 logarithmic units per drink per day. This difference in slopes is statistically significant with P = 0.032, and could represent differing hepatic sensitivities to alcohol. A borderline group by industrial chemical exposure is noted in the DD analysis of SGPT levels. This interaction is shown in Table XIV-4. Table XIV- 4 INDUSTRIAL CHEMICAL EXPOSURE AND % ABNORMAL SGPT IN RANCH HAND AND COMPARISON GROUPS Ranch Hand Exposure 8.84$ (38 of 430) No Exposure 7.19$ (42 of 584) Comparison 6.71$ (23 of 3^3) 10.1$ (42 of 416) Ranch Hand personnel exposed to industrial chemicals have a higher proportion of abnormal SGPT values than do Ranch Hand personnel who are not exposed to industrial chemicals. The situation is reversed in the comparison group. The relative risk for abnormal SCOT in the Ranch Hand group associated with industrial chemical exposure is 1.23, while the comparison relative risk is 0.66, and this difference carries a P value of 0.052. Two group-by-covariate interactions are noted in the LDH data. In the comparison group neither alcohol ingestion nor exposure to degreasing chemicals was associated with change in LDH levels, while in the Ranch Hand group, increased levels were noted to occur in association with both exposures. Specifically, in the comparison group the LDH--alcohol slope is -0.0008 logarithmic units per drink per day which is not statistically significantly different from XIV-5 �zero (P = 0.577). Also, the comparison LDH-degreasing chemical slope is -0.08 x 10"5 units per exposure day (P = 0.735 against the null hypothesis of zero slope). On the other .hand, the Ranch Hand LDH-alcohol slope is 0.0041 units per drink per day (P < 0.001 against hypothesis of zero slope) and the LDH-degreasing slope is 0.51 X 10~5 units per exposure day (P = 0.003 against zero slope hypothesis). c. Exposure Analyses Analyses within the Ranch Hand cohort are presented contrasting the hepatic clinical variables against the herbicide exposure index. For this exposure index work, separate analyses were run for each of 3 occupational groups: officers, enlisted flying and enlisted ground. The 9 hepatic variables were analyzed as continuous dependent variables after logarithmic transformation. As with the Ranch Hand^-comparison group analyses, alcohol use, industrial chemical exposure, degreasing chemical exposure and antibody to Hepatitis B surface antigen were used as adjusting covariates, and individuals with body temperature greater than or equal to 100°F were omitted from the analysis as were individuals with hepatitis B surface antigen. For this exposure index effort, alcohol use, industrial chemical exposure and degreasing chemical exposure were used as continuous variables. Table XIV-5 is a display of exposure means adjusting for covariates without invoking interaction. Table XIV-6 provides a summary of P values for the testing. Analyses of covariance or generalized linear models with and without interaction were employed. An overall or main exposure effect on GGPT levels is indicated among officers and enlisted ground personnel. However, clear-cut dose-response patterns are not-noted, rather, in the officer cohort the medium exposure subgroup has the highest mean GGPT while in the enlisted ground cohort the subgroup with low exposure has the highest GGPT. Six exposure group-by-covariate interactions were found at P _<_ 0.050. These interactions are written out in Table XIV>-7. In this table, the slope of the dependent variable with respect to the covariate of interest is provided for each of the 3 exposure levels. XIV-6 �An exposure-by-degreasing chemical interaction was noted in SCOT in officers. Low herbicide exposure is associated with a possible depression of SCOT levels with increasing degreasirig chemical exposure, while individuals in the high herbicide exposure group show increasing SCOT levels with increasing degreasing chemical exposure. Table XIV-5 ADJUSTED BIOCHEMICAL MEANS BY EXPOSURE AND OCCUPATIONAL CATEGORY, WITH TYPICAL SAMPLE SIZES Variable Occupational Category Low Exposure Medium Exposure High Exposure SCOT Officer Enl. F. Enl. G. 33.3 31 .8 33.6 32.2 33-5 32.7 33.0 31.7 34.1 SGPT Officer Enl. F. Enl. G. 20.2 18.5 21.3 19.9 20.8 21.1 19.4 18.4 20.6 GGPT Officer Enl. F. Enl. G. 37.1 39.5 45.9 40.2 37.5 37.8 40.5 41.4 43.0 Officer Enl. F. Enl. G. 6.91 8.13 7.93 7.24 7.88 7.85 7.47 7.98 8.04 T. Bili. Officer Enl. F. Enl. G. 0.56 0.53 0.58 0.55 0.56 0.58 0.57 0.54 0.60 D. Bili. Officer Enl. F. Enl. G. 0.22 0.18 0.25 0.23 0.23 0.24 0.23 0.21 0.26 LDH Officer Enl. F. Enl. G. 111.3 143.1 142.9 139.4 141 .0 140.8 139.3 149.3 144.9 Choi. Officer Enl. F. Enl. G. 214.6 214.0 208.7 213.0 212.6 210.4 209.4 222.5 211.4 Trig. Officer Enl. F. Enl. G. 111 .9 129.8 118.6 127.4 126.4 114.5 129.0 128.4 121.1 Typical Sample Sizes Officer Enl. F. Enl. G. 107 58 143 122 58 170 120 63 146 Alk. Phos. XIV-7 �Table XIV-6 SUMMARY OF P VALUES FOR EXPOSURE INDEX ANALYSIS OF NINE HEPATIC VARIABLES P Values for Models with Interaction VAR SCOT SGPT GGPT ALK PHOS TOT BID DIR BID LDH CHOL TRIG OCC CAT EXP CAT ALC 1C OFF .563 <.001 ENL.F. .885 <.001 ENL.G. .698 <.001 aHb EXP X ALC - .037 - - _ EXP X 1C -* OFF .463 •c.001 ENL.F. .909 ENL.G. .467 DC - - OFF .192 ENL.F. .685 ENL.G. .629 OFF. .643 ENL.F. .449 ENL.G. .606 OFF .992 ENL.F. .399 ENL.G. .823 OFF .516 ENL.F. .656 ENL.G. .300 OFF .290 ENL.F. .310 ENL.G. .096 .394 OFF. ENL.F. .468 ENL.G. .890 - — - - _ .029 _ .010 _ _ _ _ _ .031 .045 - _ - _ _ _ _ _ _ _ _ _ - .060 _ _ _ .050 _ _ _ _ _ _ _ _ - .086 _ — .089 .049 _ _ .018 - - - <.001 _ _ .009 EXP X antl HBsAg - _ - EXP X DC .081 .010 OFF .052 <.001 ENL.F. .427 <.001 ENL.G. .093 <.001 P Values for Models With No Interaction — — .044 _ ' _ .026 — ~ .058 - *. .006 Exp Cat .512 .538 .409 <,001 <.001 <.001 .812 .411 .862 <.001 .696 .224 .574 <.001 <.001 <.001 .280 .855 .710 .885 .560 .642 .856 .310 .697 .758 - .174 .049 .360 - .602 .343 .841 .244 .980 .768 * - Indicates P > 0.050 for main effects P > 0.100 for Interactions. XIV-8 ALC - _ .011 1C _ DC anti HBsAg .047 .035 _ _ _ _ .040 - _ .020 _ _ _ _ _ _ _ _ - .023 .008 - _ _ _ _ - - - - - - - _ .019 .034 .036 - - _ .037 _ - _ _ — — _ - - • - _ — _ _ _ _ �Table XIV-7 EXPOSURE - COVARIATE INTERACTION EFFECTS FOR NINE HEPATIC VARIABLES Exposure Level P Va 1 ue on Test of Slope Against Nul 1 Hypothesis of Zero Slope Van Occ Cat Interact Level of Interact SCOT Officers Exp x DC .009 Low Mod High -.201 x 10~4 units/day .021 x 10"4 units/day .674 x 10~4 units/day GGPT En 1 1 sted Flying Exp x ALC .4 09 Low M»d High . 8 8 unlts/drk/day 02 .056*1 units/drk/day . 2 8 unlts/drk/day 08 <.001 .002 .037 ALK PHOS Officers Exp x ALC <.001 Low Med High -.0442 unlts/drk/day .0131 unlts/drk/day -.0015 unlts/drk/day <.001 .254 .6 84 DIR Bill En 1 1 sted Antl Exp x HBsAg .0 06 Low Med High .3713 mqm/dl -.2246 mgm/dl .1752 mgm/ml .013 .071 .134 LDH Enlisted Antl Exp x HbsAg .4 09 Low Med High .0329 units -.0407 units -.0330 units .159 .085 .128 Exp x ALC .026 Low Med High . 0 9 mgm/dl/drk/day 03 -.0065 mgm/dl/drk/day .0054 mgm/dl/drk/day .284 .4 03 .147 Flying Ground CHOL En 1 1 sted Ground Slope XIV-9 .286 .924 .0 02 �Alcohol use is associated with increasing GGPT levels among enlisted flying personnel, but the increase in GGPT falls smoothly with increasing exposure levels. On the other hand, alcohol use is associated with decreasing alkaline phosphatase levels among Ranch Hand officers in the low exposure group. There are 2 interactions between exposure group and antibody to Hepatitis B antigen. Direct bilirubin levels are higher in enlisted flying personnel who' are antibody positive and are in the low or high exposure groups. Direct bilirubin levels are lower in individuals who are antibody positive but in the medium exposure group. LDH is higher among enlisted ground Ranch Handers who are antibody positive and are in the low herbicide exposure group while LDH levels are lower among antibody positive individuals in the medium and high exposure groups. An exposure-by-alcohol use interaction effect on cholesterol levels shows positive slopes in the low and high exposure categories but a negative slope in the medium exposure category. Thus, of the 6 statistically significant interactions noted in this exposure index analysis only 1, the SGOT-degreasing chemical interaction, supports an interpretation of. herbicide effect. But this interpretation is markedly weakened by the presence of the 5 uninterpretable patterns. 3. Urlnalysis Determinations Related to Porphyrin Metabolism Three components associated with porphyrin metabolism were determined and are analyzed here: uroporphyrin, coproporphyrin and d-aminolevulinic acid. Data addressing these 3 variables were analyzed looking for differences between the Ranch Hand and comparison groups and looking for associations with indexed herbicide exposure within the Ranch Hand group. In examining the uroporphyrin, coproporphyrin and d-aminolevulinic acid data for Ranch Hand - comparison group differences, adjustments were accomplished for the following 6 variables: current alcohol use in drinks per day (ALC), blood urinary nitrogen (BUN), creatinine clearance (CCL), days of exposure to industrial chemicals (1C), days of exposure to degreasing chemicals (DC) and presence or absence of antibody to hepatitis B antigen. Adjustments were accomplished treating the dependent variable and all independent variables except antibody to hepatitis B antigen as continuous variables in a generalized linear model analysis. Since the compounds uroporphyrin, coproporphyrin and d-aminolevulinic acid are all measured in 2M-hour urine collections, only data from subjects who complied with the full collection of urine are used in the analysis (620 Ranch Handers and ^39 comparisons). Also, febrile participants and individuals with HB3Ag have been removed. In the adjusted analyses the dependent variable was normalized by using a logarithmic (base 10) transformation. XIV-10 �Table XIV-8 provides uroporphyrin, coproporphyrin and d-aminolevulinic acid unadjusted means, adjusted means and percent abnormality. For uroporphyrin, values greater than 60 were considered abnormal, for coproporphyrin, values greater than 235 and for d-aminolevulinic acid, values greater than tfQOQ were counted . as abnormal. .*t \ . : ; Table XIV-8 UNADJUSTED MEANS, ADJUSTED MEANS AND PERCENT ABNORMALITY FOR THREE COMPOUNDS RELATED TO PORPHYRIN METABOLISM Unadjusted Means Adjusted Means % AbnormaI Uroporphyrin RH COM 30.5 30.8 * * 6.5? 6.8% Coproporphyrin RH COM 31.2 30.8 * * 0.2% 0.0? d - a m l n o l e v u l i n i c acid RH COM 2328.9 2383.2 2337.1 2371.4 0.0? 0.0? * adjusted means not represented due to interaction Table XIV-9 SUMMARY OF RESULTS UNMATCHED ANALYSES OF THREE COMPOUNDS RELATED TO PORPHYRIN METABOLISM P-VALUES FOR MODELS WITH INTERACTION VAR Gp ALC URO .227 COPRO .490 ALA .145 - BUN <.001 <.001 - <.001 <.001 <.001 1C DC Gp x ALC .049 CCL AntI HBsAg .014 .045 - _ — - Gp x BUN .077 .097 _ Gp x CCL _ _ Gp x Gp x Anti DC HBsAg Gp x _IC _ _ Table XIV-9 displays the detailed analyses. No overall group differences are observed. With uroporphyrin a borderline significant group-by-BUN interaction (P = 0.077) was observed. In the Ranch Hand group, the uroporphyrin-BUN slope was -0.010 uroporphyrin logarithm units per BUN unit, while the comparison slope was steeper (-0.017). A borderline group-by-BUN interaction was also noted in the coproporphyrin data. In the Ranch Hand group, the coproporphyrinBUN slope was -0.01*1 coproporphyrin logarithmic units per BUN unit, while the comparison slope was again steeper (-0.023). Lastly, a group-by-alcohol interaction was detected in the coproporphyrin data (P = 0.045). The Ranch Hand slope was positive (+0.013) while the comparison slope was negative (-0.008). XIV-11 �Table X I V - 1 0 SUMMARY OF P VALUES FOR EXPOSURE INDEX ANALYSES OF THREE COMPOUNDS RELATED TO PORPHYRIN METABOLISM EXP VAR URO COPRO ALA OCC CAT EXP CAT BUN OFF .207 ENL F. .670 ENL 6. .882 .010 OFF .630 ENL F. .498 ENL G. .699 <.001 .016 OFF .279 ENL F. .135 ENL G. .312 CCL <.001 ^C_ JDC _ a_Hb EXP x ALC EXP x x ALC BJJN CCL EXP x 1C - EXP x DC .033 Exp x Ant I HBcAg - .050 .022 .035 - .015 <.001 <.001 <.001 .016 .040 .020 - .028 - .042 - Table XIV-11 TABLE OF UNADJUSTED MEANS FOR THREE COMPOUNDS RELATED TO PORPHYRIN METABOLISM Variable Occupational Category N__ Low Exposure Medium Exposure High Exposure Uroporphyrin Officers Enlisted Fly. Enlisted Gnd. 212 106 282 28.9 38.7 31.1 26.9 27.8 32.4 31.3 31.6 29.8 Coproporphyrin Officers Enlisted Fly. Enlisted Gnd. 212 106 282 32.4 36.4 31.6 26.7 31.1 30.9 29.9 32.5 32.8 d-amino levulinic Acid Officers Enlisted Fly. Enlisted Gnd. 212 106 282 XIV-12 2221 2460 2290 2312 2510 2441 2211 2381 2271 �Table XIV-12 EXPQSURE-COVARIATE INTERACTIONS FOR THREE COMPOUNDS RELATED TO PORPHYRIN METABOLISM Variable Occupational Category P Value for Exposure Interaction Interaction Level Uropophyrin Officer Exp x DC .033 Low Med High -.000043 .000074 .000190 Coproporphyrin Enlisted Ground Exp x 1C .016 Low Med High .301 X TO'11 -.540 X 10"11 .176 X 10"11 d-amino levulinic acid Enlisted Flying Exp x ALC .028 Low Med High .00045 -.02922 .01445 d-amino levulinic acid Enlisted Ground Exp x 1C .040 Low Med High -.1450 X 10'14 -.2944 X 10"11 .0315 X 10-^ d-amino levulinic acid Enlisted Ground Exp x DC .042 Low Med High -.0538 X 10-1* .0398 X 10-4 .0394 X 10-4 The literature indicates elevated porphyrin compound excretion resulting from sufficient dioxin exposure. The pattern found here is one of higher Ranch Hand uroporphyrin or coproporphyrin levels relative to comparisons when there are concomitantly higher BUN levels, or, in the case of coproprophyrin, when there is higher alcohol ingestion. No overall group differences are observed. Tables XIV-10, XIV-11 and XIV-12 display the results of exposure index analyses within the Ranch Hand group. Starting with Table XIV-10, no statistically significant overall group differences are seen and 5 statistically significant(P £ 0.050) group-covariate interactions are noted. Table XIV-11 displays unadjusted group means for the porphyrin metabolism related variables and, as indicated by the statistical testing of overall group differences, no trends with exposure index are observed. XIV-13 �The 5 exposure-by-covariate interactions are listed in Table XIV-12; however, only the exposure index by degreasing chemical interactions follow a classical dose-response pattern. Specifically, Ranch Hand officers with greater herbicide exposure, as measured by the exposure index, have greater increases in uroporphyrin output in response to degreasing chemical exposures than do Ranch Hand officers with less herbicide exposure. The same pattern is seen in the enlisted ground d-aminolevulinic acid data. 4. Clinical Variables Sixteen of 1027 Ranch Handers (1.56%) were diagnosed as having hepatomegaly while 6 of 769 comparisons (0.78$) had that finding (P = 0.138) with an approximate 70% power. In the Ranch Hand group, the cases of hepatomegaly appear to be randomly distributed within the 3 exposure categories; however, due to the small number of cases statistical testing is not powerful. These data on hepatomegaly are shown in Table XIV-13 (febrile participants and individuals with HBsAg have been removed). Table XIV-13 CASES OF HEPATOMEGALY IN THE RANCH HAND COHORT BY OCCUPATION AND EXPOSURE CATEGORY Exposure Index Medium Low Occupational Category Officers Enlisted Flying Enlisted Ground Cases N Cases N 2 1 0 110 59 148 2 2 3 124 58 176 High Cases 2 2 1 _N 123 63 147 Eighteen of 1027 Ranch Handers (1.75?) reported an enlarged liver during response to questionnaire inquiry while 13 of 760 comparisons (1.71?) reported the same. XIV-1 �The study questionnaire also inquired about a medical history of hepatitis, jaundice, cirrhosis, and a general category called other liver conditions. Ranch Hand and comparison responses to these questions are shown in Table XIV-14, Ranch Hand respondents differ from comparisons only in the other liver category. Thirteen of the 16 Ranch Handers reporting other liver conditions have had their report verified by medical record. One comparison has had his condition verified. A display of the verified findings is shown in Table XIV-15 (febrile individuals and HBsAg positive individuals were left in the analysis). Table XIV-14 SPECIFIC LIVER DISORDERS REPORTED ON QUESTIONNAIRE Reported Event Ranch Hand Comparison P Value Yes No Yes No Hepatitis 40 1005 32 741 >0.50 Jaundice 44 1001 35 738 >0.50 Cirrhosis 4 1041 3 770 >0.50 16 1029 2 771 0.004 Other , Table XIV-15 OTHER LIVER CONDITIONS REPORTED BY STUDY PARTICIPANTS AND VERIFIED BY MEDICAL RECORDS Ranch Hand: ICD Code Code Meaning 2724 570 5739 7904 Comparison: Hyperlipidemia Liver necrosis Unspecified Enzyme elevation 5719 Chronic unspecified XIV-15 Number 1 1 10 1 1 �Table XIV-16 REPORTED SKIN PATCHES, BRUISES OR SENSITIVITY IN RANCH HAND PARTICIPANTS BY OCCUPATION AND EXPOSURE CATEGORY Exposure Index Occupational Category Cases Officers Enlisted Flying Enlisted Ground Medium Low 36 27 74 % 32.4 45.8 49.0 High N Cases % N Cases 111 59 151 48 28 82 37.5 47.5 45.8 128 59 179 44 37 76 % 35.2 56.1 51.4 N 125 66 148 Seeking historical evidence of porphyric symptoms, questions concerning skin changes that could have been associated with porphyria cutanea tarda were asked (specifically, skin patches, bruisibility or sensitivity). Of 1045 Ranch Hand respondents, 462 or 44.2$ reported these skin symptoms while 278 of 773 comparisons or 36.0$ reported these conditions. These reported cases indicate a statistically significant group difference (P <0.001); however, no regression with exposure index was noted (data given in Table XIV-16). The historical and hepatomegaly data support an interpretation of some group difference. However, no positive association with herbicide exposure has been noted. 5. Summary and Conclusion Ranch Handers have slightly greater GGPT and LDH levels than the comparisons while having lower cholesterol levels. Also, Ranch Hand SGOT, SGPT and LDH levels are more highly correlated to (and therefore may be more influenced by) materials with an hepatic effect, namely, alcohol, degreasing compounds and industrial chemicals. No group differences were noted in alkaline phosphatase or bilirubin levels. Borderline statistically significant group differences have been detected in uroporphyrin and coproporphyrin levels in association with BUN, and in coproporphyrin levels in association with alcohol ingestion. No overall group differences were detected in these compounds or delta aminolevulinic acid values. Twice as many Ranch Handers as comparisons had enlarged livers on physical examination, but this difference was not, statistically significant. Statistically significant group differences were noted in the occurrence of miscellaneous liver disorders exclusive of hepatitis, jaundice and cirrhosis, verified by XIV-16 �medical record review. Ranch Handers self reported 23% more skin changes of the type associated with porphyria cutanea tarda than did the comparison participants, and the group difference was statistically significant. Clinically apparent porphyria was not evident at physical examination. The observed group differences in liver-related biochemical variables found in the blood, and in porphyrin metabolism compounds found in the urine are most likely of minor or negligible medical importance at the present time. The verified reports of liver morbidity are of greater clinical interest. The exposure index analyses do not support an interpretation of herbicide effect with respect to any of the group differences summarized. XIV-17 �Chapter XV DERMATOLOGIC EVALUATION A thorough dermatologic assessment was deemed essential because chloracne is the only recognized definitive clinical end point following exposure to chlorophenols and dioxin. Over one-half of all veteran complaints recorded in the Veterans Administration Herbicide Registry cited dermatologic symptoms. These facts, coupled with the knowledge that chloracne is transient following a single point exposure (Homberger, 1979), suggested that there is a significant potential to misclassify adolescent acne and chloracne. While the issue of correct diagnosis could be resolved by biopsies and histopathologic characterizations in all participants, this approach was rejected on ethical grounds, as well as concern for the adverse impact of biopsy procedures on future study participation. Consequently, the dermatologic assessment was carefully planned to collect historical and distributional dermatologic data by questionnaire, followed by a detailed corroborative physical examination, supplemented by voluntary biopsies when indicated. Most data reported in this chapter are from the 10*15 Ranch Handers and the 773 originally selected comparison individuals enrolled in the study. Minor fluctuations from these denominators reflect missing dependent variable or covariate data. Relative risks and confidence intervals are shown for all dependent variables in Appendix XVIII. 1 • Questionnaire Data The in-home study questionnaire collected detailed medical histories on the occurrence of acne. These data are displayed in Table XV-1 and show that the Ranch Handers reported slightly more acne than their comparisons. Table XV-1 REPORTED OCCURRENCE OF ACNE BY GROUP Group No Acne Number Percent Reported Acne Number Percent Total Number Percent Ranch Hand 659 63.3 382 36.7 1041 100 Comparison 498 64.8 271 35.2 769 100 Reported acne group contrast: P = 0.52 XV-1 �Beginning and end dates of up to three sustained periods of acne activity re recorded for each individual on the questionnaire. Since only acne after 61 could be possibly induced by herbicide exposure, cases of post-1961 acne re placed in time reference to each individual's RVN tour(s). This temporal stribution was not statistically different with respect to group membership, ese data are reflected in Table XV-2. Table XV-2 REPORTED POST-1961 ACNE BY TIME OF THE SOUTHEAST ASIA [SEA] TOUR(S) BY GROUP roup Pre-SEA Only Number Percent Post-SEA Only Number Percent Pre- and Post-SEA* Number Percent nch Hand = 179 62 3^.6 31 17.3 86 48.0 mparison = 116 51 44.0 17 14.7 48 41.4 iported acne by group by pre/post SEA: P = 0.27 ^ported acne (Post SEA) relative risk: 1.18, 95/S Conf. int. (.67, 2.18) *Such acne could have been separate cases or the same case starting before his RVN tour and ending afterwards. Durations of the cumulative acne episodes were distributed by 5-year itervals and contrasted by group and SEA category. These data are shown in tble XV-3. XV-2 �Table XV-3 DURATION OF ACNE IN 5-YEAR CATEGORIES BY SEA TOUR AND GROUP MEMBERSHIP Pre-SEA ONLY J5_ Duration in Years 5 <Yr <10 10 <Yr <1 5 15 <Yr ^20 Total Ranch Hand 44 15 2 1 62 Comparison 38 12 0 1 51 P = 0.63 Post-SEA ONLY Ranch Hander Comparison 15 9 4 11 1 31 2 4 2 1 7 P = 0.61 Thus, these SEA tour categories suggested that there were no group differences for the pre-SEA or post-SEA acne. Questionnaire information on whether the participant consulted a physician for his acne was used as an indirect measure of the clinical severity of the acne. Of 70 Ranch Handers with acne post-1961 who were asked this question, 29 (41.4/0 responded as having visited a physician as contrasted to 15 of the 45 (33.3/0 comparisons (P = 0.38), suggesting that there was not a statistically significant difference in the clinical severity of their acne. Since chloracne, following mild to moderate exposures, is classically found in skin areas on the temples, eyes/eyelids, and ears (eyeglass distribution), questions on rash locations and combinations of locations were presented to each participant reporting acne. Qt the 117 post-SEA plus pre- and post-SEA cases of acne in Ranch Handers after SEA duty, 75 (6455) reported no acne at any of these locations, while 36 (55%) of the 65 post-SEA plus pre- and postSEA comparisons reported none. These proportions are not significantly different (P = 0.25), and the occurrence of skin disease which could potentially be chloracne does not differ in the two groups. There were only four individuals, two in each group, with acne confined exclusively to the classical chloracne areas. As further corroboration of these anatomically categorized data, a Venn diagram was constructed for post-1961 acne lesions on the temples, ears, and eyes for the Ranch Hand group and the entire comparison group. These data are shown in Figure XV-I and display remarkable visual concordance. XV-3 �Figure XV-1 VENN DIAGRAM OF POST-1961 TEMPLE, EAR, AND EYE ACNE BY GROUP ENTIRE COMPARISON GROUP RANCH HAND GROUP (POST 1961) (POST 1961) ACNE, OTHER SITES: 157 N = 202 (ACNE REPORTED) 2. ACNE. OTHER SITES: 156 N = 198 (ACNE REPORTED) Physical Examination Data All physical examination data were described using a diagnostic checklist, and abnormalities were annotated on a full body diagram. Color photographs were obtained at the dermatologist's discretion, and 14 lesions were biopsied. Of the 14 biopsies collected from 11 patients, none were suggestive of chloracne. No cases of chloracne were diagnosed. Histologic descriptions of these biopsies are presented in Table XV-4. XV- �Table XV-4 BIOPSY RESULTS Number Histologlc Description Active degeneration Inclusion cysts Epidermal cysts Basal cell carcinoma Intradermal melanosis Seborrheic keratosis Pigmented nevus Psoriasiform dermatitis Chronic inflammation Insect bite 3 2 2 1 1 1 1 1 1 1 The five most common diagnoses and the P value for group differences are shown in Table XV-5. Abnormal skin findings were prevalent but almost identical in both groups (i.e., 45.0/& in Ranch Handers, and 44.9% in the comparisons; P = 0.97). Only for the miscellaneous diagnoses of "Other Abnormalities" (which included 15 diagnostic categories) was there a statistically significant group difference, with the comparisons having more disease than the Ranch Handers. Table XV-5 PREVALENCE OF DERMATOLOGIC DIAGNOSES IN PERCENT Diagnoses Comedones Acneiform lesions Acneiform scars Cysts Hyperpigmentation Other abnormalities Any abnormality Ranch Hand N = 1045 21. 18. 11, 11. 8. 12.6 Comparison N = 773 20.7 17.5 10.4 10.5 7.1 16.3 44.9 P Value 0.60 0.66 0.57 0.46 0.35 0.03 0.97 Relative Risk 1.05 1.05 1.08 1.10 1.17 .77 1 .00 95$ Conf int (.87,1.26) (.85,1.29) (.82,1.43) (.84,1.46) (.84,1.65) (.81, .98) (.90,1.11) Based upon the four most prevalent diagnoses in Table XV-5 (comedones, acneiform lesions, acneiform scars, and dermal cysts), all of which should encompass the diagnostic possibility of chloracne, a dermatologic index was constructed for each study participant. A score of zero was given if none of the four lesions were noted, and a score of 1 was assigned if one lesion was diagnosed, etc. These data are displayed in Table XV-6. XV-5 �Table XV-6 DERMATOLOGIC INDEX SCORK BY GROUP Grout 0 Number % 1 Number % Ranch Hand (N = 1045) 633 60.6 23*1 22.4 Comparison (N = 773) 487 63.0 157 Scores 2 Number % 20.3 3 Number % 4 Number % 124 11.9 42 4.0 12 1. 12.3 27 3.5 7 0.9 95 P = 0.74 The distributions of these scores did not differ significantly, suggesting a similar crude clinical severity between the groups. 3. Questionnaire - Examination Correlations The dermatologic index was contrasted to the historical occurrence of acne by group. These data are shown in Table XV-7. Table XV-7 DERMATOLOGIC INDEX IN PERCENT BY QUESTIONNAIRE HISTORY OF ACNE BY GROUP Score 2_ 3. _4_ 21.4 18.1 9.4 9.6 2.4 2.6 0.5 0.6 • 0.72 55.3 55.1 25.1 21.8 13.4 17.7 4.5 4.1 1.7 1.4 0.84 47.3 48.4 23.2 26.6 17.7 16.9 8.9 6.4 3.0 1.6 0.82 History Group No Acne Ranch Hand Comparison 66.3 69.1 Acne S1961 Ranch Hand Comparison Acne >1961 Ranch Hand Comparison 0 1 XV-6 P Value �These data show that the dermatologic index does not differ significantly by group for any historical subset. And, as can be observed in Table XV-7, there is a positive association between the history (and time) of acne and the dermatologic index, regardless of group membership. An additional analysis of the dermatologic index for each individual who reported acne after his SEA tour (post-SEA only) did not reveal significant Ranch Hand-comparison differences (P = 0.50). 4. Exposure Index Analyses Several comparisons were made using the exposure index and both historical and examination findings in the Ranch Hand group. Two historical parameters (incidence of acne and severity of acne) and the dermatologic examination findings were contrasted to the exposure index after stratifying for occupational categories by log-linear models. The historical-exposure analyses were essentially negative. Major dermatologic lesions from the examination were contrasted to the exposure index by occupational category. This analysis is presented in Table XV-8. XV-7 �Table XV-8 PERCENTAGE OF SPECIFIC SKIN LESIONS IN RANCH HANDERS BY EXPOSURE LEVEL BY OCCUPATIONAL CATEGORY (POST 1961 DATA ONLY) Exposure Level Low Medium High Condition Qcoupational Group P Value All skin abnormalities Officers Enlisted Flying Enlisted Ground 57.1 22.2 14.3 16.7 39.5 35.8 21.4 60.0 25.0 0.20 0.17 0.40 Comedones Officers Enlisted Flying Enlisted Ground 14.3 22.2 57.1 50.0 18.6 24.5 21 .4 20.0 31.2 0.91 0.42 0.45 Acneiform Lesions Officers Enlisted Flying Enlisted Ground 0 33.3 57.1 16.7 37.2 22.6 50.0 20.0 37.5 0.08 0.23 0.21 Acneiform Scars Officers Enlisted Flying Enlisted Ground 28.6 1 1 . 1 71.4 50.0 10.9 28.3 21 .4 40.0 31 .2 0.68 0.53 0.57 Inclusion Cysts Officers Enlisted Flying Enlisted Ground 14.3 0 14.3 50.0 18.6 18.6 14.3 20.0 27.1 0.49 0.32 0.53 Hyperpigmentation Officers Enlisted Flying Enlisted Ground 0 11.1 14.3 16.7 9.3 15.1 7.1 0 3.1 0.72 0.64 0.20 Thus, of the 18 exposure analyses, none were statistically significant (although based upon small sample sizes). Similarly, the relationship between the dermatologic index and exposure index was explored. For all three occupational categories, the dermatologic index showed no significant correlation to the exposure index, as reflected in Table XV-9. XV-8 �Table XV-9 RANCH HAND DERMATOLOGIC INDEX IN ALL OCCUPATIONAL CATEGORIES BY THE EXPOSURE INDEX (POST 1961 DATA ONLY) Exposure Level Dermatologic Index > 1 0 Number Percent Number Percent Low 26 45.6 31 54.4 Medium 28 41.2 40 58.8 High 20 39.2 31 60.8 P 5. - 0.78 Summary A comprehensive dermatologic assessment was conducted by questionnaire and physical examination. The questionnaire data revealed that the incidence of past acne, its time of occurrence relative to the individual's SEA tour(s), its severity and duration, and its anatomic location did not significantly differ between the Ranch Hand and comparison groups. No cases of chloracne were diagnosed at physical examination or by biopsy. No group differences were noted for the five most prevalent dermatologic diagnoses. The category, other abnormalities (containing 15 dermatologic conditions), was significantly larger for the comparison group than for the Ranch Hand group. However, when all skin abnormalities were considered, the group rates were essentially identical. A dermatologic index was constructed to account for the number of skin abnormalities per individual (severity index) that might encompass a diagnosis of chloracne. The index was not associated with group membership but showed some correlation with a total history of past acne in both groups. There were no associations between historical or dermatological examination findings and exposure level in any occupational category of the Ranch Hand group. XV-9 �Chapter XVI-1 CARDIOVASCULAR EVALUATION 1. Introduction The effects of Herbicide Orange and its dioxin contaminant on the cardiovascular system are not well defined. Both bradycardia and tachycardia have been suggested in acute heavy exposures to the 2,4-D and 2,^,5-T components, but the cardiovascular effects following chronic low dose exposure are essentially unknown. The thrust of this cardiovascular evaluation has been to collect important data by questionnaire, physical examination, and laboratory testing, that would identify Ranch Hand-comparison group differences after accounting for the effects of confounding variables. Of the well-established risk factors for cardiovascular disease, smoking, cholesterol level or cholesterol to high density lipoprotein (HDL) ratio, and age were selected as covariates in most analyses (Brand et al, 1976). The covariates were categorized as follows: age, S^O, ^0 years 1 month - 59 years 11 months (abbreviated HO < > 60), and 60 years or more; smoking, 0 pack-years, 1-10 pack-years, and 11 or more pack-years; cholesterol, S180 mg/dl, 181-279 mg/dl, and S280 mg/dl; and cholesterol-HDL ratio, <5.3» £5.3. In complex analyses with sparse data, trichotomous covariates were reduced to dichotomous ones. The outpoint for cholesterol-HDL ratio was derived from data on rated Air Force personnel referred for cardiovascular diagnostic examination; it is an unweighted average of means of flyers verified at cardiac catheterization as having or not having occlusive coronary atherosclerosis. A more optimal approach, based upon a median HDL value of the comparison group, will be used in subsequent reports. Statistically significant interactions between these covariates were not explored in detail when there was no effect on group membership and when the interactions were consonant with the classical epidemiology of cardiovascular disease. Analyses of weak risk factors in the data will be presented in subsequent reports. Because of the low proportion of Black participants in both groups, covariate adjustment by race was not possible. Consequently, a variety of dependent variable analyses by race, unadjusted for age, smoking, and cholesterol, are discussed throughout this chapter. In addition, where adjusted group differences were found to be statistically significant, other covariates (e.g., percent body fat, current smoking, history of intermittent claudication, testosterone level, differential cortisol level, etc.) have been used to reanalyze all data in an attempt to clarify the clinical significance of the finding. Most analyses herein are based upon Ranch Hand contrasts to the "originals" of the comparison group. Where group associations are statistically significant or of general interest, other comparison group denominators have been used (e.g., matched originals only and the entire comparison group). Further, for specific analyses, participants with diabetes and pedal edema have been deleted. Small denominator fluctuations are also inherent in these analyses because of missing covariate or dependent variable information. Thus, tabular data may not be directly comparable between analyses because of the type of XVI-1-1 �covariate adjustment, or the denominator of the comparison group, or the deletion of certain medical conditions thought to confound a specific clinical diagnosis. In general, covariates having a nonsignificant association with the dependent variable were removed from the analysis. The statistical analyses are based on log-linear models (BMDP-4F), logistic regression (BMDP-LR), and generalized linear models, chi-square, t tests, and matched covariate analyses (Breslow, 1982). Relative risks and confidence intervals, computed using the hypergeometric distribution (Thomas, 1971) and the normal approximation (Fleiss, 1981), are shown for all dependent variables in Appendix XVIII. 2 * Central Cardiovascular System a. Sy s t o1ic Blood Pressure Abnormal systolic blood pressure was defined as pressure in excess of 140 mmHg by standard observer auscultation. All blood pressures were obtained in a sitting position. Second or third readings were recorded on those individuals who manifested an initial elevation. There was no significant difference in systolic blood pressure (P = 0.248) between the non-Black Ranch Hand and the non-Black original comparison group after adjusting for age, smoking, and cholesterol level. These data are reflected in Tables XVI-1-1 and XVI-1-2. Diabetics (2-hour postprandial glucose £120 mg/dl) were removed from the analyses. Table XVI-1-1 SYSTOLIC BLOOD PRESSURE RANCH HANDERS AND THE ORIGINAL COMPARISONS VERSUS AGE (NON-BLACKS ONLY) Ranch Hand Age Abnormal % Abnormal Normal Original Comparisons Abnormal % Abnormal Normal Total Both Groups Abnormal % Abnormal Normal <40 36 10.4 309 32 14.3 192 68 11.9 501 £40 113 23.1 377 94 24.6 288 207 23.7 665 Systolic pressure between groups: P = 0.248 Age versus systolic Relative risk under 40: .73,9555 Conf int ( . 4 6 , 1 . 1 8 ) pressure (unadjusted Relative risk over 40: .94, 95/5 Conf int (.73,1.20) for smoking and cholesterol): P <0.0001 The unadjusted systolic blood pressure by smoking history association, presented in Table XVI-1-2, is not significant (P-0.179) in these data. XVI-1-2 �Table XVI-1-2 SYSTOLIC BLOOD PRESSURE PARTICIPANTS BY SMOKING HISTORY (NON-BLACKS ONLY) Smoking History in Pack-Years Abnormal 0 1-10 >10 % Abnormal 17.8 16.1 20.8 70 44 161 Normal 324 230 612 0.179 Ranch Handers and original comparisons reflected in these tables were also compared on systolic blood pressure as a continuous variable with adjustment for age, smoking history, HDL ratio, and body fat, via a general linear model. There was no significant difference between the groups on systolic blood pressure (P » 0.976). The Ranch Hand and original comparison adjusted means were 133.12 and 133.15, respectively. The covariates of age and body fat were both significantly associated with systolic blood pressure (P = 0.0001). Additional categorical analyses comparing Non-Black Ranch Handers with the total non-Black comparison group adjusted for age, smoking, and cholesterol showed comparable nonsignificant intergroup differences (P = 0.366) for systolic blood pressure. The effects of age and smoking were statistically significant, P <0.0001 and P = 0.04, respectively. In addition, a chi-square analysis of Black Ranch Handers and Black individuals from the entire comparison group (diabetics removed) showed no group difference (P = 0.265) in systolic pressure. b. Diastolic Blood Pressure Diastolic blood pressure in excess of 90 mmHg was categorized as abnormal. No significant intergroup difference was noted after adjustment for age, smoking, and cholesterol level. These data are based upon non-Black, nondiabetic denominators and are presented in Table XVI-1-3. XVI-1-3 �Table XVI-1-3 DIASTOLIC BLOOD PRESSURE IN RANCH HANDERS AND THE ORIGINAL COMPARISONS VERSUS AGE (NON-BLACKS ONLY) Ranch Hand Age Abnormal %_ Abnormal Normal <40 18 >40 57 5.2 Original Comparisons Abnormal % Abnormal Normal Total Both Groups Abnormal % Abnormal Normal 327 12 5.4 212 30 5.3 539 11.6 433 53 13.9 329 110 12.6 762 Diastolic blood pressure P = 0.351 between groups: Relative risk under 40: .97,95? Conf. int. (.45,2.18) Relative risk over 40: .84,95? Conf. int. (.58,1.21) Age versus diastolic pressure (unadjusted for smoking and cholesterol): P <0.0001 The Ranch Handers and original comparisons (as represented in Table XVI-1-3) diastolic blood pressure was also compared as a continuous variable with adjustment for age, smoking history, HDL ratio, and body fat, via a general linear model. There was a borderline significant diastolic blood pressure by group by age interaction (P = 0.0585), indicating a change in the blood pressure by group association with level of age (<40, £40). However, separate analyses at each level of age revealed no significant group differences. In the under-40 age group, the diastolic blood pressure by group association was not significant (P = 0.435); the adjusted group means were 78.2 and 77.02 for Ranch Handers and comparisons, respectively. In the 40-and-over age group, the diastolic blood pressure by group association was not significant (P = 0.904); the Ranch Hand and comparison adjusted means were 80.7 and 81.7, respectively. An intergroup log linear analysis of diastolic blood pressure for Blacks and non-Blacks using original comparisons showed comparable nonsignificant results (P = 0.573). Age was a significant covariate (P <0.0001) while the history of past smoking was not. An unadjusted contrast of Black Ranch Handers and Black individuals from the entire comparison group also showed similar nonsignificant group differences (P = 0.533). c. Electrocardiograms (ECG's) ECG's were obtained on all participants, following a minimum fast of 4 hours and abstinence from tobacco for 4 hours. The vast majority of ECG's were obtained by 1 or 2 technicians on dedicated and calibrated machines. The tracings were read by a contract clinic' cardiologist and categorized into normal and abnormal groups, the latter consisting of right bundle branch block, left bundle branch block, nonspecific T wave changes, bradycardia, tachycardia, and XVI-1-4 �other diagnoses. Grave findings were immediately discussed with the participant's family physician and appropriate follow-up was arranged. As shown in Table XVl-1-4, abnormal EGG findings were not associated with group membership (P = 0.987). For both the non-Black Ranch Hand and original comparison groups, there was a highly statistically significant (P <0.0006) association between abnormal ECG's and increased age. Table XVI-1-4 EGG FINDINGS IN RANCH HANDERS AND THE ORIGINAL COMPARISONS BY AGE, ADJUSTED FOR SMOKING HISTORY AND HDL RATIO (NON-BLACKS ONLY) Ranch Hand Age Abnormal % Abnormal Normal Original Comparisons Abnormal % Abnormal Normal Total Both Groups Abnormal % Abnormal Normal <40 69 20.1 274 51 23.1 170 120 21.3 444 >40 148 30.2 342 107 28.4 269 255 29.4 611 Abnormal ECG findings between groups: P = 0.987 EGG findings in both Relative risk under 40: .87,95% Conf. int. (.62,1.23) groups by age (unRelative risk over 40: 1.06,95$ Conf. int. (.86,1.32) adjusted for smoking and HDL ratio): P = < 0.0006 When the ECG data in Table XVI-1-4 were redistributed into the categories of tachycardia, bradycardia, other abnormalities, and normal, an unadjusted analysis showed no significant differences between the Ranch Hand and original comparison group (P = 0.881). An additional cardiac assessment was made on all past or present flying personnel in both groups. Participants' names and social security numbers were computer matched to the USAF ECG Repository, the world's largest ECG repository on flying personnel (Lancaster and Ord, 1972; Hiss and Lamb, 1962). Three hundred and fifty-four Ranch Handers and 282 original comparisons had between one and 10 previous tracings on file which had been diagnostically coded by stringent criteria. Accordingly, USAF cardiologists reviewed all 636 physical examination ECG's (without knowledge of group membership) and coded them by the standardized USAF criteria. The physical examination ECG was contrasted to the past ECG's and categorized as no change or degraded (no ECG's were improved in either group). These data analyzed by group membership and age are shown in Table XVI-1-5. Blacks and diabetics were removed from the analysis. This analysis is not adjusted for elapsed time between ECG readings. XVI-1-5 �Table XVI-1-5 CLINICAL COMPARISON OF CURRENT EGG'S TO PAST EGG'S IN FLYING PERSONNEL BY GROUP MEMBERSHIP AND AGE (NON-BLACKS ONLY) Age Comparison Ranch Hand Total Degraded No Change No Change Degraded No Change Degraded Number Number Percent Number Number Percent Number Number Percent <40 45 2 4.2 29 2 6. 4 74 >40 226 271 20. 22 8. 1 182 211 17 19 8.5 408 482 4 ' 5.1 37 41 8.3 Because of sparse data in the under-40 age group, an analysis adjusted for both age and smoking was not possible; the unadjusted ECG change by group association was not significant (P = 0.652). In the 40-and-over age group, the ECG change by group association was not significant (P = 0.939), adjusted for smoking history. The smoking history covariate was borderline significant, P = 0.0852. In both the Ranch Hand and comparison groups combined, the age by ECG association (P = 0.412) was not significant. The unadjusted ECG change by smoking history association was significant (P = 0.018). An overall analysis of systolic/diastolic blood pressures and ECG abnormalities was performed by group membership and adjusted for smoking (0, 1-10, >10 pack-years), cholesterol-HDL ratio «5.3, S5.3), age «40, £40) and differential cortisol level (continuous); Blacks and diabetics were omitted. The differential cortisol level is defined as the 7:30 AM cortisol measurement minus the 9:30 AM cortisol measurement. A logistic regression analysis showed similar nonsignificant results (as in Sections a-c above) that are presented in Table XVI-1-6. Table XVI-1-6 RANCH HAND AND ORIGINAL COMPARISON GROUP CONTRAST FOLLOWING ADJUSTMENT FOR AGE, SMOKING, CHOLESTEROL-HDL RATIO, AND DIFFERENTIAL CORTISOL RESULTS (NON-BLACKS ONLY) Dependent Variable P Value Systolic Blood Pressure Diastolic Blood Pressure ECG Abnormality 0.195 0.351 0.999 XVI-1-6 �d. Heart Sounds All valvular sound abnormalities were recorded following detailed auscultation. Fourth heart sounds were considered abnormal. If the participant indicated that the heart sound abnormality was a new finding, the diagnostician confirmed the abnormality. A review of the heart sound abnormalities in the non-Black Ranch Handers and original comparisons revealed that the data were too sparse for a fully adjusted analysis. An unadjusted group comparison was nonsignificant (P = 0.414), as was the unadjusted effect of age (P = 0.375). Similarly, an unadjusted analysis of Black Ranch Handers and comparison individuals did not demonstrate statistical significance (P = 0.799). A combined race and fully adjusted (age, smoking, cholesterol level) analysis of Ranch Handers and the entire comparison group is presented in Table XVI-1-7. These data also show no group differences (P «= 0.592) but do reflect a significant association of heart sound abnormalities and increasing age (P <0.002). Table XVI-1-7 HEART SOUND ABNORMALITIES IN BLACK AND NON-BLACK RANCH HANDERS AND ALL COMPARISONS BY AGE Ranch Hand Age Abnormal % Abnormal Normal <40 5 40060 11 >60 2 1.3 2.3 11.1 367 476 16 Comparison Abnormal % Abnormal Normal 8 15 2 1.9 2.7 8.3 Abnormal heart sounds between groups: 3. 417 542 22 Total Both Groups Abnormal % Abnormal Normal 13 26 4 1.6 2.5 9.5 784 1018 38 P = 0.592 Heart sound abnormalities in both groups by age: P < 0.002 Peripheral Cardiovascular System The status of the peripheral cardiovascular system was evaluated by ophthalmoscopic examination of the eyegrounds for arterial-venous nicking and hemorrhages, auscultation of the carotid arteries, and bilateral palpation for the presence and quality of 5 peripheral pulses. The finding of a bilateral abnormality (e.g., bruits in both carotid arteries) was scored as 1 abnormality. Diminished or absent peripheral pulses were both designated as abnormal. While there is clearly recognized misclassification of the specific causes for the examination findings, it is judged to be of a minor nature; thus, the examination findings are deemed to be generally indicative of the presence XVI-1-7 �or absence of severe arteriosclerosis. Abdominal x-rays to confirm the severity of the peripheral vessel arteriosclerosis were not obtained because of the possible impact of detected asymptomatic or clinically irrelevant kidney stones upon the flying status of active pilots. a. Eyegrounds Abnormal funduscopic findings were not associated with group membership (P = 0.965), but were highly correlated with increased age (P < 0.0001), as reflected in Table XVI-1-8. The additional covariates of smoking history and cholesterol-HDL ratio were nonsignificant in the analysis. Table XVI-1-8 FUNDUSCOPIC ABNORMALITIES IN RANCH HANDERS AND ORIGINAL COMPARISONS BY AGE (NON-BLACKS ONLY) Ranch Hand_ Age Abnormal % Abnormal Normal _ Comparison_ Abnormal % Abnormal Normal Total _ Both Groups _ Abnormal % Abnormal Normal 8 2.3 333 6 2.7 214 14 2.5 547 42 <40 8.7 441 31 8.4 339 73 8.6 780 Funduscopic abnormalities between groups: P = 0.965 Funduscopic abnormalRelative risk under 40: .86,95? Conf. int. (.26,2.97) ities in both groups Relative risk over 40: 1.04,95? Conf. int. (.65,1.67) by age (unadjusted for smoking and cholesterol-HDL ratio) P <0.0001 An unadjusted contrast of Black Ranch Handers and Black individuals from the entire comparison group showed similar nonsignificant results (P = 0.860). b. Carotid Bruits The prevalence of carotid bruits in both groups combined was 1.47/5. Because of sparse data, an unadjusted analysis comparing non-Black Ranch. Handers with non-Black original comparisons was performed; the group by carotid bruits association was nonsignificant (P = 0.269), as was the unadjusted age by carotid bruits association (P = 0.353). However, the larger analysis of both Black and non-Black Ranch Handers with the entire comparison group showed a group membership association of interest (P = 0.183) and a significant relationship between bruits and increasing age (P = 0.03). XVI-1-8 �c. Peripheral Pulses The absence or diminished quality of 5 peripheral pulses was determined by detailed clinical palpation. One or more abnormal pulses were found in 12.8%(106/829) of the non-Black Ranch Handers as contrasted to 9.4$ (56/596) in the non-Black original comparisons (P = 0.05) giving an unadjusted relative risk of 1.36 with a 95% confidence interval (.99, 1.88). The reader is referred to Appendix XVIII for complete relative risks and confidence intervals. Data on specific pulses are presented in Table XVI-1-9. The covariates of cholesterol-HDL ratio and percent body fat (<25%, S25/0 were noncontributory in all of the analyses. Thus, the pulse variables were adjusted for age «40, S40) and smoking (0, 1-10, >10 pack-years). Blacks, diabetics, and individuals with peripheral pitting edema were omitted from the analysis. Since most abnormalities were concentrated in the over 40 and > 10 pack-year group, these data were re-analyzed on that subset with the results shown in column three of Table XVI-1-9. Table XVI-1-9 SUMMARY OF PERIPHERAL PULSE QUALITY: RANCH HANDERS AND ORIGINAL COMPARISONS (NON-BLACKS ONLY) Pulse Examined,- Unadjusted P Value Number of and Direction of Participants Group Abnormalities Unadjusted P Value for Age ^40 Years and >10 Pack-Years Unadjusted P Value Age Versus Pulse (Groups Combined) Radial N = 1414 0.147 (RH > C) Sparse Data 0.668 Femoral N = 1414 0.147 (RH > C) 0.117 (RH > C) 0.157 Popliteal N = 1414 0.0255 (RH > C) 0.0159 (RH > C) 0.0065 0.0375 0.0003 Dorsalis Pedis N = 1413 Posterior Tibial N • 1413 0.0644 (0.0406)* (RH > C) 0.312 (0.250)* (RH > C) (RH > C) 0.123 (RH > C) *Adjusted for age and smoking XVI-1-9 0.0022 �Although only two pulses reached statistical significance (P 50.05) in Table XVI-1-9, the consistent directional findings in all peripheral pulses were sufficient to merit additional clarifying analyses. Further, these directional findings were present after accounting for diabetes and the clinically confounding physical effects of peripheral pitting edema and obesity. Accordingly, various aggregates of pulses were constructed to determine more precisely the anatomic patterns of the abnormalities. This approach, adjusted by age and smoking history, is displayed in Table XVI-1-10. Table XVI-1-10 SUMMARY OF PERIPHERAL PULSE ABNORMALITY COMBINATIONS: RANCH HANDERS AND ORIGINAL COMPARISONS ADJUSTED BY AGE AND SMOKING HISTORY (NON-BLACKS ONLY) Pulse Abnormalities Combination Adjusted P Value and Direction of Group Abnormalities Unadjusted P Value Age Versus Pulse Combination Leg Pulses* (Femoral, Popliteal, Dorsalis Pedis, Posterior Tibial) 0.03.02 (RH > C) 0.0001 All Pulses (Carotid, Femoral, Radial, Popliteal, Dorsalis Pedis, Posterior Tibial) 0.0257 (RH > C) 0.0005 Peripheral Pulses (Radial, Femoral, Popliteal, Dorsalis Pedis, Posterior Tibial) 0.0235 (RH > C) 0.0002 *In nondiabetic, non-Black, Ranch Handers and the original comparisons, leg pulses were associated with a history of intermittent claudication (P = 0.0113), and this association was the same in both groups (P = 0.962). The data in Table XVI-1-10 did not point to specific anatomic groupings but rather suggested a generalized phenomenon. As a result of this finding, the pulse data were reanalyzed using testosterone and differential cortisol results as new covariates. No substantial change in the significance of the pulse findings was observed. In order to provide a complete approach to the peripheral pulse findings, 2 supplemental contrasts using other denominators were performed: 1) an analysis of both Black and non-Black Ranch Handers versus Black and non-Black comparisons from the entire comparison group, adjusted for XVI-1-10 �age, smoking history in pack-years, and cholesterol level; and 2) an unadjusted analysis of Black Ranch Handers versus Black comparisons from the entire comparison set. The data from these analyses are presented in Table XVI-1-11. Table XVI-1-11 SUMMARY OF PERIPHERAL PULSE QUALITY: ALL RANCH HANDERS VERSUS ALL COMPARISONS*, ASSOCIATION OF AGE, UNADJUSTED CONTRAST OF BLACK RANCH HANDERS AND BLACK COMPARISONS Blacks and Non-Blacks P Value and Direction of Pulse Examined, Group Abnormalities Number of Participants Blacks Only P Value of Age Association Both Groups** Unadjusted P Value Radial N = 1884 0.047 (RH > C) 0.012 0.890 Femoral N = 1882 0.134 (RH > C) 0.007 0.219 Popliteal N = 1883 0.0174 (RH > C) <0.001 0.219, Dorsalis Pedis N = 1881 0.006 (RH > C) <0.001 0.789 Posterior Tibial N = 1882 0.067 (RH > C) <0.001 0.557 *Adjusted for age, smoking, and cholesterol level **Unadjusted for smoking and cholesterol The data in Table XVI-1-11 are thus corroborative of diminished pulse quality in the Ranch Hand group. These data also weakly suggest that the Ranch Hand - comparison pulse differences may be aggregated in the non-Black population (or may be spurious due to small sample size). A matched pair analysis (matching variables: age, job, race) of data sets for 3 pulses (see Table XVI-1-9), adjusting for percent body fat and smoking history, are shown in Table XVI-1-12. Due to sparse data, only main effects were included in these analyses. XVI-1-11 �Table XVI-1-12 MATCHED PAIR ANALYSIS FOR THREE PERIPHERAL PULSES: RANCH HANDERS VERSUS ORIGINAL COMPARISONS (NON-BLACKS ONLY) Pulse Variables P Value and Direction of Group Abnormalities Popliteal Pulse 0.053 (RH > C) Dorsalis Pedis 0.050 (RH > C) Posterior Tibial 0.081 (RH > C) Thus, the data in Table XVI-1-12 reaffirm the overall finding of significant peripheral pulse deficits in the Ranch Hand group. *(. Risk Factors in Central and Peripheral Cardiovascular Disease This section emphasizes cardiovascular disease relationships that are highlighted by significant risk factors or combinations of risk factors identified in the preceding sections or in the general literature. a. Cholesterol and HDL Cholesterol Nondiabetic non-Black Ranch Handers and the non-Black original comparisons were contrasted for continuous cholesterol and HDL levels via a general linear model, adjusting for age (<40, S^O), smoking history (0, 1-10, >10 packyears), and body fat (<25%, £25%). Although no group membership differences were found for cholesterol and HDL, several of the covariates were of profound influence. These data are shown in Table XVI-1-13. XVI-1-12 �Table XVI-1-13 CHOLESTEROL AND HDL IN RANCH HANDERS AND ORIGINAL COMPARISONS (NON-BLACKS ONLY) Adjusted Ranch Hand - Comparison P Value Age Cholesterol 0.355 0.038 0.002 0.919 HDL 0.178 0.788 0.028 0.0001 Dependent Variable Covariate P Values Smoking Body Fat Similar results were found in the contrast of nondiabetic Blacks. Because of small sample size, covariate adjustment was not possible. The contrasts were made by t tests and the results are shown in Table XVI-1-14. Table XVI-1-14 CHOLESTEROL AND HDL RESULTS IN RANCH HANDERS AND ORIGINAL COMPARISONS (BLACKS ONLY) IN Ranch Hand Standard Mean Deviation N Comparison Standard Mean Deviation Cholesterol 49 214.3 34.6 37 209.8 41 .3 0.595 HDL 49 55.5 17.2 37 52.4 14.6 0.375 P Value b. Age, Past Smoking, Current Smoking Risk Factors Several analyses have shown the substantial effects of age and smoking on the cardiovascular system. Because of the unknown influence of antismoking campaigns in recent years on Air Force personnel, the covariate of smoking history (0, 1-10, >10 pack-years) may not be fully appropriate, particularly if smoking ceased several years before the examination. Consequently, all dependent variables were reanalyzed for group differences restricting to older (>40), heavy past smokers (>10 pack-years), adjusted for current smoking (yes, no). These contrasts are presented in Table XVI-1-15. Blacks and diabetics were removed for the analysis. XVI-1-13 �Table XVI-1-15 RANCH HANDERS AND ORIGINAL COMPARISONS ADJUSTED FOR CURRENT SMOKING (NON-BLACKS, > 10 YEARS, > 10 PACK YEARS ONLY) Dependent Variable(s) P Value and Direction of Group Significance V Systolic Blood Pressure Diastolic Blood Pressure ECG Abnormalities Heart Sound Abnormalities Eyegrounds Carotid Bruits Radial Pulse Femoral Pulse Popliteal Pulse Dorsalis Pedis Pulse Posterior Tlbial Pulse All Pulses Leg Pulses 0.571 0.350 0.322 0.833 0.628 0.026 0.258 0.033 0.001 0.002 0.051 0.002 0.003 RH > C RH RH RH RH RH RH > > > > > > C C C C C C These specific data, when compared to the broader previous analyses in Table XVI-1-9, show decreasing P values. In addition, there is a suggestion that the peripheral pulse deficits are targeted in the older heavy smokers who are currently still smoking. c. Reported and Verified Heart Disease All participants were asked 2 questions during the in-home interview that were intended to capture a history of heart disease. The questions were: "Did you ever have a heart condition?" and "Did you ever have any other major health condition?" All affirmative responses were medically coded by the International Classification of Diseases, 9th Edition, Clinically Modified (ICD CM). Twenty-seven distinct cardiac classifications were identified for the Ranch Hand group and 19 were found in the comparison group. Medical records were sought on all of these individuals in order to verify the reported conditions. Table XVI-1-16 summarizes the verification results for the specific question on past heart disease. XVI-1-14 �'t ,,,a' Table XVI-1-16 MEDICAL RECORD VERIFICATION OF REPORTED HEART DISEASE Ranch Hand Group Original Comparison Group Number of reported cardiac conditions 139 Medical Records Reviewed 117 ?96 '•''fe.i -81 Medical Records Pending -22 ^tf- % Cardiac Conditions Verified 82.9 85.2 % Cardiac Conditions Unsupported 17.1 !l^«8 Overall, these data show a high confirmation proportion of reported cardiac conditions. Since Table XVI-1-16 does not include :results from the second overlapping question (Other major conditions?) and siri&%:individuals may have multiple heart disease responses, the following analyses have different numerators and denominators. All Ranch Handers (diabetics, Blacks, edemics included;) were contrasted to the original comparisons for reported heart disease and reported heart attacks. This analysis was supplemented by an analysis on verified heart disease and heart attacks; all these data are summarized in Table XVI-1-17. The unadjusted relative risk and 95% confidence interval for verified heart disease are 1.00 and (.79, 1.27). Table XVI-1-17 f : f."f RANCH HAND AND ORIGINAL COMPARISON GROUPS VERSUS REPORTED AND VERIFIED HEART DISEASE AND HEART:ATTACKS Heart Disease Parameter Ranch Hand Yes ^Jo Comparison Yes |> k Reported Reported Verified Verified 181 10 1 47 7 136 4 109 3 Heart Heart Heart Heart Disease Attack Disease Attack 864 1035 898 1038 XVI-1-15 ' 637 769 664 770 ; P Value 0.878 0.296 0.982 0.432 �While the lack of group differences in Table XVI-1-17 is of interest, and the good agreement between subjective responses and medically verified responses is notable, additional covariate analyses were conducted to rule out any hidden effect of a risk factor interaction that might be associated with group membership. Thus, Ranch Handers and their comparisons were again contrasted for reported heart disease and verified heart disease, adjusting for the covariates of age, smoking, body fat or HDL. As age was confounding for both reported and verified disease, the analyses are age specific. Further, there are significant interactions between smoking, group membership, and disease; these findings are shown in Table XVI-1H8. Table XVI-1-18 RANCH HAND AND ORIGINAL COMPARISON GROUP: COVARIATE ANALYSES OF REPORTED AND VERIFIED HEART DISEASE Adjusted Intergroup P Value and Direction of Association Parameter and Covariates Reported Heart Disease:* Body Fat, smoking <40 **£40, less than 10 pack-years >40, greater than 10 pack-years 0.530 0.0038 0.139 (RH = C) (RH < C) (RH = C) 0.506 0.008 0.0712 (RH = C) (RH < C) (RH > C) Verified Heart Disease* HDL, smoking <40 , less than 10 pack-years , greater than 10 pack-years *Age confounding variable **Group "- heart disease - smoking interaction: P = 0.0054 ***Group - heart disease - smoking interaction: P = 0.004? These data, in contrast to Table XVI-1-17, demonstrate associations of significance. Young Ranch Handers are equivalent to their young comparisons for both reported and verified heart disease; whereas, the older Ranch Handers smoking more than 10 pack-years are manifesting more verified heart disease than their counterparts. Conversely, older Ranch Handers smoking less than 10 pack-years are faring significantly better than their comparisons for both reported and verified heart disease. These associations, in light of essentially negative blood pressure and ECG findings at the physical examination, XVI-1-16 �could be speculatively attributed to a wide array of post hoc explanations: e.g., a true disease process that will evolve more clearly in the future, an enigmatic finding akin to the peripheral pulse deficits, chance, etc. d. Cardiovascular Examlnation Findings and Verifled Hlstorrloalr. Heart Disease The cardiovascular examination findings were contrasted to the history of cardiovascular disease as verified by detailed medical record review. The purposes of this analysis were to determine the degree of positive correlation between the examination and the past medical history, and to determine if peripheral pulse abnormalities were associated with known cardiovascular disease. These data are presented in Table XVI-1-19. Table XVI-1-19 ASSOCIATION OF CENTRAL AND PERIPHERAL CARDIOVASCULAR ABNORMALITIES WITH VERIFIED HEART DISEASE BY AGE: RANCH HANDERS VERSUS ORIGINAL COMPARISONS* (NON-BLACKS ONLY) Dependent^Variable P Value (Unadjusted) Dependent Variable l^^H^J^^^Ili^lJiE^^JPA?.®3^. Systolic Blood Pressure Diastolic Blood Pressure Electrocardiogram Heart Sounds Carotid Bruits Radial Pulse Femoral Pulse (£40) Posterior Tibial Pulse (>40) Popliteal Pulse (£40) Dorsalis Pedis Pulse (£40) All Pulses «40) (£40) Peripheral Pulses «40) (£40) Leg Pulses «40) (£40) <0.00001 <0.00001 <0.00001 0.292 0.084 0.023 0.14? 0.103 0.074 0.002 0.0004 ._ --..„ °-°007 n nno° °2 ' 03 *Pitting edema omitted for pulse analyses XVI-1-17 P Value (Adjusted for Age) Ranch Hand VersusComparison 0.229 0.391 0.875 0.316 0.223 0.152 0.104 0.082 0.022 0.094 °'205 0.0691 0.261 0.048 0.369 0.044 �Systolic, diastolic blood pressure and EGG abnormalities at physical examination showed exceptionally significant (P = 0) associations with medical record histories of cardiac disease, regardless of group membership or age. While moderately positive associations are to be expected, the unusual strength of the associations suggests that very few new cases of hypertension or EGG abnormalities were diagnosed at examination, reflecting perhaps, up-to-date medical records due to the overall medical sophistication and free access to medical care by most members of both groups. The association of carotid bruits and previously diagnosed cardiovascular disease was marginally positive but based upon small numbers. Table XVI-1-19 was most revealing for the peripheral pulse abnormalities. For the radial pulse, the data were too sparse for age adjustment but for all other pulse abnormalities, age was confounding, primarily due to a relative lack of abnormalities in the under-40 age group. A remarkably consistent observation in the 40-and-older age group was that significant or borderline significant Ranch Hand - comparison differences were found almost exclusively in those individuals without a history of cardiovascular disease. This uniform pattern is best exemplified by the popliteal pulse data, as shown in Table XVI-1-20. Table XVI-1-20 ASSOCIATION OF POPLITEAL PULSE ABNORMALITIES WITH VERIFIED HISTORY OF CARDIOVASCULAR DISEASE BY AGE AND GROUP MEMBERSHIP* History of Cardiovascular D i sease Group Membership Popliteal Pulse Findings in £40 Age Group Abnormal Normal Yes (Verified by record review) Ranch Hand Comparison 2 2 68 59 No Ranch Hand Comparison 11 0 404 313 Popliteal pulse by disease history: P = 0.074 Popliteal pulse by disease by group interaction: P = 0.022 *No pulse abnormalities in <40 group Interpretation of this intriguing finding at the baseline physical examination is not clear. The fact that the abnormal pulses, regardless of group membership, are associated with increased age, heavy past smoking, current smoking (and possibly race), and verified past heart disease and are largely substantiated by the use of 3 related denominators suggest that the finding is real rather than spurious. While there was most likely a tendency to diagnose additional abnormal pulses, given the first abnormal pulse, this XVI-1-18 �possible examination bias would not likely aggregate in the Ranch Hand group (because of the blind examination) nor in individuals without a history of prior cardiovascular disease. The speculative interpretation of concern is that the finding of substantial "subclinioal" peripheral pulse abnormalities (i.e., without a history of past cardiovascular disease) in the Ranch Handers may be a precursor to either clinically manifest arterial disease or central cardiovascular abnormalities. This possibility will receive detailed attention at the first follow-up examination because an analysis of onset times for verified heart disease (adjusted for race, occupation, and age) did not show a significant difference between the Ranch Hand and comparison group (P = 0.395). This finding suggests that if the observed pulse abnormalities are a precursor to central cardiovascular disease, this pathogenesis is not manifested by premature heart disease at this time. 5. Exposure Index Analyses All of the dependent variables within the Ranch Hand group were compared to the exposure index. Systolic and diastolic blood pressure elevations, and EGG, heart sound, and eyeground abnormalities were adjusted for age (<40, £40). The peripheral pulse analyses were not age adjusted because of sparse data; subjects with peripheral pitting edema were omitted from these comparisons. The exposure index was stratified into 3 categories: low, medium, and high. All analyses were performed on each of 3 occupational categories: officer, flying enlisted, and ground enlisted. This analysis is presented in Table XVI-1-21. Separate age analyses were performed when age was found to be a confounding variable. When some data were too small for valid analysis, the word sparse is written instead of a P value. Table XVI-1-21 SUMMARY OF EXPOSURE INDEX ANALYSES WITHIN THE , RANCH HAND GROUP* P Value Dependent Variable** Systolic Blood Pressure Occupation Adjusted for Age Age (***°Unadjusted for Age) <40 £40 Officer Flying Enlisted Ground Enlisted 0.731 Officer Flying Enlisted Ground Enlisted 0.313 EGG Officer Flying Enlisted Ground Enlisted 0.858 0.209 0.450 Heart Sounds Officer Flying Enlisted Ground Enlisted 0.397*** 0.395*** Diastolic Blood Pressure XVI-1-19 0.560 0.746 0.499 0.701 Sparse 0.739 0.567 0.214 0.255 0.638 �Table XVI-1-21 (Cont'd) SUMMARY OF EXPOSURE INDEX ANALYSES WITHIN THE RANCH HAND GROUP1 Dependent Variable** Eyegrounds OcGupatlon P Value Adjusted for Age Age (***=UnadJusted for Age) <40 £40 Officer Flying Enlisted Ground Enlisted 0.513 0.395*** Carotid Bruits Officer Flying Enlisted Ground Enlisted 0.616 0.992 0.094 Popliteal Pulse Officer Flying Enlisted Ground Enlisted Sparse 0.814 Dorsalis Pedis Pulse Officer Flying Enlisted Ground Enlisted 0.288 0.719 0.531 Posterior Tibial Pulse Officer Flying Enlisted Ground Enlisted 0.643 Sparse 0.654 All Pulses Officer Flying Enlisted Ground Enlisted 0.305 0.624 0.624 Peripheral Pulses Officer Flying Enlisted Ground Enlisted 0.338 0.784 0.746 Leg Pulses Officer Flying Enlisted Ground Enlisted 0.350 0.784 0.882 0.255 0.638 Sparse *Peripheral edema omitted for peripheral pulse analyses **Radial and femoral pulses omitted; data too sparse ***Unadjusted for age. The data in Table XVI-1-21 clearly indicate that there is no detectable association between the herbicide exposure index adjusted by occupational category and any of the cardiovascular variables. XVI-1-20 �6. Summary Central cardiovascular system abnormalities, as manifested by elevated systolic or diastolic blood pressure, abnormal ECG's, and abnormal heart sounds, showed no statistically significant Ranch Hand - comparison group differences, but did reflect a strong correlation to increased age and, to a lesser degree, heavy past smoking. The 3 risk factors of age, smoking, and cholesterol were strongly associated with each other. Unadjusted analyses of Blacks were essentially negative. The prevalence of funduscopic abnormalities and carotid bruits was not associated with group membership but was significantly dependent upon age. Abnormal peripheral pulses were associated with the Ranch Hand group. A series of detailed covariate analyses showed that pulse abnormalities, regardless of group membership, were associated with increased age (S^O years), heavy past smoking, current smoking, and a verified history of past cardiovascular disease. Substantial Ranch Hand pulse abnormalities were also found in members without prior cardiovascular disease. All significant or borderline significant pulse findings in the Ranch Handers were largely sustained regardless of the comparison group used (originals, matched originals, or all comparisons). Both the femoral and carotid pulses revealed substantial, but statistically nonsignificant, abnormalities in the Ranch Hand group. More biologic credence is assigned to the large artery observations in light of the small artery findings. Peripheral pulse abnormalities will merit extensive clinical inquiry at the first follow-up examination. The history of cardiovascular disease obtained during the in-home interview was verified by a review of medical records. Both reported and verified past heart disease and heart attacks were adjusted by age, smoking, and body fat or HDL. This analysis revealed that the older (£*IO years) smoking Ranch Handers manifested significantly more verified heart disease than their equivalent comparisons. Alternatively, the older less smoking Ranch Handers have substantially less reported and verified cardiovascular disease than their comparisons. Detailed herbicide exposure analyses showed no associations to any of the central or peripheral cardiovascular findings. Future reports will explore a theoretical synergism between cigarette smoking and herbicide exposure. XVI-1-21 �Chapter XVI-2 IMMUNOLOGY 1. Introduction Recent experimental data in animals have suggested that TCDD has deleterious effects on the immune system (Dean et al, 1984). As a result, the Science Panel Committee recommended that the immunotoxic potential of TCDD be evaluated during the physical examination portion of this study. Parameters selected for assessment included: (1) the enumeration of T-lymphocytes, T-lymphocyte subsets and B-lymphocytes using monoclonal surface marker analysis and (2) functional ability of lymphocyte to respond to selected antigen or mitogen stimuli in the lymphocyte transformation assay. Five hundred ninety-two participants were randomly selected for this examination using the terminal digit of the participant's case number. This selection occurred during the time period March 1982 through September 1982. Of the 592 participants, 297 were Ranch Handers and 295 were comparisons. Of the 295 comparisons, 180 were original comparisons. The statistical testing presented in this chapter is all based on this basic set of 297 Ranch Handers and 180 original comparisons. However for each test performed, differing data deletions occurred. Specifically, data from professed homosexuals were removed from all analyses. Also, data were removed from all analyses if covariate information (age, smoking, alcohol use) was missing. Finally, data were removed from certain analyses (T-j-j, T^, Tij, TQ, Tij/Tg, BI counts and percentages) if: (1) differential counts were unavailable, (2) if samples exhibited greater than 30% background fluorescence, or (3) if samples had a T^ or T-) 1 proportion of less than 10$. Surface marker analysis and lymphocyte function studies were performed on purified mononuclear cells obtained from heparinized whole blood drawn at Kelsey-Seybold Clinic early on the second day of the examination period. Peripheral blood mononuclear leukocytes (PEL) were separated from erythrocytes and polymorphonuclear leukocytes using a density gradient centrifugation technique. Unfortunately, blood specimens were collected and processed in glass tubes with resultant variable loss of adherent PEL. White cell differential counts were not obtained on purified PEL so that the number of lymphocytes actually placed into functional assays could not be ascertained. Due to these laboratory difficulties, coupled with relatively small sample sizes, exposure index analyses are not provided in this chapter. 2• Analysis of I_mmunological^ Cell Count_JData Mouse monoclonal antibodies directed against various lymphocyte surface antigens were incubated with PEL. Following washing, fluorescent anti-mouse antibodies were added. After the cells had been stored for a variable period in paraformaldehyde, the presence or absence of fluorescent antibody on each PBL was determined and counted using a cytofluorograph. The percentage of cells positive for each surface marker is reported as the number of fluorescent XVI-2-1 �cells divided by the total number of lymphocytes in a given specimen. Since differential counts were not obtained on the purified PEL, a 250 cell differential count was performed at the recommendation of the Peer Review Committee on paraformaldehyde-fixed cells. These cells had been stored for 6 to 12 months. Although cell morphology was not optimal, determination of the percentage of lymphocytes in each specimen was possible. The number of surface marker positive cells per mm3 was calculated by multiplying the percent marker positive cells by the total lymphocyte count. The cells counted and analyzed for this report are classified as having TJI , Tg, Ti|, TQ, or BI cell surface markers. The T|-| surface marker identifies thymus dependent lymphocytes which form rosettes with sheep erythrocytes (also called E+ cells). The Tj surface marker is found on nearly 100$ of circulating T-lymphocytes cells (Reinherz and Schlossman, 1980). Cells with Tj| cell surface markers proliferate in response to soluble antigens and have an inducer or helper function in T-T, T-B and T-macrophage interactions (Reinherz and Schlossman, 1980). JQ cells have cytotoxic and suppressor functions (Reinherz and Schlossman, 1980). B1 cells, or bursa equivalent cells, are producers of immunoglobulins (David, 1979). The number of TII, Tj., Tij, TQ, and B-| positive cells per mm3 are provided below by group, along with the TII/TS ratio and total lymphocyte count. Additionally, percentages of T-||, T^, TH, TS, and B-| positive cells are reported by group. The data were analyzed for statistically significant group differences using the Kolmogorov-Smirnov Two Sample Test. Also, crude group (Ranch Hand versus comparison) means were contrasted, and then the groups were contrasted while adjusting for age, smoking history in pack-years and alcohol intake measured as drink-years. The literature does not yet provide clear guidance to the selection of covariates for analysis as attempted here. Age, smoking and alcohol were chosen based on the observation that these variables frequently correlate with general measures of health and impact upon hematologic parameters. Group interactions with age, smoking or alcohol indicate group differences associated with these covariables. When group-covariate interaction is observed, group and associated covariate main effects are not reported, rather the interaction is detailed. The probability level used to indicate an interaction of interest is P = 0.100. In the absence of interaction, group and covariate main effects are reported in the usual manner. When P > 0.100 for all interaptions, P values for the reduced model, consisting of main effects only, are provided. Table XVI-2-1 provides the results of Kolmogorov-Smirnov testing of the number of surface marker positive cells per mm3. A borderline statistical difference is seen in the B-| count with Ranch Handers having lower values. However, BI cells are an adherent set of cells. The purification process resulted in a variable loss of adherent cells, therefore, this data must be interpreted with extreme caution. Table XVI-2-2 provides the KolmogorovSmirnov testing of cell percentages and no statistically significant differences are observed. Table XVI-2-3 provides unadjusted means for the number of surface marker positive cells per mm3. No statistically significant group mean XVI-2-2 �differences are observed. Table XVI-2-4 provides unadjusted means for the cell percentages, and again no statistically significant group mean differences are observed. Both counts and percentages are provided to aid with interpretation. Table XVI-2-1 KOLMOGOROV-SMIRNOV TESTING OF NUMBER OF SURFACE MARKER POSITIVE CELLS (THOUSANDS/mm3) Percentiles Variable Group N W% 50% 9055 Tn COMP RH 144 235 0.77 0.70 1.23 1.25 2.02 1.96 0.74 T3 COMP RH 0.73 0.70 1.28 1.27 2.13 1.96 0.39 233 147 231 0.48 0.398 0.78 0.794 1.42 1.251 0.81 147 235 0.277 0.296 0.604 0.569 1.168 0.985 RH 147 231 0.64 0.64 1.38 1.41 2.62 2.70 0.78 B-j COMP RH 147 235 0.022 0.023 0.071 0.071 0.247 0.188 0.097 TLC COMP RH 177 290 1.35 1.34 1.91 1.92 2.74 2.54 0.63 TH COMP RH TS COMP RH TH/TS COMP COMP = comparison group RH = Ranch Hand group XVI-2-3 �Table XVI-2-2. KOLMOGOROV-SMIRNOV TESTING OF PERCENTAGE. QF SURFACE MARKER POSITIVE CELLS (THOUSANDS/DP3) Percentiles Variable N ' 1 0% 50$ 90$ 66,0 68,0 87.5 88.4 0.90 P Value Tn COMP RH 144 235 42,0 41.6 T 3 COMP RH 144 233 48,5 48.4 66,5 66.0 83.5 83.6 0.79 T4 COMP RH 147 231 26.8 23.0 42,0 44.0 58.0 61,0 0.45 T 8 COMP RH 147 235 17.8 16.6 31,0 29,0 47.0 49.0 0,82 B, COMP RH 147 235 1.0 1.0 3.0 4.0 13.2 10.4 0.48 . COMP = comparison, group RH = Ranch Hand group XVI-2-4 �Table XVI-2-3 UNADJUSTED MEANS FOR NUMBER OF SURFACE MARKER POSITIVE CELLS (THOUSANDS/mm) AND P VALUES FOR TESTS BETWEEN GROUPS MEANS Group N COMP 139 228 1.33 1 .29 0.050 0.034 0.47 139 226 1.36 1 .29 0.052 0.031 0.21 142 224 0.877 0.846 0.038 0.027 0.49 142 228 0.660 0.606 0.029 0.020 0.11 RH 142 224 1.54 1.65 0.075 0.075 0.34 B1 COMP RH 142 228 0.117 0.102 0.011 0.008 0.26 TLC COMP RH 171 280 2.00 1.92 0.046 0.028 0.14 Variable TH RH T3 COMP RH Ti| COMP RH Tg COMP RH TH/TS COMP RH TLC SEM COMP = = = = Unadjusted Means comparison group Ranch Hand group total lymphocyte count standard error of the means XVI-2-5 SEM P Values �Table XVI-2-4 UNADJUSTED MEANS FOR PERCENTAGE OF SURFACE MARKER POSITIVE CELLS AND P VALUES FOR TESTS BETWEEN GROUPS MEANS Variable Tn Group N Unadjusted Means SEM Ti, Tg 139 65.0 1.44 228 65.7 1.20 COMP 139 65.6 1.22 RH T3 COMP RH 226 65.1 0.97 COMP RH 142 224 42.1 43.1 1.13 1.07 COMP 142 32.0 1 .02 RH B1 P^ Values 228 30.8 ' Qf71 0 75 0.53 0.80 COMP 142 5.80 0.50 RH 228 5.35 0 36 0.41 0>i)8 COMP = comparison group RH = Ranch Hand group SEM = standard error of the means Table XVI-2-5 provides the adjusted surface marker positive cell count means, along with P values for main (group, age, smoking and alcohol) and interaction (group by age, group by smoking, and group by alcohol) effects. No main or interaction effect associated with group is noted to be statistically significant. The number of lymphocytes and Tg positive cells per mm3 decreased with increasing age in both the Ranch Hand and comparison groups. The effect was -0.0043 thousand cells per mm3 per year of life for Tg and was -0.0110 thousand cells per mm3 per year of life for the lymphocyte count. Smoking was observed to be associated with increased cell counts on all variables except for B-) positive cells. Specifically, the slope was 0.0036 thousand cells per mm3 per pack-year for T-\ 1 ; 0.0076 thousand cells per mm3 per pack-year for T3; 0.0070 thousand cells per mm3 per pack-year for T4; 0.0022 thousand cells per mm3 per pack-year for Tg; and 0.0083 thousand cells per mm3 per pack-year for total lymphocyte count. XVI-2-6 �Table XVI-2-5 ADJUSTED MEANS, PLUS MAIN AND INTERACTION P VALUES FOR THE NUMBER OF MARKER POSITIVE CELLS (THOUSANDS/mm3) P Values for P Value A for Gp x Gp x Gp x | Alco Age Smkng Alco Adj ' d Adj ' d Age Smkng Mean Means Effect Effect Effect Effect Effect Effect Variable Group (Gp) T11 COMP 139 RH 228 1.29 T 3 COMP RH 139 1.35 0.38 226 1.30 <0.001 Til COMP RH 142 0.864 0.82 224 0.854 <0.001 T8 COMP RH 142 228 T4/T8 COMP RH 142 1.52 224 1.66 COMP RH 142 0.117 228 0.102 COMP RH 171 1.99 280 1.92 TLC N 1.33 0.52 0.660 0.12 0.606 0.057 0.029 0.025 0.22 0.27 0.20 <0.001 <0.001 COMP = comparison group RH = Ranch Hand group = P > 0.050 for main effects or P > 0.100 for interactions. When P > 0.100 for all interactions, P values for the reduced model, consisting of main effects only, are provided. TLC = total lymphocyte count Table XVI-2-6 shows adjusted means for percentage of surface marker positive cells. No statistically significant overall group differences are observed. The T^ and TH percentages are influenced by smoking, but this effect is essentially the same in both study groups. The effect of smoking on the Tg percentage is 0.124 percentage points per pack-year, while the effect of smoking on the TH percentage is 0.171 percentage points per year. A weak indication of a group specific alcohol intake effect was noted on the T-|-| percentage. The association of alcohol use with the percentage of T-)-| positive cells was 0.0980? per drink-year in the comparison group and -0.0042$ per drink-year in XVI-2-7 �the Ranch Hand group. This pattern could reflect a diminished Ranch Hand immunological response to drinking in reference to the comparisons; the biological relevance of this borderline finding is uncertain at this time. Table XVI-2-6 ADJUSTED MEANS AND OTHER MAIN AND INTERACTION EFFECTS FOR PERCENTAGE OF SURFACE MARKER POSITIVE CELLS Variable Group (Gp) T11 COMP P Value for Gp x Gp x Gp x Adj'd Adj'd Age Smkng Alco Age Smkng Alco Mean Means Effect Effect Effect Effect Effect Effect * RH 139 226 * - COMP RH 139 226 65.2 65.4 0.92 - 0.005 COMP RH 41.6 43.4 0.27 - <0.001 224 COMP RH 142 32.0 0.34 228 30.7 COMP RH 142 228 0.087 5.79 0.52 5.36 COMP = comparison group = Ranch Hand group RH * = that a group interaction effect was noted rendering overall group mean differences and the associated main effect not meaningful. = P > 0.050 or P > 0.100 per footnote in Table XVI-2-3. In summary, the lymphocyte surface marker analyses reported in Tables XVI-2-5 and XVI-2-6 show no detectable differences between the Ranch Hand arid comparison groups on these measures, except possibly for the borderline group difference in the T-|-| percentage by alcohol use association. 3. T and B Cell Functional Studies T and B lymphocyte function was determined by measuring the ability of these cells to transform in response to antigen or mitogen stimuli. Briefly, this assay is performed by culturing PBL in the presence of mitogens (plant lecthins which stimulate the cells to divide) or antigen. After a certain length of incubation time, the rate of DNA synthesis is estimated by adding tritiated thymidine (a radioactive DNA precursor). Thus, the counts per minute XVI-2-8 �of thymidinc incorporated into the cell culture is a measure of the ability of those lymphocyte to proliferate in response to the added stimulus. Mitogona stimulate lymphocytes non-specifically. Phytohemagglutin (PHA) and concanavallin A (conA) stimulate T-lymphocytes to divide, while pokeweed mitogen (PW) stimulates B-lymphocytes through a T-lymphocyte. On the other hand, antigen require that lymphocytes recognize specifically antigen as a substance to which the host has been exposed. Tetanus toxoid (TT) is a T-lymphocyte dependent B-lymphocyte recall antigen. Kolmogorov-Smirnov testing of the 4 stimulation and 2 control measurements are shown in Table XVI-2-7. No statistically significant group differences are noted. Unadjusted group mean net counts per minute for the stimulation studies and control measurements are shown in Table XVI-2-8. No statistically significant group differences are noted except in Control #1 where the Ranch Hand group was found to have a lower unstimulated proliferation rate. A comparable differential is also noted in Control #2, but is not statistically significant. The group differences noted are of unknown biological significance. Table XVI-2-7 KOLMOGOROV-SMIRNOV TESTING OF T AND B CELL FUNCTIONAL STUDIES 1035 Percentiles 50% 90% P Value 168 279 138 140 448 374 1483 1320 0.20 COMP RH 168 279 13596 17741 58394 54190 99104 91724 0.38 After PHA COMP RH 168 279 30143 33027 84339 79342 135684 130064 0.51 Control #2 COMP RH 168 142 132 404 388 1079 917 0.85 After PW COMP RH 168 274 12232 12700 27916 29623 53662 58288 0.64 After TT COMP RH 168 274 1001 866 3719 3726 16058 13979 0.81 Group N Control #1 COMP RH After conA Variable COMP = comparison group RH = Ranch Hand group XVI-2-9 �Table XVI-2-8 UNADJUSTED MEANS FOR T AND B CELL FUNCTIONAL STUDIES BY GROUP, AND P VALUES FOR TESTS BETWEEN GROUP MEANS Unadjusted Means (nCPM) P Value for Unadj' d Means Variable Group Control #1 COMP RH 163 269 652 535 After conA COMP RH 163 269 57454 54637 2248 1658 0.31 After PHA COMP RH 163 269 83808 80433 3048 2244 0.37 Control #2 COMP RH 163 264 523 480 After PW COMP RH 163 264 32092 33710 1337 1151 0.37 After TT COMP RH 163 264 6848 7051 650 787 0.86 COMP RH. nCPM SEM = = = = SEM 49.2 29.4 37.1 23.9 0.031 0.31 comparison group Ranch Hand group net counts per minute (stimulated CPM - control CPM). standard error of the mean Table XVI-2-9 shows adjusted net CPM means. A statistically significant group difference is noted in Control #1. Other group effects are noted as interactions with smoking and alcohol. Specifically, smoking was associated with a decreased proliferation rate to concanavallin A stimulation,(-113 nCPM per pack-year) in the comparison group, while smoking was associated with an increased proliferation rate in the Ranch Hand cohort (+169 CPM per pack-year). Two comparable group differences were observed as interactions of concanavallin A and phytohemagglutinin stimulation with alcohol use. Alcohol use was associated with an increased proliferation after concanavallin A stimulation in the comparison group (+212 CPM per drink-year), while an increase of 12 CPM per drink-year was found in the Ranch Hand cohort. Alcohol use in the comparison group increased proliferation after phytohemagglutinin by 167 CPM per drinkyear, while alcohol use in the Ranch Hand group decreased proliferation by 76 CPM per drink-year. This alcohol effect has no known biologic explanation. The finding is of questionable significance and will need to be examined further in subsequent immunologic analyses. XVI-2-10 �In addition to these group specific effects, some effects not associated with group were observed. Age and smoking were covariates which were found to be highly statistically significant. Lymphoproliferative responses to phytohemagglutinin and concanavallin A decreased monotonically in both Ranch Hand and comparison groups with advancing age. Lymphocyte response to pokeweed mitogen increased with increasing pack-years in both Ranch Hand and comparison groups. Table XVI-2-9 ADJUSTED MEANS, PLUS MAIN AND INTERACTION P VALUES FOR T AND B CELL FUNCTIONAL STUDIES BY GROUP P Value for Gp x Gp x Gp x Adj'd Adj'd Age Smkng Alco Age Smkng Alco Mean Means Effect Effect Effect Effect Effect Effect Variable Group (Gp) Control #1 COMP RH 163 269 After conA COMP RH 163 269 After PHA COMP RH 163 269 Control #2 COMP RH 163 264 After PW COMP •RH 163 264 31982 0.32 33778 After TT COMP RH 163 264 6929 0.95 7001 657 0.023 532 * # <0.001 0.089 0.025 * * 518 484 » x <0.001 0.041 0.41 0.01 COMP = comparison group RH = Ranch Hand group = P > 0.050 or P > 0.100 per footnote in Table XVI-2-3. 4. Summary The analysis of these data has provided a valuable insight into the rapidly changing area of clinical immunology. Analysis has revealed no statistically significant differences in mean TII, T^, Tij, TQ, TIJ/TS ratio or B-| 1 counts between the Ranch Hand and comparison groups. Similarly, there were no statistically significant overall mean differences in PHA, conA, PW, or TT stimulation responses between the groups. There were significant differences in XVI-2-11 �unstimulated (control) thymidine incorporation (P = 0.023) with less activity in the Ranch Hand group. In both groups, lymphoproliferative responsiveness to PHA and conA decreased significantly with increasing age, and total lymphocyte counts were correlated with age and smoking. The subsets of T-lymphocytes Ti), TQ, and T-| 1) also were correlated with smoking. From the clinical vantage point, the immunological findings do not present a picture indicative of immunological alteration in the herbicide-exposed group. However these data are of such quality that concern must be taken for a possibility of both false positive and false negative statements. Due to previously defined difficulties in surface marker analyses and lymphocyte stimulation assays, these data cannot be reliably referenced to other published data. Nonetheless, no gross adverse immunological effects were noted between the herbicide-exposed group and the comparison group. XVI-2-12 �Chapter XVI-3 HEMATOLOGICAL VARIABLES In this section, 8 hematological variables are reported. These 8 variables are listed in Table XVI-3-1 along with abbreviations used, units of measure, and normal ranges employed in the analyses. Ranch Hand-comparison group differences have been analyzed using general linear models with all variables except the group indicator treated as continuous variables. Group differences have also been evaluated using log-linear models with all variables treated as categorical. In both the general linear and log'-linear model analy^ ses, the hematological variables were adjusted for smoking history available from the questionnaire as pack-years of cigarette use (Wintrobe, 1974). In the general linear models analyses, pack-years were used directly as a continuous variable. In the log-linear models, smoking history was treated as a tricotomous variable by grouping together: (1) nonsmokers, (2) smokers with 10 packyears or less contact, and (3) smokers with greater than 10 pack~years cigarette smoking. Also, in the log-linear models analyses, the dependent (hematologic) variable was dichotomized as normal (within range) or abnormal (out of range). Analyses using the exposure index were also accomplished using the Ranch Hand participant data. These within-group analyses were performed in much the same manner as the Ranch Hand-comparison group contrasts, except that in the within-group analyses, exposure category took the place of the cohort indicator. Data on all Ranch Hand and original comparison participants are presented in this section. Table XVI-3-1 HEMATOLOGICAL VARIABLES STUDIED Variable Name Abbreviation Red Blood Cell Count RBC White Blood Cell Count WBC Hemoglobin Hgb Hematocrit Mean Corpuscular Volume Mean Corpuscular Hemoglobin Mean Corpuscular Hemoglobin Concentration Platelet Count Units Of Measure Normal Range Hot MCV Million per Cubic mm Thousand per Cubic mm Grams per 100 ml ml/100 ml Cubic Micra 42.0 - 52.0 80.0 - 101 .0 MCH Micromicrogram 27.0 - 31 .0 MCHC Percent 32.0 - 36.0 PLT Thousands Per Cubic mm 150 - 450 XVI-3-1 4.6 *- 6.2 4.8 - 10.8 14.0 - 18.0 �Table XVI~3~2 provides the results of the Ranch Hand - comparison group contrasts. The abbreviation CC is used to denote linear model analyses on continuously distributed data, DD denotes categorical log linear analyses. Two group differences are seen in Table XVI-3-2. The Ranch Hand group has a statistically significantly larger red blood cell corpuscular volume than does the comparison group (P = 0.05 in the CC analysis) and, perhaps paralleling this finding on corpuscular volume, the Ranch Hand group has a larger mean corpuscular hemoglobin (P = 0.04 in the CC analysis). In performing these analyses of group differences, smoking history was an important variable in essentially all instances. All of the hematological variables except RBC and MCHC increase with cigarette use. A summary of P values and slopes is provided in Table XVI-3~3In Table XVI-3-1* analyses are provided within the Ranch Hand group, examining for differences between exposure categories. Sample sizes in these analyses are provided in Table XVI~3i-5. Table XVI-3-6 provides variable means and percents by occupation and exposure group. Table XVI-3-2 P VALUES FOR RANCH HAND-COMPARISON GROUP DIFFERENCES, ADJUSTED MEANS, AND ABNORMAL PERCENTAGES Var Anal Group Pack-yr Group x Pack-yr RH Adj'd Mean Comp. Adj'd Mean RH ABN % Com ABN % RBC CC DD 0.62 0.36 0.08 0.65 0.71 5.20 NA 5.21 NA NA 7.43 NA 6.28 WBC CC DD 0.14 0.62 <0.001 0.48 0.83 7.51 NA 7.38 NA NA 12.45 NA 11.65 HGB CC DD 0.15 0.97 <0.001 0.77 0.65 16.04 NA 15.97 NA NA 3.28 NA 3.27 HCT CC DD 0.23 0.62 <0.001 0.25 0.32 46.16 NA 46.01 NA NA 8.30 NA 7.59 MCV CC DD 0.05 0.70 <0.001 0.58 0.71 89.04 NA 88.60 NA NA 3.76 NA 3.40 MCH CC DD <0.001 0.04 0.005 0.73 0.64 30.83 NA 30.66 NA NA 46.24 NA 39.66 MCHC CC DD 0.63 0.47 0.005 0.15 0.84 34.68 NA 34.66 NA NA 94 .6 NA 10.47 PLT CC DD 0.06 0.16 <0.001 0.76 0.33 276.74 NA 271.48 NA NA 1.16 NA 1.97 XVI-3-2 �Table XVI-3-3 SMOKING EFFECTS ON HEMATOLOGIC VARIABLES AS SEEN BY CONTINUOUS VARIABLE LINEAR MODELS P Value for Smoking Effect Dependent Variable Smoking Slope (Units/Pack-yr) RBC 0.08 -0.00089 WBC <0.001 0.0389 HGB <0.001 0.00743 HCT <0.001 0.0266 MCV <0.001 0.0675 MCH <0.001 0.0200 MCHC 0.005 "0.00376 PLT <0.001 0.322 Variable XVI-3-3 �Table XVI-3-4 P-VALUES FOR RANCH HAND OCCUPATION AND EXPOSURE GROUP ANALYSES Var Occ Cat Generalized Linear Model Exp Pack-yr Exp X Pack-yr Effect Effect Log Linear Model Exp Pack-yr Exp X Effect Effect Pack-yr 0.83 0.35 * 0.66 0.50 0.09 0.59 0.22 <0.001 0.26 0.09 0.52 0.51 0.85 0.47 0.06 0.69 0.62 0.75 0.74 <0.001 0.07 0.03 0.68 0.40 0.38 0.27 0.19 0.46 0.32 0.13 0.23 0.56 0.48 0.26 0.77 0.50 0.19 <0.001 0.001 0.008 0.37 0.22 0.23 * * 0.19 * * 0.28 0.01 0.06 0.49 OFF ENL F. ENL G. 0.38 0.84 0.45 <0.001 <0.001 <0.001 0.58 0.18 0.19 0.98 0.83 0.39 0.93 0.84 0.45 0.18 0.61 0.49 MCH OFF ENL F. ENL G. 0.38 # 0.84 <0.001 # <0.001 0.84 0.08 0.51 0.05 0.47 0.99 0.04 0.01 0.05 0.43 0.38 0.47 MCHC OFF ENL F. ENL G. 0.24 0.77 0.65 0.01 0.003 0.73 0.32 0.59 0.55 0.03 0.88 0.39 0.08 0.08 0.60 0.97 0.63 0.17 PLT OFF ENL F. ENL G. 0.66 0.26 0.97 0.02 <0.001 0.91 0.56 0.17 0.71 0.30 0.24 0.32 0.95 0.93 0.88 0.99 0.95 0.58 OFF ENL F. ENL G. 0.69 * 0.06 OFF ENL F. ENL G. * 0.61 * HGB OFF ENL F. ENL G. HCT RBC 0.83 # 0.13 0.53 0.03 0.26 <0.001 * 0.37 0.59 0.08 OFF ENL F. ENL G. MCV WBC * * *P values not relevant due to Exposure by Pack-year interaction term. XVI-3-4 �Table XVI-3-5 SAMPLE SIZES FOR RANCH HAND OCCUPATION AND EXPOSURE GROUP ANALYSES Occupational Category Exposure Category Officer Enlisted FlyIng Enlisted Ground Low 111 56 150 Medium 128 58 178 High 125 65 146 In Table XVI-S-iJ, 2 statistically significant (P < 0.05) overall exposure group effects are seen and 7 exposure-smoking interaction effects (P £ 0.10) are also present. First, the overall exposure group effects will be described. The 2 overall exposure group effects occur in the Ranch Hand officer cohort and involve the variables MCH and MCHC. An increasing dose-response relationship is clear in the MCH data, and the high exposure group also has the highest rate of mean corpuscular hemoglobin concentration (MCHC) abnormalities. These findings are suggestive of a herbicide effect, however, similar trends are not noted in the other 2 occupational categories thus decreasing the likelihood of a bonafide herbicide effect by raising the possibility that an unknown confounding variable is operative. XVI-3-5 �Table XVI-3-6 HEMATOLOGICAL VARIABLE MEAN AND PERCENTS FOR RANCH HAND OCCUPATION-EXPOSURE GROUP ANALYSES Var Adjusted Variable Means ENL ENL Ground Exp Level OFF Flying Percent Abnormal** ENL ENL Officers Flying Ground 5 .23 5 .34 5 .27 8.11 9• 38 8.80 8.93 8.62 6.45 4.00 6.74 8.22 7.63* 7.66* 7.81* 11 .71 7.03 10 .53 16 .07 13 .79 21 .54 12.00 14.04 12.33 16 .04 16 .26 16 .09 3 .60 2.34 0 .80 3 .57 1 .72 9.23 4.67 2.25 4.11 45.36 46 .22 45. 40 46 .42 45.59 46 .84 46 .36 46 .82 46 .39 11 .71 10 .94 11 .20 8.93 8.62 10 .77 8.00 3-37 6.16 MCV Low 89.02 90 .09 Medium 89.84 89 .53 89.56 89 .70 High 88 .75 88 .10 88 .46 3 .60 3 .91 4.00 3 .57 1 .72 3.08 2.67 5.06 3.42 MCH Low Medium High 30 .61 30 .50 30 .56 41 .44 52 .34 58 .40 46 .43 44 .83 53 .85 40.67 41.01 42.47 MCHC Low 34.80 34.56 Medium 34.73 34.65 High 34.94 34.52 34.54 34.66 34.61 9.91 6.25 16.00 8.93 6.90 7.69 10.67 6.74 9.59 PLT Low 262.13 294.48 Medium 268.20 290.97 High 264.09 277.78 280.94 282.09 282.53 0.00 1.56 0.00 3.57 0.00 0.00 2.67 0.56 1.37 RBC Low Medium High 5.11 5.07 5.11 WBC Low Medium High 7.03* 8.25 6.93* 7 .91 7.15* 7.89 HGB Low Medium High 15.82 15.80 15.95 15 .99 16 .11 16 .19 HCT Low Medium High 5 .15* 5 .20* 5 .24* 30.94 31 .08* 31.14 30 .97* 31.22 30 .91* *Unadjusted means interaction. given due to smoking (pack-years) by dependent variable **A11 percents given are unadjusted. XVI-3-6 �The general linear model analysis of the red blood cell count shows an interesting interaction with smoking in Ranch Hand enlisted flying personnel. In the low exposure set of enlisted flying Ranch Handers, smoking cigarettes is associated with increasing RBC values (slope = 0.00562), but the medium exposed and high exposed individuals show decreasing RBC values with smoking (slopes -0.00124 and -0.00457 respectively). This gradient of slopes with exposure is suggestive of a true herbicide effect. Log-linear analysis of the red blood cell count shows a smoking-exposure interaction among Ranch Hand officers. The data for these officers is given in Table XIV-3-7. Table XVI-3-7 SMOKING-EXPOSURE INTERACTIONS ON RBC IN RANCH HAND OFFICERS % ABNORMAL RBC Exposure Zero Pk-Yrs 1HO Pk-Yrs >10 Pk-Yrs Low Med High 0.00 8.51 9.52 16.67 10.53 5.88 13.16 9.68 9.09 . This interaction is compatible with an herbicide effect, and reinforces the finding in the enlisted flying personnel. The WBC count in Ranch Hand officers shows a smoking-exposure interaction (P <0.001). In the low exposure officer set, cigarette use is associated with an increased WBC value (slope = 0.0691), but this association is less in the higher exposure categories (slope in medium exposure category = 0.0251, and slope in the high exposure category is 0.0307). These data suggest that the correlation of leucocyte count to cigarette smoking might be affected by herbicide exposure in Ranch Hand officers. This pattern of decreasing association of leucocyte counts to cigarette smoking with increasing exposure is also suggested by the data for Ranch Hand enlisted ground personnel. In the low exposure set, cigarrette use is also associated with increased WBC values (slope = 0.0466) but this association is least in the high exposed group (slope = 0.0192). An exposure - pack-year interaction in the HCT data was noted in the officer cohort (P = 0.01) and an interaction was also seen in the enlisted flying group. The data describing these interactions is shown in Table XIV~3~8. Relatively smooth dose-response trends are seen in each officer smoking category, but the same regularity is not apparent in the enlisted flying group. It is of interest that the HCT pattern seen in the officer data of Table XIV-S-S appears to parallel the RBC pattern in the officer data of Table XIV-3-7. XVI-3-7 �Table XIV-3-8 SMOKING-EXPOSURE INTERACTIONS ON HOT IN RANCH HAND OFFICERS AND ENLISTED FLYING PERSONNEL Occupation Exposure Zero Pk-yr Abnormal HCT 1-10 Pk-yr >10 Pk-yr Officers Low Med High 6.12 8.51 23.81 16.67 15.79 11.76 15.79 11.29 3.03 Enlisted Flying Low 37.50 0.00 5.00 Med 0.00 33-33 5.13 High 18.18 16.67 7.U Lastly, a smoking-exposure interaction is seen in the MCH data in the flying enlisted group. In the low exposure group the MCH - pack-year slope is -0.00^78, while this slope is positive in the medium and high exposure sets (0.0207 and 0.03083 respectively). Summary and Conclusions The ranch hand group has a higher mean corpuscular volume and mean corpuscular hemoglobin than does the comparison group. Also, a dose-response pattern of increasing mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration was found in the Ranch Hand officer cohort. Seven hematologic variable by cigarette use by exposure level interactions were also found. Five of these interactions involved decreasing associations of hematologic measures with smoking with increasing exposure levels. One interaction (for MCH) showed increasing associations with smoking at increased exposure levels, and one interaction was uninterpretable. These statistical findings display some degree of consistency. However, the statistical differences do not appear to be significant in terms of current medical morbidity. XVI-3-8 �Chapter XVI-4 PULMONARY FUNCTION AND DISEASE Bronchitis, cough, dyspnea and acute respiratory irritation and distress have been reported as acute effects following exposure to phenoxy herbicides and dioxin (Berwick, 1970; Bauer et al, 1961; Bashirov, 1969). Little is known about the presence or absence of chronic pulmonary disease following herbicide exposure. These acute effects and the high likelihood of inhalation exposure to herbicide among operation Ranch Hand personnel in Vietnam prompted the evaluation of the pulmonary status of the study participants. In-home questionnaire responses concerning history of pulmonary disease were reviewed to determine the history of reported pulmonary disease in the Ranch Hand and comparison groups. The analysis of past pulmonary disease included data from the total comparison group. All other analyses in this subchapter were performed on all Ranch Hand individuals (1045) and the subset of original comparisons (773) who participated in the physical examination, except for a few individuals omitted due to missing pulmonary function data. Table XVI-4-1 presents the distribution of reported pulmonary disease in the Ranch Hand group, the entire comparison group, and in the subset of original comparisons. Table XVI-4-1 DISTRIBUTION OF REPORTED PULMONARY DISEASE IN THE RANCH HAND AND COMPARISON GROUPS Group Original Comparison Ranch Hand Total Comparison Tuberculosis and fungal infection (010-018; 114-116) 9 11 10 Pneumonia and Acute infections (480.-487; 460-466) 10 6 11 1 3 2 Diagnosis (ICD-9 Code) Neoplasia (160-165; 212) Chronic sinusitis and other upper respiratory disease (470-478; 480-519) 426 689 \ \ / / P=0.20 687 \ \ / / P=0.63 The distribution of reported disease is not significantly different between the Ranch Hand group and either the original comparisons or the entire comparison group. XVI-4-1 �Two measures of pulmonary function obtained during the physical examination and a third variable, derived from the other two, were analyzed. The forced expiratory volume in one second (FEV-| ) and the forced vital capacity (FVC) were determined. Prior to being analyzed, these two quantities were expressed as a percent of the predicted values for healthy, nonsmoking males (Morris et al, 1971). The third variable analyzed was the derived ratio of FEV-\ to FVC. Group differences were tested using both an unadjusted one-way analysis of variance and an analysis of covariance adjusting for age and smoking habits. The results of the analysis of the unadjusted mean values for the FVC, FEV-) and the FEV^FVC ratio are presented in Table XVI-4-2. Table XVI-4-2 ANALYSIS OF THE UNADJUSTED MEANS OF PULMONARY FUNCTION PARAMETER Mean Parameter Std. Dev. P Value FVC (^Predicted) Ranch Hand Comparison 1033 761 98.87% 98.84$ 13.15 12.98 0.97 FEV-] (% Predicted) Ranch Hand Comparison 1033 761 105.58$ 105.8755 15.65 15.36 0.69 Ranch Hand Comparison 1035 764 0.0663 0.0670 0.87 /FVC 0.8031$ 0.8026$ There are no significant unadjusted group differences between the Ranch Hand and comparison group. However, there were statistically significant interactions between age, group and pulmonary function in the analysis of both FVC and FEV-| (p = 0.04 and 0.01 respectively). Similarly, smoking .habits interacted significantly with the FEV/FVC ratio (P = 0.03). As a result, fully adjusted testing was considered to be inappropriate. However, comparison of the regression planes using the mean values of the covariables revealed P values of 0.86, 0.79, and 0.85 respectively for the FVC, FEV-] and FEV-|/FVC ratio. These values are observed to be quite similar to those seen in the unadjusted analyses. An analysis of variance of the unadjusted means for low, medium, and high exposure among the Ranch Hand group was conducted in each occupational category. These analyses revealed no consistent association between exposure level and pulmonary function. The results are presented in Table XVI-4-3. The only significant findings were in the FEV-|/FVC ratio in the enlisted categories. However, these findings were inconsistent, with the lowest exposed individuals in the enlisted flying category having the lowest mean ratio (percent performance) and higher exposed individuals doing better. In the enlisted ground personnel the mean ratio was lowest in the most heavily exposed group. Thus, while statistically significant, these findings do not conform to classic dose-response relationships. XVI-4-2 �Table XVI-4-3 HERBICIDE EXPOSURE ANALYSIS OF PULMONARY FUNCTION PARAMETERS, UNADJUSTED FOR COVARIATES OF AGE AND SMOKING I FVC (% Predicted) Low Medium High 110 128 125 Low Medium High 110 128 125 Low Medium High 110 128 125 Low Medium High 56 57 65 99.84 95.78 96.68 14,.19 11..88 14..12 Low Medium High Officer Exposure Level (% Predicted) Occupational Category 56 57 65 102.75 104.13 103.80 17,.36 14.,52 Low Medium High 56 58 65 Low Medium High 150 178 145 98.22 98.44 97.70 12.17 13-88 11.97 0.87 Low Medium High 150 178 145 105.60 105.00 102.47 14, 54 15, 42 14, 85 0.16 Low Medium High 150 178 146 0.817 0.819 Parameter /FVC Enlisted Flying FVC /FVC Enlisted Ground FVC FEVi FEV-j /FVC Std Dev P Value 100.81 99.61 101.40 12.80 13.53 12.96 0.55 108.17 107.2? 108.94 15.46 16.37 14.46 0.69 Mean 0.799 0.792 0.798 0.067 0.062 0.056 0.64 0^24 0.90 16.89 0.768 0.070 0.819 0.106 0.803 0.063 0.794 0 .056 0 .058 0.068 0.003 0.0005 Analyses of covariance adjusting for age and smoking were possible in some of the occupational categories, and the results of these analyses are presented in Table XVI-4-4. XVI-4-3 �Table XVI-4-4 ANALYSES OF PULMONARY FUNCTION AND HERBICIDE EXPOSURE, ADJUSTED FOR SMOKING AND AGE Occupational Category Parameter P Value for the Exposure _ Analysis ___ Officer FVC 0.26 0.28 0.68 Enlisted Flying FVC 0.13* FEV-j Enlisted Ground 0.90* FEV^FVC O.OOM FVC FEV-, 0.62 0.47 0.03* *= Significant covariable interaction These adjusted analyses identified significant associations in the FEV-j / FVC ratio in both enlisted categories. However, there was significant interaction between exposure level, the FEV-|/FVC ratio, smoking habits and age in the enlisted ground category. As noted in Table XVI'-4-i|, there was also interaction in the enlisted flying category for both FVC and FEV-] . When the regression planes were compared using the mean values of the age and smoking covariables, the resultant P values were as follows: Enlisted flying, FVC P = 0.10; Enlisted flying FEV-) p = 0.98; Enlisted ground FEVi/FVC P = 0.02. These P values are essentially the same as those observed in the interactions. They are also similar to those seen in the unadjusted analyses. As noted in the unadjusted analysis in Table XVI-il-3 the pattern did not suggest a consistent dose response. Summary In a few instances the results of the statistical analyses revealed significant (P % 0.05) or suggestive (P = 0.10 to 0.20) differences in pulmonary function. There were no differences detected between the Ranch Hand and comparison groups. Where significant differences were noted in the exposure index analyses, they were isolated and inconsistent in character. There were differences in the age by smoking by exposure interaction in the two groups, but it is not possible to characterize these further at this time. It may be possible to clarify these differences during follow-up phases of the study. In summary, there is no indication in the baseline physical examination that exposure to herbicide in Vietnam adversely affected pulmonary function as measured 10 to 20 years after the exposure. �Chapter XVI-5 RENAL DISEASE AND FUNCTION 1 . Introduction Overt kidney disease is not an acknowledged clinical end point following chronic exposure to low doses of Herbicide Orange or dioxin. However, since both 2,4-0 and 2,4,5-T are excreted by the kidney as unmetabolized compounds, it is understandable that acute ,renal dysfunction, as measured by a variety of laboratory tests, has been reported following acute, high dose exposure to phenoxy herbicides and dioxin. Consequently, in this study, renal function and disease were determined by general laboratory testing and history obtained by a review-of-systems questionnaire administered at the examination site. The laboratory tests emphasized measures of glomerular function rather than those of tubular function. Age of the subject (£1(0, >40 years) and 2-hour postprandial glucose levels «120, £120 mg/dl) were used as dichotomous covariates in all log-linear analyses, but were used as continuous variables in the analyses of covariance. Because of the small numbers of Black participants, the analyses are not race specific. The Ranch Hand denominator consists of all fully compliant individuals (1045) minus those few for whom covariate or dependent variable data were missing. The comparison group denominator is formed by the 773 original comparisons (i.e., shifted and replaced comparisons omitted) minus those few with missing data. Relative risks and confidence intervals are shown for all dependent variables in Appendix XVIII. 2. Laboratory Test Results The presence of occult urinary blood and protein was measured by standard reagent strips for urinalysis. The results are shown in Table XVI-5-1. After these data were placed into normal-abnormal categories, log-linear models were fitted using the covariates of age and 2-hour postprandial glucose results. These covariates were not confounding or involved in higher order interactions. Therefore, unadjusted probability values from the likelihood-ratio chi-square test statistics are used. XVI-5-1 �Table XVI-5-1 URINARY OCCULT BLOOD AND PROTEIN RESULTS BY GROUP MEMBERSHIP Occult 0 Number (50 Blood Protein >0 Number (50 0 Number (50 >0 Number (%) Comparison (N = 773) 763 (98.7) 10 (1.3) 753 (97.4) 20 (2.6) Ranch Hand (N = 1045) 030 (98.7) 14 (1.3) 030 (98.7) 14 (1.4) Occult blood group contrast P = 0.94 Relative risk: 1.037, 95% Conf. Int. (.46, 1.18) Protein group contrast P = 0.0545 Relative risk: .50, 95$ Conf. Int. (.24, 1.07) The data in Table 'XVI-5-1 show that there is no statistically significant difference in the prevalence of urinary occult blood between the Ranch Hand and comparison groups. However, the prevalence of proteinuria is borderline significant (P = 0.0545), comparisons greater than Ranch Handers. For blood urea nitrogen (BUN), urine specific gravities, and the finding of white blood cells (WBC's) in the urine, abnormalities were too sparse for log-linear analysis. Distributional data of these 3 variables were tested by an analysis of covariance, again using age and 2-hour postprandial glucose levels as continuous covariates. These data analyses and the interaction of the covariates are displayed in Table XVI~5~2. XVI-5-2 �Table XVI-5-2 MEAN BUN, URINE SPECIFIC GRAVITY AND WHITE CELL RESULTS BY GROUP MEMBERSHIP: ANALYSIS BY COVARIANCE BUN (mg/dl) P Value WBC/HPF 14.65 13-99 Comparison Ranch Hand (Adjusted Means) Specific Gravity 1.02103 1.02099 1.204 1.192 0.91 0.83 0.18 Dependent Variable Covariate Relationship P-Values Age: < 0.001 Glucose: 0.36 < 0.001 < 0.001 0.53 0.59 The data in Table XVI-5-2 show that there are no statistically significant differences in the mean BUN, specific gravity, or urinary white cells between the Ranch Hand and comparison groups, although the directional difference in the mean BUN (P = 0.18), comparison greater than Ranch Hand, is of interest. As expected, the age covariate was significantly related to BUN and specific gravity, while the glucose covariate was associated only with the specific gravity. The pattern of such classical covariate effects lends credence to the lack of group differences for these 3 dependent variables. Urine creatinine clearance levels were determined by the formula: Concentration of urine creatinine X urine volume Concentration of plasma creatinine Plasma creatinine was determined from blood samples obtained at the start of the 24-hour urine collection. Noncompliance to the full 24-hour urine collection was determined by direct questioning at the end of the sample collection and was noted to occur slightly more frequently in the comparison group (P =0.18), and significantly more (P <0.001) in older members of both groups. Air Force monitors at the examination facility frequently noted that the study participants were not fully conscientious about collecting a complete specimen, thereby casting some doubt on the overall accuracy of the creatinine clearance data. The data were not adjusted for cases of mild congestive heart failure or for high dose aspirin usage because of the rarity of these conditions in a young ambulatory population. Notwithstanding, the creatinine clearance results were tested by a log-linear model with age and glucose levels as covariates, after removing the known noncompliants. The abnormality outpoint of <110 ml/min was based upon data from the USAFSAM clinical data base, but this application produced unduly high abnormality proportions of 39.3$ and 37.4? for the Ranch XVI-5-3 �Handera and comparisons, respectively (P = 0.52). Therefore, continuous creatinine clearance values were subjected to an analysis of variance. These data are presented in Table XVI-5-3. Table XVI-5-3 MEAN VALUES OF CREATININE CLEARANCE BY GROUP, UNADJUSTED FOR COVARIATES Group Number Mean (ml/min) Standard Deviation Comparison 439 119.43 30.70 Ranch Hand 628 116.60 31.26 0.142 The concordance between group percents under 110 ml/min and the group means shown in Table XVI-5-3 is due to the left tail skew of the Ranch Hand creatinine clearance distribution as compared with that of the original comparisons. These are shown in Figure XVI-5-1. Figure XVI-5-1 CREATININE CLEARANCE FREQUENCY DISTRIBUTION BY GROUP 30-69 70-109 110-149 150-189 CLEARANCE (ML/MIN) XVI-5-4 190-230 HI RANCH HAND El COMPARISON �An analysis of covariance using age and glucose values was also performed. The glucose slopes were nonhomogeneous (P = 0.075), indicating that the group creatinine clearance difference varies with the level of glucose. 3. Questionnaire Versus Laboratory Results Log-linear models were fitted to data obtained at the time of physical examination from the question, "Have you ever had kidney disease?" with age and the 2-hour postprandial glucose level as covariates. This analysis is presented in Table XVI-5-4. These data show that the Ranch Hand group reported significantly more past kidney disease than the comparison group. Age and glucose values were not statistically significant as adjusting variables. Table XVI-5-4 HISTORY OF KIDNEY DISEASE BY GROUP Group History of Kidney Disease No (%) Yes (%) Comparison 745 (96.5) 27 (3.5) Ranch Hand 985 (94.4) 58 (5.6) 1043 Report disease group contrast: P = 0.039 (unadjusted) Relative risk: 1.6, 95% Conf. Int. (1.00, 2.59) Although analyses of 6 clinical variables had been negative with respect to group membership, it was theoretically possible that cumulative numbers of abnormalities might corroborate the historical findings. To test this notion, abnormalities were scored for 5 of the variables which exceeded normal range, i.e., BUN >26 mg/dl, creatinine clearance <110 ml/min, presence of occult blood, urine WBC ^5/HPF, and the presence of urine protein. These data were analyzed by a log-linear model, using age and glucose values as covariates. The results are presented in Table XVI-5-5. XVI-5-5 �Table XVI-5-5 ABNORMALITIES FROM FIVE RENAL FUNCTION TESTS BY HISTORY OF KIDNEY DISEASE AND GROUP MEMBERSHIP Group Abnormalities No^History;_Jjf)_ History ($) Total Comparison 0 £ 1 406 (96.4) 339 (96.6) 15 (3.6) 12 (3.4) 421 351 Ranch Hand 0 2: 1 524 (94.4) 462 (94.5) 31 (5.6) 27 (5.5) 555 489 P = 0.94 (History by abnormality interaction) These data show that the reporting of kidney disease is associated only with group membership and not with abnormal findings on the physical examination. 4. Herbicide Exposure Analyses Each Ranch Hand member was placed into an occupational stratum of flying officer, flying enlisted, or ground enlisted, which was further categorized into low, medium, or high exposure to herbicide (see Chapter VIII). Nonflying officers were assigned to the "low" exposure category of the flying officer group because of their nonherbicide administrative duties. Log-linear models were constructed for the variable of history of kidney disease, creatinine clearance, occult blood, and urinary protein; analyses of covariance were performed on the variables of BUN and urinary WBC's. Both tests used covariate adjustments based on age and 2-hour postprandial glucose results. Of the 18 exposure analyses, only 1 was borderline significant; these data are presented in Table XVI-5-6. Table XVI-5-6 HISTORY OF KIDNEY DISEASE IN RANCH HAND FLYING ENLISTED PERSONNEL BY EXPOSURE CATEGORY Ranch Hand Occupational Category Flying Enlisted Exposure Low Med High History of Kidney Disease No (%) Yes (%) 58 (98.3) 52 (88.1) 64 (97.0) P = 0.0504 XVI-5-6 1 (1.7) 7 (11 .9) 2 (3.0) Total 59 59 66 �While these exposure data are borderline significant, the association is nonlinear from low to high and is based upon very low numbers of positive histories. 5. Summary Six clinical measures of renal function and data from a review-of-systems questionnaire were tested for group membership differences by log-linear models or analysis of covariance with age and 2-hour postprandial glucose results as covariates when appropriate. A two^fold increase in proteinuria (P = 0.05*15) was found in the comparison group. Ranch Hand versus comparison group creatinine clearance differences were difficult to assess due to manifest compliance problems to the 24-hour urine collection process. While the Ranch Handers reported a significantly higher history (P = 0.0389) of past kidney disease, these historical differences were not correlated to cumulative abnormalities of 5 clinical variables. Herbicide exposure analyses in the Ranch Hand group were essentially negative. XVI-5-7 �Chapter XVI-6 ENDOCRINE FUNCTION 1. Introduction TCDD is known to produce a broad spectrum of metabolic phenomena in animal experimental subjects treated with sufficiently large doses. The pattern of effects is quite complex. Hypothyroxinemia has been produced in rats (Potter et al, 1983), and this may be associated with increased biliary elimination of thyroxine (Bastomsky, 1977). Hypoglycemia has been produced in rats (Gasiewicz et al, 1980, Potter et al, 1983) at the same time that serum and pancreatic insulin levels fell (Potter et al, 1983). TCDD has been observed to reduce hepatic catabolism of testosterone in the rat (Nienstedt et al, 1979). Based on animal data, the physical examination in this study obtained data for thyroid function (T3 uptake, serum T4 and the free thyroxine index or FTI), glucose metabolism (blood glucose level taken 2 hours after a standard carbohydrate load) and serum testosterone level. These 5 variables are listed in Table XVI-6-1 together with a description of normal and abnormal levels provided by the Kelsey-Seybold contract effort. Table XVI-6-1 FIVE ENDOCRINOLOGICAL VARIABLES AND THEIR NORMAL AND ABNORMAL LEVELS Variable Name Variable Abbreviation Abnormal (Low) Normal Range Abnormal (High) 27%-37% T3 Uptake T3 Serum T4 T4 Free Thyr6xine Index FTI 2 Hour Postprandial Glucose GLU 2 HR NA <120 mg/dl Serum Testosterone TEST <400 ng/dl 400-1200 ng/dl <4.7 yg/dl 4.7-12.5 ug/dl >12.5 1.3-^.6 >_120 mg/dl >1200 ng/dl Each study subject was asked to follow a standardized diet prior to arrival at the examination site. Not all participants complied with the diet. Table XVI-6-2 shows dietary compliance by group. XVI-6-1 �Table XVI-6-2 DIETARY COMPLIANCE BY GROUP Group Complied with Diet Did Not Comply With Diet Dietary Compliance Unknown Ranch Hand 896 (86?) 96 53 Comparison 676 (87%) 70 27 The groups are not different as regards dietary compliance (P = 0.262). Also dietary compliance was not found to be associated with the likelihood of being in the high abnormal GLU 2 HR category. Thus, in Tables XVI-6-3 and XVI-6-5 participants were used irrespective of dietary compliance status. 2. Data Analysis Table XVI-6-3 shows unadjusted percentages of the 5 endocrinological variables by variable level and group. (For this table and all other analyses in this chapter, all Ranch Hand participants (N = 10*15) and all original controls (N = 773) were used as the basic data set). In the analysis of thyroid hormones, data from individuals with thyroidectomies were removed (7 Ranch Handers and 3 original comparisons), and in the analysis of testosterone, data from individuals with orchiectomies (5 Ranch Handers and 1 original comparison) were removed. Other denominator variations occurred due to missing covariates. A group difference in T3 uptake is noted in Table XVI-6-3. The Ranch Hand group has fewer individuals in the low category and more individuals in the high category than does the comparison group. The same directionality is noted with the T4 and FTI variables. No group differences are found in GLU 2 HR or TEST. Since hormone levels can be correlated with age and physical habitus, an analysis of the 5 endocrinological variables was attempted adjusting for age in years (dichotomized as less than or equal to 40 years and greater than 40 years) and for percent body fat (trichotomized as less than 10?, 10-25?, greater than 25?). There are too few abnormalities for a full analysis of any of the 5 endocrinological variables. However, for T3 and TEST, analyses could be performed on those individuals with 10? body fat or greater and having low abnormal or normal dependent variable values. Similarly, an analysis of GLU 2 HR values was possible on those individuals with 10? body fat or greater. The data for these 3 adjusted analyses are presented in Tables XVI-6-4, XVI-6-5 and XVI-6-6. Log-linear models were used in these analyses. XVI-6-2 �Table XVI-6-3 UNADJUSTED PERCENTAGES FOR FIVE ENDOCRINOLOGICAL VARIABLES BY VARIABLE LEVEL AND GROUP Variable Level Variable Low Normal High P Value For Group Difference RH COM 1032 767 5.72$ 8.47$ 93.41$ 91.26$ 0.87$ 0.26$ 0.020 RH COM 1033 767 0.10$ 0.39$ 99.13$ 99.22$ 0.77$ 0.39$ 0.250 FT I RH COM 1033 767 0.00$ 0.26$ 99.71$ 99.74$ 0.29$ 0.00$ 0.085 GLU 2 HR RH COM 1040 770 NA NA 84.81$ 82.73$ 15.19$ 17.27$ 0.234 TEST RH COM 1034 769 4.93$ 6.37$ 94.58$ 93.11$ 0.48$ 0.52$ 0.414 T3 Table XVl<-6-4 shows a group difference in T3 uptake which is age specific (P = 0.005). There are more low T3 values in the comparison group than in the Ranch Hand group in the 40 and under-40 age group, but the groups are similar above 40 years Of age. A highly statistically significant association of T3 hypothyroxinemia with body fat is noted within the groups (P = 0.004). Table XVI-6-5 shows no group difference in the observed proportions of hyperglycemia (>_ 120 mg/dl). Age and body fat are seen to influence these proportions (P < 0.001 in both instances), and the effect is about the same in both groups. Table XVI-6-6 shows no group difference in the observed proportions of low testosterone. Age and body fat both influence these proportions (P = 0.022 for age and P < 0.001 for body fat), and the effect is approximately the same in both groups. Using the categories for normal and abnormal levels shown in Table XVI-6-1, it was not possible to meaningfully carry out an exposure index analysis of the 5 endocrinological variables, due to sample size limitations. XVI-6-3 �Table XVI-6-4 PERCENT OF ABNORMALLY LOW Tj VALUES BY GROUP, AGE AND BODY FAT CATEGORY* % T3 Low Abnormal in 10-25? Body Fat Subgroup % T3 Low Abnormal in > 25% Body Fat Subgroup Age <40 RH 2.59 (9/347) 6.58 (5/76) _<40 COM 7.89 (18/228) 19.15 (9/47) >40 RH 6.49 (30/462) 10.94 (14/128 >40 * Group COM 7.43 (28/377) 9.26 (10/108) Abnormally high individuals and lean individuals (less than ^0% body fat) were removed from the analysis due to sample size limitations. Table XVI-6-5 PERCENT ABNORMAL GLU 2 HR VALUES BY GROUP, AGE AND BODY FAT CATEGORY* % GLU 2 HR in Abnormal Category in 10-2555 Body Fat Subgroup % GLU 2 HR in Abnormal Category in >25% Body Fat Subgroup Age £40 RH 6.25 (22/352) 17.11 (13/76) <_40 COM 6.55 (15/229) 17.02 (8/47) >40 RH 18.01 (85/472) 28.46 (37/130) >40 * Group COM 18.25 (69/378) 36.36 (40/110) Lean individuals (less than *\Q% body fat) were removed from the analysis due to sample size limitations. XVI-6-4 �Table XVI-6-6 PERCENT ABNORMAL LOW TESTOSTERONE VALUES BY GROUP, AGE AND BODY FAT CATEGORY* Age Group % Testosterone Low Abnormal in 10-25? Body Fat Subgroup % Testosterone Low Abnormal in > 25% Body Fat Subgroup 2.00 7.89 (6/76) 3.52 (8/227) 10.64 (5A7) 3.46 (16/463) 16.15 (21/130 it.00 * (7/350) (15/375) 19.09 (21/110) Abnormally high individuals and lean individuals (less than 10% body fat) were removed from the analysis due to sample size limitations. Analysis of covariance is less vulnerable to the data limitations of sparse or empty cells than are log-linear models. Thus, the Ranch Hand group was contrasted with the comparison group in terms of the 5 endocrinological variables using analysis of covariance adjusting for age and percent body fat. In these analyses, all variables except group indicators were used as continuous variables. In the analysis of thyroid hormones, data from individuals with thyroidectomies were removed, and in the analysis of testosterone levels, individuals with orchiectomies were removed. In the analysis of glucose levels, all participant data were used irrespective of dietary compliance as compliance was not found to influence glucose levels. Table XVI-6-7 provides unadjusted and adjusted means. When a group-by-age or group-by-body fat interaction was observed with P < 0.10, adjusted means, and age and body fat main effects are not reported. One overall group difference is noted in Table XVI-6-7. Specifically, the Ranch Handers show a higher testosterone level than do comparison participants (P = 0.02 unadjusted, 0.06 adjusted). Both increasing age and increasing body fat were found to be associated with decreasing testosterone level with slopes being -3.8 ng/dl per year of life and -12.6 ng/dl per % body fat. XVI-6-5 �Table XVI-6-7 RANCH HAND - COMPARISON GROUP MEANS OF ENDOCRINE VARIABLES P Variable Group N Unadj'd Mean T3 Com 770 30.14 Uptake RH 1037 30.28 T, Com 770 8.39 (ug/dl) RH 1038 8.46 FTI Com 770 2.51 RH 1038 2.54 GLU 2HR Com 773 102 (mg/dl) RH 1045 104 TEST Com 772 634 (ng/dl) RH 1039 P Value for Value for Remarks about Unadj'd Adj'd Adj'd Adjusting Means Mean Means Covariates 654 0.21 Group-by-age interaction (P = 0.026) 0.31 8.39 0.38 None significant at P<.05 0.13 Age (P<.001) 8.45 0.07 2.51 2.54 0.37 * % Body fat (P<.001) * Group-by-age interaction (P-.006) 0.02 637 652 XVI-6-6 0.06 Age (P<.001) % Body fat (P<.001) �Two other group differences are noted in Table XVI-6-7; however, these are associated with group-by-age interactions. In both the Ranch Hand and comparison groups, decreasing T3 uptake is observed associated with advancing age, but the slope was found to be -0*0068? per year in the comparison group while it is -O.Q4955& per year in the Ranch Hand group. Glucose levels, measured 2 hours into the glucose tolerance test, were observed to increase with age in both the comparison and Ranch Hand group; however, the rate of increase is 0.77 mg/dl per year. in the comparison group and 1.53 mg/dl per year in the Ranch Hand group. Dose-response data within the Ranch Hand group are provided in Tables XVI-6-8, XVI-6-9 and XVI-6-10. No overall statistically significant doseresponse relationships were detected; however, 5 exposure group by covariate interactions were noted. These interactions are summarized in Table XVI-6-11. No interactions are seen with respect to the variables T3 or T4. XVI-6-7 �Table XVI-6-8 RANCH HAND OFFICERS ENDOCRINE DOSE-RESPONSE DATA P P Value for Unadj'd Adj'd Mean Mean 30.6 125 30.6 30.6 L 110 8.21 126 8.15 8.15 125 8.22 8.22 L 110 2.51 126 2.4? 125 2.49 L 111 106.7 M 128 104.2 H 125 106.8 L 111 614.8 M 127 614.2 H 123 604.5 Value for Remarks about Adj'd Adjusting Mean Covariates 30.7 H TEST 126 M GLU 2 HR 30.9 H FTI 110 M T4 L H T3 N M Variable Unadj'd Mean Group 0.39 0.12 30.8 8.23 0.88 Age (P-0.033) % Body fat (P-0.039) 0.89 None 0.59 * * Age-exposure interaction (P=0.042) 0.90 * * % Body fatexposure interaction (P-0.041) 0.85 * * % Body fatexposure interaction (P-0.011) XVI-6-8 �Table XVI-6-9 RANCH HAND - FLYING ENLISTED PERSONNEL ENDOCRINE DOSE-RESPONSE DATA Variable Group N P Value for Unad j ' d Unadj'd Adj'd Mean Mean Mean 30.0 64 30.0 30.1 L 59 8.85 59 8.48 8.49 64 8.48 8.50 L 59 2.60 59 2.51 H 64 2.60 L 59 102.3 M 59 105.9 108.0 H 66 105.6 103.8 L 59 663.5 M 58 657.8 653.5 H 66 658.5 666.7 Remarks about Adjusting Covariates 30.0 M TEST 59 H GLU 2 HR 29.6 M FTI 59 H T4 L M T3 P Value for Adj'd Mean 0.57 0.32 0.45 0.88 0.98 XVI-6-9 29.6 8.85 * 102.3 659.8 0.59 None 0.32 None * % Body fatexposure interaction (P=0.03) 0.78 Age (P=0.01) 0.90 % Body fat (P<0.001 ) �Table XVI-6-10 RANCH HAND - GROUND ENLISTED PERSONNEL ENDOCRINE DOSE-RESPONSE DATA Variable Group N P Value for Unad j ' d Unad j ' d Mean Mean P Value for Remarks about Ad j ' d Adj'd Adjusting Mean Mean Covariates 30.2 148 30.3. 151 8.58 177 8.67 8.67 148 8.59 8.58 L 151 2.55 177 2.58 2.56 H 148 2.60 2.61 L 151 99.9 M 179 104.8 H 148 103.7 L 151 686.4 M 179 680.5 678.2 H 146 683.0 684.4 Age (P<0.001) 30.4 L 0.18 30.1 M TEST 176 H GLU 2 HR 29.8 M FTI 151 H T4 L M T3 0.30 0.89 0.69 0.60 0.97 XVI-6-10 29.9 8.59 2.55 * 685.6 % Body fat (P<0.003) 0.89 None 0.53 Age (P-0.01) % Body fat (P-0.03) * % Body fatexposure interaction (P-0.09) 0.93 Age (P-0.02) % Body fat (P<0.001) �Table XVI-6-11 ENDOCRINE DOSE - COVARIATE INTERACTIONS T3 Ranch Hand No Officers interactions FTI T4 No interactions GLU 2 Hr Age-exposure % Body fatinteraction exposure interaction (P-0.042) (P=0.041) TEST % Body fatexposure interaction (P-0.011) Ranch Hand No Flying interactions Enlisted No interactions % Body fatexposure interaction (P-0.03) No interaction Ranch Hand No Ground interactions Enlisted No interactions No interactions % Body fat- No interactions exposure interaction (P-0.09) No interactions The FTI shows an age*-exposure interaction among the officers and a % body fatexposure interaction in the flying enlisted Ranch Hand group. Among the officers, FTI increased by 0.00*11 per year of life in the low exposure group but decreased by 0.0127 and 0.0079 per year in the medium and high exposure groups respectively. No effect of body fat was suggested by the officer data. Among the flying enlisted, FTI did not appear affected by age, but increased with increasing % body fat in the low and medium exposure groups (0.00295 and 0.00378 per % body fat respectively) while it decreased with body fat (-0.0241 per % body fat) in the high exposure group. These FTI effects are interesting; however, the lack of consistency between occupational and exposure categories leads to doubt that an actual herbicide effect exists. Both Ranch Hand officers and ground enlisted personnel show comparable body fat-exposure interactions affecting glucose levels. The glucose level-body fat slopes are given in Table XVI-6-12. In both the officer and ground enlisted categories, the low exposed individuals show a decreasing blood glucose with increasing % body fat, but this relationship changes to a positive correlation in the medium and high exposure categories. XVI-6-11 �Table XVI-6-12 CHANGE IN GLUCOSE LEVEL PER % BODY FAT (mg/dl PER % BODY FAT) BY HERBICIDE EXPOSURE LEVEL IN TWO RANCH HAND GROUPS Exposure Category Ranch Hand Officers Ranch Hand Ground Enlisted Low M.18 -0.30 Medium +2.94 +1.75 High +1.26 +1.36 A % body fat by exposure interaction is also observed to affect testosterone levels in Ranch Hand officers with a very low probability that the effect could be due to chance (P = 0.011). Low exposed officers show a decrease in serum testosterone levels of 4.5 ng/dl per % body fat while medium and high exposed officers show decreases of 16.6 ng/dl and 15.3 ng/dl per % body fat respectively. 3. Summary The Ranch Hand group was found to differ from the comparison group with respect to proportions of individuals in normal and abnormal thyroid hormone categories. The difference is a tendency toward hyperthyroxinemia which is directionally opposite to what would be expected on the basis of subacute animal studies. On the other hand, decreasing T3 uptakes are associated with advancing age in both groups with the slope being much steeper in the Ranch Hand group. Finally, no meaningful association of thyroid hormone levels with the exposure index were found. Thus, in sum, no definite herbicide effect on thyroid function can be considered demonstrated; however, it also cannot be confidently asserted that a herbicide effect on thyroid function has not occurred. As a group, Ranch Hand personnel have higher testosterone levels than comparison individuals and Ranch Hand officers evidence a decrease in testosterone level with increasing body fat that is related to herbicide exposure category (higher exposures are associated with greater decreases in testosterone with body fat). Since subacute animal studies have shown decreased catabolism of testosterone, higher serum levels could be expected. Thus, this finding in the present study may reflect an herbicide effect, whose long-term impact will require further clinical evaluation. Overall, Ranch Hand blood glucose levels are not statistically significantly different from those of comparison individuals. However, positive associations of glucose levels with age are greater in the Ranch Hand group than in the comparison group, and in both the Ranch Hand officer and ground enlisted groups significant exposure - body fat interactions exist on glucose levels. Thus, a subtle toxicological effect of herbicide on glucose metabolism may have been detected. It will be important and interesting to follow these groups in time with respect to the incidence of diabetes. XVI-6-12 �Chapter XVII INDIVIDUAL HEALTH ASSESSMENT 1. Personal Habi ts and Character1stics The personal characteristics of the Ranch Hand and comparison individuals were obtained from the in-home questionnaire. The areas of tobacco, alcohol, and marijuana use, personal and family income, education, religion, active duty, retired/separated status, and risk-taking behavior received particular attention. The number of Ranch Hand and comparison group individuals reporting a listing of past traumatic injuries, poisonings, and/or toxic effects (ICD9-CM Codes 960-999) were also determined. The smoking and alcohol use habits of the study subjects are displayed in Table XVII-1. XVII-1 �Table XVI1-1 HISTORY OF TOBACCO AND ALCOHOL USE AMONG THE STUDY PARTICIPANTS Group Original Comparisons Habit Current Use of Cigarettes Past History of Cigarettes Past History of Cigar Use Yes ($) All Comparisons Ranch Hand No Yes ($) No Past History of Marijuana Use 478 (45.7?) 567 / \ / \ 484 (39.6$) / / P = 0.003 739 552 (72.3/0 212 \ \ P = 0.67 758 (73.2$) 278 / \ / \ 861 (71.150 / / P = 0.28 350 92 (11.9$) \ \ 680 99 (9.5$) / / 942 \ \ 157 (20.4$) 613 \ \ P = 0.62 22 (2.8$) \ \ 750 Past History of Alcohol Use 141 (11.5$) 1081 / / P = 0.12 200 (19.4$) 829 / \ / \ 53 (5.1$) 992 / \ / \ P = 0.02 Current Use of Alcohol No 313 (40.550 459 \ \ P = 0.03 P = 0.10 Past History of Pipe Use Yes ($) 246 (20.2$) / / P = 0.64 970 62 (5.1$) 1160 / / P = 1.00 447 (58.6$) 316 \ \ P,= 0.89 J 609 (58.9$) 425 694 (57.3$) / \ / / \ / P = 0.43 518 478 (63.0$) 281 \ \ P = 0.74 635 (62.2$) 386 / \ / \ 421 XVII-2 773 (64.7$) / / P = 0.21 �The mean number of cigarettes currently smoked and the mean number of alcohols-containing drinks consumed per day by those currently reporting use of these substances were determined. Similarly, the mean pack-years, cigar-years, pipe-years, drink-years and marijuana joint-years were determined for the groups in the study. These data are presented in Table XVII-2. Table XVII-2 MEAN USE OF TOBACCO PRODUCTS AND ALCOHOL IN THOSE REPORTING USE OF THESE SUBSTANCES Mean Usage Level Substance Original Comparisons Mean (Median) Ranch Hand Mean (Median) All Comparisons Mean (Median) Cigarettes per day (current use) 28.28 (30) 27.21 (25) 27.72 (30) Cigarette pack-years (cumulative) 23. (20.12) 23.89 (20.91) 22.92 (19-58) Cigar-years (cumulative) 21.26 (8.11) 19.12 (9.38) 20.80 (7.33) Pipe-years (cumulative) 26.96 (6) 26.32 (7.23) 26.26 (5.71) Marijuana Joint-years (cumulative) 7.60 (2.52) 7.12 (3.54) 8.26 (2.88) Alcohol drinks per day (current use) 2.33 (2) 2.35 (2) 2.38 (2) Drink-years (cumulative) 36.48 (26.31) 40.48 XVII-3 (24.23) 34.87 (25.08) �In most of the cumulative measurements (e.g., pack-years) the median level of use was lower than the mean level, indicating that the heavy users of these substances skewed the distributions. However, in the measurements of current use, there was little evidence for this effect. The median income levels of the Ranch Handers and the original comparison were the same with personal income ranging from $20,000 - $24,999 and total family income ranging from $30,000 - $34,999. The median personal income of the entire comparison group was also in the $20,000 - $24,999 range, but the median family income remained in this same category. The educational backgrounds of the groups were not significantly different. Religious preferences of the groups were also similar. These data are shown in Tables XVII-3 and XVII-4. Table XVII-3 EDUCATIONAL BACKGROUND BY GROUP Group Educational Level Original Comparisons Number (%) High School/GED Associate Degree BA/BS Degree Graduate Degree Unknown 430 53 152 132 6 Ranch Hand Rai Number (%} (55.63) 580 (6.86) 6? (19.66) 197 (17.07) 187 (0.78) 14 \ / \ / P = 0.78 XVII-4 (55.50) (6.41) (18.85) (17.89) (1.34) \ \ All Comparisons Number (%) 661 96 249 206 12 P = 0.48 (54.01) (7.84) (20.34) (16.83) (0.98) / / �Table XVII-4 RELIGIOUS PREFERENCE BY GROUP Group Religion Original Comparisons Number (50 Protestant Catholic Jewish Other None 699 218 9 34 85 Ranch Hand Number (50 (66.89) (68.69) 531 (20.86) 162 (20.96) 12 (0.86) (1.55) 20 (3.25) (2.59) (6.21) (8.13) \ /' \ \ \ P = 0.29 All Comparisons Number (%) 816 263 16 49 80 (66.68) (21.49) (1.3D (4.00) (6.54) 0.50 The current military status of each individual was determined as either active duty, retired, separated, reserve status, or deceased, and there were no statistically significant differences between the Ranch Handers and the subset of original comparisons (P = 0.23); however, there was a significant difference (P = 0.01) between the Ranch Handers and the total comparison group. These data are presented in Table XVII-5. Table XVII-5 MILITARY STATUS BY GROUP Group Military Status Original Comparisons Number (%) Active Duty Retired Separated Reserve Forces Deceased* 113 420 196 39 4 Ranch Hand Number (%) (14.64) (14.66) 153 (54.40) 515 (49.33) (29.21) (25.39) 305 64 (5.05) (6.13) (0.52) 7 (0.67) \ / \ /' \ \ P = 0.23 All Comparisons Number (50 184 593 247 69 6 (16.74) (53.96) (22.47) (6.28) (0.55) P = 0.01 *Deceased subsequent to the physical examination. Risk-taking behavior patterns were assessed by a series of questions (i.e., "Have you participated three or more times in activity?") that emphasized participation in potentially dangerous recreational activities. These data are tabulated in Table XVII^-6. XVII-5 �Table XVII-6 RISK-TAKING BEHAVIOR BY GROUP Group Activity Scuba Diving Auto, Boat or Motorcycle Racing Original Comparisons Yes (%} No 88 (11.40) 684 103 (9.87) \ / \ / P = 0.29 77 (9.97) \ \ 695 All Comparisons Yes (%} No_ Ranch Hand Yes (%) No 941 \ \ 155 (12.68) 106? / / P = 0.04 132 (12.64) 912 / \ / \ 140 (11.46) 1082 / / P = 0.39 P = 0.08 Acrobatic Flying 25 (3.24) \ \ 747 29 (2.78) / / 1015 \ \ 39 (3-19) 1183 / / P = 0.57 14 (1 .3*0 / / 1030 \ \ 29 (2.37) 1193 / / P = 0.07 6 (0.57) / / 1038 \ \ P = 0.57 Sky Diving 12 (1.55) \ \ 760 P = 0.71 Hang Gliding 4 (0.52) \ \ 768 P = 0.87 Mountain Climbing 35 (4.53) \ \ 737 172 (22.3) \ \ 61 (5.84) / / 601 1209 / / P = 0.20 P = 0.22 One or More Risk-taking activities 13 (1.06) 253 (24.2) / / P = 0.33 XVII-6 983 63 (5.16) 1159 \ / \ / . P = 0.47 792 308 (25.2) \ \ P - 0.60 916 / / �Only in motor vehicle racing (automobile, boats and motorcycles) was there a borderline suggestion of a difference in risk-taking behavior between the Ranch Handers and the original comparison subset. In contrast, there was a statistically significant difference between the Ranch Handers and the entire comparison group in scuba diving (P = 0.0*1) and a borderline difference (P = 0.07) in sky diving. In both of these instances, the comparisons had higher rates of participation. In combining all activities, there was no significant difference in risk-taking behavior between the Ranch Handers and the original or entire comparison group. Table XVII-7 contains the distribution of reported past injuries and poisonings by ICD code for each group. Conditional unadjusted chi-square testing reveals no significant group differences in these distributions. Table XVII-7 DISTRIBUTION OF REPORTED INJURIES AND POISONINGS BY GROUP Group Injury (ICD Code) Fractures, Dislocations, Sprains (800-848) Original Comparisons All Compa^risons Ranch Hand 11 11 Intracranial, chest; abdominal and pelvic injuries; open wounds; nerve and spinal cord injuries (850-897; 925-929; 950-957) 3 4 Late effects; superficial injuries and contusions; burns (905-924; 940-949) 5 2 6 Traumatic complications (958-959) 5 9 8 Poisonings, toxic effects; other specified causes (960-989) 3 \ \ 0 / \ / \ P =0.23 XVTI-7 17 ' • 8 4 / / P = 0.31 �2. Health Abnormalities Detected at Physical Examination Throughout previous chapters, health of the participants has been assessed in a variety of interrelated ways. Normal-abnormal categorizations, or continuously distributed clinical variables have been defined organ system by isolated organ system, categorized into physical, mental, reproductive, biochemical, and machine-results parameters, all of which were qualified by overall historic and diagnostic impressions. This research approach has not been suitable to assess total individual health. Since such a task would involve complete listings of all past abnormalities and current normalitiesabnormalities by individual, these citations would exceed the scope of this report. This chapter section attempts to assess the overall health of individuals in three ways: the summation of abnormalities of major components of each of the 12 organ systems; the summation of a weighted score of the same abnormalities; and a summary count of medical codes for historical disease and disease suspected/detected at the physical examination. a. Summation of Individual Abnormalities In 8 of the 12 clinical areas, virtually all individuals were found to have complete examination data, and all of the selected parameters of individual health could be evaluated. Table XVII-8 provides the number of Ranch Hand and original comparison group individuals with incomplete data who were not included in the tabulation for each organ system. Table XVII-8 DISTRIBUTION OF INDIVIDUALS WITH INCOMPLETE DATA OMITTED FROM ANALYSIS OF INDIVIDUAL HEALTH Organ System General Health Malignancy Reproductive Neurological Psychological Hepatic Dermatology Cardiovascular Hematologic Pulmonary Renal Endocrine Ranch Hand 8 0 473 31 4 0 " 0 4 0 5 0 9 XVII-8 Comparison 6 0 352 19 0 0 0 3 0 3 0 3 �The assessment of the reproductive system is based solely on the sperm count. Those individuals noncompliant for the collection of semen or those having had vasectomies or orchiectomies were excluded from this analysis. In the psychologic, hepatic and neurologic clinical areas, there were sufficient numbers of individuals with missing data to warrant separate analyses of individuals with complete data and individuals with partial data. The data and results of the analysis of abnormalities by organ system are presented in Table XVII-9. As noted for the psychologic, neurologic and hepatic data, subset analyses were accomplished. XVII-9 �Table XVI1-9 COUNT DATA NUMBER OF HEALTH ABNORMALITIES BY ORGAN SYSTEM AND GROUP (UNADJUSTED FOR MATCHING VARIABLES OR RISK FACTORS) Organ System Group 0 Number of Abnormalities 1 2 3 4 General Health RH C 791 573 228 186 18 8 Ma 1 1 gnancy RH C 997 755 48 17 0 1 RH C 374 263 198 158 0 Reproductive Neurological - _ Unadjusted P Values 5-6 _ 0.27 0.01 - - 1 2 3 0.34 4-9 (Full Data Subset) RH C 113 112 268 179 238 186 126 92 84 57 0.17 (Subset with 1 Missing Parameter) RH C 59 40 64 46 36 27 20 9 6 6 0.79 0 1 2 3 4 RH C 341 243 301 234 121 75 10 3 - RH C 143 129 114 83 11 6 - - RH C 184 134 206 134 143 94 68 54 26 18 3 7 0.45 (Subset with 3 Missing Parameters) RH C 114 74 134 115 90 77 44 42 29 24 4 0 0.27 Dermato logic RH C 470 347 575 426 - - Cardiovascular RH C 491 365 324 232 151 117 53 42 16 12 Hemato logic RH C 428 341 432 311 147 98 35 20 3 3 0.59 Pulmonary RH C 655 463 289 232 52 56 32 15 12 4 0.05 Renal RH C 1002 740 42 31 1 2 - Endocrine RH C 787 551 207 182 36 33 5-6 Psychological (Full Data Subset) (Subset with 1 Missing Parameter) 0.29 0.38 Hepatic (Ful 1 Data Subset) XVII-10 6 4 0.97 - - 6 2 0.92 0.70 0.20 �These data demonstrate statistically significant group differences only for malignancy (a result of the identified increase in skin cancer in the Ranch Hand Group) and in pulmonary function (due to more abnormalities in the comparison group). All other analyses were not statistically significant. The reader is cautioned that the data in Table XVII-9 are crude counts, unadjusted for the matching variables or risk factors known to affect organ system parameters. The number of abnormalities per organ system may be considered a crude index of severity. All individuals and their abnormality counts were summed, regardless of the degree of completeness of their data. The frequency distribution of these abnormalities is shown in Figure XVII-1. Figure XVII-1 EXAMINATION ABNORMALITIES 20 10 0-2 3-4 5-6 7-8 9-10 1M3 NUMBER OF ABNORMALITIES I RANCH HAND COMPARISON There was a maximum of 61 abnormalities in this analysis. The median number of abnormalities in both the Ranch Hand and comparison groups was seven. There were 0.96$ of the Ranch Handers and 1.55% comparison individuals who had no abnormalities, and 2.58$ and 2.07%, respectively, with 16 or more abnormalities. Log linear analysis of these distributions revealed no differences between the groups for numbers of abnormalities or degree of completeness of data (P values of 0.26 and 0.59, respectively). XVI1-11 �b. Weighted Score of Individual Abnormalities The count of abnormalities (Table XVII-9) was subjected to a weighting scale of 1 to 10 depending on the clinical seriousness of each abnormality. While such weighting is arbitrary, the resulting data serve as a complementary analytic technique to the basic count of abnormalities in which, for example, acne is considered to be equivalent to systemic cancer or a major EGG abnormality. The assignment of a weight to each abnormality was made before organ system results were known. Appendix VII contains a listing of all parameters and their relative weight scores for each organ system. The weighted score histogram is depicted in Figure XVII-2. Figure XVII-2 ABNORMALITY WEIGHTED SCORE 0-9 10-19 20-29 30-39 SCORE 4049 ="49 • RANCH HAND H COMPARISON Scores between zero and nine were achieved by 9.09/5 of the Ranch Handers and 7.24$ of the comparisons, with 8.805? of the Ranch Handers and 8.02$ of the comparisons scoring above 50 (out of a maximum possible score of 236). The median score was in the 20 to 24 range for both groups. The weighted score analysis showed statistical significance for cancer, again due to the aggregation of skin cancer in the Ranch Hand group. Statistical differences of interest were noted for renal disease (P = 0.09), general health (P = 0.114), and hepatic disease (P = 0.11). The relevance of these P values is minimal in view XVII-12 �of the predominantly negative analyses observed in the clinical chapters. All weighted scores were combined across clinical areas and no statistically significant differences were noted (P = 0.20). From these analyses on crude and weighted abnormalities, it is clear that there were not significantly more ill or more severely ill individuals in the Ranch Hand group than in the comparison group. c. Physical Examination Diagnostic Codes The diseases or conditions listed by the diagnostician in the diagnostic summary of the review of systems, the medical history, and the physical examination were coded according to the 9th ICD^-CM manual. These diseases were coded as being reported by history, or suspected or actually diagnosed conditions. One individual could account for more than one diagnosed disease or condition. The diagnostician listed 219 suspected diseases among the 10^5 Ranch Handers and 160 suspected conditions in the 773 original comparisons (P = 0.91). In both groups, there were 0.21 suspected diagnoses per individual. Similarly, 19^9 definitive diagnoses were made in the Ranch Handers and 1^37 in the original comparisons yielding an average of 1.87 diagnoses per Ranch Hander and 1.86 per comparison individual (P = 0.96). While the mean numbers of suspected and definitive diagnoses were essentially the same in both groups, the mean number of diseases and conditions reported by the participants were different in the two groups. There were 113 diseases reported by history in the Ranch Handers, but only 57 in the comparisons (mean number of conditions of 0.11 per person and 0.07 per person (P = 0.02), respectively). The similarity in diagnosed and suspected conditions in the two groups parallels the findings in the analysis of examination abnormalities. The difference in reported conditions may reflect differential reporting, or actual difference in past health. However, if past illness was different in the two groups, these experiences have apparently not resulted in long-term sequelae detected at the examination. 3- Summary The anecdotal comments of the examining physicians and psychologists suggested that the study participants were remarkably healthy both physically and mentally for a group of mid-aged men. These comments were made about the entire group of participants based on the medical experience of each examiner, without knowledge of which individuals were Ranch Handers and which were comparisons. The statistical analyses discussed in this chapter support the clinical impressions of the examiners. Both the Ranch Handers and the original comparisons had somewhat similar health habits, although significantly more Ranch Handers are current cigarette smokers and more had reported smoking marijuana in the past. The two groups were also similar in risk-taking activities, religion, education, income, and military status. XVII-13 �The distribution of identified health abnormalities by individual, and weighted scores of these abnormalities were not significantly different in Ranch Hand and comparison groups. Similarly, the mean number of diagnoses individual at the conclusion of the examination was not different in the groups. the the per two Overall, the health of individuals in the two groups appears to be quite comparable. As individuals, they seem to be in quite good health for men of their age. These findings and observations are most likely a result of the healthy worker effect, previously noted in the baseline mortality study. XVII-14 �Chapter XVIII FUTURE COMMITMENTS The large volume and complexity of the data collected during this baseline phase of the Ranch Hand II study have made it difficult to completely fulfill all aspects of the analytic plan envisioned in the study protocol. While most of the major anticipated analyses have been completed and included in this report, other important tasks remain to be done. The results cited in this report logically lead toward a commitment by the USAF and the study principal investigators to pursue further evaluations of these data, and follow the study participants over time. There are 5 key areas requiring additional effort: (1) database refinement, (2) definition of requirements and examination refinements for the follow-up phase of the study, (3) refinement and expansion of exposure indices (4) additional statistical analyses and (5) collaborative activities with other organizations involved in herbicide/dioxin research. 1. Database Refinement The database derived from the questionnaire and from the physical examination was very extensive in size and scope, and a quality control program was initiated to identify coding, keypunching, and editing errors in the database provided by the contractors. This data validation has been an on-going task, and is not yet complete in some areas. After the remaining questionnaire and physical examination data have been validated by comparison with the source documents, epidemiologic and statistical analyses of these data will be completed. Additionally, validation of illnesses and conditions reported on the in-home questionnaire will continue to be accomplished as medical records and birth certificates are received. Methods of validating smoking histories, and a reassessment of flying status and its impact on compliance will be pursued. The completion of this process will provide a verified database for subsequent analyses. This process will also allow an assessment of the degree of differential reporting present in the study. 2. Follow-up^ Examination Requirements One of the purposes of the baseline phase was to identify clinical areas requiring in-depth evaluation in the follow-up portions of the study. Focused questionnaire and physical examination formats will be developed for use during the reexamination scheduled for 1985. At that time detailed evaluation of skin cancer, and known risk factors affecting its occurrence will be obtained. Additional data on fertility and reproductive history will be gathered and updates of conceptions and live births occurring since the baseline questionnaire will be obtained. The cardiovascular status of the participants will also be closely examined, using doppler measurements of peripheral pulses and electrocardiographic monitoring during stress testing. New, fully validated psychological scales will be used to assess additional psychological parameters such as sleep patterns. Further immunologic evaluations with strict laboratory quality control will also be accomplished. Steps will also be taken to insure that all participants comply with dietary and 24-hour urine collection requirements. At XVIII-1 �the time of the follow-up physical examination, all participants will be requested to authorize an autopsy at the time of their deaths and have copies of those reports and tissue specimens provided to the Air Force. The participants will also be asked to forward copies of hospitalization summaries and other significant medical events to the Air Force for inclusion in their records at Brooks AFB. 3. Exposure Index Refinement The index of exposure to phenoxy herbicide and dioxin used in this report is not as complete or refined as planned in the study protocol. As it is currently calculated, each of the major occupational categories (Officers, Enlisted Flying, and Enlisted Ground) must be analyzed separately since the index is not necessarily equivalent in each category. A series of flights in a C-123 aircraft is planned. The aircraft will be configured and flown to simulate the Vietnam spray missions and a herbicide simulant will be released. Industrial hygiene sampling techniques will be used to measure differential exposure for aircrewmembers, ground support personnel, and administrative staff members. These data will then be used to calculate a weighting factor for use in the exposure index. In this way, a common index can be applied to all 3 occupational categories. The individual records of flying time ("Form 5's") will be used wherever possible to more clearly define the opportunity for in-flight exposures. Adjustment of the exposure analyses for confounding factors such as age and time spent in Southeast Asia will also be conducted to refine the index and make it more specifically a measure of herbicide exposure. This exposure index will also be modified to assess the degree of exposure to other chemicals such as arsenical herbicides (Herbicide Blue) and malathion. **• Additional Statistical Analyses Expanded statistical analyses and procedures are planned on the baseline data of this study. More detailed statistical power estimates will be developed for the analyses contained in this report, and an overall assessment of the ability of this study to detect adverse health effects in the populations studied will be made. Specifically, the analyses of reported and verified birth defects will be reaccomplished with the nature of the anomalies categorized as severe, moderate, and of minor medical consequence. The defects will also be classified as being congenital or teratogenic in origin. The results of the semen analyses and the father's occupation will also be considered. Efforts will be made to more fully define and correct sources of potential bias in the subsets of the comparison group so that all analyses can be conducted using the entire group of comparison individuals. This will maximize study power, and allow the use of the replacement strategy outlined in the protocol. Additional matched pair analyses will also be conducted in each clinical area, thus taking full advantage of the most powerful statistical techniques. The full spectrum of clinical end points and covariables will be analyzed as well. Case by case reviews of individuals with testicular, bladder, oropharyngeal, and skin cancer and those with pulse abnormalities will be conducted. This review may highlight additional risk factors and may suggest alternative epidemiologic and statistical methodologies for subsequent reanalysis (e.g., case-control studies). XVIII-2 �Other techniques will be used to address correlations between clinical areas in the data. An organ system does not operate independently, and interactions between systems will be evaluated in subsequent reports. The effects of differential reporting are potentially significant in this study, and analyses aimed at differences in reporting between groups, and between study participants and their spouses will be evaluated. Questionnaire data was collected from the next-of-kin of deceased individuals and from totally noncompliant individuals, and time constraints have not permitted an analysis of these data. However, these are potentially valuable sources of information and appropriate evaluation will be conducted as time permits. Additional testing using more multi-variate techniques, expanded model-fitting, and goodness-of'-fit testing will also be carried out via contract. 5. Collaborative Activities Over the past 5 years, the principal investigators have worked closely with other organization and scientists involved in the herbicide/dioxin issue, and these collaborative activities will be strengthened and expanded. The common problems encountered by this study and the studies of Vietnam veterans being conducted by the Centers for Disease Control and the Veterans Administration can be more effectively resolved through the sharing of approaches and solutions. Collaboration has benefited all of these studies in the past, and should continue to be of benefit in the future. In addition to U.S. governmental agencies, the principal investigators have interacted with the. epidemiologic staffs at DOW Chemical Company, Monsanto Company and with researchers in Australia, New Zealand and Europe. The value of these interactions cannot be overstated, and these contacts will be maintained as the study progresses. More importantly, a closer working relationship will be developed between the principal investigators and the Advisory Committee on Special Studies Relating to the Possible Long-Term Health Effects of Phenoxy Herbicide and Contaminants. Continued coordination with this panel will be invaluable as the complex findings of this study emerge over time. XVIII-3 �Chapter XIX INTERPRETATION OF STUDY RESULTS AND CONCLUSIONS 1. Introduction This section presents a cautionary note to both scientific and lay readers who may wish to assert that this study, in whole or in part, is supportive or nonsupportive of a causal relationship between exposure, to Herbicide Orange (and its dioxin contaminant) and adverse health. It is important to recognize that this observational study cannot prove the "negative," nor can it be construed as "definitive" science. The process of determining causality is complex and must entail a methodical consideration of many factors (Lilienfeld and Lilienfeld, 1980). 2. Causality Factors j In general, the following factors are very important in making an inference of causality: strength of association; dose-response; biologic plausibility; consistency; time relationships; specificity; and coherence. In an epidemiologic study, not all these factors are required to be present in order to make a correct inference, but clearly, substantial conflict between one or more factors casts doubt 6n an inference of causality. In this study, numerous group differences (associations) were detected and expressed in terms of probability (P) values. In any given analysis, statistically significant P values «0.05) represent the strength of the association, but in and of themselves, do not imply an herbicide causation. As expected under the null hypothesis, most a_ priori hypothesis tests were negative (P >0.05), but the validity of these findings must be assessed by the power of the given test. As expected, many positive associations were found in the clarifying analyses, or' as expressions of the influence of specific risk factors (e.g., age, smoking, etc.). Highly significant associations must also be viewed in the context of relative risk. A very significant association with a relative risk of less than two is generally of minor interest from the traditional epidemiologic perspective. In this study, only four objectively determined group differences of P <0.05 had a relative risk of two or greater. Moreover, statistically significant differences in the group means of a laboratory parameter were often detected, but the overall distributions were similar, the values were within normal range, and the clinical relevance of these shifts was not readily apparent (e.g., LDH, testosterone, T3, etc.). A positive linear dose response relationship is a substantial feature in establishing a cause and effect association. A careful counting of the 388 exposure index analyses cited in this report shows that only 11? are statistically significant, and only 2.855 are increasing from low to high XIX-1 �exposure. While these proportions are suggestive of chance associations, this possibility should be modified by the fact that positive exposure analyses, although not totally consistent throughout all occupational categories, tend to aggregate in only several of the organ systems. Additionally, it is recognized that the exposure index has not been fitted to the most specific format, as further experimental studies are still in progress. Thus, the exposure index used herein is a very indirect measure of exposure, making these analyses less certain than the observed group differences. Numerous other subcategorical exposure analyses (also predominantly negative) were accomplished, but were not included at the discretion of the author. Descriptive opinions of the positive exposure associations were often the sole choice of the responsible principal investigator within each chapter. The time interval from herbicide exposure to onset of subclinical or clinical manifestations is an important concept for proper interpretation of these study findings. The observational period for the detection of possible latent health effects ranges from 10-20 years for all Ranch Handers. While 10-20 years may be insufficient time for the induction of many systemic cancers, and possibly skin cancer, clearly it is of sufficient length to have already "caused" transient biochemical aberrations, birth outcome abnormalities, fertility problems, chloracne, porphyria cutanea tarda, neurologic sequelae, psychological deficits, etc. Thus, if the above acute/subacute conditions are found attributable in these data, it must be acknowledged that the end result of many of the disease processes is being observed. That notion must be reconciled with essentially identical mortality rates in both groups to date, as many of the proposed diseases would most likely have exerted a subtle mortality influence. Alternatively, the suggestion that the release of dioxin from fat may result in slow systemic poisoning, if true, may account for a delay of clinical manifestations beyond classically accepted latent periods. Another influential time-onset relationship is that of "crossover," i.e., a sequential time-disease association based upon a linkage to a pulsed exposure. While many pre/post-SEA analyses have been performed in this study, reapplication of exposure to herbicides (to complete the crossover) via non-SEA vocations or avocations has not, as yet, been exploited. Other causal factors merit comment. The finding of no cases of soft tissue sarcoma, porphyria cutanea tarda or chloracne in the Ranch Hand group may reflect a lack of specificity and/or a weak toxicity of the received dose of the putative agent (dioxin), or may reflect the low statistical power to detect group differences for these diseases in this study. The absence of these three diseases may also suggest that a synergism with a yet-to-be-discovered factor is required to induce disease. Findings of this study are, as yet, not fully consistent with other human dioxin studies performed in industrial populations. However, this inconsistency may be attributable to different exposure levels. In terms of biological plausibility, there is no discernible syndrome or symptom cluster that has emerged from this study that makes sense, has an XIX-2 �identifiable pathogenesis, or has an analogous animal model. A systemic poisoning theory carries with it the expectation of finding more biochemical abnormalities than were detected in this study. 3. Other Factors Chloracne has been proposed as a prerequisite to systemic disease. This premise is not wholly consistent with spectrum of illness concepts or other studies which have suggested attributable soft tissue sarcoma in predominantly nonchloracne populations. However, if the premise is true to the extent that the induction of chloracne represents moderate to high exposures to dioxin, then overall, it may be inferred that the Ranch Hand group (with no chloracne) has received relatively low exposure vis-a-vis industrial populations. Assuming a dose-response hierarchy, this inference may be extended to the contemplated studies of U.S. military ground personnel, for if the Ranch Hand study is deemed "negative," so probably will be the other studies of comparable size. The question of the validity of this study is paramount. Overall, the processes of data collection have been quite good. To the extent possible, biases have been minimized in both the data collection and data analytic phases. Notwithstanding, a general predominance of adverse findings can be noted in the Ranch Hand group. A closer inspection of this aggregation suggests that most statistically significant findings are found in the subjective data sets, as contrasted to the objective measures. Many of these subjective findings in the Ranch Hand group are in various stages of medical record verification at this time. Unfortunately, some areas, e.g., psychological testing by questionnaire, can never be totally verified. Throughout this study, there is a suggestion of differential reporting (MMPI K and Hypochondriasis scales), albeit unanalyzed, that must temper the interpretation of the subjective results. For the objective data, there is good evidence that the laboratory measurements and the clinical assessments were reasonably accurate. This study has duplicated the classical effects of numerous risk factors (age, smoking, alcohol, etc.) on the clinical measurements throughout all organ systems. The detected effects of age and smoking in the functional and count immunologic tests are new observations, to the best of our knowledge. Thus, the effects of these risk factors have been taken into account throughout the study and lend strong credence to the accuracy of the overall group associations, whether statistically significant or not. It is our belief that this physical examination has reflected the true health status of all participants and groups to the maximum extent possible. XIX-3 �4. Conclusions a. Preface This section places into context the thousands of statistical tests which have been accomplished on the enormous data bases generated by the population ascertainment efforts, and the administration of the in-home questionnaire and the physical examination. The total baseline study, including all preparatory tasks and the Baseline Mortality Report, has spanned more than 5 years, has required approximately 100 man-years of in-house work, and has cost about $11M in direct and indirect costs. The Ranch Hand study has been characterized by solid resource support and stringent timetables throughout all levels of government, intense media interest, and outstanding participation of the study subjects. As part of the mosaic of all dioxin research, the Ranch Hand study has been directed to the herbicide-health effect issue in veterans, and specifically, to heavily exposed Air Force personnel. b. Study Performance Aspects Of all live Ranch Hand and comparison individuals who were selected for this study, almost all (99.5%) were contacted, eliminating a major element of bias concern. Participation in the in-home questionnaire was 97% and 93% for the Ranch Handers and comparisons, respectively; and similarly 87% and 76% for physical examination. Differential compliance to the examination may have introduced a participation bias, a bias that is potentially related to the true health status of the participant. Age, race, participation in flying, and military status were also significant factors in determining attendance at the examination, but the relative contribution of each factor has not as yet been determined. Traditionally, individuals in either military or civilian commercial flying occupations do not readily volunteer for physical examinations that might disclose even minor ailments that jeopardize their flying careers. Early in the study, it was discovered that 18% of the comparison group was ineligible for the study because of inappropriate selection due to a computer programming error. Some selected USAF organizational units containing cargo-hauling aircraft were found not to be engaged in RVN duties (a study requirement). Thus, the direction of the error was for overselection and not for underselection of the comparison group. Ineligible individuals were removed from the randomly ordered comparison set. The replacements for the ineligibles were the next-in-line proper comparisons. For both these "shifted" comparisons and the next-in-line comparisons who were also used as substitutes for noncompliant individuals, later statistical analyses suggested that they differed from the original eligible comparisons in a variety of subtle and often opposite ways. Because of the possible bias suggested in their use, and because of the time constraints of this report, a conservative management decision was made to base the bulk of statistical tests upon a contrast of the original comparisons to the Ranch Hand group. Several analyses, using the entire XIX-4 �comparison group, were also performed and found not to differ consistently from the analyses based upon the original comparison group. For those analyses which showed differences between the original versus the total comparison group contrast, it is unclear whether these differences are primarily due to true subset variances or to a sample size effect. A full clarification of the complex biases (selection, compliance, overreporting, etc.) must be conducted before the first follow-up phase of the study. Most of the stringent quality control aspects of the study were monitored and maintained throughout the data collection phases. As a USAF contract requirement, all contractors were required to maintain "blindness" with respect to the exposure status of each individual, thereby reducing examiner bias to an absolute minimum. In addition, by contract all data are the property of the USAF. Study codes were not provided to the contractors. c. Clinical Aspects In terms of overall health, the Ranch Handers perceive their state of health to be poorer than that of the comparisons. This finding parallels the examiner's independent assessment. Percent body fat is similar in both groups as are the hematocrit determinations. A higher proportion of abnormal red cell sedimentation rates is found in comparisons under 40 years of age. The proportions are the same in both groups older than 40. The sedimentation rate, hematocrit, percent body fat, self-perception of health, and age are associated pairwise irrespective of group; these relationships are expected as all variables are traditional indicators of nonspecific illness. There are no significant group differences for malignant or benign systemic tumors. One case of soft tissue sarcoma is noted in a member of the comparison group. A slight nonsignificant aggregation of genitourinary cancers is identified in the Ranch Hand group, and an aggregation of digestive system cancers is observed in the comparison group. Two Ranch Hand bladder cancers are noted at earlier-than-expected ages. A borderline association between systemic cancer and s,mpking is observed in both groups. Significantly more nonmelanotic skin cancer is observed and verified by medical record review in the Ranch Handers. The predominant cancer, basal cell carcinoma, is the most common skin cancer in the U.S. White male population, and a proper excision is curative. While this finding is of interest, it is emphasized that these data are not adjusted for sunlight exposure, the recognized primary cause of these cancers. This analysis must await more complete data to be collected at the first follow-up examination. Overall there is no consistent data to show that the Ranch Handers are developing uncommon systemic cancers, or cancer in unusual sites, or at a younger age. Both systemic and skin cancers in the Ranch Hand group do not correlate consistently with the herbicide exposure index. XIX-5 �The fertility and reproductive analyses show mixed findings. As these results are largely based upon subjective self-reports, and must be verified by complete medical record and birth certificate reviews, the findings are judged preliminary at this time. A semen analysis on those participants willing and able to provide a specimen shows essentially identical sperm counts and percent abnormal forms between groups. The finding of an increase in sperm count by age is discounted as physiologically significant because of concomitant noncompliance by increasing age. Four measures of fertility show no difference between the Ranch Hand and comparison groups: number of childless marriages; couples with the desired number of children; the fertility index; and the infertility index. There are no significant findings in conception outcomes for miscarriages; stillbirths, induced abortions, or live births. With respect to live birth outcomes, no group differences are observed for prematurity, learning disability, or infant deaths. Birth defects, as cited by parental history, show no group differences for severe or moderate classifications; however, for minor birth defects (simple birth marks, birth rashes, port wine stains, etc.) Ranch Hand offspring show a significant excess. Reported neonatal deaths and physical handicaps significantly predominate in the Ranch Hand group when contrasted to the full comparison group. All analyses are adjusted for as many of the relevant risk factors as possible, e.g., maternal age, maternal smoking, maternal use of alcohol, paternal age, pre/post-RVN service, etc. Herbicide exposure analyses show several findings of statistical significance but the patterns of association are not fully consistent across all occupational categories. A thorough neurological assessment of the cranial nerves, peripheral nerves, and central nervous system functioning does not disclose any substantive Ranch Hand-comparison group differences. Past history of neurological disorders is similar for both groups. An increased proportion of abnormal Babinski reflexes are noted in the Ranch Handers but this finding is not statistically significant. Detailed nerve conduction velocities are not associated with group membership but are profoundly influenced by alcohol and diabetes. Similarly, abnormalities in sensation to light touch, vibration, and two reflexes are related to abnormal postprandial glucose levels. Exposure index analyses are predominantly negative. Detailed psychologic evaluations from the in-home questionnaire and physical examination show consistent findings. Educational level of the participant profoundly influences most all of the subjective test results. Due to the inherently high correlation between military rank and educational level, these variables are considered interchangeable. It is emphasized that the majority of psychologic data are based upon highly subjective self-reporting, most of which can never be fully verified by medical record reviews. There are no group differences for reported past emotional or psychological illnesses. However, the high school educated (mostly enlisted) Ranch Handers demonstrate significant findings or deficits in the following categories: fatigue, anger, anxiety, erosion, fear, startle, psychosomatic behavior, hypochondria, XIX-6 �Iriity, and manla/hypomanla. It is noted that the high school educated comparisons exhibit a higher degree of denial in most of these categories. These findings are not observed in the college educated Ranch Handers (mostly officers). The Ranch Hand group demonstrates significant hypochondria, depression, hysteria and schizophrenia vis-a-vis the comparison group, after adjustment for education. In sharp contrast, there are no substantial group differences for the more "objective functional and performance psychologic tests (e.g., Halstead-Reitan battery, IQ testing). Almost all exposure index analyses are negative. In full context, differential reporting is strongly suggested, albeit unproven. The roles of an overreporting bias and the Post-Vietnam Stress Syndrome will be clarified in subsequent follow-up psychological evaluations. The hepatic status is assessed by 9 biochemical tests and a variety of questionnaire and medical record data. The results are mixed. Ranch Hand GGPT and LDH levels are slightly higher while cholesterol levels are lower than the comparisons. Alcohol history is associated with most enzymatic elevations in both groups. Ranch Handers report significantly more skin changes compatible with a historical diagnosis of porphyria cutanea tarda (PCT). However, laboratory determinations for delta-aminolevulinic acid, uropo'rphyrin and coproporphyrin are similar between groups and no cases of PCT were diagnosed at the physcial examination. Reported miscellaneous liver disorders, verified by medical record reviews, are found significantly more in the Ranch Handers. The exposure index analyses are generally inconsistent. A comprehensive dermatologic evaluation reveals no substantial findings in the Ranch Hand group. No cases of chloracne are diagnosed clinically or by biopsy of suspicious lesions. Questionnaire data show that the incidence, severity, duration, and anatomic locations of past acne do not portray a pattern consistent with significant historical chloracne in the Ranch Handers. The classical "eyeglass" distribution of acne (suggesting chloracne) is the same in both groups. Historical acne correlates with the total cumulative acne found at physical examination. All exposure index analyses are negative. Examination of the central cardiovascular system reveals no remarkable differences between the groups for systolic blood pressure, diastolic blood pressure, abnormal electrocardiograms, past versus present electrocardiograms, or abnormal heart sounds. As expected, abnormalities in most of these parameters are significantly associated with age, smoking, and a past history of heart disease. The three risk factors: age, smoking, and cholesterol level are strongly associated with each other, and HDL cholesterol is significantly influenced by percent body fat and smoking. An analysis of questionnaire data shows that the Ranch Handers are not having premature heart attacks or generalized heart disease, although subset analyses show differing age and smoking effects. As an unexpected finding, two peripheral pulses are significantly diminished or absent in the Ranch Handers, and several other pulses show weak group differences. Clarifying statistical analyses show that XIX-7 �the the aggregate of Ranch Hand peripheral pulses, predominantly leg pulses, are significantly associated with age, past smoking, current smoking, and verified past heart disease. The weak but similar directional findings in the Ranch Hand carotid and femoral pulses are assigned more significance in view of the peripheral pulse observations. State-of-the-art measurement techniques and a specific medical questionnaire will be used to determine the relevance of these pulse deficits at the first follow-up examination. Detailed herbicide exposure analyses show no associations to any of the central or peripheral cardiovascular findings. Detailed immunological tests, via B and T lymphocyte enumeration and lymphocyte function studies on a randomized subset of all participants, do not demonstrate significant group differences. Because of the high variability of the quality control data, an independent peer review panel evaluated testing methodology and established criteria for analysis. The numbers of T-|-|, Tg, Tij, Tg, B-), positive cells and total lymphocyte counts are similar in both groups. Smoking history is observed to significantly affect the TII, T3» Ti|, Tg, marker counts and the total lymphocyte count. Age is seen to affect the Tg count and the total lymphocyte count. No group differences are observed for the functional studies using phytohemagglutinin, concanavallln A, pokeweed mitogen, and tetanus toxoid. Although the baseline proliferation rate (Control #1) was significantly lower in the Ranch Handers, the biologic relevance of this finding is unclear, particularly in the absence of group differences for concanavallin A and phytohemagglutinin stimulation studies. Age is observed to profoundly affect concanavallin A and phytohemagglutinin results while smoking history is seen to significantly influence pokeweed mitogen results. Because of the overall variability of quality control data, interpretation of a specific individual's immunocompetence is not attempted. Of 8 measured blood elements and parameters, the mean corpuscular volume and the mean corpuscular hemoglobin level are statistically significantly elevated in the Ranch Hand group, but the relative differences are exceptionally minor and are not of clinical relevance or understanding at this time. Seven of the 8 blood measurements are significantly affected by smoking history. Several exposure index analyses demonstrate positive correlations but a consistent pattern by occupational strata is not observed. There is no group difference in the distribution of reported past pulmonary disease. Forced expiratory volume for one second and forced vital capacity measurements obtained at the physical examination do not reveal group differences that are consistent in character. There are age/smoking/exposure interactions but it is not possible to further delineate these findings at this time. Several statistically significant herbicide exposure index analyses do not conform to classic dose-response relationships. XIX-8 �Ranch Handers report significantly more kidney disease than the comparisons but this history is not corroborated by 6 laboratory measurements obtained at the physical exam. Proteinuria is of borderline significance in the comparison group. Creatinine clearance may be considered of borderline significance in the Ranch Handers, depending on the laboratory value chosen to determine the abnormal category. Because of the substantial problem of compliance to the 2*1 hour urine collection, little credence is assigned to the creatinine clearance results. Age is observed to influence the blood urea nitrogen and urine specific gravity results while diabetes affected only the specific gravity results. Herbicide exposure analyses are essentially unrevealing. A comprehensive assessment of thyroid function and insulin and testosterone production show mixed results. Distributional shifts are noted in thyroid function between the Ranch Hand and comparison groups but the test results are generally within the limits of normal values. There are no group differences for diabetes as determined by abnormal 2 hour 'postprandial glucose levels. Age and percent body fat determinations are associated with abnormalities in T^ uptake, 2 hour postprandial glucose- levels, and testosterone levels. Herbicide exposure analyses show a variety of positive correlations but many are inconsistent across occupational strata. Evaluations of personal habits and individual health show that Ranch Handers currently smoke cigarettes more than the comparisons, equally participate in high risk sports activities, and have a similar background of traumatic injuries. An unrefined assessment of the total number of abnormalities found at the physical examination show no Ranch Hand aggregations in the high range nor do arbitrary clinically weighted scores. Overall, both groups are comparable in most health respects, and are probably faring better than similarly aged men in the general population. d. Final Conclusion This study has disclosed numerous medical findings, mostly of a minor or undetermined nature, that require detailed follow-up. In full context, the baseline study results should be viewed as reassuring to the Ranch Handers and to their families at this time, because this study has not identified statistical group differences . for illnesses commonly .attributed to dioxin exposure. 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Wintrobe MM, Lee GR, Boggs DR, Bithell TC, Athens JW, Foerster J. Hematology, Lea & Febiger, Philadelphia, 1974. Clinical Wolfe WH, Lathrop GD. A Medical Surveillance Program for Scientists Exposed to Dioxins and Furans. Tucker RE, Young AL, Gray AP, eds. Human and Environmental Risks of Chlorinated Dioxins and Related Compounds. Plenum Press, New York, 1983: 707-716. Young AL, Calcagni JA, Thalken CE, Tremblay JW. The Toxicology, Environmental Fate, and Human Risk of Herbicide Orange and Its Associated Dioxin, Technical Report OEHL-TR-78-92, USAF Occupational and Environmental Health Laboratory, Brooks AF&, Texas, 247 p, 1978. Zack J, Suskind R. The Mortality Experience of Workers Exposed to Tetrachlorodibenzodioxin as a Trichlorephenol Process Accident. J Occup Med 22: 11-14, 1980. REF-7 �Appendix I PRINCIPAL INVESTIGATORS AND KEY PERSONNEL A. Principal Investigators George D. Lathrop, MD, MPH, PhD, FACPM Colonel, USAF, MC Chief, Epidemiology Division William H. Wolfe, MD, MPH< -SLColonel, USAF, MC Chief, Epidemiology Services Branch Epidemiology Division Richard A. Albanese, MD, GM-15 Chief, Biomathematical Modeling Branch Data Sciences Division Patricia M. Moynahan, BSN, MS Colonel, USAF, NC Chief, Occupational Epidemiology Section Epidemiology Division B. Coinyesti gators Joel E. Michalek, PhD, GS-13 Mathematical Statistician Data Sciences Division Alton J. Rahe, MS, GS-13 Mathematical Statistician Data Sciences Division John R. Herbold, DVM, MPH, PhD, Dipl ACVPM Lt Colonel, USAF, BSC Chief, Disease Surveillance Section Epidemiology Division Richard C. McNee, MS, GM-13 Chief, Advanced Analysis Branch Data Sciences Division AI-1 �C. Contributors F. Page Armstrong, BSN Lt Colonel, USAF, NC Infection Control Consultant Epidemiology Division William J. Besich, BS, GS-12 Computer Systems Analyst Data Sciences Division Vincent V. Elequin, BS, RRA, GS-11 Medical Record Librarian Epidemiology Division William G, Jackson Jr., MS, 03-12 Mathematical Statistician Data Sciences Division Thomas V. Murphy, MBA, GS-9 Statistical Assistant Data Sciences Division William E. Nixon, BS, GM-13 Computer Systems Analyst Data Sciences Division Carolyn J. Oakley, BA, GS-11 Mathematical Statistician Data Sciences Division Kenneth P. Pankratz MSgt, USAF NCOIC, Project Ranch Hand II Epidemiology Division Melody Prihoda, MS, GS-9 Mathematical Statistician Data Sciences Division Vianney V. F. Simonnet, BS 1st Lieutenant, USAF Chief, Data Control Epidemiology Division Clarence F. Watson, Jr., MD, MPH, FACPM Life Extension Institute 540 North Michigan Avenue Chicago IL 60611 AI-2 �Thomas J. White, MA Senior Subject Matter Specialist Data Sciences Division James A. Wright, MD, MPH, FACPM Major, USAF, MC Chief, Preventive Medicine Headquarters Pacific Air Force Hickam AFB HI 96853 D. Medical Specialty Consultants Jerry J. Tomasovic, MD Colonel, USAF, MC Department of Neurology Wilford Hall USAF Medical Center Lackland AFB TX John S. Silva, MD Major, USAF, MC Department of Surgery USAF Medical Center Keesler Keesler AFB MS Richard N. Boswell, MD Lt Colonel USAF, MC Department of Medicine Wilford Hall USAF Medical Center Lackland AFB TX John W. White, MD Colonel, USAF, MC Department of Dermatology Wilford Hall USAF Medical Center Lackland AFB TX Gary L. Mueller, MD Lt Colonel, USAF, MC Department of Medicine Wilford Hall USAF Medical Center Lackland AFB TX Leonard Gardner, PhD Captain, USAF, BSC Department of Neuropsychology Clinical Sciences Division AI-3 �E< Ifflrcuriology, Review Panel J. George Bekesi, MD Dept 6f Neoplastic Disease and the Environmental Sciences Laboratory Mount Sinai School of Medicine New York NY 10029 Richard N. Boswell, MD Lt Col, USAF, MC Department of Medicine Wilford Hall USAF Medical Center Lackland AFB tX 78236 Jack H. Dean, MD Immunotoxicology Division Chemical Industries Institute of Technology Research Triangle Park NC John S. Silva, MD (Chair) Major, USAF, MC Department of Surgery USAF Medical Center Keesler Keesler AFB MS 39534 F. Management Personnel Project Director: Royce Moser, Jr., MD, MPH, FACPM Colonel, USAF, MC Commander, USAF School of Aerospace Medicine Project Resource Manager: G. Ray Sims, BS, MA, MSEE Major, USAF Chief, Engineering Division Director for Systems Acquisition Aerospace Medical Division Air Force Systems Command Coordinator: John H. Wolcott, PhD Colonel, USAF, BSC Deputy Chief of Staff for Medical and Life Sciences HQ, Air Force Systems Command �Air Force Surgeon General Coordinator: Robert A. Capell, BS, MS Lt Colonel, USAF, BSC Assistant for Bioenvironmental Engineering Office of the Surgeon General G. On-Site Physical Examination Monitors George D. Lathrop, MD, MPH, PhD, FACPM Colonel, USAF, MC Chief, Epidemiology Division William H. Wolfe, MD, MPH, FACPM Lt Colonel, USAF, MC Chief, Epidemiology Services Branch Epidemiology Division James A. Wright, MD, MPH, FACPM Major, USAF, MC Chief, Preventive Medicine Headquarters, Pacific Air Force Hickam AFB HI 96853 Clarence F. Watson, Jr., MD, MPH, FACPM Colonel, USAF, MC (Ret) Life Extension Institute 540 North Michigan Avenue Chicago IL 60611 Roy L. DeHart, MD, MPH, MS, FACPM Colonel, USAF, MC (Ret) Director, Times of Oklahoma, Inc. 1511 North Sheridan Rd Tulsa OK 71115 James A. Boydstun, MD Colonel, USAF, MC Deputy Surgeon AF Systems Command Andrews AFB MD 20334 Paul H. Grundy, MD, MPH, FACPM Captain, USAF, MC US Military Training Mission Dhahran, Saudi Arabia AI-5 �Appendix II ADVISORY COMMITTEE ON SPECIAL STUDIES RELATING TO THE POSSIBLE LONG-TERM HEALTH EFFECTS OF PHENOXY HERBICIDES AND CONTAMINANTS George W. Corastock, MD, MPH, DrPH Professor" of Epidemiology Johns Hopkins University Johns Hopkins Research Center Box 2067 Hagerstown MD 21740 John Doull, PhD, MD Professor of Pharmacology and Toxicology Department of Pharmacology University of Kansas Medical Center Kansas City KA 66103 Robert W. Miller, MD, MPH, DrPH (Chair) Chief, Epidemiology Branch National Cancer Institute Bethesda MD 20205 Richard R. Monson, MD, ScD Professor of Epidemiology Harvard School of Public Health 677 Huntington Avenue Boston MA 02115 John A. Moore DVM, MS (Former Chair) Director, Toxicology Research and Testing Program National Institute of Environmental Health Sciences P.O. Box 12233 Research Triangle Park NC 27709 Norton Nelson, PhD Professor of Environmental Medicine Institute of Environmental Medicine New York University Medical Center 550 First Ave New York NY 10016 Alan P. Poland, MS, MD Associate Professor of Oncology McCardle Laboratory for Cancer Research University of Wisconsin-Madison Madison WI 53706 Irving J. Selikoff, MD Director, Environmental Sciences Laboratory Mt Sinai School of Medicine New York NY 10029 All �Appendix III CONTRACT MANAGEMENT The Aerospace Medical Division, Air Force Systems Command, Brooks AFB TX, was designated as the primary management agency responsible for the Air Force Health Study. The program is managed by the Commander, USAF School of Aerospace Medicine, with scientific, technical, and business management support from the Epidemiology Division and the Data Sciences Division of the USAF School of Aerospace Medicine and business support from the Director for Systems Acquisition, Aerospace Medical Division, respectively. The Commander, USAF School of Aerospace Medicine, coordinates business and technical inputs from the interfacing organizations and consolidates program status and direction. He is responsible for informing higher headquarters of management or technical situations which could impact the success of the program. The 3303rd Contracting Squadron, Air Training Command, Randolph AFB TX, provides all procurement support to the Ranch Hand II Program. Contracted efforts, to date, have included software development, statement of work preparation, questionnaire development, questionnaire administration and the conduct of physical examination. To the maximum extent practical, fixed price contracts with cost reimbursement for travel, lodging and stipend expenses were used. The contractor(s) provided data as required to the contracting agency and the Program Manager. Reports were provided on technical progress, expenditure of funds, and overall program progress against the contractual schedules. Data were used to assess program progress and to initiate corrective actions where required. A contract to assist in the development of a statement of work for the questionnaires was let to Research Statistics, Inc., Houston TX, at a cost of $11 ,900. The study questionnaire was developed by the National Opinion Research Center, New York NY, a nationally recognized survey research firm. A sole source contract was awarded on 26 September 1980 and was concluded on 31 July 1981 at a total cost of $3^8,000. Louis Harris and Associates, Inc., New York NY, was competitively selected to administer the questionnaire and awarded a contract on 18 September 1981. The original effort was scheduled for completion in April 1982, but due to data collection as well as questionnaire/physical examination contractor interface requirements, the contract was extended to November 1982. The final cost for the questionnaire administration effort was $1.076 million. AIII-1 �A formal source selection process was also used to select the Kelsey-Seybold Clinic, P.A., Houston TX, as the single site for conducting the physical examinations. The Initial contract period was scheduled for 10 months (23 November 1981 - 30 September 1982) but was extended to 15 December 1982. The total contract cost was $6.161 million, Which included the physical examinations, travel expenses, lodging, meals and stipend allowances. An Air Force on-site physician monitor in-briefed all study participants and conducted quality control checks on all medical aspects of the physical examination. Additional medical and contracting specialists periodically visited the examination site to ensure adherence to all aspects of the contract. All three contracting efforts were characterized by this type of close interaction and control. AIII-2 �Appendix IV KELSEY-SEYBOLD NORMAL VALUE REPORT BLOOD CHEMISTRY AGE-ADJUSTED NORMALS AGES PARAMETERS 10 - 29 Years BUN (mg/dl): 10-26 Great (mg/dl): 0.7-1.4 Glue (mg/dl): 70-115 Choi (mg/dl): 106-210 Trig (mg/dl): 30-110 HDL (mg/dl): 32-72 T Bil (mg/dl): 0^2-1 .'2 D Bil (mg/dl): 0-0.36 Alk Phos (U/dl): 2.5-9.7 SCOT (U/L): 0-41 SGPT (U/L): 0-45 GGTP (U/L): 15~85 LDH (U/L): 0-200 CPK (U/L): 35-232 Alcohol (mg/dl): None 30 - 39 Years BUN (mg/dl): 10-26 Great (mg/dl): 0.7-1.4 Glue (mg/dl): 70H15 Choi (mg/dl): 119-240 Trig (mg/dl): 30-150 HDL (mg/dl): 32~72 T Bil (mg/dl): 0.2-1.2 D Bil (mg/dl): 0-0.36 Alk Phos (U/dl): 2.5~9.7 SCOT (U/L): 0-41 SGPT (U/L): 0-45 GGTP (U/L): 15-85 LDH (U/L): 0-200 CPK (U/L): 35-232 Alcohol (mg/dl): None 40 - 49 Years BUN (mg/dl): 10-26 Great (mg/dl): 0.7-1.4 Glue (mg/dl): 70-115 Choi (mg/dl): 131-265 Trig (mg/dl): 30-160 HDL (mg/dl): 32~72 T Bil (mg/dl): 0.2-1.2 AIV-1 �D Bil (mg/dl): 0-0.36 Alk Phos (U/dl): 2.5~9.7 SCOT (U/L): 0-41 SGPT (U/L): 0-45 GGTP (U/L): 15~85 LDH (U/L): 0-200 CPK (U/L): 35-232 Alcohol (mg/dl): None 50 - years and older BUN (mg/dl): 10-26 Great (mg/dl): 0.7~1.4 Glue (mg/dl): 80-125 Choi (mg/dl): 144-265 Trig (mg/dl): 30-190 HDL (mg/dl): 32-72 T Bil (mg/dl): 0.2-1.2 D Bil (mg/dl): 0-0.36 Alk Phos (U/dl): 2.5-9.7 SCOT (U/L): 0-41 SGPT (U/L): 0-45 GGTP (U/L): 15-85 LDH (U/L): 0-200 CPK (U/L): 35-232 Alcohol (mg/dl): None Unknown BUN (mg/dl): 10*-26 Great (mg/dl): 0.7-1.4 Glue (mg/dl): 70-125 Choi (mg/dl): 106-265 Trig (mg/dl): 30-190 HDL (mg/dl): 32-72 T Bil (mg/dl): 0.2H.2 D Bil (mg/dl): 0-0.36 Alk Phos (U/dl): 2.5~9.7 SGOT (U/L): 0-41 SGPT (U/L): 0-45 GGTP (U/L): 15~85 LDH (U/L): 0-200 CPK (U/L): 35-232 Alcohol (mg/dl): None AIV-2 �Appendix V DEFINITION OF BIRTH DEFECTS, LEARNING DISABILITIES AND PHYSICAL, MENTAL OR MOTOR IMPAIRMENTS Birth Defects ICD-9 Code 7*10 741 742 745 746 747 748 749 750 751 752 753 754 755 756 757 758 759 216 228 239.2 363.2 426.7 524.0 550 550.1 550.9 553.1 553.29 658.8 685.1 778.6 Condition Anencephalus and similar anomalies Spina Bifida Other nervous system anomalies Anomalies of eye Anomalies of ear, face, and neck Bulbus cordis/cardiac septal closure anomalies Other anomalies heart (valves) Other anomalies of circulatory system Other anomalies of respiratory system Cleft palate and cleft lip Other anomalies of upper alimentary tract Other anomalies of digestive system Anomalies of genital organs Anomalies of urinary system Certain congenital musculoskeletal deformities Other anomalies of limbs Other musculoskeletal anomalies Anomalies of the integument Chromosomal anomalies Other and unspecified anomalies Benign neoplasm of skin Hemangioma and Lymphangioma, any site Neoplasms of unspecified nature of bone, skin, connective tissue Chorioretinitis Wolff-Parkinson-White syndrome Major anomalies of jaw size Inguinal hernia gangrene Inguinal hernia with obstruction, no mention of gangrene Inguinal hernia, no mention of obstruction or gangrene Umbilical hernia Epigastric hernia Amniotic bands (constricting bands) Pilonidal Sinus or dimple Hydrocele AV-1 �Learning Disabilities (Developmental Delays) 313 314 315 317 318 319 Disturbance of emotions specific to childhood and adolescence Hyperkinetic syndrome of childhood Specific delays in development Mild mental retardation Other specified mental retardation Unspecified mental retardation Physical, Mental, Motor Impairments 760 761 762 763 764 765 766 767 768 769 770 771 772 773 774 775 776 777 778 270 271 272 273 274 275 276 Fetus or newborn affected by maternal conditions which may be unrelated to present pregnancy Fetus or newborn affected by maternal complications of pregnancy Fetus or newborn affected by complications of placenta, cord and membrane Fetus or newborn affected by other complications of labor and delivery Slow fetal growth and fetal malnutrition Disorders relating to short gestation and unspecified low birthweight Disorders relating to long gestation and high birthweight Birth trauma Intrauterine hypoxia and birth asphyxia Respiratory distress syndrome Other respiratory conditions of fetus and newborn Infections specific to the perinatal period Fetal and neonatal hemorrhage Hemolytic disease of fetus or newborn, due to isoimmunization Other perinatal jaundice Endocrine and metabolic disturbances specific to the fetus and newborn Hematological disorders of fetus and newborn Perinatal disorders of digestive system Conditions involving the integument and temperature regulation of fetus and newborn Disorders of amino-acid transport and metabolism Disorders of carbohydrate transport and metabolism Disorders of lipoid metabolism Disorders of plasma protein metabolism Gout Disorders of mineral metabolism Disorders of fluid, electrolyte, and acid-~base balance AV~2 �277 278 279 340 3^1 3^3 359 250 Other and unspecified disorders of metabolism Obesity and other hyperalimentation Disorders involving the immune mechanism Multiple sclerosis Other demyelinating diseases of central nervous system Infantile cerebral palsy Other paralytic syndromes Epilepsy Muscular dystrophies and other myopathies Diabetes mellitus AV-3 �Appendix VI PHYSICAL EXAMINATION FORMS Patient History and Health Questionnaire Conduct of the Examination (Internal Medicine) Neurological Examination Specialty Examination-Dermatology Pulmonary Function Diagnostic Summary AVI-1 �Pg. 1 of 7 KS# NAME DATE: PATIENT'S HISTORY AND HEALTH QUESTIONNAIRE FAMILY HISTORY; HAVE ANY MEMBERS OF YOUR FAMILY EVER HAD THE FOLLOWING? IF SO, PLEASE CHECK BELOW AND NOTE WHICH FAMILY MEMBER. Mother Father Sister Child Brother Diabetes Epilepsy Cancer High Blood Pressure Heart Disease Stroke Allergy Stomacn Trouble Nervous Trouble Blood Disease Deformities Arthritis Other familial diseases: Please list: FATHER: Living-Age Dead-Age _ MOTHER: Living-Age Dead-Age NUMBER BROTHERS: Living Condition of Health? Cause of Death? Condition of Health? Cause of Death? Ages: Dead Causes: NUMBER SISTERS: Ages: Dead Causes: Living ARE YOU MARRIED? WIFE'S AGE: NO. OF YEARS HUSBAND'S AGE Health of Husband or Wife? If spouse dead, give age, year, and cause of death:_ Previous Marriages?_ NUMBER OF CHILDREN: Boys: _ All Healthy? If yes, explain Gives dates: Ages: Girls: Any dead?_ Any birth defects?_ PLEASE LIST HERE ANY PHYSICAL OR NERVOUS COMPLAINTS WHICH YOU HAVE: KS-AF-1 AVI-2 Ages: �Pg. 2 of 7 PERSONAL HISTORY Allergy or severe reaction to medicines, foods, plants, chemicals, etc.: Please list: List Average Do you take regular exercise? What is your usual weight? What is the most you ever weighed? At what age or year? Have you lost or gained weight? If so, how much? Hours worked per day: Hours sleep per night: Days worked per week: Days vacation per year: Number cigarettes per day: Other tobacco per day: Cups coffee per day: Alcoholic drinks per day: PUT A CIRCLE AROUND ANY OF THE FOLLOWING CONDITIONS WHICH YOU NOW HAVE OR HAVE HAD IN THE PAST: Cataracts Tonsillitis Sinusitis Goiter Hay fever Asthma Bronchitis Pleurisy Pneumonia Tuberculosis Breast Trouble Heart Trouble Stomach Trouble Gallstones Ulcer Jaundice Liver trouble Hepatitis Worms Dysentery Colitis Loss of sensation Loss of sex drive Polio Mumps Measles Hemorrhoids Skin Trouble Acne Excess hair growth Change of skin color Other Malaria Arthritis Gout Kidney Trouble Kidney Stones Bladder Trouble Rheumatic fever Anemia Prostate Trouble Syphyilis Diabetes Gonorrhea Hernia (rupture) Varicose Veins Phlebitis Fainting Fits or convulsions Nervous Breakdown Depression Paralysis Muscle Pain Muscle weakness Numbness AVI-3 Cancer or Tumor Rheumatoid Arthritis Severe A r t h r i t i s Systemic Lupus E r y t h e r n a t o s u ; Scleroderma �Pg. 3 of 7 ' PAST HISTORY: Please list previous operations, injuries, serious illnesses, etc. and year; including those checked off above. 1. 2. 3. 4. ; 5. . 6. When was your last physical examination? Any abnormality found? Are you under any medical treatment now? List any medications you take now or occasionally: PERSONAL PHYSICIAN: Name Street Address City, State § Zip Code IF YOU HAVE HAD REPEATED CASES OF ANY OF THE FOLLOWING IN THE PAST YEAR, PLEASE CIRCLE Pneumonia Kidney Infections Skin Boils Other Infections (specify) Ks-AF-1 rev. AVI-4 �Pg. 4 of 7 IF YOU HAVE ANY OF THE FOLLOWING COMPLAINTS, PLEASE CIRCLE YES, IF NOT, CIRCLE NO. THE DOCTOR WILL ASK ABOUT DETAILS LATER. ANSWER ALL QUESTIONS. IF IN DOUBT, GUESS YES OR NO. Severe headaches or head pains .............. Yes Do you have: Any disturbance in vision ... ............ Yes Pain or discomfort in eyes ............... Yes Wear glasses .......... . ............ Yes Constant noise in ears . . . . . . ............ Yes Hard of hearing ........ . ............ Yes Ear ache with colds ( ) plane flights ( ) ....... Yes Chronic running ear ...... .... ......... Yes Chronic stuffy or runny nose ............... Yes Need to use nose drops frequently ............ Yes Bad nose bleeds at times ............ ^ . . . . Yes Frequent severe colds or sore throat ........... Yes Any known dental problems ................ Yes Soreness or bleeding of gums ............... Yes More than a year since teeth checked ... ........ Yes Sore mouth or tongue ................... Yes Goiter or thryoid trouble ................ Yes Thyroid test -- too high ( ) too low ( ) ........ Yes Feeling of lump in the throat .............. Yes Need to take thyroid medicine .............. Yes Hoarseness at times ................ ... Yes Recent or chronic cough ................. Yes Chronic coughing up of sputum ........... ... Yes Ever coughed up blood .................. Yes Ache all over ...................... Yes Having chills or fever .................. Yes Severe soaking night sweats ............... Yes Lived with anyone having T.B ............... Yes Worried about your heart . * ............... Yes Blood pressure -- too high ( ) too low ( ) ...... Yes Pains in heart or chest ................. Yes Pounding or skipping of heart .............. Yes Heart starts racing suddenly ............... Yes Shortness of breath or wheezing ............. Yes KS-AF-1 No No No No No No No No No No No No No No No No No No No No No No No No No No No No No No No No No No �Pg. 5 of 7 Trouble getting a deep breath Swelling ankles Leg cramps in bed or sitting still Leg cramps while walking Pain or trouble with swallowing Poor appetite -- recently ( ) always ( ) Nausea or vomiting Vomiting of blood Belching, bloating or indigestion Yellow skin or eyes (jaundice) Burning or hunger pains in stomach Use antacids for stomach burning Soreness or pain in stomach, abdomen Suspect ulcers or stomach trouble Cramps in stomach or low down Loose bowels or diarrhea Black or tarry stools (bowel movement) Fresh or bright blood with stools Miicus (slime or plegm) in stools Constipation Use laxatives ( ) or enemas ( ) frequently v Recent change in bowel habits Rectal trouble or pain List any foods which always disagree: Pain in the kidney region Get up nights to urinate (Number of times Blood or pus in urine Albumin in urine Sugar in urine Spells of frequent urination Severe burning or pain on urination Pains over bladder or low down Trouble starting urine Urinary stream has become weak Hard to empty bladder completely Lose control of passing urine Painful or sore genitals (privates) KS-AF-1 AVI-6 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes ) Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes '. Yes Yes No No No No No No No No No No No No No No No No No No No No No No No No No No No No No No No No No No No No �Pg. 6 of 7 Swollen or painful joints . . . . . ..... Stiffness of muscles or joints . Severe pains in arms or legs . Painful feet Backache Pains in neck , . . . * Easy to sunburn Itch or rash (where?) ____ , _ Subject to acne . . * Subject to boils or infections Subject ot athlete's foot, skin fungus Subject to hives or skin reactions Easy bleeding or bruising Mole or sore which is not healing Swelling, lump, or soreness anywhere on body (where?)_ Severe dizziness Numbness or tingling (where?) , ; _ Twitching muscles (where?) Generalized weakness Muscle weakness Nail biting Sleep walking Bed wetting after age 12 Chronically tired or overworked Irregular living habits Can't go to sleep Or stay asleep Nearly always in poor health Prom sickly or nervous family Considered to be a nervous person Tremble and sweat easily Have trouble making up your mind Easily mixed up or confused Clumsy or have frequent accidents Feel sad, lonely or depressed Cry often Wish you were dead Worry continually .* _, , ._ » . KSAF1 AVT-7 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No No No No No No No No No No No No No No Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No No No No No No No No No No No No No No No No No No No No No No No �Page 7 of 7 Upset by little things Yes No A perfectionist Yes No Sensitive or feelings easily hurt Yes No . Yes No Often act on sudden impulse Yes No Easily angered or have violent rages Yes No Frequently keyed up and jittery Yes No Easily scared by sudden noise Yes No Yes No Yes i No . . . . Yes No Often misunderstood Have bad dreams or thoughts " Suspect a serious disease or cancer Having trouble getting along with someone at home or work Have you ever been exposed to any of the following substances or types of radiation? Exposure is defined as skin or respiratory contact more than one day's duration. 1. Coal tar Yes No 2. creosote Yes No 3. anthrocene Yes No 4. benezene Yes No 5. benzidine Yes No 6. naphthylamine . . . . . Yes No 7. aminodiphenyl Yes No 8. mustard gas Yes No 9. vinyl chloride Yes No 10. chloromethyl ether Yes No 11. arsenic Yes No 12. chromstes Yes No 13. asbestos Yes No 14. cutting oils Yes No 15. trichloroethylene Yes No AVl-8 �Page 7a <^, 16. U l t r a - v i o l e t l i g h t ( o t h e r than sun) Yes No 17. x-rays Yes No 18. ionizing radiation1-1' Yes No COMMENTS: 1. (other than r o u t i n e ) ' For each " Y E S " exposure in the preceding l i s t , u l e a s e fill out the f o l l o w i n g : Type of Exposure (coal t a r , e t c ) . __ ^ A. Was exposure received on the job? B. If y e s , job t i t l e _ C. If no, how exposure received D. Circle frequency of exposure that best fits your experience: Daily E. 2. Yes Ho t __ ^ Weekly u Monthly In what year(s) were you exposed? .^^ ^.^ u ___ _ Yearly _>_• Type of Exposure (coal tar, etc) A; Was exposure received on the job? B. If yes, job title C. If no, how exposure received D. Circle frequency of exposure that best fits your experience: Daily E. 3. Weekly Yes Monthly In what year(s) were you exposed?___ Type of Exposure (coal tar, etc) NO Yearly ____ : .___ _ A. Was exposure received on the job? B. If yes, job title C. If no, how exposure received D. Circle frequency of exposure that best fits your experience: Daily E. Weekly Yes ,, Monthly In what year(s) were you exposed? __ ... _ AVI-9 No Yearly �CONDUCT OF THE EXAMINATION NAME DATE DATE OF BIRTH (DOB) CASE NO. PHYSICAL EXAMINATION 1. General Appearance a. b. c. d. Appearance/Stated Age: ( ) Younger Than Well -nourished ( ) ( ) Obese Appearance of illness or distress Hair distribution: ( ) Normal Specify: ( ( ( ( ) Older Than ( ) Same As ) Under -nourished ) Yes ( ) No ) Abnormal Weight (Undressed) kg Sitting Blood Pressure Right Arm at Heart Level Systolic Diastolic Temp. Oral F. 2. Height (cm) 3. •Pulse rate Regular: ( ) Yes ( ) No * a. Irregular ( ) b. Irregularly irregular ( ) c. VPBs per minute Describe any irregularities: •4. Eye Grounds: ( ) Normal ( )" Abnormal Describe any vascular lesions, hemorrhages, exudates, or papilledema: ( ( ( ( ) A-V nicking ) t light reflex ) Arteriolar spasm ) Papilledema ( ) Hemorrhage s ( ) Exudates ( ) Disk Pallo ( ) t Cupping 5. Arcus Senilis: 6. ENT: ( ) Normal ( ) .Abnormal Right Tympanic Membranes intact ( ) fes ' Left Tympanic Membranes intact ( ) fes ' Nasal Ulcerations . . ) fes ( ' 7. ( ) Present ( ) Absent 5a. Abnormal Ocular Pigmentation ( ) Yes ( ) No Neck (Especially thyroid gland): Thyroid gland 'palpable Enlarged Nodules Tenderness J ( ( ( ) ) ) ) Describe any abnormality: ( ) No ( J No ( ) No ' (. ) Normal AVI-10 . ( ) Abnormal Parotid gland enlargement Carotid pulse absent Carotid bruit r . Right ( Right ( Right ( Left ( ) Left ( ) Left ( ) �;8. Thorax and Lungs: ( ( ( ( ( ( ) Normal C 3 Abnormal ) Asymmetrical ^expansion ) Hyperresonance 3 Dullness . ) WheeZes ) Rales Circumference at nipple level: Expiration 9. Describe any abnormality especially basilar rales: Heart: ( ) Normal cm Inspiration cm ( ) Abnormal Displacement of apical ijnpulse ( ). Yes C 3No Heart sounds normal ( ) Yes ( 3 Ho ( ) S1 Precordial thrust ( ) Yes C 3No ( ) S2 ( ) S3 ( )S Heart and Other Observations Murmur Ao P.u.. Apex Mitral (It. Tat) Sys f~3 (} Dia ( ) (3 (3 Describe •any enlargement , irregularity of rate , murmurs, or thrills: , . „ „ , . 1 . , , 10. ( ) No ( ) Yes ,-„-,,,! | .. , -- , J...J..,.|__.±. ,,..., -„, J , , , .. „,-,-. , . ,,,,, , „ , .- .„ J -.„.„„._, . Abdomen: ( ) Normal ( ) Abnormal Waist Measurement ( ) Heptomegaly Describe any abnormality with special cm. Liver span attention to the spleen and liver: ( ) Spleenomegaly Tenderness Liver ( ) Tenderness Other () OtVif^T mn*t*? * ( 11. Extremities: \ —..-.. ( ) Normal. ( ) Abnormal . ( ) Absence, specify: ( ) Edema Pitting ( 3 Non-pitting ( ) ( ) Clubbing of nails ( ) Varicosities • ( } Loss of hair on toes right ( ) Loss of hair on toes left .KS-AF-6 ._,«_,....... AVI-11 Describe any edema or signs of vascular insufficiency: �12. Peripheral Pulses Radial Femoral Popliteal Dorsalis Pedis Posterior Tibial Nonrlal Dimin. Absent 1 1 : Comments: ! ! 1 1 i * 13. Musculoskeletal : ( ) Normal ( ) Abnormal MUSCLE SPINE Weakness ( ) Scoliosis Kyphosis Tenderness ( )' Abnormal Consistency ( ) Tenderness ' Atrophy ( ) • Tenderness level Decreased range of motion Comments : ... , . ,. . _,. Pf'Hrir f i l t -,^-.r Sninr SIR RT Spine SLR LFT « C C C C C ) ) ) ) ) () () C ) Normal ( ) Abnormal ( ) Varicocele ( )Hemorrhoids ( ) Epididymis () Prostatic enlargement ( ) Scrotal mass Enlarged Atrophic emdia. ( ) Rectal mass ( ) } ( Comments : ( ) ( ) 14. Genitourinary /Rectal/Hernia ( ) Inguinal hernia Rt. ( ) Inguinal hernia Lft. ; Absent Testes;Rt. ( ) Testes Lft. ( ) 15. Lymph Nodes (Check all areas) Cervical ' Occipital Supraclavicular Axillary Epitrachlear Inguinal . Femoral Enlarged ( ) () () () () C ) C ) ( ) Tender C C C C C C C Normal Hard ) ) ) ) ) ) ) ( C ( C C ( ( ) ) ) ) ) ) ) Fixed ( ) ( ) C D C ) C ) C ) C ) ( ) Abnormal -Specify: Confluent C) C ) () () C ) C) C) 16. Nervous System - Separate Examination Page 3 of 4 KS-AF-6 AVI-12 �17. Other Tests Ordered: ( Tests ordered (Specify) ) Yes ( ) No Signed: Examining Physician Examining facility: Printed Name of Examining Physician Form 531 incl. KS-AF-6 AVI-13 Page 4 of 4 �or (.) A N A T O M I C A L FIGURE NAME Date: (Sioned - Examiner) Standard Form 53 AVI-1.4 �Name: Date: No. JSianed - Examiner) EXAMI MAT I ON - EXAMINER AVI-15 - (1 Of 2) �NEUROLOGICAL EXAMINATION DATE NAME CASE NO. Yes HEAD S NECK Normal to Palpations/Inspections Specify: ( ) Scar No ( ) ( ) C ) Assemraetry ( ) Depression Neck Range of Motion - Normal Decreased ( ) Left C ) Right ( ) Forward ( ) Back C ) MOTOR SYSTEM Handedness ) Right ) Left Gait - Normal or ( ( ( ( ) Broad Based ) Ataxic ) Small Stepped ) Other Comments MUSCLE STATUS {Strength. Tone, Volume, Tenderness, 1 Increased Right Left Normal Rt. Arm Swing Left Arm Swing Muscle Bulk Tone - upper ext. Lower ext. Strength - Distal Wrist Extensors Ankle/Toe Dors/. Flexors Proximal Deltoids Hip Flexors Abnormal ( ) ( ) ( ) C ) ( ) ( ) ( ) ( ) • C C Decreased Right Left C ) ( ) ) C ) ( ) ( ) C ) AVI-16 ) ) ( ) ( ) ) () ) () C C C ) ( ( ^ KS-AF-4 rev. ) ( ) ) C ) Fibrillations) C ) ( ) C ) C ) ( }- • �c Neurological ExaminaL. Page 2 Yes No ABNORMAL MOVEMENTS (Tremors, Tics, choreas, etc) fMABiMiiSM " If yes (1-4*) Tenderness If yes, (1-4+) Tremor (if yes, specify below) Upjier Upper Lbwer Lower Extremities Extremities Extremities Extremities Rt. Lt. Rt. Lt. ( ) Resting ( 3 ( 3 b. Intention Normal Equilibfatory - Eyes Open Right Foot Left Foot Equilibratory - Eyes Closed Right Foot Lefit Foot ( 3 Non-Equilibratory Normal Finger to Nose Finger t6 Finger Abnormal Finger to Nose to Finger Heel'-Knee-Shin Succession Movements (Including cheek, rebound posture-holding) Rapidly Alternative Movements Handwriting (if indicated) Speech (articulation, aphasia, agnosia) Grossly . if abnormal specify ( ) Dysarthia ' ( ) Aphasia KS-AF-4 ( ( AVI-17 ». ) 3 [ ) ( 3 [ 3 ( 3 C ( 3 ) (3 ( 3 i 3 3 ( 3 Normal SKILLED ACTS- PRAXIS Both } ; ( ) ( ) j Lett (3 ( Heel to Knee a. b. Other Abnormal Kt. c. 3 ( 3 COORDINATION a. Essential C (3 {. ( 3 ( 3 Abnormal �Neurological Examination Page 3 Reflexes (Code Oabsent, l=sluggish, 2 = a c t i v e , 3«verv a c t i v e , 4«trans1ent clonus, 5=sustained clonus, 6=other SPECIFY UNDER COMMENTS BELOW) Right Biceps Triceps PatellarAchilles Cremasteric Abdominal ( ( ( ( ( ( Left ) ) ) ) ) ) ( ( ( ( ( ( ) ) ) ) ) ) Abnormal No, Yes Babinski Present? ( ) ( ) COMMENTS MENINGEAL IMITATION Normal Abnormal Rt. Straight leg raising ( Both Left ( ) ) SENSORY SYSTEM (tactile, pain vibration, position . If positive sensory signs are present summarize below and indicate details on Anatomical - Standard Form 531) Normal L i g h t Touch Pin Prick V i b r a t i o n (6 ankle, 128hz Tuning Fork) Position (Great Toe) CRANIAL NERVES Right-smell L e f t - sme'll C ) (. ) ( ) Present C ) AVI-18 KS-AF-4 Abnormal Rt.left Absent ( ) ( ) Both �Neurological Examination Page 4 Normal Abnorma1 . _„_ TT~ FUNDUS - Right: lT~abnormal: ( ) bisk Pollar Atrophy ( ) Exudate ( ) Papilledema ( ) Hemorrhage Fundus - Left: If abnormal: ( ) Disk Pollar Atrophy ( ) Exudate ( ) Papilledema ( ) Hemorrhage FIELDS - Right Fields - Left C ) ( ) to confrontation PUPILS fnm Size Shape, position Light, reaction Position of Eyeballs C ) C ) ( ) equal ( ) unequal difference ( ) round ( ) other rt. ( ) other left ( ) normal ( ) abnormal rt.( ). abnormal left ( C ) ) ) ) normal deviation medial rt. ( ) deviation lateral rt deviation medial It. ( ) deviation lateral It deviation medial both ( ) deviation lateral C ) Movements if abnormal describe NYSTAGMUS ( ) rotary ( ) horizontal ( ) vertical ( ( C Draw position: ( PTOSIS ) None ) right MOTOR Clench. Jaw, rt. Clench" Jaw, left SENSORY Symme tr i c C ) ( ) Normal v ( ) ( ) Sensory right Sensory left VC.AC-d »-rt»r l AVI-19 ) left Deviated Left RigHt ( ) C ) ( ) C ) Abnormal \r__ 1 \ T -) ) ( ) None �Neu.ro logical Examination Page S ( -') present r i g h t ( ) present l e f t CORNEAL REFLEX ( ( ) Absent Right ) Absent left MOTOR RIGHT Palpebral Fissure ( PALATE AND UVULA Movement No Yes ( ) C ) Normal Smile Rt. Normal Smile Left ) C Normal ( ) ) Abnormal Normal Deviation C ) Palatal Reflex Rt. Palatal Reflex Left ( ( ) normal ) normal Tongue-Protruded Atrophy ( C ) Central ) No Rt. ( ) ( ( ) abnormal ) abnormal ( ( ) Left )Yes )Right MENTAL STATUS (Alert, clear, cooperative, etc) Gross abnormalities If yes, specify: ( ) yes C ) no ADDITIONAL COMMENTS: Signed Examining Physician KS-AF-4 Left ( ) AVI-20 �Ol C L J . M L . I I CLINICAL RECORD Neurology LA; ."Illin I .(2 of 2) ' A N A T O M I C A L FIGURE NAME Date: (Sirtned - E x a m i n e r ) iCrvT'S IO£H7 i r i C ^ / of - r ;'/ I »n .n [ > / . » t-": /V/i cr.»— y, ,; I HEKI5TC ftUtii.*ih--C For Standard Form 53] . KS-AF-4 AVI-21 �Name: Date: No. jSigned - Examiner) SPECIALTY EXAMINATION - NEUROLOGY - (1 of 2) Standard Form 531 KS-AF-4 AVI-22 �UALTY EXAMINATION - OERMATOIO( NAME_ Oate_ No. Skin: Normal Abnormal ( ( ) - Indicate type and location of lesions on the anatomical figure - attached ( ) Comedones ( ) Palmer Keratosis ( ) Acneifom .lesions ( .) Petechiae ( ) Acnelfprjn Scars ( ) Ecchymoses .'•' . V*; '' - ( ) Deplgjnenjtation ( ) Conjunctiva (- ) InclusliWKGysts ( ) Oral Mucosa ( ) Cutls Rhpmpptdalis ( ) Finger Nails ( } Hyperpigmentation ( ) Toe^Nails ( ) Jaundice ( ) Soles of Feet (" ) ^eniiatpgriaph^ia ( •-')•••' ( : J^ .****** •Photographs taken? If so indicate area> photographed: (ONLY: SUSPECT. LESIONS) ( ) Face (right) ( ) Neck ( ) Chest ( ) Face (left) ( ) Shoulders ( ) Stomach ( ) Face (Full) BIOPSY ( Yes No •) Skin Biopsy Performed (Check if yes) Consent Form obtained? ' ( ) ( ) ^ COMMENTS: Biopsy location .•' Signed AVI-23 �SPECIALTY EXAMINATION - DERMATOLOGY CLINICAL RECORD (2 of 2) ANATOMICAL FIGURE NAME Date: (Sinned - Examiner)_ T ( f ^ T 'S J D I K 1 i r 1C AT ION (F oi ifft-dc-r ~ r it i *n o n f i it t i iff : /V«r*»«"— V* j.', / i / > ! . H K C S I S T C I NO. AUvA.tK.-C Furra an Standard Form 531 , KS-AF-2 AVI-24 �Name: Date: No. _(_Sjqned - Examiner) _SPECIALTY_ EXAMINATION - DERMATOLOGY - ANATOMICAL FIGURE ( 1 of 2) Standard Form 531 KS-AF-2 AVI-25 �P U L M O N A R Y F U N C T I O N Test Date NAME_ Age Case No. Actual Predicted FVC FEV-1 FEV-1/FVC 'Comments regarding test performance: Testing Technician *complete only if performance is questioned - i.e., cold, bronchitis, etc. Equipment Used: Breon Spirometer COMMENTS OF REVIEWING PHYSICIAN Signature_ Reviewing Physician KS-AF-3 rev. AVI-26 �NUMBER: NERVE -:!_,.? J ' | RiST W ! GAIN i i 5K C I1 RECORD SITE 5K BELOW ELBOW ! ABOVE ELBOW I 1 ANKLE FIBULAS >: ' R A • ! ; H[A[^ : I .o t CM 1 j ; CM j ! i ! CM | ji CM 1 14 CM ! i. j i i ! i i I i .10 { i i 1 2K i DIFF. (STMr-CURR. | C.V. | LAT. 2K i i ?£SGS£AL DISTANCE .5K f ] TEMPERATURE: AGE: ! M • j !j ' | l i I ! r ! i ! 1 ! 1 i f I i 1 1 I i . ! �-DIAGNOSTIC SUMMARY *. SYNOPSIS OF POSITIVE FINDINGS Medical History: 1. 2. • . 3. y ; ' '" ~ ' " " " " " " ' * """"" ' ~ I J ™"' — *" '-> •""• "~" •«"""'» ,,.— 4. 5. iWSICAL EXAMINATION 1. General 1. (Complete below and continue on additional page - reference no.) Dermatologic Neurological Including Nerve Conduction Studies Psychological (Bianary Provided) KS-AF-7 • AVI ~28 �DIAGNOSTIC SUMMA *v SYNOPSIS OF POSITIVE FINDINGS Medical History: 1. 2. . • ..,_,...,.,.,, . ____ 3. 4. 5. PHYSICALEXAMINATION (Complete below and continue on additional,page - reference no.) 1. General 2. Dermatologic 3. Neurological Including Nerve Conduction Studies Psychological (Bianary Provided) AVI-29 of. �Appendix VII EXAMINATION PARAMETERS AND ABNORMALITY WEIGHTS USED IN ASSESSING INDIVIDUAL HEALTH Relative Weight Assigned to an Abnormality Organ System Parameter Hematologic RBC WBC Hemoglob'in/Hematocrit RBC Indices (MCV/MCH/MCHC) Platelets Cancer Skin Cancer Systemic Cancer Endocrine T3 Tij FTI Glucose 2-hour Postprandial Testosterone 2 2 3 2 it 3 10 3 6 3 it i» it Pulmonary FEV 1 FVC FEV 1/FVC Ratio X-ray Hepatic Enzymes (SGOT, SGPT, GGTP, Alkaline Phosphatase) Total Bilirubin Direct Bilirubin LDH Cholesterol HDL Triglycerides Uroporphyrins Coproporphyrins ALA Hepatomegaly Reproductive Sperm Count Psychological MMPI (10 Major Scales) Halstead-Reitan IQ Scores (VRQ, PRQ, FLQ) 3 3 3 it 5 4 it 3 3 6 AVII-1 it 5 �General Health Examiner's Assessment Percent Body Fat Sedimentation Rate Systolic Blood Pressure Diastolic Blood Pressure ECG Heart Sounds Eye Grounds Proximal Pulses (Carotid/Femoral) Distal Pulses (Popliteal/Dorsal is Pedis/Posterior Tibial) 3 3 2 7 8 9 7 6 5 BUN Occult Blood WBC in Urine Protein in Urine Specific Gravity 5 2 2 Dermatologic Normal/Abnormal 1 Neurological Smell (Bilateral) Visual Fields (Bilateral) Pupils (Reaction and Movement) Sensation/Corneal Reflex/Jaw Clench (Bilateral) Smile/Palpebral Fissure Palate Movement and Reflex/Neck Range of Motion Speech/Tongue Protrusion Pinprick/Light Touch/Vibration Sense Muscle Status Central Function (Finger-to-Nose/ Romberg/Tremor/Gait) Babinski Tendon Reflexes (Patellar/ Archilles/Biceps) Ulnar Velocities (Above and Below) Peroneal Velocities 1 3 3 3 Cardiovascular Renal 5 AVII-2 3 3 3 3 3 3 4 5 3 3 �Appendix V I I I TOTAL MORTALITY AND MORBIDITY STUDY SITE SPECIFIC MALIGNANT NEOPLASMS Site ICD Code (9th Ed) Mortality Comparison Ranch Hand (First cohort only) Lip, oral cavity, Pharynx (140-149) 1 Morbidity Comparison Ranch Hand 0 S R t 2 0 0 Digestive organs, peritoneum (150-159) Respiratory, intrathoracic (160-165) 0 1 2* 1 0 0 Bone, connective tissue, skin, breast (170-175) 0 0 0 1 Genitourinary organs (179-189) 1 1 6 2 Brain (191-192) 0 1 1 0 0 0 Thyroid (193) 0 0 0 1 0 0 Lymphatic and hematopoietic tissue (200-208) 0 1 0 0 0 No site specification (199) J_ J_ 0_ 0_ £ 0_ TOTAL 4 10 13 0 = Original S = Shifted R = Replaced *Includes 1 Ranch Hand and 1 comparison who expired following interview. AVI II 10 0 1 1 2 �Appendix IX GENERAL HEALTH ANALYSES USING DATA FROM ALL COMPARISONS SELF-PERCEPTION OF HEALTH BY GROUP All Comparisons Number(?) , Ranch Hand Number (jt) Perception Excellent Good Fair Poor 180(10) 523(11) 113(12) 16( 1) 1192 p=0.05 392(38) 159(15) 53( 5) 1039 SELF-PERCEPTION OF HEALTH BY GROUP MEMBERSHIP AND OCCUPATIONAL CATEGORY Occupational Group Excellent Perception of Health Good Fair/Poor p value Officer, flying Ranch Hand Comparison 198 225 121 115 12 10 0.66 Enlisted, flying Ranch Hand Comparison 59 65 83 89 12 13 0.97 Enlisted, ground Ranch Hand Comparison 126 176 225 280 127 103 0.005 DISTRIBUTION OF BODY FAT (PERCENT) Lean <10!0 Obese Q25?) 13 12 Ranch Hand Comparison Normal (10-25?) 821 961 208 217 P = 0.83 PERCENTILE DISTRIBUTION OF SEDIMENTATION RATE RESULTS 5% Ranch Hand Comparison 0 0 25% 50% 75% 95% 1 1 2 2 1 1 12 12 AIX �Appendix X FERTILITY AND REPRODUCTIVE ANALYSES; RANCH HANDERS VERSUS ALL COMPARISONS ANALYSES OF CONCEPTION OUTCOMES, UNADJUSTED FOR MATERNAL COVARIABLES (COMPLETE AND PARTIAL DATA SUBSETS); RANCH HANDERS VERSUS ALL COMPARISONS Yes Pre-SEA (%) Yes No Post/-SEA (?) No Miscarriage Ranch Hand Comparison 295 (14.4) 282 (11.9) 1754 2089 190 (16.0) 233 (14.0) P = 0.01 1001 1430 P •= 0.15 Stillbirth Ranch Hand Comparison 13 (0.6) 21 (0.9) 2036 2350 16 (1.3) 12 (0.7) P = 0.34 1175 1651 P = 0.10 Induced Abortion Ranch Hand Comparison 13 (0.6) 18 (0.8) 2036 2353 62 65 P = 0.62 (5.2) (6.0) 1129 1563 P = 0.36 Live Birth Ranch Hand Comparison 1723 (84.1) 2042 (86.1) 326 329 917 (77.0) 1309 (78.7) P = 0.06 274 354 P = 0.27 AX-1 �CONCEPTION OUTCOMES (COMPLETE DATA SUBSET) BY GROUP MEMBERSHIP AND TIME; RANCH HANDERS VERSUS ALL COMPARISONS Yes Pre-SEA (*) No Post-SEA (*) No Yes Miscarriage Ranch Hand Comparison 239 233 (13.7) (11.6) 1505 1776 156 (15.0) 883 188 (13-2) 1238 P = 0.20 P = 0.05 Stillbirth Ranch Hand Comparison 9 13 (0.5) (0.6) 1735 1996 12 12 (1.2) 1027 (0.8) 1414 P = 0.43 = 0.60 Induced Abortion (0.5) (0.4) Ranch Hand Comparison 1736 2001 37 53 (3.6) (3.7) 1002 1373 0.84 = 0.76 Live Birth Ranch Hand Comparison 1487 1752 (85.3) (87.2) 257 257 833 (80.2) 1170 (82.0) 206 256 0.24 0.08 RESULTS OF THE ANALYSIS OF CONCEPTION OUTCOMES RANCH HANDERS VERSUS ALL COMPARISONS Relationship P value Miscarriage by Group by Pre/Post-SEA 0.70 Stillbirth by Group by Pre/Post-SEA 1.00 Induced Abortion by Group by Pre/Post-SEA 1 .00 Live Birth by Group by Pre/Post-SEA 0.78 AX-2 �ANALYSES OF LIVE BIRTH OUTCOMES, UNADJUSTED FOR MATERNAL COVARIABLES (COMPLETE AND PARTIAL DATA SUBSETS); RANCH HANDERS VERSUS ALL COMPARISONS Yes Pre-SEA (%) No Yes Post-SEA (%) No Learning D1sabi1ity Ranch Hand Comparison 61 81 (3-5) (8.0) 1662 1961 77 81 P = 0.49 (8.4) (6.2) 840 1228 P = 0.05 Physical Handicaps Ranch Hand Comparison 144 176 (8.4) (8.6) 1579 1866 132 130 P = 0.77 (14.4) 785 (9.9) 1179 P = <0.01 Infant Death Ranch Hand Comparison 8 4 (0.5) (0.2) 1715 2038 4 3 P = 0.15 (0.4) 913 (0.2) 1306 P = 0.39 Birth Defects Ranch Hand Comparison 90 123 (5.2) (6.0) 1633 1919 80 84 P = 0.29 (8.7) 837 (6.4) 1225 P = 0.04 Neonatal Death Ranch Hand Comparison 25 28 (1.5) (1.4) 1698 2014 P = 0.84 AX-3 14 3 (1.5) 903 (0.4) 1305 P = <0.01 �LIVE BIRTH OUTCOMES (COMPLETE DATA SUBSET); RANCH HANDERS VERSUS ALL COMPARISONS No Yes Post-SEA (%) No 1430 1680 75 74 (9.0) 758 (6.3) 1096 (9.0) (9.1) 1353 1592 126 118 (15.1) 707 (10.1) 1052 7 (0.5) 3 (0.2) 1480 1749 3 1 78 (5.2) 113 (6.4) 1409 1639 76 77 (9.1) 757 (6.6) 1093 20 (1.3) 28 (1.6) 1467 1724 14 4 (1.7) 819 (0.3) 1166 Yes Pre-SEA (%) Learning Disability Ranch Hand Comparison 57 (3.8) 72 (4.1) Physical Handicap Ranch Hand Comparison 134 160 Infant Death Ranch Hand Comparison (0.4) (0.1) 830 1169 Birth Defects Ranch Hand Comparison Neonatal Death Ranch Hand Comparison RESULTS OF THE ANALYSIS OF LIVE BIRTH OUTCOMES; RANCH HANDERS VERSUS ALL COMPARISON Relationship P Value Learning Disability by Group by Pre-Post SEA 0.12 Physical Handicap by Group by Pre-Post SEA 0.02 Infant Death by Group by Pre-Post SEA 1.0 Birth Defects by Group by Pre-Post SEA 0.02 Neonatal Death by Group by Pre-Post SEA 0.03 AX-4 �Appendix XI INTRODUCTORY LETTERS Secretary of Air Force USAF Surgeon General with Fact Sheet AXI-1 �D E P A R T M E N T OF THE AIR FORCE WASHINGTON. D C 2O33O OFFICE OF T H E S E C R E T A R Y James W. Doe 1215 Middle Grove Norfork, MD 23456 Dear Mr Doe The Air Force will soon begin conducting a very comprehensive health assessment of certain Air Force members who served our Nation in the Vietnam conflict. This health assessment is part of a medical study designed to help determine if you or your fellow Vietnam veterans may have had any compromise to your health as a result of exposure to the complex environment of Southeast Asia. Scientists at the USAF School of Aerospace Medicine have been given the responsibility for conducting this important project. The Air Force Surgeon General will contact you soon with more details and ask for your voluntary participation. A major focus of the President's program for veterans is the resolution of health issues raised by them. The Air Force and I are committed to doing our part in resolving these issues. I ask that you help us and all Vietnam veterans by voluntarily participating in this major study. Sincerely, Verne Orr Secretary of the Air Force AXI-2 �DEPARTMENT OF THE AIR FORCE HEADQUARTERS UNITED STATES AIR FORCE BOLUNG AFB DC 2O332 James W. Doe 1215 Middle Grove Norfork, MD 23456 Dear Mr Doe The Air Force is conducting a very comprehensive health assessment of certain Air Force members who served our Nation in the Vietnam conflict. The USAF School of Aerospace Medicine has been given the responsibility for conducting this study. The purpose of the study is to determine whether there may be any causal relationship between health problems and exposure to the complex and unique environment of the war in Southeast Asia. Simply stated, we do not know if such health effects exist. You are being asked to voluntarily participate in this study because of your unique Southeast Asia experience. Your participation is critical to the success of this study. However, you should not view this invitation to participate as a cause for alarm nor as an implication that you are at risk for any known disease. To insure the scientific validity of the study, both an in-depth interview and a detailed physical examination will be conducted. The administration of the interview will begin soon under the direction of a nationally recognized health survey organization. You will be contacted by phone or letter to arrange a convenient time for an in-home interview which will take from two to three hours. Shortly after the interview you will again be contacted to schedule a physical examination at a nationally recognized civilian medical facility. The physical examination will take approximately four days. Every effort will be made to minimize disruption of your normal activities and to facilitate your participation in the study. Travel and per diem will be paid by the Air Force. For those not precluded by law, a stipend of $100 per day will be paid as a partial compensation for your time. Our intent is to maintain all individual health data in strictest confidence. In case outside parties attempt to gain access to the data, the Air Force and the Department of Justice are committed to protect this individual confidentiality. Only in the event of an adverse final court decision, or in the highly unlikely instance where serious medical deficiencies must be shared with appropriate medical authorities to protect public health and safety, will any personal health data be revealed. You are referred to the Fact Sheet for further information regarding this matter. AXI-3 �This is perhaps one of the most important health studies undertaken by the Air Force. Your voluntary participation is critical to its success. Although you may feel healthy, numerous Vietnam veterans believe that they have illnesses which may be attributable to service in Southeast?Asia. The only way we can get clarification of these difficult questions is through your cooperation and participation. Sincerely PAUL W. MYERS 1 Atch Lieutenant General, USAF, MC Surgeon General Fact Sheet AXI-4 �FACT SHEET INTRODUCTION - The USAF School of Aerospace Medicine, Brooks AFB, Texas, is conducting the study. You are being invited to participate in this study because of your specific duties and period of assignment in Southeast Asia. PURPOSE - To determine whether there is a causal relationship between adverse health effects and exposure to the complex environment of Southeast Asia. METHODS - An in-depth health questionnaire will be administered to you by a member of a health evaluation team from Louis Harris and Associates, Inc. - A complete profile of your current health will be obtained by a physical examination which will be conducted by a nationally recognized outpatient clinic* - Follow-up abbreviated health questionnaires and physical examinations will be conducted at years 3, 5, 10, 15, and 20 of the study. - Travel expenses (including board and lodging) for the physical examination will be paid by the Air Force. - Stipend of $100 per day will be paid to study participants who are not on active duty, Government employed or otherwise precluded by law from receiving such a stipend. - Confidentiality is to be maintained except in two cases: - A judicial order to release personal medical data following an Air Force and Justice Department defended lawsuit. Serious medical findings which impact public health and safety. Two examples of situations in which public health and safety would raise the questions of disclosure are: a participatnt has typhoid fever, a participant who directly impacts the safety of others either in his profession, or as a volunteer, is found to have a serious nerve, heart or mental disorder. In this instance a committee composed of a physician (whose specialty is the area of the identified problem), a physician of your choice, a flight surgeon, a judge advocate (lawyer) and a representative from your field of expertise will be convened to review the medical findings. Before any disclosure Is made to medical authorities, the committee must determine that the findings jeopardize the public health and safety. AXI-5 �BENEFITS TO YOU - You will receive a complete health review and physical examination of top level executive calibre at no cost to yourself. - You will be completely informed of all examination results. - The Information from this study will be provided to a physician of your choice if you so request. - Questions concerning the study may be referred to the USAF School of Aerospace Medicine, Epidemiology Division, Brooks Air Force Base, Texas 78235, or by calling collect AC 512 536-3309. - If you have recently changed your address or have an unlisted phone number, please advise the USAF School of Aerospace Medicine at the above address and phone number so that your records may be properly updated. AXI-6 �Appendix XII OCCUPATIONAL CATEGORY AND RACE OF THE FULLY COMPLIANT POPULATION IN PERCENT AND COUNTS Occupation Code Ranch Hand % Counts Comparisons Original Shifted Replaced % Counts % Counts % Counts Won- Black 1 2 3 Officerr-Pilot 82 Officer-Navigator 96 Officers-Other 83 278 76 20 71 81 77 218 58 10 78 100 67 32 6 8 59 71 100 94 12 7 Officer Subtotal 374 73 286 78 46 61 113 Enlisted-Fit Eng Enlisted-Other 93 86 172 436 84 75 141 301 94 75 17 91 70 75 26 133 Enlisted Subtotal 88 608 77 442 77 108 74 159 8? 982 76 728 77 154 68 272 Officer-Pilot 67 Officer-Navigator 100 Officer-Other 0 4 2 0 80 100 100 4 2 1 f 0* 0* 0* - * * * Officer Subtotal 67 6 88 7 ~ 0* 1 * 93 90 13 44 67 76 10 28 69 0 9 83 55 5 11 Enlisted Subtotal 90 4 5 85 57 73 38 69 9 62 16 88 63 75 45 69 9 62 16 87 1045 76 773 77 163 68 288 Total Non-Black Black 1 2 3 4 5 Enlisted-Fit Eng Enlisted-Other Total Black Entire Population AXII �Appendix XIII SELF-REPORTED REASONS FOR NONCOMPLIANCE TO QUESTIONNAIRE Reason Fear of Physical Job Commitment Dissatisfaction with the Military No Time - No Interest No Travel, Distance, Family Confidentiality/ Active Duty Health Reasons Passive Refusals* TOTAL Ranch Hand - Original Shifted Replaced Total 12 (242) 2 (22) 14 (112) 2 (3%) 2 (3%) - 3 (92) 9 (13) 1 (82) 1 (22) 11 (82) 23 (68?) 36 (5150 9 (752) 15 (292) 60 (452) 2 (5%) 0 6 (18$) 10 (14*) 2 (162) 12 (242) 1 (22) 10 (202) 22 (172) 1 (12) 23 (172) 34 11. (16« 70 12 ^Unresponsive to scheduling attempts. AXIII 51 133 �Appendix XIV SELF-REPORTED REASONS FOR NONCOMPLIANCE TO PHYSICAL EXAMINATION Reason Ranch Hand Fear of Physical 6 (5%) Job Commitment 29 (2450 Dissatisfaction With the Military 5 (450 No Time - No Interest 53 (13*) No Travel-Distance 4 (450 Family ConfidentialityActive Duty 11 (951) Health Reasons 5 (450 Passive Refusals* 9 (7$) Original 3 (2$) 51 (29%) r Shifted Replaced Total 3 (4$) 6 (2?) 10 (21%) 20 (24$) 81 (27$) - T". 0 94 (53%) 17 (46$) 10 (5?) 4 (11?) 7 (950 21 (7$) 8 (450 3 (250 10 (550 2 (555) 1 (3$) 3 (8$) 6 (750 1 (150 2 (355) 16 (5%) 5 (2$) 15 (555) 122 179 *Unresponsive to scheduling attempts. AXIV 37 43 (52JO 154 (5250 82 298 �Appendix XV COEFFICIENT OF VARIATION FOR TRI-LEVEL CONTROLS Control values were analyzed on 15 different laboratory tests for the period from January 14 thru December 13, 1982. Triplicate values were collected on each laboratory test at each of three different ranges (I, II, and III) except for triglyceride and alcohol which each had only ranges II & III. These control data were received from 91 groups of study participants reporting for physical examination (usually 2 groups per week). A total of 91 sets of control values were received for II & III and a total of 78 for I. A one-way analysis of variance procedure was used, on each trilevel laboratory test to determine whether or not the data varied significantly among the 91 (or 78) groups. The error term used was the pooled variance (o£) from the {* triplicate values recorded for each group. The group means differed signifi" cantly at the 0.01 level on nearly all of the analyses (40 out of 42). Hence, the variability among the groups was significantly more than can be explained by the variability among the triplicate readings. A variance component for the group-to-group variability (o^) was estimated from the one-way analysis of variance and the standard deviation of a single measurement/group was estimated as: 7 /XO °e « + ° Each coefficient of variation given in the table below was computed as: o x 100 x CV5& where the x is the mean of the control values for each trilevel/laboratory test. Ninety-five percent confidence limits were computed as follows: / N(N-1)y2 <.. N(N-1)y2 V where v2 is the square of the observed CV, N = 91 or 78 (depending on the trilevel of interest) and o and u are the population parameters associated with o and k respectively. The interval for the CV$'s marked with an asterisk in the table below did not contain the USAFSAM required CV%, implying that the estimated CV$ differed significantly from the required at the 5% level. The estimate exceeded the required on 12 of the 40 trilevel sets. The average CV$ was not tested. AXV-1 �SAMPLE MEAN, STANDARD DEVIATION AM) COEFFICIENT OF VARIATION FOR TRI-LEVEL CONTROLS USED FOR 15 BIOCHEMICAL ASSAYS Test x 6.6 0.296 Creatinine 0.602 - 16.6 0.415 45.9 1.6970.024 0.702 _n III CV% 0* BUN USAFSAM Require- I III II CVJt CV% Average 1.53 2.84 2.00 1.40 0.93 1.16 2.50 1.41 0.69 1.19 3.50 1.49 1.89 1.50 4.50* 2.50* 5.6370.053 nent Glucose 49.4 0.719 100.2 1.408 212.6 1.457 1.46 Cholesterol 104.2 2.357 151.7 2.257 2.15* 2.04* 72.39 1.869 177.4 2.464 2.58* 1.39 1.98 2.10 31.6 0.786 1.535 5.42* 2.48 4.06* 3.99 3.50 2.236 115.8 Triglycerides HDL 20.5 1.111 37.8 Total Bilirubin 0.930 0.040 1.4370.045 5.4700.133 Conjugated Bilirubin 0.400 0.043 0.8110.043 2.3830.110 Alk Phos 5.2740.203 9.8550.273 28.37 .438 4.34* 3.12* 2.42* 3.29 10.74* 5.33 1.50 4.60 6.89 6.00 3.85* 2.77 1.54 2.72 2.70 SCOT 38.32 1.18 56.73 1.41 171.2 2.18 3.08 2.48 1.27 2.28 4.00 SGPT 28.16 2.697 26.65.0.999 101.6 1.133 2.70 3.75 1.12 2.52 5.00 GGPT 31.97 0.985 43.68 1.033 186.79 2.20 3.08 2.37 1.18 2.21 5.00 2.612 441.7 1.35 1.57 0.93 1.28 2.20 2.08 4.00 2.57 2.88 5.00 1.54 1.53 1.54 LDH CPK Alcohol 147.9 65.5 1.997 165.8 1.362 139.1 5.559 48.5 0.749 4.104 440.9 11.34 99.2 1.518 *P<0.05, reject the hypothesis that the sample CV% came from the population with required AXV-2 �Appendix XVI SPECIFIC RULES FOR ENTRY INTO THE MORBIDITY STUDY RULES CIRCUMSTANCES Ranch Hander (RH) Dies Following Initial Data Collection Control Followed Throughout and Replaced as Necessary RH Dies of Combat Cause Medical Records Reviewed; No Control Set Formed RH Dies of Noncombat Cause Prior to Initial Data Collection 1st Order Surrogate Interview Accomplished; Control Selected and Followed Throughout; as Necessary RH Noncompliant for Baseline Questionnaire and Physical Control Followed Throughout the Study; Replaced as Necessary RH Compliant for Questionnaire Noncompliant for Baseline Physical Examination Control Followed Throughout the Study; Replaced as Necessary RH Noncompliant During Follow-up Control Followed Throughout the Study; Replaced as Necessary Control Dies Following Initial Data Collection Not Replaced in the Prospective Study of Morbidity Control Dies of Combat Cause Medical Records Reviewed; Excluded from Further Study Control Dies of Noncombat Cause Prior to Initial Data Collection Included in Mortality and Retrospective Morbidity Studies; Surrogate Interview Accomplished. Not Included in Prospective Morbidity Study and Replaced by a Living Compliant Control. Control Noncompliant for Baseline Physical Examination Control Followed Throughout Study Replace as Necessary Control Noncompliant During Follow-up Control Followed Throughout Study Replace as Necessary Noncompliant Control Returns to Study Both Primary and Replacement Controls will be Continued in Study AXVI �Appendix XVII PERCENT COMPLIANCE BY FLYING CODE AND MILITARY STATUS OF THE RANCH HAND AND COMPARISON POPULATION NON-BLACK OFFICERS Military Status** and Flying Code* Fully Compliant Participation Tart Tally NonCompliant Compliant Total Ranch Hand 19 .4 10 .3 36 ,5 3 .8 4 .8 11 .1 AF RF SVF AN RN SVN TOTAL 84.7 3.2 3.5 11.6 0.0 1.6 1.9 100 100 100 100 100 100 12.1 3.2 100 8.9 0.0 39,3 10.0 2.3 8.5 100 100 100 100 100 100 9.3 100 12.5 0.0 0.0 0.0 4.0 0.0 100 100 100 100 100 100 Comparison Original AF RF SVF 58.9 86.0 39.3 75.0 86.6 62.9 AN RN SVN TOTAL Comparison 72.9 17.8 Shifted 87.5 100.0 37.5 75.0 96.0 61.5 AF RF SVF AN RN SVN TOTAL Comparison 78.0 18.6 Replaced 7.9 0.0 43,.3 1 1 ,,1 10.4 17.4 57.9 83.3 32.4 88.9 77.1 63.0 AF RF SVF AN RN SVN TOTAL 61.4 20.7 Flying Nonflying Active Retired **SV - Separated/Reserve *F *N **A **R 100 = = = = AXVII 100 100 100 100 100 100 17.9 100 �Appendix XVIII RELATIVE RISKS FOR SELECTED CLINICAL END POINTS CLINICAL PARAMETERS Self Perception of Poorer Health S40 yrs Self Perception of Poorer Health >40 yrs Older Than Stated Age Lean by Body Fat Obese by Body Fat Sed Rate S40 Sed Rate >40 Skin Cancer Systemic Cancer Percent* RH C Relative Risk Confidential Interval Exact Normal Approx 19.3 10.6 1.82 (1.18,2.10) (1.17,2.87) 21.4 0.8 1.2 19.8 0.5 5.8 15.8 0.1 0.9 20.3 4.2 5.4 1.35 5.92 1.37 0.97 0.13 1.07 (1.05,1.76) (.80,262.37) (.51,1.043) (.80,1.18) (1.05,1.75) (.76,126.11) (.51,3.78) (.80,1.18) (.66,1.78) (.66,1.77) 2.35 1.20 (1.18,5.11) (.46,3.33) (1.16,4.90) (.47,3.15) 3-35 1.24 1.42 1.03 Childless Marriages Not Having Desired Children Abnormal Sperm Miscarriage Stillbirth Induced Abortion Non-live Birth Learning Disability Physical Handicaps Infant Death Birth Defects Neonatal Death 20.9 19.5 1.07 (.93,1.23) (.93,1.23) 18.3 4.6 15.9 1.3 5.2 23.0 8.4 13.8 -0.5 8.7 1.5 19.9 4.6 13.6 0.8 6.8 22.1 6.9 11.4 0.4 6.5 0.4 0.92 0.99 1.17 1 .60 0.76 1.04 1.22 1.21 1.35 1.35 3-78 (.76,1.10) (.54,1.86) (.95,1.45) (.65,4.30) (.54,1.087) (.89,1.22) (.86,1.75) (.93,1.58) (.26,8.67) (.94,1.95) (1.06,20.45) (.76,1.10) (.54,1.83) (.95,1.45) (.65,4.06) (.54,1.09) (.88,1.22) (.86,1.75) (.93,1.58) (.28,7.09) (.95,1.94) (1.03,16.50) Reported Neuro Disease Smell, Left Smell, Right Visual Fields, Left Visual Fields, Right Light Reaction Ocular Movement Sensation, Left Sensation, Right Corneal Reflex Jaw Clench Smile Palpebral Fissure Balance Gag Reflex Speech Tongue in Midline Palate and Uvula Neck Motion Pin Prick 5.18 4.59 .1.82 1.56 1.43 1.63 .26 0.29 .39 0.19 .52 0.77 34.8 35.3 .52 .67 .38 .39 .19 .13 .096 0 .26 .38 5.65 5.43 19.9 19.5 1.44 1.68 .28 o.30 .45 .29 .13 3^92 3.23 9.41 9.56 .89 1;17 1.14 1.12 .49 1.48 .99 1.29 .99 1.48 (.58,1.37) (.54,2.63) (.51,2.68) (.13,13.28) (.041,4.31) (.40,6.68) (.86,1;12) (.33,6.03) (.17,6.74) (.077,87.25) (.58,1.37) (.55,2;55) (.51,2.59) (.15,9.46) (.06,3.60) (.41,5.80) (.86,1.13) (.34,5.25) (.19,5.54) (.11,41.17) 1.48 1.04 1.04 .86 (.21,16.35) (.70,1.57) (.86,1.27) (.38,1.94) (.24,11.59) (.70,1.56) (.86,1.26) (.39,1.89) 1.50 2.22 1.21 .98 (.22,16.60) (.18,116.45) (.73,2.06) (.73,1.33) (.24,11.78) (.21,55.29) (.73,2.04) (.73,1.33) *Categorical values displayed as % abnormal with relative risk. AXVIII-1 �Appendix XVIII (Cont) RELATIVE RISKS FOR SELECTED CLINICAL END POINTS CLINICAL PARAMETERS RH Percent* C Relative Risk 95/5 Confidential Interval Exact Normal Approx Light Touch Muscle Status Vibration Patellar Reflex Achilles Reflex Biceps Reflex Babinski Tremor Coordination Romberg Gait 7.08 3.56 7.56 0.385 3.77 0.771 0.871 5.29 4.62 19.9 2.31 7.46 .95 3.62 .98 8.76 .86 .59 0.649 1.12 3.37 0.519 1.49 0.259 3.36 4.01 1.32 3.88 1.89 1.04 19.2 1.27 1.83 (.67,1.35) (.59,1.65) (.62,1.20) (.12,2.75) (.67,1.90) (.40,6.72) (.70,31.96) (.84,2.10) (.75,1.93) (.86,1.26) (.64,2.65) (.67,1.35) (.59,1.64) (.62,1.20) (.14,2.53) (.67,1.88) (.41,5.84) (.69,22.50) (.84,2.08) (.74,1.91) (.-86,1.26) (.64,2.58) Psychological Illness Isolation U14) Halstead-Reitan SCOT SGPT GGPT Alk Phos T Bill D Bili 3-45 4.62 33.5 13.9 7.8 10.8 17.3 1.8 29.0 1.7 26.0 34.7 2.07 2.34 33.5 14.8 8.6 10.3 16.9 2.0 29.7 2.1 27.7 36.1 1.67 1.97 1.00 .93 .91 1.053 1.020 .90 .98 .80 .94 .96 (.91,3.20) (1.14,3.58) (.85,1.17) (.74,1.18) (.66,1.26) (.79,1.40) (.83,1.26) (.43,1.90) (.84,1.13) (.38,1.67) (.80,1.10) (.85,1.10) (.90,3.12) (1.13,3.50) (.86,1.17) (.-74,1.18) (.66,1.26) (.79,1.40) (.83,1 .26) (.44,1.87) (.84,1.13) (.39,1.65) (.80,1.097) (.85,1.097) Uroporphyrins Coproporphyrins d-Aminolevulinic Acid 6.5 0.2 0.0 6.8 0.0 0.0 .94 (.58,155) (.58,1.54) Verified Hepatitis Jaundice Cirrhosis Other Hepatic Verified Reported Hepatomegaley Observed Hepatomegaley Skin Patches, etc., Reported Reported Acne (Post SEA) Reported Acne Severity Reported Chloracne Comedones Acneiform Lesions Acneiform Scars Cysts Hyperpigmentation Other Abnorms Any Abnormality 3.83 4.14 4.53 .39 .39 1.71 0.78 .93 ;93 .99 3.93 1.02 2.00 (.57,1.51) (.59,1.48) (.17,6.72) (1.13,21.07) (.48,2.26) (.75,6.21) (.57,1.50) (.59,1.47) (.19,5.52) (1.09,16.99) (.48,2.20) (.74,5.69) 1.23 1.18 1.24 .80 1.050 1.047 1.082 1.11 1.17 .78 1.00 (1.09,1 .40) (.67,2.18) (.74,2.21) (.55,1.21) (.87,1.26) (.85,1.29) (.82,1.43) (.84,1.46) (.84,1.65) (.61, .98) ( . 90 , 1 . 1 1 ) (1.09,1.39) (.67,2.15) (.74,2.20) (.55,1.21) (.87,1.26) (.85,1 .29) (.82,1.43) (.84,1.46) (.84,1.64) (.61, .98) (.90,1.11) LDH Choi Trig 4.21 .38 1.53 1.75 1.56 44.2 17.3 41.4 36 21.7 18.3 11.2 11 .6 8.3 12.6 45.0 36.0 14.7 33.3 45 20.7 17.5 10.4 10.5 7.1 16.3 44.9 AXVIII-2 �Appendix XVIII (Cont) RELATIVE RISKS FOR SELECTED CLINICAL END POINTS CLINICAL PARAMETERS Percent* C RH Relative Risk 95% Confidential Interval Normal Approx Exact Systolic Blood Pressure 10.4 14.3 .73 (.46,1.18) (.46,1.17) 23.1 24.6 .94 (.73,1.20) (.73,1.20) 5.2 5.4 .97 (.45,1.28) (.46,2.12) .84 13-9 23.1 .87 28.4 1.061 6.4 .66 8.5 .95 .86 2.7 8.4 1.038 9.5 1.35 .98 17.6 .52 1.85 .96 14.06 14.10 1.00 .670 .390 1.73 (.58,1.21) (.62,1.23) (.86,1.32) (.05,8.73) (.49,1.88) (.27,2.97) (.65,1.67) (.99,1.88) (.80,1.21) (.54,8.05) (.79,1.27) (.40,10.32) (.58,1.21) (.62,1.22) (.86,1.32) (.068,6.43) (.49,1.86) (.28,2.76) (.65,1.66) (.99,1.88) (.80,1.21) (.54,6.97) (.79,1.27) (.41,8.39) RBC WBC HGB HCT MCU MCH MCHC PLT 7.43 6.28 12.45 11.65 3.28 •3.'27 8.30 7.59 3.76 3.40 46.24 39.66 9.46 10.47 1.16 1.97 (.82,1.71) (.82,1.71) (.82,1.40) (.82,1.39) (.59,1.74) (.59,1.72) (.78,1.53) (.78,1.53) (.66,1.90) (.66,1.86) (1.043,1.30) (1.043,1.31) (.68,1.21) (.68,1.21) (.25,1.34) (.26,1.32) Occult Blood in Urine Protein in Urine Reported Kidney Disease T3+ T3 + 1.341 1.293 1.037 2.6 .50 1.3 1.60 5.6 3.5 .26 3.34 .87 5.72 8.47 .68 .77 • 39 1.98 .10 .39 .25 .29 0 0 .26 .88 15.19 17.27 .48 .52 .93 .77 4.93 6.37 <40 yrs Systolic Blood Pressure £40 yrs Diastolic Blood Pressure <40 yrs Diastolic Blood Pressure yrs EGG Findings <40 yrs EGG Findings <:40 yrs EGG A <40 yrs EGG A £40 yrs Eye gnds <40 yrs Eye gnds £40 yrs Peripheral Pulses Reported Heart Disease Reported Heart Attack Verified Heart Disease Verified Heart Attack T4 + FTIt FTI+ GLU TEST* TEST* 11.6 20.1 30.2 4.2 8.1 2.3 8.7 12.8 17.3 AXVIII-3 1.18 1.069 1.003 1.094 1.11 1.17 .90 .59 (.43,2.60) (.24,1.07) (1.00,2.59) (.69,31.77) (.47, .96) (.48,11.55) (.005,3.08) (.44,2.50) (.25,1.067) (1.00,2.56) (.68,22.37) (.47, .96) (.48,9.38) (1.13,2.64) (.71,1.09) (.20,4.67) (.52,1.16) (.71,1.094) (.22,4.098) (.52,1.15) �Appendix XVIII (Cont) MEAN SHIFTS FOR SELECTED CLINICAL END POINTS CLINICAL PARAMETERS R MEAN VALUE H C Conceptions per Participants 2.80 Mean Number of Marriages 1.24 Ulnar Nerve Cond (Above) 55.89 Ulnar Nerve Cond (Below) 60.52 Peroneal 48.23 Fatigue Score (HS ed) 15.33 Anger Score (HS ed) 11.27 Erosion (HS ed) 22.34 Anxiety (HS ed) 24.62 Depression (HS ed) 5.79 Fatigue (Coll ed) 12.79 Anger (Coll ed) 9.55 Erosion (Coll ed) 20.19 Anxiety (Coll ed) 21.23 Depression (Coll ed) 5.22 Cornell Index (HS ed) 9.21 Cornell Index (Coll ed) 3.66 MMPI Validity Scale (HS ed) 1.85 MMPI Defensiveness Scale (HS ed) 51.99 MMPI Consistency (HS ed) 51.95 MMPI Denial (HS ed) 53.95 MMPI Hypochondria (HS ed) 59.74 MMPI Depression (HS ed) 60.47 MMPI Hysteria (HS ed) 60.12 MMPI Psychopathic (HS ed) 56.38 MMPI Masc/Fem (HS ed) 55.94 MMPI Paranoia (HS ed) 51.72 MMPI Anxiety (HS ed) 57.27 MMPI Schizo (HS ed) 57.53 MMPI Mania (HS ed) 56.03 MMPI Social (HS ed) 52.31 MMPI Validity (Coll ed) 1.48 MMPI Defensiveness (Coll ed) 50.26 MMPI Consistency (Coll ed) 48.74 MMPI Denial (Coll ed) 58.46 MMPI Hypochondria (Coll ed) 55.42 MMPI Depression (Coll ed) 55.34 MMPI Hysteria (Coll ed) 59.75 MMPI Psychopathic (Coll ed) 55.21 MMPI Masc/Fem (Coll ed) 59.15 MMPI Paranoia (Coll ed) 53.62 MMPI Anxiety (Coll ed) 53.62 MMPI Schizo (Coll ed) 54.70 MMPI Mania (Coll ed) 55.22 MMPI Social Introversion (Coll ed) 46.83 Verbal IQ (HS ed) 110.61 Verbal IQ (Coll ed) 117.00 Perf IQ (HS ed) 102.40 Perf IQ (Coll ed) 113.70 AXVIII-4 MEAN SHIFT 2.79 1.22 56.12 60.71 48.93 13.64 9.99 20.00 21.91 5.30 12.83 9.46 19.90 20.51 4.46 6.44 3.44 1.73 52.03 50.65 55.63 57.22 58.39 58.90 55.89 54.85 50.68 55.59 55;97 54.49 50.80 1.95 50.33 48.44 58.41 54.65 54.57 59.32 55.66 57.87 53.26 54.18 54.89 54.05 .0036 .0164 -0.004 -0.003 -0.014 .1239 .1281 .1170 .1237 .0925 -.0031 .0095 .0146 .0351 .1704 .4301 .0640 .0694 -.0008 .0257 -.0302 .0440 .0356 .0207 .0088 .0199 .0205 .0302 .0279 .0283 .0297 -.241 -.0014 .0062 .0009 .0141 .0141 .0072 -.0081 .0221 .0068 -.0103 -.0035 .0216 47.50 101.73 116.84 104.14 112.37 -.0141 .0873 .0014 -.0167 .0118 �Appendix XVIII (Cont) MEAN SHIFTS FOR SELECTED CLINICAL END POINTS CLINICAL PARAMETERS R MEAN VALUE H C MEAN SHIFT Full Scale IQ (HS ed) Full Scale IQ (Coll ed) 101.18 117.30 102.74 116.59 -.0152 .0061 SCOT SGPT GGPT Alk Phos T Bill D Bill LDH Choi 33.0 20.3 10.1 7.69 .57 .23 142.1 212.2 33.1 20.5 39.3 7.52 .58 .24 141.7 216.6 -.0030 -.0098 .0204 .0226 -.0172 -.0417 .0028 -.0203 Trig Uroporphyrins Coproporphyrins d-Aminolevulinic Acid 121.9 30.2 30.8 2337.1 AXVIII-5 124.1 30.8 30.8 2371.4 -.0177 -0.0195 0.0 -0.0145 �Appendix XIX SPOUSE AND PARTICIPANT REPORTED BIRTH DEFECTS NOT MEETING STUDY CRITERIA Original Total Ranch Hand Comparison Comparison I CD NAME 140-239 NeopI asms Malignant melanoma-skin Uncertain behavior of skin Unspecified nature, ovarian 240-279 EndocrIne-MetaboIi c-Nutr i 11onaI-1mmune Gout Cystic flbrosis HypogammaglobulInemla Alblnlsm(ocular) 280-289 Blood & Blood-Forming Chronic lymphadenitis 0 1 2 290-319 Mental 8 2 8 16 23 Hyperkinetlc syndrome Dyslexia Learning dlsabiIIty Mental retardation 320-389 Nervous System & Sense Organs Epllepsy Meningitis Unspecified brain damage Polyneuropathy Visual disturbance LagophthaImos Esotropla Cerebral palsy Congenital deafness Endophthalmltls AmbIyopIa Acoustic nerve disorder Hearing loss Chronic otltls media 390-459 Heart Disease Unspecified 0 2 460-519 Respiratory 4 6 21 AIlergy Asthma Pulmonary congestion & hypostasis Unspecified disease of respiratory system 520-579 Digestive Tooth disorders Esophagitis Unspecified hernia Ruptured rectum 580-629 Genitourinary Kidney disorders 2 680-709 Skin and Subcutaneous Tissue Eczema Unspecified skin disorders 2 AXIX-1 �Appendix XIX (continued) SPOUSE AND PARTICIPANT REPORTED BIRTH DEFECTS NOT MEETING STUDY CRITERIA Or IgInaI TotaI Ranch Hand Comparison Comparison ICO NAME 710-739 Musculoskeletal & Connective Tissue Arthralgla Juvenile osteochondrosls of spine Sco11os i s Arthrogryposis Foot Deformity 760-779 Conditions Originating In the Perinatal Period Premature Hyaline membrane disease Birth trauma Atelectasls Perinatal Infection RH ISO Immunization Neonatal jaundice Transient neonatal electrolyte disturbance Unspecified hematological disorder Complications of labor & delivery ABO ISO Immunization FetaI hemorrhage 32 31 42 780-799 Symptoms, Signs, and ill-Defined Conditions Sudden death syndrome Functional & undlagnosed cardiac murmurs Enlarged lymph glands Others Jaundice, not of newborn Rash Other umbilical hernia SwelI ing or lump Lack of physiological development Billuria 26 15 18 120 81 122 TOTAL AXIX-2 �Appendix XX OBSERVED CANCER VERSUS SEER* DATA EXPECTED IN 1174 RANCH HANDERS (RH) AND 956 ORIGINAL COMPARISONS (COM) (QUESTIONNAIRE COMPLIANT) Probability Observed of Probability of Olbserved or Larger Cancer Type Expected Observed RH RH RH RH RH Testicle Bladder Digestive Lip and Oral Genitourinary 1 .09656 1.05838 4.00809 1.31739 3.59195 2 2 0 it 6 .2009 .1945 .0180 .0336 .0822 ;•; .1545 COM COM COM COM COM Testicle Bladder Digestive Lip and Oral Genitourinary .912751 .927593 3.52238 1.15221 3.11509 0 1 4 2 2 .4012 .3671 .1898 .2099 .2154 1.0000 .6047 .4684 .3201 .8179 *Surveillance, Epidemiology, and End Results (SEER) ^Statistically significant deficit ***Statistically significant excess AXX .2997 .2857 1.0000** .0448*** � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 058 Folder The folder containing the original item. 1573 Series The series number of the original item. Series III Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Lathrop, George D. Patricia M. Moynahan Richard A. Albanese William H. Wolfe Description An account of the resource <strong>Corporate Author: </strong>United States Air Force School of Aerospace Medicine, Aerospace Medical Division (AFSC), Brooks AFB, Texas Date A point or period of time associated with an event in the lifecycle of the resource February 24 1984 Title A name given to the resource An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides: Baseline Morbidity Study Results Subject The topic of the resource Air Force Health Study ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/4ca43099304adab60cb910c56dd30288.pdf 11fc206d9fa1651135565ef9cbb253a7 PDF Text Text Item ID Number 01570 Aether Lathrop, George D. Corporate Author United States Air Force School of Aerospace Medicine, Report/Article Title Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides: Study Protocol Journal/Book Title Yeer MODth/Day December Color D Number of Images 192 Descrlpton Notes Wednesday, May 23, 2001 Page 1571 of 1608 �ALV1N L. YOUNG, Major, USAF Consultant, Environmental Sciences Report SAM-TR- 82-44 EPIDEMIOLOGIC INVESTIGATION OF HEALTH EFFECTS IN AIR FORCE PERSONNEL FOLLOWING EXPOSURE TO HERBICIDES: STUDY PROTOCOL George William Richard Patricia D. H. A. M. Lathrop, Colonel, USAF, MC Wolfe, Lieutenant Colonel, USAF, MC Albanese, M.D. Mpynahan, Colonel, USAF, NC December 1982 Initial Report for Period October 1978 - December 1982 Approved for public release; distribution unlimited. Prepared for: The Surgeon General United States Air Force Washington, D.C. 20314 USAF SCHOOL OF AEROSPACE MEDICINE Aerospace Medical Division (AFSC) Brooks Air Force Base; Texas 78235 �NOTICES This initial report was submitted by personnel of the Epidemiology Division and the Data Sciences Division, USAF School of Aerospace Medicine, Aerospace Medical Division, AFSC, Brooks Air Force Base, Texas, under job order 2767-00-01. When Government drawings, specifications, or other data are used for any purpose other than in connection with a definitely Government-related procurement, the United States Government incurs no responsibility or any obligation whatsoever. The fact that the Government may have formulated or in any way supplied the said drawings, specifications, or other data, is not to be regarded by implication, or otherwise in any manner construed, as licensing the holder, or any other person or corporation; or as conveying any rights or permission to manufacture, use, or sell any patented invention that may in any way be related thereto. The Office of Public Affairs has reviewed this report, and it is releasable to the National Technical Information Service, where it will be available to the general public, including foreign nationals. This report has been reviewed and is approved for publication. WILLIAM H. W0fcfE, Lt Col, USAF, MC Project Scientist ROY L. DEHART Colonel, USAF, MC Commander G E O R G E . LATHROP, Colonel, USAF, MC Supervisor �UNCLASSIFIED SECURITY CLASSIFICATION OF THIS P A G E (When Data Entered) READ INSTRUCTIONS BEFORE COMPLETING FORM REPORT DOCUMENTATION PAGE 1. REPORT NUMBER 2. GOVT ACCESSION NO SAM-TR-82-44 4. TITLE (and Subtitle) 3. RECIPIENT'S C A T A L O G NUMBER 5. TYPE. OE REPORT 4 PERIOD COVERED Initial Report October 1978 - December 1982 EPIDEMIOLOGIC INVESTIGATION OF HEALTH EFFECTS IN AIR FORCE PERSONNEL FOLLOWING EXPOSURE TO HERBICIDES: STUDY PROTOCOL 6. P E R F O R M I N G O^G. R E P O R T N U M B E R 7. AUTHOR(s) 8. C O N T R A C T OR G R A N T N U M B E R f s ; George D. Lathrop, Colonel, USAF, MC William H. Wolfe, Lieutenant Colonel, USAF, MC Richard A. Albanese, M.D. Pat.Hrla M., Mnynahan, Colonel, USAF. NC 9. P E R F O R M I N G ORGANIZATION N A M E AND ADDRESS 10. P R O G R A M ELEMENT. PROJECT, TASK AREA a WORK UNIT NUMBERS USAF School of Aerospace Medicine (EK) Aerospace Medical Division (AFSC) Brooks...Air Force Base, Texas 78235 65306F 2767-00-01 12. REPORT DATE 11. CONTROLLING OFFICE NAME AND ADDRESS December 1982 USAF School of Aerospace Medicine (EK) Aerospace Medical Division (AFSC) <3. NUMBER OF PAGES 185 4. MONITORING AGENCY NAME ft ADDRESSfM different from Controlling Office) 15. SECURITY CLASS, (of this report) Unclassified o. DECLASSIFI CATION/DOWN GRADING" SCHEDULE 6. DISTRIBUTION STATEMENT (of this Report) Approved for public release; distribution unlimited. 7. DISTRIBUTION STATEMENT (of the abstract entered In Block 20, It dltlerent from Report) 8. SUPPLEMENTARY NOTES 9. KEY WORDS (Continue on reverse aide If necessary and Identify by block number) Epidemiologic investigation Study design protocol Air Force Health Study RANCH HAND Matched cohort design 20. Nonconcurrent prospective design Defoliants Phenoxy herbicides Herbicide Orange Agent Orange 2,4-D 2,4,5-T Dioxin TCDD A B S T R A C T (Continue on reverse side If necessary and identity by block number) In 1979 the United States Air Force (USAF) made the commitment to Congress and to the White House to conduct an epidemiologic study of the possible health effects from chemical exposure in Air Force personnel who conducted aerial herbicide dissemination missions in Vietnam (Operation RANCH HAND). The urpose of this epidemiologic investigation is to determine whether long-term i FORM J A N 73 EDITION OF i MOV 65 is onsoi. !:TE UNCLASSIFIED S E C U R I T Y C L A S S I F I C A T I O N OF THIS P A G E ("IVhen Data Entered) �UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PAGE(HT>en Data Entered; 20. ABSTRACT (Continued) health effects exist and can be attributed to occupational exposure to herbicides. This study uses a matched cohort design in a nonconcurrent prospective setting incorporating mortality, morbidity, and followup studies. Detailed computer searches of Air Force personnel records, with several crossreferencing techniques, have ensured total ascertainment of the RANCH HAND population. The unique circumstances of exposure in this population of 1264 individuals will permit a semiquantitative estimate of exposure. A comparison group will be formed from a population of 23,978 flight crew members and support personnel who were assigned to duty in Southeast Asia (SEA), but were not occupationally exposed to herbicides. These individuals will be matched to RANCH HAND personnel for the variables of age, type of job, and race. Since both the exposed subjects and their selected controls performed similar combat or combat-related jobs, many of the physical and psychophysiologic effects of combat stress and the SEA environment will also be equivalent in the two groups. In the analysis of mortality, each exposed subject and five randomly selected controls will be followed yearly for at least 20 years, constituting a 1:5 mortality design. The first of the mortality controls will be selected and entered into the questionnaire and physical examination phases of the study, producing a 1:1 morbidity design. The initial questionnaire will look backwards in time and will reconstruct occupational, social, and medical data to quantitate morbidity endpoints and confounding factors. All RANCH HAND personnel and their primary controls will be asked to participate in a comprehensive physical examination, with special emphasis being placed on dermatologic, neuropsychiatn'c, hepatic, immunologic, reproductive, and neoplastic conditions. The questionnaire will be developed and administered by a civilian opinion research organization of national stature under contract to the U.S. Air Force. In-home, face-to-face interviews will be conducted to maximize data quality. Medical and occupational data will be obtained from the study subjects. Fertility data will be obtained from the subject's spouse and/or former spouses whenever possible, preferably by face-to-face interview. In addition, next-of-kin interviews will be obtained for all study subjects who have died of noncombat-related causes between the time of their assignment to SEA and the initiation of this study. The physical examination will be conducted under Air Force contract at a single center by a civilian medical organization of national stature. Blind assessment protocols and strict quality control measures will be used to avoid bias and limit data variability,. Adaptive physical examinations and questionnaires will be developed for use in years 3, 5, 10, 15, and 20 of the followup study. Expected biases arid study difficulties include risk-taking behavior bias in the predominantly volunteer RANCH HAND group, response bias, interviewer bias, loss to study bias, and variability of procedures performed. UNCLASSIFIED S E C U R I T Y CLASSIFICATION OF THIS PAGE (Wien Dalit Entnrfd) �PREFACE In 1979 the United States Air Force (USAF) made the commitment to the Congress and the White House to conduct an epidemiologic study of possible health effects resulting from chemical exposure to Air Force personnel who conducted aerial herbicide dissemination missions in Vietnam (Operation RANCH HAND). The purpose of this epidemiologic investigation is to determine whether long-term health effects exist and, if so, whether they can be attributed to occupational exposure to herbicides or their contaminants. The study protocol for this effort incorporates a matched cohort design in a nonconcurrent prospective setting. The scientific protocol of the Air Force Health Study is presented here and is the result of a maturation process which began in October 1978. At that time, an epidemiologic strategy was developed. After approval of the basic approach was obtained from the USAF Surgeon General in early 1979, fullscale protocol development began in preparation for a series of peer reviews by a variety of expert panels. Throughout this review process, the advice and recommendations of each panel were used to enhance the protocol where appropriate. The following discussion summarizes key recommendations made by each review panel. These reviews were independent of one another, and the approval of one version of the protocol does not imply that those reviewers have approved the protocol in its final form. Although several members of the panels reviewing early protocol versions have received periodic courtesy progress reports, they have not had the opportunity to formally review the final product. The University of Texas School of Public Health, Houston, Texas, conducted the first review on 8 June 1979. The reviewers stressed the need to insure that the population groups selected for the study were fully ascertained, and that sources of potential bias should be carefully addressed. The advantages of face-to-face interview technique over telephone techniques were discussed as well. On 6 and 7 August 1979, a panel appointed by the USAF Scientific Advisory Board recommended that face-to-face interviews should be used and that the mortality phase of the study be expanded from a 1:1 to a 1:3 design to increase statistical power. Toxicologic aspects of the study and their impact on the scope of the physical examination were extensively discussed. A subcommittee of the Armed Forces Epidemiologic Board conducted a review on 30 and 31 August 1979. The committee members recommended the appointment of an independent monitoring panel to oversee the conduct of the study on a periodic basis. They felt that it was necessary to expand the mortality study to a 1:5 design, with subjects randomly drawn from a 1:10 cohort matrix. Quality control concerns and the advisability of using a single examination center were also recommended. The National Academy of Sciences (NAS) reviewed the protocol on 18 December 1979. The NAS recommendations stressed the need to place increased emphasis on reproductive endpoints, and to expand statistical power calculations, methods of population ascertainment, location, and long-term followup. They reiterated the value of ongoing peer review by a monitoring group. They also strongly encouraged the Air Force to conduct the • • N.idy by contract to an independent agency to avoid the appearance of conflict (•> interest. Following the NAS review, additional reviews by the Science I ,:!iel of the Agent Orange Working Group and the Advisory Committee on Special �Studies Relating to the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants were obtained. A subcommittee of this Advisory Group, chaired by Dr. John Moore, Director of Toxicology and Testing Programs, National Institute of Environmental Health Sciences, was appointed to monitor the study. Reviews by this subcommittee continue on a regular basis. The edition of the protocol presented in this technical report is the protocol in effect at the time the physical examination phase of the study began in January 1982. Subsequently, circumstances beyond the control of the principal investigators led to some modifications in portions of the design. These modifications are discussed in annexes to the basic protocol (Chapters XVII, XVIII, XIX of this report) and are summarized. The principal investigators' increasing knowledge of the operational environment of the Vietnam War and the herbicide dissemination programs, and a more complete knowledge of the advantages and limitations of available records, contributed to the refinement of this document. Initially, an individual-specific exposure index or estimate was planned, but these highly specific estimates of exposure were not feasible. Objective data sources were not available to permit development of the index on the individual level, and therefore the use of a more generalized index is required. The initial ascertainment of the control population was conducted by a computer search of the Air Force personnel records system coupled with a manual search of noncomputerized records. This process resulted in the inadvertent overselection of some comparison individuals who were subsequently found not to meet the criteria for inclusion in the study. These ineligible individuals were removed from the study cohorts, and appropriate subjects were substituted for them. Analysis of the problem revealed that there was true overselection of subjects, and that no eligible subjects had been overlooked. Thus, the statistical and scientific validity of the study has been preserved. As a result of this event, the comparison cohort matrix was reduced from 1:10 to 1:8. This reduction will have minimal consequences, since the 1:5 mortality analytic design and the 1:1 morbidity design are maintained. The primary focus of this study is the potential effects of herbicide/ dioxin exposure on health outcomes. However, the flexibility of the statistical methodology, the comprehensive nature of the data being collected, and the high rates of participation in the questionnaire and examination process will permit the analysis of other factors. This final protocol represents a synthesis of the comments of all of the peer reviews, coupled with the increasing sophistication of knowledge concerning record sources and operational features of the war. The evolution of this document has occurred over a four-year span of time. This evolutionary process is outlined in the following table. Refinements of concepts and procedures were the only changes made to the study design since November 1979. There have been no substantive changes in study design methods or procedures since that time. Analytic techniques may be further refined to represent state-of-the-art statistical methodology. ii �PROTOCOL EVOLUTION Protocol Version 1 2 Major Areas of Change Date 6 June 1979 1979 - Expanded discussion of epidemiclogic design - Expanded statistical analytic strategy - Consideration of bias sources 30 July 1979 - Discussion of exposure index - Development of survival analysis techniques - Expanded discussion of physical examination procedures 30 August - Expanded discussion of exposure concepts - Expansion of mortality study to a 1:3 design - Discussion of compliance factors - Further expansion of physical examination procedures 10 July 1979 31 October 1979 - Expansion of mortality cohorts to - Single center examinations - Discussion of the replacement concept for bias correction 28 November 1979 » Expanded exposure index discussion - More detailed discussion of statistical analytic strategy 8 October 1980 - Increased emphasis on fertility and reproductive endpoints - Enlarged discussion of the mortality analysis - Enlarged discussion of statistical power - Discussion of Quality Control methods 26 November 1980 - Presentation of refined data on study population demographic characteristics in �9 15 June 1981 - Discussion of matching procedures - Consideration of time-in-study effects 10 September 1981 - Expanded discussion of matching procedures and results 11 28 January 1982 - Refinement of the exposure index - Presentation of modified performance schedules IV �ACKNOWLEDGMENT The services of many staff members and consultants of the United States Air Force School of Aerospace Medicine are acknowledged. Special acknowledgment is made to the following co-investigators: Clarence F. Watson, Jr., M.D., M.P.H.; Alvin L. Young, B.S., M.S., Ph.D.; Joel E. Michalek, Ph.D.; Phelps P. Crump, Ph.D.; Richard C. McNee, M.S.; Alton J. Rahe, M.S.; Michael A, Sairi, M.D., M.P.H., and T.M.; Richie S. Dryden, M.D., M.P.H.; James A. Wright, M.D., M.P.H., who provided consultation on study design and physical examination development. In addition, special acknowledgment is made to the United States Air Force School of Aerospace Medicine, Management and Air Training Command Procurement Personnel: Hugh F. Mulligan, Colonel, USAF, BSC, Chief, Program Acquisition Division; Donald F. Norville, Air Training Command Contracting Officer, Randolph Air Force Base, Texas, who coordinated the requirements for the physical examination implementation contract. �PROJECT RANCH HAND II EXECUTIVE SUMMARY OF THE PROTOCOL The Air Force has made the commitment to Congress and to the White House to conduct an epidemiologic study of possible health effects in the Air Force personnel (RANCH HAND) who conducted aerial herbicide missions in Vietnam. The purpose of this investigation is to determine whether long-term health effects exist and can be attributed to occupational exposure to Herbicide Orange. The extensive use of herbicides in Vietnam between 1962 and 1971 was terminated when it became known that TCDD, a contaminant present in 2,4,5-Tcontaining herbicides, caused congenital abnormalities when administered to pregnant rodents. Subsequent extensive research into the toxicity of TCDD in animals remains equivocal from the point of view of human population risks. Presently, the potential for teratogenicity and carcinogen!city of TCDD seems to be significant, but species specific. The scientific literature on the toxicity of the components of Herbicide Orange reveals that the two main ingredients, 2,4-D and 2,4,5-T, have extremely low toxicity, and are distinctly different in nature than TCDD. TCDD has been shown to be embryotoxic at markedly lower doses in animals. Only recently have comprehensive prospective studies in humans been undertaken. Most previous epidemiologic studies dealing with TCDD exposure in humans have suffered from weakness in design and statistical power. These studies have only validated a link between TCDD exposure and the subsequent development of chloracne. However, the public's perception of the toxicity of Herbicide Orange/TCDD is generally different from that of the scientific community. A review of veteran inquiries submitted to the Veterans Aiiniini strati on reveals an awesome spectrum of alleged symptoms and diseases. This study uses a matched cohort design in a nonconcurrent prospective setting incorporating mortality, morbidity, and followup studies. Detailed computer searches of Air Force personnel records, with several cross-referencing techniques, have ensured total ascertainment of the RANCH HAND population. The unique circumstances of exposure in this population of 1264 individuals will permit a semi-quantitative estimate of exposure. Specifically, since there was a documented higher concentration of TCDD contamination prior to 1965, this factor will be incorporated in the development of an exposure index. A control group will be formed from a population of 23,978 C-130 crewmembers and support personnel who were assigned to duty in Southeast Asia (SEA), but were not occupationally exposed to herbicides. Control Individuals will be matched to RANCH HAND personnel for the variables of age, type of job, and race. Since both the exposed subjects and their selected controls performed similar combat or combat-related jobs, many of the physical and psycho-physiologic effects of combat stress and the SEA environment will also be equivalent in the two groups. Ten statistically equivalent matches for each exposed subject will form the control set for each exposed subject. In the analysis of mortality, each exposed subject and a 50% random selection from each control set will be followed yearly for at least 20 years, constituting a 1:5 mortality design. The first of the randomized mortality controls w1Tl be selected and entered into the questionnaire and physical examination �phases of the study, producing a 1:1 morbidity design. The initial questionnaire will look backwards in time and will reconstruct occupational, social, and medical data to quantitate morbidity endpoints and confounding factors. Subsequent questionnaires and physical examinations will constitute a followup morbidity study of living exposed subjects and suitable living controls. In this followup phase, primary controls who are noncompliant will be replaced by another suitable control from the control set so that both statistical power and loss to study bias in the followup study may be improved. Controls dying after the initiation of the followup will not be replaced. All RANCH HAND personnel and their primary controls will be asked to complete a questionnaire and participate in a comprehensive physical examination, with special emphasis being placed on dermatologic, neuropsychiatric, hepatic, immunologic, reproductive, and neoplastic conditions. The questionnaire will be developed and administered by a civilian opinion research organization of national stature under contract to the U.S. Air Force. In-home, face-to-face interviews will b,e conducted to maximize data quality; however, noncompliant individuals will be requested to participate in a shortened telephone interview. Medical and occupational data will be obtained from the study subjects. Fertility data will be obtained from the subject's spouse and/or former spouses whenever possible, preferably by faceto-face interview. In addition, next-of-kin interviews will be obtained for all study subjects who have died of non-combat-related causes between the time of their assignment to SEA and the initiation of this study. The physical examinations will be conducted under Air Force contract at a single center by a civilian medical organization of national stature. Blind assessment protocols and strict quality control measures will be used to avoid bias and limit data variability. A $100 per day stipend will be paid to all eligible subjects to maximize participation in the study. Adaptive physical examinations and questionnaires will be developed for use in years 3, 5, 10, 15, and 20 of the followup study. Expected biases and study difficulties include risktaking behavior bias in the predominantly volunteer RANCH HAND group, response bias, interviewer bias, loss to study bias, and variability of procedures performed. Since this study is dealing with nonspecific clinical endpoints, identification or elucidation of a disease state or syndrome by statistical methodology is a prime thrust of the investigation. Inferences about a disease state will be developed by identifying symptom complexes or physical findings which in themselves may represent disease. By comparison of symptoms, signs, and laboratory tests within and between groups, a logical decision-making scheme can be utilized to calculate relative risks from baseline data. If appropriate, these results will be used to sharpen adaptive approaches in the followup study. By the use of combinational and correlational analysis, statements about the probability of a disease state, a subclinical state, and/or over-reporting bias will be attempted. In addition, the application of regression techniques to a normalized exposure index among exposed individuals exhibiting symptoms and/or signs will also assist in the clarification of a disease state or syndrome. Mortality data will be analyzed using several different approaches, including age and age-disease specific rates, standardized mortality rates, and modified life table approaches, as well as more sophisticated logistic and multiplicative models. Analysis of questionnaire and vii �physical examination data will utilize log-linear models for dichotomous or polytomous data to verify the appropriateness of the standard statistical methodologies (e.g., McNemar's test for dichotomous rates). Continuous variables will undergo covariance analysis to remove noncontrolled effects, followed by the use of a paired difference statistic. Some data will naturally fall into groups or batteries (e.g., fertility/reproduction, liver function tests); in which case, group scoring techniques will be used as appropriate. viil �CONTENTS I. II. III. IV. Purpose of the Investigation „ Synopsis of Background A. The USAF Commitment B. The Peer Review Process C. The Military Use of Herbicides 2 2 2 3 Goals of the Investigation 6 Synopsis and Discussion of Literature A. Overview B. Pharmacokinetics of 2,4-D, 2,4,5-T and TCDD.. C. Proposed Cellular Mechanisms of Action 7 7 7 for TCDD D. E. F. 6. V. 9 Animal Studies Case Reports Veteran Concerns Epidemiologic Studies 10 11 12 13 Epidemiologic Study Design... A. Design Considerations , B. Selection and Ascertainment of the Populations for Study C. Overview of Statistical Methodology D. Mortality Study ... E. Morbidity Study 17 17 18 28 31 37 F. Followup Study 43 G. Determination of "Disease" H. Exposure Indices VI. 1 , 48 50 Special Statistical Considerations A. False Reporting/Misrepresentation 55 55 B. Adequacy of Sample Sizes 56 C. The Replacement Concept D. Statistical Analysis of Large Data Sets E. Time-In-Study Effects 62 74 74 IX �CONTENTS (Continued) Page VII. VIII. IX. X. XI. XII. XIII. XIV. XV. XVI. XVII. XVIII. XIX. Data Repository , Recognized Study Difficulties and Corrective Measures A. Medical Precedence B. Group Accountability Bias C. "Risk Taking" Behavior Bias D. Response Bias E. Interviewer Bias.... F. Changes to the Protocol.. G. Loss to Study—Statistical and Bias Consi derat i ons H. Statistical Power Limitations I. Variability of Procedures J. Confounding Exposure Factors . 77 .. 79 79 79 80 81 82 82 83 85 86 86 Quality Assurance and Management Considerations A. Quality Control. B. Management Structure 88 88 90 Reporting Procedures 93 Questionnai re 94 Physical Examination Design A. General Instructions B. Conduct of the Examination C. Special Procedures 96 96 97 103 Principal Investigators, Co-Investigators and Contributors........ 112 Selected Bibliography. 115 Appendi x 125 Examiner's Handbook A. General Instructions B. Conduct of the Examination C. Examination Format D. Special Procedures.... E. Forms 138 138 139 140 146 160 Annex 1 - Exposure Index Construction 166 Annex 2 - Comparison Group Ineligibility ., 168 Annex 3 - Supplemental Analysis 170 Glossary of Abbreviations 171 �List of Figures F_igure ^No^ Page 1 Mortality Analysis Cohorts 2 Mortality Matrix.. 25 3 Selection Procedure for the Questionnaire, Physical Examination, and Followup Study 28 4 Design Schematic.... 29 5 Effect of Non-Random Loss to Study in The Control Population 45 6 The Replacement Strategy 46 7 Control Replacement for Morbidity and Followup Studies 47 8 Interpretation of Horizontal Comparisons 49 9 False Reporting/Misrepresentation 55 10 Misrepresentation in Ranch Hand II 56 11 Apparent Relative Risk Versus Specificity 57 12 Power Versus Relative Risk, 1:5 Mortality Study by Three Disease Incidences. 67 Power Curves of the Marine Study Considering Relative Exposure and Misclassification of the Study Population; 5,900 Marines 68 Power Curves of the Marine Study Considering Relative Exposure and Misclassification of the Study Population; 21,900 Marines 69 15 Rationale of Replacement 84 16 Management Structure, 91 13 14 A-l A-2 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) .. 25 135 Estimated Identification/Participation of RANCH HAND Population A-3 136 Study Design Format 137 �List of Tables Table No. 1 Page Estimated Quantities of Herbicides and TCDD Sprayed in RVN, Jan 1963 - Feb 1972 2 4 Summary of Descriptive Characteristics of Patients in the VA Herbicide Registry, as of 10 February 1981... 13 3 VA Herbicide Registry Symptom Reporting 13 4 Feasibility of Identifying Aircraft Maintenance Personnel (Total Population) Exposed to Herbicide Orange 19 Comparisons of the Study Group to Possible Control Groups by Known and Estimated Factors. 23 6 Results of the Matching Process (1:10) 26 7 Stratified Format of Age-Specific Death Rates 32 8 Format of McNemar's Test... 35 9 Format of Categorical Representation of Retinal Changes 42 10 Format of Pairing for Grades of Retinal Findings 42 11 Power Calculations.,... 12 Power Calculations for the Dichotomous Variable Case as a Function of Efficacy of Paired Designs 59 13 Power Calculations as a Function of Herbicide Effect.... 61 14 Mortality Analysis. Power Comparison of the RANCH HAND Study to the Marine Population; 5,900 Marines, Rare Disease 63 Mortality Analysis. Power Comparison of the RANCH HAND Study to the Marine Population; 5,900 Marines, Common Disease 64 Mortality Analysis. Power Comparison of the RANCH HAND Study to the Marine Population; 21,900 Marines, Rare Disease 65 5 15 16 ,. 58 �List of Tables (Continued) Table No. 17 18 Page Mortality Analysis. Power Comparison of the RANCH HAND Study to the Marine Population; 21,900 Marines, Common Disease... 66 Control Distributions by Examination, Matching 1000 RANCH HAND Personnel... 71 19 Factors Affecting Compliance 73 20 Titne-In-Study Effects 76 A-l Summary of 2,4-D, 2,4,5-T and TCDD Animal Studies 126 A-2 "Symptom Complex" Derived from Literature Review of Case Studies Exposed to 2,4-D, 2,4,5-T and/or TCDD 127 Detailed Listing of Symptoms/Signs by Major Category from Literature Review of Case Studies Exposed to 2,4-D, 2,4,5-T and/or TCDD 128 Age Comparison of Exposed Subjects and their Matched Controls 130 A-5 Statistical Description of the Matching Process 131 A-6 Specific Rules For Entry Into the Morbidity Study 132 A-7 Schedule and Mode of Contacts with Study Subjects 133 A-8 Monte Carlo Simulation.... 134 A-3 A-4 xiii �PROJECT RANCH HAND II EPIDEMIOLOGIC INVESTIGATION OF HEALTH EFFECTS IN AIR FORCE PERSONNEL FOLLOWING EXPOSURE TO HERBICIDE ORANGE MATCHED COHORT DESIGN I. Purpose of the Investigation The purpose of this epidemiologic investigation is to determine whether long-term health effects exist and can be attributed to occupational exposure to Herbicide Orange. �II. Synopsis of Background A. The USAF Commitment Since 19713 news media presentations have focused attention on possible adverse health effects in former military personnel, allegedly due to Herbicide Orange [a mixture of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxy-acetic acid (2,4,5-T)] which was used as a defoliant during the Vietnam Conflict. Other herbicides containing 2,4,5-T were also used extensively, and as commonly used by the news media, the term "Herbicide Orange" refers to all of these 2,4,5-T products. These herbicides were contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Figure A-l, Section X V ) , and the presence of this toxin is the basis for much of the concern over exposure to these defoliants. Claims for compensation have been filed against the Veterans Administration (VA), by more than 3,000 veterans. In response to Congress, the General Accounting Office (6AO) investigated the issue and subsequently recommended that the Department of Defense (DOD) conduct a longterm epidemiologic study of the problem. The Department of the Air Force has made a formal commitment to the Congress and the White House to conduct such a study. On 16 September 1980, the White House directed the DOD to initiate the RANCH HAND study with reasonable speed and high quality. This decision was subsequently reaffirmed by the new administration. B. The Peer Review Process This protocol has received rigorous peer review. From the outset, the Air Force principal investigators have acknowledged the scientific complexities of the effort and voluntarily sought outside peer review and consultative guidance. The following reviews have been conducted: Reviewing Agency Date University of Texas, School of Public Health June 1979 Air Force Scientific Advisory Board August 1979 Armed Forces Epidemiologic Board August 1979 National Research Council, National Academy of Sciences December 1979 Members of each independent review agency were provided copies of the protocol and key references in advance of the review. An extensive briefing of the protocol was presented to three of the four agencies. Each review group provided a report of their opinions and recommendations. The Air Force principal investigators responded to reports from the first three peer reviews and indicated concurrence or nonconcurrence with each of the recommendations. Most of �the peer group recommendations were gratefully accepted and incorporated appropriately within the protocol. Because the National Research Council's report cited "major deficiencies in design" and emphasized public credibility issues, the protocol was referred to the Interagency Work Group to Study the Possible Long-Tehn Health Effects of Phenoxy Herbicides and Contaminants for an additional scientific review and recommendations to the White House as to whether the Air Force should conduct this study. This review was conducted in June 1980 and resulted in an affirmative recommendation. The White House subsequently directed that the study be formally started. C. The Military Use of Herbicides Research and development on phenoxy herbicides began in the early 1940s, when most of the initial phytotoxic screening programs and the development of application technologies were sponsored by the DOD. The herbicide, 2,4,5-T, was first commercially produced in the United States in 1944. During the years from 1961 through 1969, the DOD procured 53 million pounds of this herbicide (approximately 34 percent of the total US production) for use in the Republic of Vietnam (RVN). However, 8.9 million pounds of that amount were not sprayed in Vietnam, but were destroyed by at-sea incineration in 1977. The first sustained DOD operational use of herbicides was initiated during the Vietnam Conflict (Operation RANCH HAND) and the first shipment of herbicides used in RANCH HAND was received at Tan Son Nhut Air Base, (RVN), on 9 January 1962. The use of these compounds was intended to accomplish two objectives: (1) the defoliation of vegetation to improve visibility and thus decrease the risk of ambush, and (2) the destruction of enemy crops. Four 2,4,5-T-containing herbicides were used by the military during the period 1962-1970. These four included: (1) Herbicide Purple (used from 1962 through 1964) n-butyl n-butyl iso-butyl (2) 2,4,5-T 2,4,5-T 60% 40% Herbicide Gree.n (used from 1962 through 1964) n-butyl (4) 50% 30% 20% Herbicide Pink (used from 1962 through 1964) n-butyl iso-butyl (3) 2,4-D 2,4,5-T 2,4,5-T 2,4,5-T 100% Herbicide Orange (used from early 1965 through 15 April 1970) n-butyl n-butyl 2,4-D 2,4,5-T 50% 50% �Analyses of archived samples of Herbicide Purple suggest that the mean concentration of TCDD may have been approximately 33 ppm (Range: 17 to 47 ppm TCDD) while archived samples of Herbicide Orange had a mean concentration of approximately 2 ppm (Range: <0.02 to 15 ppm TCDD). In addition, two other herbicides were widely used in RVN. These were Herbicide Blue, an organic arsenical formulated from the sodium salt of cacodylic acid, and Herbicide White, a water soluble triisopropanolamine salt formulation of 2,4-D and picloram. The amounts of the various herbicides used in RVN from January 1962 through February 1972 are shown in Table 1. Table 1. ESTIMATED QUANTITIES OF HERBICIDES AND TCDD SPRAYED IN RVN, JAN 1962-FEB 1972 CHEMICAL POUNDS 2,4-D 2,4,5-T TCDD 55,940,150 44,232,600 368 Picloram Cacodylic Acid Herbicide Total 3,041,800 3,548,710 106,763,260 Ninety-six percent of the 2,4,5-T disseminated in RVN was contained in Herbicide Orange; the remaining 4 percent in Herbicides Green, Pink, and Purple. However, Herbicides Green, Pink and Purple contained approximately 40 percent of the estimated amount of TCDD disseminated in RVN. Green, Pink and Purple were sprayed as defoliants on less than 90,000 acres from 1962 through 1964, a period when only a sma1! force of U.S. military personnel were in RVN. Ninety percent of all the Herbicide Orange (containing 38.3 million pounds of 2,4,5-T and 203 Ib of TCDD) was used in defoliation operations on 2.9 million acres of inland forests and mangrove forests of RVN. Most of the herbicide used in RVN was sprayed from aircraft. RANCH HAND aircraft, the C-123, disseminated 88 percent of all herbicide. Helicopters and ground application equipment used by personnel from all branches of the U.S. Armed Forces applied the remaining 12 percent, primarily Herbicide Blue, to maintain visibility around base perimeters. Concurrent with the change to Herbicide Orange, the scope of aerial use shifted from four aircrews on temporary assignments, to 36 permanently assigned aircrews, and additional support personnel. Following the announcement in October 1969 that the administration of 2,4,5-T to pregnant rodents �caused an increase in the rate of congenital abnormalities, the DOD confined Herbicide Orange spray operations to nonpopulated areas and in April 1970, all uses of the 2,4,5-T containing herbicides were halted. Other non-2,4,5-T herbicides continued to be used until June 1971 and Operation RANCH HAND was officially deactivated in October 1971. In March 1972, all remaining stocks of 2,4,5-T-containing herbicides were removed from RVN, and transported to Johnston Island, Pacific Ocean, for open storage (Project PACER IVY), and eventual incineration at sea in 1977 (Project PACER HO). In 1979, the Environmental Protection Agency (EPA) suspended the use of herbicides containing 2,4,5-T because an epidemiologic study in the United States attributed abortogenic effects to its use. �Ill. Goal s of the Investigation The health goals of this investigation are: (1) to identify veteran and active duty individuals with adverse health effects (physical and psychological ) if any, which are attributable to herbicide exposure, and (2) to identify other individuals at risk of developing future adverse health effects, if such exist. Spinoffs from the primary health goals are clearly evident. Increasing media emphasis, in tandem with rising veteran concern and Congressional action, have caused numerous governmental agencies to pursue the issue from several scientific perspectives. The RANCH HAND study is an important part of the overall scientific mosaic, but in itself, may not be definitive in answering the herbicide question. Nevertheless, it is clear that data and conclusions arising from this investigation, whether positive, negative, or indeterminant, will be used as a substantative data base upon which government can formulate policy decisions. With numerous individual and class action lawsuits pending, currently totaling in excess of $44 billion, the primary governmental decision will concern compensation for attributable adverse health. As the award of compensation to any veteran is solely controlled by the Veterans Administration, this Air Force study in no way represents a "conflict" but rather constitutes another reaffirrnation that "The Air Force cares for its own." �IV• Synopsis and Discussion of J-i A. Overview More than 20,000 scientific articles relating to the phenoxy herbicides have been published since the 1940's. Many of the articles cite herbicidecaused health effects in a variety of animal species, but most early studies used a myriad of herbicide formulations and unknowingly dealt with physically and chemically impure compounds, and the assay technology was far short of today's state-of-the-art. Many human studies have ascribed cause and effect relationships but have suffered from problems of clinical empiricism or questionable methodology. The only consistent chronic clinical finding associated with exposure to 2,4,5-T herbicide and TCDD has been chloracne, recognized by most workers as the herald sign of overexposure to the herbicide and other chloracneigens. It is now recognized that the chloracne was caused by the presence of TCDD rather than 2,4,5-T. Sequelae from chloracne, localized or systemic, appear to be unusual according to the preponderance of the literature. It is appropriate to note that sustained, worldwide usage of herbicides for 30 years has not yet evoked a readily identifiable disease state. It is clear from the literature and the usage history of herbicides that if there are significant attributable long-term health effects, they are either reasonably rare, or of such nonspecific commonality that they blend unnoticeably into the symptoms, syndromes, or diseases associated with increasing age or other similar factors. B - Pharmacokinetics of2,4-D, 2,4,5-T and TCDD (1) LM The pharmocokinetics of 2,4-D have been well studied in animals. 2,4-D is readily absorbed after oral administration, and is initially distributed in high concentrations to the central nervous system and liver. Eventually, all tissues are involved, with the kidneys accumulating twenty times the concentration of the other tissues. The plasma half-life of 2,4-D is approximately 3 to 12 hours, with elimination from the body through the kidneys at a dose-dependent rate. Generally, high doses or repeated lower doses result in tissue accumulation. The majority of 2,4-D is eliminated unmetabolized; however, esters of 2,4-D have been shown to undergo hydrolysis prior to excretion. Muscle and fat show the lowest accumulation of 2,4-D on repeated exposure, whereas the kidneys and liver show the highest accumulations. Within 24 hours of ' ingle-dose administration of 2,4-D, 16.8% was present in the uterus, placenta, fetus and amniotic fluid in gravid rats. In addition, 2,4-D was found in the milk of lactating rats for up to six days following single-dose exposure. (2) ldi5-T The pharmacokinetcs of 2,4,5-T have been well studied in animals. In all animals, 2,4,5-T has been shown to be readily abosrbed upon oral administration. However, beyond this point, 2,4,5-T has shown marked variations in its pharmacokinetit.s depending on the species tested. These differences are thought to be due to variations in species, age, dosage levels, routes of administration �and chemical formulations used in the various studies. Generally, the distribution is ubiquitous throughout the body except in hamsters, which show no placental passage, and in mice, which show placental passage only in late gestation. Clearance from plasma and from the body varies greatly among species with rats showing faster clearance than dogs, mice and man. In addition, this clearance appears to be generally dose-dependent. The biological half-life of 2,4,5-T in rats, as estimated by tissue analyses and urinary clearance at administered dosages of 5 mg/kg, is 4.7 hours. However, at 200 mg/kg, the half-life in rats is prolonged to 25 hours. Excretion of 2,4,5-T is primarily via the kidneys. The elimination of 2,4,5-T at low doses is essentially achieved in an unmetabolized form. However, at higher or more chronic doses, elimination involves the liver in a more active role (i.e*, conjugation). Higher doses and repeated lower doses appear to result in accumulation in animal tissues. (3) Phenoxy Herbicides in Humans Relatively few studies have dealt with the pharmacokinetics of 2,4-D and 2,4,5-T in humans. Numerous reports of occupational exposures in industry and in commercial and private herbicide applications have supported percutaneous entry as a major route of exposure. Rapid absorption of 2,4-D and 2,4,5-T has been observed after oral administration. The primary mode of excretion of the phenoxy herbicides is via the urine with 74% of 2,4-D and 63%-72% of 2,4,5-T being cleared from the body within the first 96 hours. The majority of the herbicide is unmetabolised prior to excretion and the biological half-life of 2,4-D and 2,4,5-T in humans (as estimated by tissue analyses and urinary excretion) is 33 hours and 18 hourc, respectively. Tissue analysis has revealed an ubiquitous distribution of the herbicides after absorption. Limited studies on the accumulation of the phenoxy herbicides following repeated doses suggest that such accumulation in humans is unlikely. This is in contrast to numerous animal studies on 2,4-D and 2,4,5-T which show that such accumulation does occur. No specific data are available on the odor threshold of Herbicide Orange. Data are available however, on the odor threshold of a butyl ester formulation of 2,4,5-T. The odor threshold was found to be about 0.3 ppb 3 (the taste threshold was 1.3 ppb). A Threshold Limit Value (TLV) of 10 mg/m for both 2,4-D or 2,4,5-T has been adopted by the American Conference of Governmental Industrial Hygienists. Thp TLV is a time-weighted average concentration for a normal 8-hour workday/40-hour workweek to which workers may be repeatedly exposed, day after day, without adverse effect. Analysis of ambient air samples collected adjacent to and downwind from actual dedrumming operations involving Herbicide Orange were at least two orders of magnitude below the TLVs. (4) TCDD Information on the absorption, distribution and excretion of TCDD has been mostly derived from animal models. Studies in rats, mice and guinea pigs generally show that intestinal absorption of TCDD is relatively complete, with a large proportion being stored unmetabolized in the liver. The majority of this TCDD is assumed to be localized in the liver microsomes (centrifugation 8 �techniques). Initially, adipose tissue accumulates TCDD, followed later by accumulation in the liver, adrenals, kidneys and lungs. The level of TCDD in the liver and adipose tissue is about ten-fold greater than in other body tissues; however, significant species variability has been observed. The biological half-life of TCDD varies by species, but is reported to range from 12 to 50 days. The major route of excretion is via the feces with urinary excretion occurring at a much reduced rate. TCDD has three proposed mechanisms of action by effects, both documented and suspected, can be understood. able information in this area is derived from animal, models. The few human studies dealing with mechanisms are cal manifestation of chloracne. which its variety of All currently availplant, and bacterial limited to the clini- TCDD's ability to induce a variety of microsomal enzymes is well documented. The induction of aryl hydrocarbon hydroxylase, delta-aminolevulinic acid synthetase, and cytochrome P-448/P-450 associated enzymes has been implicated in the development of cutaneous porphyria. The induction of aryl hydrocarbon hydroxylase and other mixed function oxygenases/oxidases has been associated with carcinogenesis and tumorogenesis. In addition, TCDD has been shown to be a possible promoter or cocarcinogen of known carcinogens. In some nonhuman studies, TCDD produced a protective effect against endocrine tumors (e.g., pituitary, uterine, pancreatic, adrenal, and mammary tumors). TCDD's induction of UDP-glucuronyl transferase, an important enzyme in steroid metabolism, may explain this peculiar effect. The induction of DT-diaphorase and lysosomal acid proteinases has been implicated in TCDD's neuropathic effects. These and other biochemical alterations may account for TCDD's clinical manifestation of chloracne resulting from an over production of keratin in the sebaceous ducts. (2) DNA/TCDD Interact 1 on . Alterations in the structure and fidelity of transcription of DNA due to TCDD have been indirectly demonstrated, TCDD, because of its planar ring structure, may "intercalate" with DNA causing "frame-shift" mutations in a manner similar to that seen with the acridine family of compounds. A few laboratory studies with bacterial systems (Escherichia coli and SaJjroQeljla. typ n i mu rium) and one plant system (the Af ri can "Blood*" Li ly ) have implicated TCDD as being capable of producing chromosomal aberrations and perhaps a weak dominant lethal effect. This hypothesized DNA/TCDD interaction could explain the development of chloracne, as well as the suggested mutagenic and carcinogenic effects, if similar mechanisms occur in mammalian species, A nonspecific or as yet unspecified toxicity continues to serve as reasonable mechanism for TCDD's hepatic and thymus toxicity. TCDD has been �described by some as "one of the most potent, low molecular weight toxins known", with extremely low concentrations producing severe Jiver damage and death in various animal studies. The immune suppression effect of TCDD has been shown to result specifically from its T-cell (thymus) toxicity. If bioaccumulation and persistence of TCDD occur in human adipose tissue, it could be released into the circulation under situations of weight loss (e.g., life style modification, medical indications, or disease). Such hypothesized reemergence of the agent could result in low doses being either detectable and/ or toxic at some later point in time. If TCDD's primary toxicity results from low doses (e.g., a mutagenic/carcinogenic effect) rather than high doses (e.g., cellular poisoning and cell death), then the deposition of TCDD in the adipose tissue may have greater significance with respect to delayed effects on the long-term health of the exposed individual. This possibility raises a theoretical dose-response paradox which might "explain" the prevailing preponderance of symptoms in populations which may have been exposed to relatively low doses of TCDD (see Section IV D). However, persistence of TCDD in humans has not been demonstrated. Attempts to measure TCDD in human tissue are limited by technical difficulty in differentiating between the 2,3,7,8 isomer found in 2,4,5-T and the other 21 isomers from non-herbicide sources. There is also no reasonable method to determine whether tissue TCDD is from an RVN exposure, or from a more recent environmental source. D. Animal Studies A comparison of animal toxicity studies is difficult due to variations in experimental designs which include differences in (1) the species, age, and sex of animals used; (2) the level, route, and length of exposure to chemicals; (3) the purity of the chemicals used; and (4) the criteria measured and the time sequence of data collection. Animals have shown a wide range of toxic effects, but this range may serve as a guide to anticipate the potential toxic effects in humans following exposure to Herbicide Orange. A summarization of the literature is presented in Table A»l of the Appendix, "Section XV. It is apparent that the toxic effects of 2,4-D and 2,4,5-T are markedly different 1 rom the effects of TCDD. TCDD is approximately 1000 times more toxic in acute studies. In addition, the slower clearance time of TCDD may account for the significantly lower daily doses required to elicit chronic toxicity. A consistent finding in TCDD toxicity is depletion of the lymphoid tissues throughout the host. This is readily characterized by involution of the thymus in all species studied. In relation to the chronic maternal toxic dose, the embryotoxic dose is markedly lower for TCDD than for 2,4-D and 2,4,5-T. Both 2,4,5-T and 2,4-D appear to be very weak teratogens and/or carcinogens at best, but these evaluations are complicated by varying levels of contamination by various dibenzo-p-dioxins. TCDD appears to have significant teratogenic and carcinogenic potentials which appear to be species specific. The most striking observation noted in the literature is a marked variation in response among species. Examples of these variations are in the areas of acute toxicity (TCDD's LDso in guinea pigs is 1 yg/kg compared to 1000 yg/kg 10 �in dogs), excretion (2,4,5-T plasma half-life in rats in 4.7 hrs compared to 77 hrs in dogs), and oncogenicity. Even among strains of the same species (rats) variations in oncogenicity were noted following 2,4,5-T exposures. As noted earlier, this high variability between species is an important consideration in the designing1 of human studies. A second area of interest noted in the literature is a hypothetical dose-response paradox in nonhuman primates (rhesus monkey) following exposure to TCDD. Animals in a chronic exposure study fed a low level of TCDD in feed [e.g., 50-500 parts per trillion (ppt)] have shown signs of disease only after several months when total TCDD consumption was approximately 1 ug/kg body weight. Unfortunately, animals receiving comparable amounts of TCDD in a single-dose acute toxicity studies (LD50 determinations) have not been observed for the emergence of chronic effects. Therefore, it remains unclear whether the toxicity demonstrated in chronic exposure studies is dependent upon repetitive, cumulative exposure or whether similar toxicity would also be demonstrated following an equivalent single dose after a comparable observation period. Much concern has been raised over the potential of 2,4-D, 2,4,5-T or TCDD to induce genetic change in male animals which are subsequently passed on to the progeny of these exposed animals. In a recent experimental study by Lamb, Moore, and Marks, 150 male mice were exposed to various concentrations of the three chemicals in their food for eight weeks. Acute toxicity was evident with all dosages, as animals lost weight and had dose-related liver and thymus abnormalities, but these effects were reversed upon return to a normal diet. These exposures did not result in abnormalities in sperm concentration, motility or morphology. After the exposure period, the mice were mated, and no dose-related differences in mating frequency, fertility or reproducitve success were evident between the chemically exposed mice and their 50 nonexposed controls. Much of the medical literature on 2,4-D, 2,4,5-T and TCDD exposures in humans is based on individual case reports following acute exposures. Since most of the patients discussed in these reports were exposed to multiple chemical agents, it is difficult to determine which agents were responsible for specific symptoms. Nevertheless, the general areas of dermatologic and neuropsychiatric disease have been of primary interest in most investigations. Since the neuropsychiatric symptoms of herbicide exposure are numerous and largely subjective in nature, they have been extremely difficult to assess from a clinical 'tandpoint. In addition, hepatic dysfunction, and renal, gastrointestinal and cardiac disturbances have been "linked" to exposures to these chlorophenolic compounds. A multitude of symptoms have been attributed to 2,4-D and the ones reported most consistently are listed in the Appendix, Table A-2. Components of some of these selected symptoms/signs are described in Table A-3 of the Appendix. The asthenic syndrome, peripheral neuropathy, and hepatic dysfunction are 11 �of particular interest. Other symptoms of acute systemic toxicity occur, but with 2,4-D exposure has been extensively described. It has an early onset, causes prolonged disability of variable degree, and recovery has been incomplete in many cases. Electromyography in some patients has demonstrated denervation, and some studies have detected decreases in nerve conduction velocities. One autopsy study demonstrated a demyelination process within the brain of a 76year-old male who committed suicide by ingesting 2,4-D in kerosene. (2) 2.4.5-T/TCDD The human effects of 2,4,5-T are difficult to evaluate since the chemical is contaminated with TCDD in the manufacturing process. The effects of TCDD itself have been determined from studies of trichlorophenol workers, and from laboratory workers using TCDD. Symptom/sign complexes attributable to exposure to 2,4,5-T and TCDD are listed in Tables A-2 and A-3 of the Appendix. Chloracne usually begins in the zygomatic/temporal region and is often found on and behind the pinna of the ear. This is an oily acne-like skin condition characterized by comedones and inclusion cysts which may result in extensive scarring. In severe cases following heavy exposure, spread of lesions to the throat, back and inguinal areas has been noted. This skin condition is frequently preceded by erythema and blepharoconjunctivitis. Active lesions usually disappear within two years, but have been found 30 years after exposure. Porphyria cutanea tarda and hypothyroidism have also been linked to 2,4,5-T/TCDD exposure. Other symptoms such as asthenia, liver and re'nal dysfunction, neuropathy, and gastrointestinal and cardiac disturbances are probably due to mechanisms similar or identical to those of 2,4-D. With the exception of chloracne and possible disorders of porphyrin metabolism, all of these effects have been acute or subacute in nature. Numerous instances of alleged disease due to 2,4-D/2,4,5-T exposure have been the subject of heavy media attention, particularly an episode of alleged 2,4,5-T exposure in Globe, Arizona, in 1969. Despite extensive scientific review and analysis with negative findings, the Globe incident continues to be cited in news media presentations. An incident in Missouri in 1971 in which six children, two adults and numerous animals were exposed to TCDD-contaminated oil is frequently described as well. Many of the animals died and the humans developed chloracne and other ocute toxic effects; however, all humans were healthy after five years of follow-up study. A final prospective assessment of fertility, teratogenesis and carcinogenesis, in these individuals will probably be made in the future. F. Vete r a n Concerns The Veterans Administration provided the USAF with data on 46,771 patients participating in the Herbicide Registry. Numerous media presentations emphasizing both military and civilian herbicide exposures have described a remarkably wide spectrum of health effects being claimed by the veterans. Three compensation claims have been allowed for service-connected acneiform skin lesions (but not chloracne), 16 claims for other skin conditions, and an additional three claims for other diagnoses. A direct causal relationship between a disease and a specific exposure is not necessary to receive compensation. 12 �If the condition is shown to have occurred during active duty or within a reasonable time after separation, it is compensable, regardless of cause. Current Veterans Administration guidelines state that the only chronic residual of defoliant exposure has been chloracne. Table 2 summarizes the descriptive characteristics of 46,771 patients in the VA Herbicide Registry as of 31 August 1980. Table 3 summarizes symptoms from these patients by category. Table 2 SUMMARY OF DESCRIPTIVE CHARACTERISTICS OF PATIENTS IN THE VA HERBICIDE REGISTRY, AS OF 10 FEBRUARY 1981 Total Number of Registered Patients: 46,771 Branch of Service of Registered Patients: Army Marine Corps Air Force Navy Other 66.3% 18.9% 7.3% 5.9% 1.6% Table 3 VA HERBICIDE REGISTRY SYMPTOM REPORTING Number of Registered Patients: 46,771 Number of Symptomatic Patients: 34,145 (73%) Mean Number of Symptoms per Symptomatic Patient: 2.6 Symptom £ategory Number of Pati&nits Dermatologic Psychiatric/Psychological Headflche Peripheral Neuropathy Asthenia Gastrointestinal Sexual Dysfunction Other No symptoms Percent of Percent of Regi i ste_red Patjents Syjnpjtomatijc Patmits 18,675 11,745 6,021 5,729 5,637 5,454 2,105 20,702 12,626 39.9 25.1 12.9 12.3 12.0 11.7 4.5 44.3 — 13 54.7 34.4 17.6 16.8 16.5 16.0 6.2 27.0 �Study design implications that can be drawn from these data are limited because registered veterans may not be truly representative of the exposed population. The demonstrated lack of an easily identifiable symptom complex on review of the registry data clearly substantiates the need for a comprehensive evaluation of individual patients. 6. Epidemiologic Studies Epidemiologic studies of occupational groups have validated links between exposure to TCDD and the development of chloracne. Associations between TCDD and psychological abnormalities have also been suggested. A series of studies published from 1978-1980 by Hardell, Sandstrom, Axel son, and others in Sweden evaluated occupational exposure to chlorophenolic compounds in cancer patients. They found an association between cancer and exposure, but were unable to assess causality due to methodological limitations. Preliminary results of a case-control study of soft tissue sarcoma in New Zealand (Smith) did not detect any unusual clustering of occupations among the sarcoma cases. Tung (1973) reported an abnormal increase in the occurrence of primary carcinoma of the liver in Vietnam (26 cases per year during 1955-1961 versus 144 cases per year during (1962-1968). He attributed the increase to a suspected carcinogenic effect of TCDD. His published study, however, has been criticized for failure to contain sufficient data and descriptions of methodology to verify his conclusions, and the role of aflatoxin as an alternative cause of liver cancer was not addressed. His study is generally considered to be an empiric clinical observation. A study sponsored hy the EPA in 1979 in Alsea, Oregon, found a statistically significant increase in spontaneous abortion in areas where 2,4,5-T herbicide was routinely used in reforestation programs. The EPA concluded that "for all its complexity, this analysis is a correlation analysis, and correlation does not necessarily mean causation." Nevertheless, this study was used by the EPA to institute the ban on most uses of 2,4,5-T containing products. This report has been the subject of intense scientific criticism. Differences in the availability of specialty obstetrical care and in the patterns of health care delivery existed between the exposed and control areas; these differences were not taken into consideration by the researchers. Variations in the ascertainment of spontaneous abortions in each of the areas severely limited the validity of the data, and of the conclusions derived from them. A recent study conducted in Australia (1978) was unable to find an association between neural tube birth defects and the use of 2,4,5-T herbicide. A reproductive study of the wives of 370 2,4,5-T/TCDD exposed workers at the Dow Chemical Company in Midland, Michigan was recently completed (Cook and Bodner). No differences in fertility patterns, fetal wastage, or birth defects were detected. Epidemiologic studies are continuing in Seveso, Italy, where a population of 220,000 was potentially exposed to TCDD following an industrial accident in July 1976. These studies have involved investigations of more than 30,000 children, and detailed clinical examinations of 1,024 persons, including the most severely exposed children and adults. Recent data (Homberger, et al., 14 �1979) indicated that most cases of chloracne from this incident cleared rapidly. To date, the growth and development of newborn infants and children, iinmunological response, chromosomal aberrations, the response to the challenges of infectious diseases, and the morbidity and mortality patterns of the study population have not been significantly altered by TCDD exposure. Thirty-eight cases of birth defects were reported in early 1977, approximately 6-8 months after the industrial accident. However, the authors ascribe this increase to an artifact of surveillance. Analysis of surveillance data on the occurrence of spontaneous abortions after July 1976 is compromised by the lack of valid baselines for the pre-accident period. The social pressures operating in the Seveso population prior to the accident fostered underreporting of birth defects, while the atmosphere after the accident made the occurrence of a birth defect more socially acceptable. The post accident congenital malformation rate is not significantly different than the rate in similar areas of Central Europe. Another progress report on the aftermath of the Seveso accident (Pocchiari, et al. 1979) has revealed: (1) a decrease in the prevalence and severity of chloracne in the exposed population; (2) an increase in clinical and subclinical neurologic disease as demonstrated by delayed peripheral nerve conduction velocities; and (3) increases in the prevalence of hepatomegaly (8%) and alterations in liver function tests, which returned to normal over an 18 month period of follow-up. Thus far, immunologic, cytogenetic, and embryomorphologic analyses have been unable to detect significant differences between exposed and non-exposed individuals. A 2,4,5-T Dispute Resolution Conference was held in Arlington, Virginia, from 3 to 7 June 1979. Fifty-six recognized experts from the United States and seven foreign nations were actively involved in the deliberations of the conference. Human Exposure, Carcinogenicity/Mutagenicity, and Teratogenicity Working Groups independently reached the conclusions that there was no valid scientific evidence linking fetotoxicity, teratogenicity or carcinogenicity in humans in a cause and effect relationship to 2,4,5-T/TCDD exposures. The Human Exposure Working Group also concluded that there were no epidemiologic data associating TCDD with any long-term health effects in humans other than persistent chloracne. While they did not find evidence of serious long-term health effects, neither could they find strong evidence for "lack of effect. Most previous epidemiologic studies have not had sufficient statistical power to detect increased risks of low incidence/prevalence conditions in the observed populations, and the period of observation in many prospective studies has been less than ideal. Several potentially valuable epidemiologic studies are currently in progress. Two independent and comprehensive studies of workers exposed to TCDD at a Monsanto manufacturing plant in Nitro, West Virginia, are currently being conducted (Mt. Sinai Medical Center, New York, and the Kettering Laboratory, University of Cincinnati, Ohio). These chemical industry workers were exposed over long periods of time, and were previously evaluated in 1953 and 1956, following an industrial accident which occurred in 1949. Zack and Suskind of the Kettering Laboratory have reported a follow-up study of 122 workers, 28 years 15 �after heavy exposures to TCDD. There were 32 deaths in the group, and the relative risks of death were 0.69 for all causes, and 1.0 for malignancy; however, no firm conclusions can be drawn due to the small numbers involved. A Czechoslovakian study involving a 10 year followup of TCDD exposed workers, and a US National Cancer Institute (NCI) mortality study of 4,400 structural pest control workers are also underway. Preliminary results of a larger study of long-term morbidity by Suskind at the Nitro site have failed to reveal significant abnormalities other than persistent mild chloracne and decreased nerve conduction velocities, possibly associated with alcohol intake. These new studies, and the continuing evaluations of the Seveso, Italy, population, should continue to provide valuable data. The large study groups involved in the Seveso and NCI studies should provide good statistical power, and the Nitro, West Virginia, and Czechoslovakian efforts will evaluate the effects of exposure after prolonged periods of time (10-30 years). The results of these studies should fill major gaps in the knowledge of 2,4,5-T/TCDD epidemiology, and should prove to be useful in evaluating the long-term effects of these compounds on health and reproductive outcomes. 16 �V. Epidemiologic Study Desi gn: Matched Cohort A. DesjjnConjsicleratjions The goal of this study clearly mandates a comprehensive epidemiologic approach, incorporating mortality, and historical, current, and followup morbidity studies. Exposure to herbicides during the 1962-1971 time period may have initiated long-term health effects that may or may not be progressive. If such effects are detectable by a review of the subject's past medical history, and can be verified, direct links to compensation issues can be made. Current health status, as mirrored by a large number of recent VA claims and inquiries, is of major interest, because such claims and inquiries may indicate medical conditions that might be confirmed by a comprehensive physical examination. If analyses of both mortality and morbidity data yield only indeterminant or weakly suggestive findings, it may be that sufficient time has not yet passed for substantial emergence of longterm health effects. This dictates a requirement for a follow-up element to the study. Methodological shortcomings are inherent in each element of this comprehensive study. To some extent, the classical deficiencies of each particular epidemiologic approach are compensated by the concurrent use of the other elements. For example, the low chance of identifying a relatively uncommon disease solely by the use of a mortality study is offset by the inclusion of a current morbidity study. The relatively quick feedback that can be attained from current morbidity and mortality studies will serve to better define the follow-up study, and will help to alleviate problems that arise as a result of changes in diagnostic criteria and methods over time. Nevertheless, problems that can affect ascertainment of disease in all phases of the study will remain. Inaccurate patient recall of antecedent events, the distortion of information by knowledge of anticipated symptomatology, and participant or observer knowledge of their exposure status can only be corrected to a limited extent by review of records for symptom validation and "blind" assessment protocols. In addition, fundamental problems dealing with adequate selection of a control group and limiting loss to study can influence any comprehensive epidemiologic investigation. These and other pitfalls in study design will be discussed in more detail in Section VIII. The management of this project will be conducted through standard Air Force Research and Development procedures, including program monitors at Air Force Headquarters and Air Force Systems Command, and a Program Management office at Brooks AFB, Texas, Contract monitors will insure that all contractual efforts are conducted according to strict quality assurance procedures, and an on-site monitor will insure that the physical examinations are conducted in strict accordance with the study protocol. Since the study has three elements and confronts a health issue with incompletely specified or uncertain endpoints, strong potential bias, and severe time contraints, the following design represents the best overall framework for achieving validity. The design process is complex and in itself time dependent. 17 �B. Selection and Ascertainment of the Populations for Study (1) The Exposed Military Groups (a) Operation RANCH HAND Personnel Operation RANCH HAND personnel flew C-123 aircraft in RVN during 1962-1971. Data from hand-compiled lists obtained through the RANCH HAND Association (a reunion organization), Air Force personnel records, unit historical records, and actual C-123 flight orders, place the herbicide exposed population at approximately 1264 individuals. Of those personnel confirmed as RANCH HAND participants, 25% are still on active or reserve duty, with the remainder being composed of retired, separated, or deceased persons. To identify all RANCH HAND participants, an indepth search was conducted of all organizational records stored at the Military Records Division, National Personnel Records Center (NPRC), St. Louis, Missouri. Introductory letters will be sent to the last known address of all identified persons, and nonresponse will be pursued by cross-locator systems available within the government (e.g., Social Security Administration, VA, Internal Revenue Service). Significant efforts will be made to account for at least 99% of the total population (see Figure A-2, Section XV). Because of the limited number of RANCH HAND personnel, no subsampling of the exposed group is planned in any phase of the study. All members will be strongly encouraged to participate in all phases of the investigation. All RANCH HAND personnel are males currently ranging in age from 30-69 years (mean = 42.4 years). The normal C-123 crew composition was one pilot, one copilot/navigator (both officers), and one spray equipment console operator (enlisted) in the rear of the aircraft. The aircrew officerenlisted ratio is 2.2:1; however, the inclusion of RANCH HAND support personnel (predominantly enlisted) in the st-jdy will make the overall officerenlisted ratio 1:1.7. Approximately 98% of the officers and 92% of the enlisted men were Caucasian. Attempts have been made to identify all maintenance personnel assigned to the RANCH HAND units. Maintenance of the RANCH HAND aircraft was performed within a step-wise organizational structure. Routine daily maintenance (primary) was conducted by flight line support personnel who were often dedicated exclusively to RANCH HAND operations. More extensive maintenance (secondary) was carried out by consolidated support units at the base level, which were also responsible for non-RANCH HAND C-123s as well. Major aircraft overhauls and modification were conducted by maintenance units at Clark Air Base, Philippines. The maintenance personnel in these centralized units were not directly assigned to RANCH HAND, and their exposures to RANCH HAND C-123 aircraft and herbicide cannot be validated. From 1962 through 1964, the primary flight line maintenance teams were dedicated to RANCH HAND aircraft, and these individuals have been identified by the mechanisms described above. In 1965, flight line maintenance was performed by personnel of the centralized maintenance organization (secondary), and it is not feasible to adequately identify all of these individuals from available records. After 1966, the RANCH HAND organization transferred their 18 �base of operations to a new location, and primary maintenance was once again performed by personnel assigned specifically to RANCH HAND. These individuals have been readily identified. Thus, maintenance personnel directly assigned to RANCH HAND will be included in the study. These complexities are summarized in Table 4. Table 4 FEASIBILITY OF IDENTIFYING AIRCRAFT MAINTENANCE PERSONNEL (TOTAL POPULATION) EXPOSED TO HERBICIDE ORANGE Primary Maint Pers^ojinel Secondary Maint_ Personnel2 Jan 1962-Jul 1964 Yes No Aug 1964-Dec 1966 Yes/No3 No Jan 1967-Oct 1971 Yes No Time 1 individual assigned to RH; total number (denominator) known individual not assigned specifically to RH, although may have serviced the aircraft; denominator not ascertainable 3 other documents permit ascertainment of a portion of this group Because of the significant combat hazard associated with low, slow flying missions, some early RANCH HAND crewmembers were elite volunteers (see RiskTaking Bias, Section VIII, C). In fact, RANCH HAND crewmembers comprised one of the most highly decorated units during the RVN Conflict. Anecdotal stories reveal that most crew members were, on occasion, heavily exposed to Herbicide Orange due to normal or combat induced equipment malfunctions within the aircraft. Many former RANCH HAND personnel are expected to be currently employed in the aerospace industry as commercial airline pilots, airline managers, and flight mechanics. RANCH HAND personnel still on active duty are expected to be found in senior management positions. (^) Alternat^ Exjjosec^ Populations (I) Introduction The principal investigators, members of all of the peer review committees, and independent consultants have clearly recognized that the statistical power of this RANCH HAND study is suboptimal for the detection of specific uncommon conditions or diseases. This limitation is inherent because the size of the RANCH HAND population is fixed at approximately 1200 individuals, and it cannot be increased. 19 �A brief review of alternate military populations is in order to highlight the significant advantages of the RANCH HAND population. The desire to achieve more optimal statistical power by merely increasing the size of the population under study must be balanced with a careful analytic process which assesses the exposure level of alternate populations, and categorizes them as either additive or nonadditive to the RANCH HAND study population. (2) U.S. Army Ground Personnel Some U.S. Arrrjy personnel were undoubtedly exposed to herbicides during their duty in Vietnam; however, the objective ascertainment of exposed individuals is not possible. Any attempts to identify individuals assigned to combat units which may have been exposed would result in an unacceptable degree of misclassification since U.S. Army personnel records do not exist which would allow the accurate identification of soldiers below the battalion level. This lack of demoninator data, and the high degree of misclassification in determining the exposure status of Army troops makes this population unsuitable for inclusion in the framework of the RANCH HAND Study. (!) Ancillary Air Force Groups (Non-RANCH HAND Personnel) Air Force handlers of herbicide drums in RVN were exposed to herbicides because of drum leakage. As the drum handlers were ad lib participants, no personnel designator was assigned to these individuals, thus prohibiting computer tracking and identification. The size of this population is unknown, but it is expected to be small (less than 200), as the majority of drum handlers are known to have been Vietnamese. Additional groups such as U.S. Army helicopter crews, casual observers (both Army and Air Force), and experimental fighter-bomber personnel who may have occasionally conducted spray operations were also potentially exposed. However, population-at-risk determinations for all of these groups cannot be made, and any identification of individuals exposed in these situations must rely on self-selection or incomplete ascertainment. Also, the selection of suitable control groups for a study of these individuals is difficult if not impossible. ( ) U'S» Manne Corps Troops i On 16 November 1979, the GAO released a report which suggested that a herbicide-exposed population of nearly 22,000 U.S. Marine Corps troops could be identified, and that this identified group would be appropriate to study. Records exist which locate Marine Corps battalion headquarters near the C-123 spray paths. The GAO made several improper assumptions to conclude that all of the identified marines were in fact exposed. Specifically, all battalion troops were assumed to be located at the battalion headquarters. Further, the effect of prevailing winds on the direction of spray drift, and the photodegradation of the chemicals were not considered by the GAO. The National Research Council panel considered the GAO analysis, and proposed a study of 5900 marines who were "near" spray paths on the same day 20 �as the spraying. The "exposed" group was to be contrasted with the mortality experience of 212,000 presumably unexposed controls (also marines). The RANCH HAND study described in this protocol consists of approximately 1200 exposed individuals and 6000 controls for the mortality study phase. Despite the fact that the RANCH HAND Study involves a smaller sample size than the proposed Marine effort, the RANCH HAND Study is more powerful statistically. Specifically, lower exposure to herbicide by a conservative factor of from 1/10 to 1/1000 and misclassification in Marine exposure groups renders the Marine Study far less powerful than the RANCH HAND effort. As described in Section VI, misclassification and: decreased exposure are seen to be independent factors additively decrementing Marine Study statistical power. Even when all 21,900 marines within the herbicide spray paths up to 28 days following the spray operations are considered exposed, the RANCH HAND Study is noted to be significantly superior. (5.) Conclusions The Operation RANCH HAND participants are the most suitable of the military populations to study in evaluating the longterm effects of herbicide/dioxin exposures. The RANCH HAND group had a much higher level of exposure which was sustained over a prolonged period of time. This increased level of exposure implies that RANCH HAND personnel would be more likely to develop more acute and chronic symptoms from the exposure, and would manifest them sooner than the other exposed military personnel. The addition of significantly less exposed and/or misclassified groups to the RANCH HAND population for the attractive purpose of increasing statistical power would constitute an egregious dilutional error, (2) Control^ Group (Not exposed to Herbicide Orange) A review of all specialized flight units present in Southeast Asia during the RVN conflict, reveals clearly that there is no absolutely ideal control group for the RANCH HAND population, C-130 aircrew members and support personnel were selected because of sufficient population size, similar training profiles, and psychologic similarities to the RANCH HAND group. Total ascertainment of the C-130 population is being conducted by computer and hand selectipn for specific military flying organizations, and foreign country service> during the interval from 1962 thru 1970. Over 2.3 million personnel records have been reviewed, and the approximate C-130 population size is 23,978 individuals. Aircrew members who flew C-130 aircraft in Southeast Asia during 1962-1970 were selected as controls for the RANCH HAND aircrew population. The C-130 flight line maintenance population were ascertained from personnel records by similar mechanisms, and served as the specific control population for the RANCH HAND support personnel. The proportions on active duty, and non-active duty status are expected to parallel the patterns in the exposed group. Another possible control group» the non-RANCH HAND C-123 population, is known to be too small (approximately 3000) to provide adequate sampl i n g flexibility and replacement under the proposed matched variable concept 21 �(see below and Section VI). Also, many of the RANCH HAND aircraft were reconfigured for transport and insecticide missions and thus, the non-RANCH HAND C-123 crews responsible for these other missions may have been exposed to significant Herbicide Orange residue in these aircraft. Therefore, this group may not have been truly unexposed to herbicides, and was discarded as an appropriate control population. Crewmembers of C-7 transport aircraft were also considered as a potential control group; however, because of small sample size (1000-2000) and the fact that they served in RVN only during the post 1967 era, they were also dropped from consideration. The normal crew composition of a C-130 is three officers and two enlisted personnel. The control group is considered to be "pure" from the standpoint of lack of occupational exposure to herbicide. The entire control group will be considered "nonvolunteer" with respect to abnormally high combat risk. While in general they will possess lifestyle characteristics and socioeconomic backgrounds similar to the exposed group, their overall combat morbidity/mortality and the resultant stress influences upon general health may be slightly less than in the exposed group. For those separated and retired C-130 controls, similar proportions to the exposed group are expected to be employed in the aerospace industry. Known and estimated factors of the control and exposed populations are summarized in Table 5. (3) Matching Procedures and Rationale Each member of the exposed group has been computer matched to a set of C-130 controls comprised of approximately 10 individuals using three variables. Since the u;o groups are highly selected and inherently similar with respect to many variables, very close matches are feasible. This epidemiologic design incorporates a matched concept because: (1) a matched cohort design will provide maximum test power throughout the entire study, and (2) statistical intergroup comparisons may be made without normalization by three key variables known to effect symptom frequencies of interest, thus providing greater power for complex statistical testing. It is apparent that following the match, both exposed and control populations will be very nearly identical with respect to the three influencing variables so that a replacement concept is feasible (see F below). In the event that frequent match breaks occur, stratification techniques can be used. The selection of the control group produces an inherent match for equivalent SEA experience, and additional matching has been conducted for (1) age, by year of birth and closest month possible, (2) Air Force Speciality Code (AFSC) as an absolute match, and (3) race (Caucasian versus nonCaucasian) as an absolute match. Specific rationale for these variables is as follows: (1) the age match controls for the many clinical symptoms and signs associated with advancing age, (2) AFSC controls for officer-enlisted status (as well as crewmember-noncrewmember status), a variable strongly linked to educational background, current socio-economic status, and moderately linked to age (5 year median difference) and socio-economic background, and (3) race controls for differences in chronic disease development, socio-economic background, etc. 22 �Table 5 COMPARISON OF THE STUDY GROUP TO POSSIBLE CONTROL GROUPS BY KNOWN AND ESTIMATED FACTORS KNOWN FACTORS STUDY GROUP RANCH HAND C-123 POSSIBLE CONTROL GROUPS Non-RANCH HAND C-123 C-7 C-13( POPULATION SIZE 1264 3000 1200 23,97* OFFICER/ENLISTED RATIO 1:1.7 1:2 1:2 1:2 AIRCRAFT FUEL (AV-GAS) tvs CO YES (+JP-4)* YES (+JP-4)* YES NO (JP-4 OCCUPATIONAL HERBICIDE EXPOSURE YES YES/NO** NO NO OCCUPATIONAL INSECTICIDE EXPOSURE 2+ 0 0 0 COMBAT HAZARD 4+ 3+ 3+ 2+ RVN-IN COUNTRY ASSIGNMENT 4+ 4+ 4+ 2+ ESTIMATED FACTORS *In 1968, aircraft were modified with a JP-4 booster. **Contaminated aircraft reconfigured for transport may have resulted in exposure to non-RANCH HAND personnel �The inherent match for SEA experience controls for combat-induced physiologic, psychophysiologic, and other related morbidity and mortality disorders. Additionally, this inherent match may reflect the effects of alcohol consumption, the use of chemoprophylactic and/or illicit drugs, and the acquisition of tropical diseases associated with life in SEA. The comparisons of the exposed (RANCH HAND) subjects and their selected sets of controls are detailed in Appendix Table A-4. Only 4 of the ten categorical AFSC/case strata had less than ten controls for each exposed subject. The group of Caucasian pilots had a mean of only 9.5 controls per exposed subject, due to the extreme ages of several individuals, and the strata of Black pilots and other Black officers had means of 2.7 and 5.0 controls respectively. However, since there were only seven black officers in the exposed group and only thirty controls, high numbers of tight rnatchos could not be achieved. Black enlisted aircrewmembers had a mean of 9.8 controls each. (4) Computer Science and Statistical Petal 1s of the Matching Process As described above, the matching for this project has been performed using three variables: occupational category, race and age. Five occupational categories (officer/pilot, officer/navigator, officer/other, enlisted/flight engineer, and enlisted/other) have been used to reflect socioeconomic status and aeronautical rating. The variable of race has been dichotomized into black and non-black. Ten matched controls have been selected for each exposed subject, regardless of current vital status. The computer method applied to select the control subjects is an adaptation of a procedure studied by Raynor and Kupper (Nearest Neighbor Matching on a Continuous Variable, Technical Report, Department of Biostatistics, University of North Carolina, 1979). As the first step, the RANu! HAND and control groups were partitioned into ten strata using the categorical occupational and race variables. The Raynor and Kupper matching procedure was then applied iteratively within each of the strata to match for the continuous variable of age, given in months. The Raynor-Kupper procedure involves the following steps: STEP #1. The RANCH HAND cohort in a given strata is randomly permuted. STEP #2. The first RANCH HAND subject in the permuted set is selected for matching. STEP #3. The closest available control is assigned to the selected RANCH HAND subject using the absolute value of the difference between the months of birth of the RANCH HAND and the control subjects. If the closest available control is further than 60 months from the selected RANCH HAND subject, a blank is assigned. Tied assignments are broken randomly. STEP #4. Step #3 is repeated for all RANCH HAND subjects in the strata proceeding down through the permuted set, until the entire RANCH HAND cohort is exhausted. STEP #5. Steps #1 through #4 are repeated ten times for each RANCH HAND subject to construct a 1:10 study set. At the completion of the matching activity, the RANCH HAND - Control study matrices for each of the ten occupation-race strata can be diagrammatically represented as in Figure #1. 24 �Figure 1. MORTALITY ANALYSIS COHORTS 10 1 19 1 R "2 r2j 1 R 3 p U R r 4 3,l * ^Hjl I 5 t. 1j O • •*• 9 *•* v i ,io U r2 j 2 r ^2,3 r ^2,4'*** • P f ^3,2 P 3j3 P "3^4**** • p ^3 , 10 pt J /"* HjO ^i^^q.**** fj/ /* • ^2,10 "4 ,10 1200,3 1200,l 12 QO,10 Figure 2. MORTALITY MATRIX RANCH HAND COHORT Rl _,, , CONTROL COHORTS cr c i,i,m' c i,2,m' *** '10 15m 16 ••• ^ , 10 j,5,m R 1200 ,5,m' Ci2oo,i,m' C12oo,2,m' C i200,e' C 1200,10' In each row of this matrix the controls are ordered from nearest to farthest in terms of age of the matched RANCH HAND person. The next operation defining the control group involved randomization of all of the controls in each row of each stratum matrix to negate the ordering by age. Then, the first five members of each control set for each RANCH HAND person are identified as being subjects in the mortality portion of the study. The resulting occupation-race strata matrices now have the form shown in Figure 2. In Figure 2, Cj^' or Cj^^1 may be equivalent to any Cj^ of Figure 1 due to the randomization process. Table 6 summarizes the results of the matching process, and Appendix Table A-5 provides a more complete statistical description of the process. In these tables, the age difference between the month of birth of the control and the month of birth of the RANCH HAND person, (counting months from 1900) and the cumulative number of controls and the cumulative percentage with this difference are shown. 25 �Table 6. RESULTS OF THE MATCHING PROCESS (1:10) Age Difference (in Months) Cumulative Number of Controls Cumu1 ative Percent 0 8612 70.6 1 10287 84.3 2 10749 88.1 3 10984 90.1 4 11167 91.6 5 11322 92.8 6 11410 93.5 12 11688 95.8 24 11921 97.7 36 12028 98.6 48 12129 99.4 60 12197 100.0 (5) Study Group Selection Procedures (a) Mo rta1i ty An a 1/s i s A 50% random sample of each control set will be drawn and used to comprise a 1:5 mortality analysis, as described in section (4). The vital status of each subject in this sample and of all exposed subjects will be ascertained at a minimum frequency of every five years for the 20 year duration of the study. Those individuals dying of combat causes will be excluded from the mortality analysis as it is assumed that combat death is independent of herbicide effect. Further, the known differential combat death rate between the RANCH HAND and control groups can be attributed to the hazardous and unique nature of the RANCH HAND mission. Twenty-two RANCH HAND personnel (15 officers and 7 enlisted) died in combat. Medical record reviews will be accomplished to assess the illness experience of these individuals prior to combat mortality. (b) Historical Morbidity Study Retrospective or historical health data will be gathered on each exposed subject and from the first randomly selected mortality control from his set by questionnaire techniques. Living but noncompliant controls in 26 �the historical morbidity study will be replaced by a compliant control selected from the control set. In order to avoid an information gap for data on deceased individuals, surrogate interviews will be obtained from the first order next-of-kin of exposed and control subjects dying of noncombat related causes between the date of their assignment to Southeast Asia and the initiation of this study. Since the validity and accuracy of surrogate derived data may not be equivalent to data obtained directly from living study subjects and their spouses, these data will be subsetted for analysis. All available medical records, (military, VA, and civilian) will be reviewed for all subjects selected for this morbidity analysis. (c) Prospect 1 ve Morbidity Study A baseline physical examination and review of systems will be conducted, and a prospective or followup approach will be used to assess the current state of health of study subjects using a series of questionnaires and physical examinations over the next 20 years. Each living exposed subject and the randomly selected primary control will be incTuefe'd "in the questionnaire and physical examination phases. In this prospective study of morbidity, primary controls who are deceased, unaccountable or unwilling to participate in the followup studies, will be replaced by a willing subject from the remainder of the control set (Figure 3). The selected control for a RANCH HANDER dying of a noncombat cause will be retained throughout the questionnaire, physical examination, and followup phases of the study. Since the control's vital status and volunteerism should be independent of the matching sequence, many primary controls should enter the study. The remaining members of the control set will be used as replacement candidates for possible use later in the study (see section F below). All replacement controls will be clearly identified for the purposes of subset analysis so that population differences, if any, between the first randomly assigned selectees (noncompliant) and the replacements (compliant) can be assessed. Specific rules and procedures for study entry are found in Table A-6 and Figure A-3 of the Appendix. (d ) Thne Jnterreljitedness of the £pjn_pa_r1_soni Groups It should be clear from the foregoing discussion that the study populations of the mortality, historical morbidity, and prospective followup phases are highly related but different. Once selected, the mortality control cohorts will remain unchanged throughout the 20 years of observation. The population under study in the historical morbidity phase will initially be a randomly selected subset of the mortality comparison group; however, some of these primary controls may be decreased or noncompliant for the voluntary aspects of this phase of the study. In this phase, noncompliant controls will be replaced, but deceased controls will not, as surrogate interviews with the next-of-kin will be used to reconstruct morbidity data. The subsetting arid replacement procedures create the difference between the mortality and historical morbidity comparison groups. The population in the prospective morbidity phase is the comparison group from the retrospective phase plus additional replacements for the deceased controls. Thus, it is clear that the comparison groups are slightly different, but they would be identical if no deaths recurred since 1962 and all primary controls were compliant. 27 �Figure 3. SELECTION PROCEDURE FOR THE QUESTIONNAIRE, PHYSICAL EXAMINATION, AND FOLLOW-UP STUDY LIVING RANCH HAND INDIVIDUAL CONTROL INDIVIDUALS Randomly Selected Mortality Controls Ji ^ ** t t * ** - t Deceased Unwilling Volunteer Replacement Candidates C. 0verview of Stat i st i ca1 Methodology The design of the study is presented in schematic form in Figure 4. R' refers to RANCH HAND personnel and C" refers to the collection of all possible control individuals. As defined, P' and C" will contain individuals who are deceased of noncombat causes. Combat deaths 1are excluded from R 1 and C". Since C" is approximately 20 times larger than R , a randomized subsample C' and C" will be obtained. C 1 will be constructed from C" by computer selection of the ten matched controls for each exposed study subject. As previously noted, close matches will be nude for the variables of age, AFSC, and race. The matched controls will form tan cohorts, Ci through C 10 , as shown in Figure 1. A 50% random sample from each of the matched control sets of 10 will be selected for inclusion in the mortality assessment so that a group, C' is obtained that consists of 5 matched controls for each exposed subject. These controls will be designated as initial replacement candidates for the morbidity and follow-up studies. The remaining individuals in the control set will be additional replacement candidates in the event that replacement must occur beyond the members of the mortality set (see Figure 3). C' will be constructed without regard to whether the individual is currently living or dead so that an assessment of noncombat mortality can be accomplished. 28 �FIGURE 4 DESIGN SCHEMATIC EXPOSED R 1:5 ro MORTALITY ANALYSIS UNUSED PHYSICAL EXAMINATION �Referring again to Figure 4, R and C indicate living RANCH HAND members and primary matched controls. If ITIR' is the proportion of R' found to be deceased, then R » (1 - mR')R' The questionnaire will provide data concerning specific symptoms and other findings in the R and C groups. Thus, various questionnaire finding rates in R, SR, will be calculated and compared with the corresponding rates in C, so The questionnaire will allow allocation of RANCH HAND personnel into those with symptoms on questionnaire, indicated by RS, and those without, R?. Similarly, the control Jndividuals will be placed into symptomatic, indicated CS, and asymptomatic, C"$" groups. The physical examination performed on individuals from R and C will allow estimation and comparison of rates of physical findings in these groups. Rates of abnormal physical findings can be symbolically indicated as fR and fc for RANCH HAND and control groups respectively. Comparison of these rates is very important and details will be discussed below. Let fRs be the rate of physical findings among RANCH HAND personnel with findings by questionnaire and let fR$ be the rate of physical findings among RANCH HAND people with no findings on their questionnaire. For most disease processes it would be expected that fR$ should be a larger rate than fRS*. If fRS is observe1! to be equal to or less than fR$", an interpretation of over-reporting may be warranted, although the possibility of subclinical disease is recognized. Rates fcs and ^CS" w^l a^so be estimated, and comparisons between fR$, fc$> fR$ and fc$"will be accomplished. The eight rates IDR', me', SR, SQ, fRs» fRs", fcs, fCS; and their refinements fully characterize this study. As depicted in Figure 4, "vertical comparisons of these rates provide relative risks mR'/mc'' S S R/ C» fR/fc» fRS/fCS and fRS/fcs" which are of central importance in defining herbicide effects. "Horizontal comparisons" relate fR to SR, fRS to fRs, fc to sj and fcs to fcs**. Specifically, the ratio fR/SR is the ratio of physical findings to reported symptoms in the RANCH HAND population. This ratio may be contrasted with the ratio fg/sr, and if fR/SR is less than fc/sc over-reporting is suggested. Likewise, if fRs is less to than fR^", over-reporting is further suggested. A comparison of fRS/fRS fCS/^CS contrasts the odds of findings given symptoms in the RANCH HAND population with the odds of findings given symptoms in the control group. If these odds are lower in the RANCH HAND group, overreporting is again implied. Further discussion of these rates is presented in Section V.G. During the questionnaire and physical examination phases of this study, only one of the five randomly selected mortality study controls will be used for each RANCH HAND individual. If this control is unwilling to participate, another mortality study control will be used as indicated in Figures 3 30 �and 7. These replacements will be carefully labelled for purposes of statistical analysis. A detailed discussion of this replacement concept is found in Section VI. D. Mortality Study (1) Introduction The mortality s retrospective morbidity, and follow-up studies are components of a "non-concurrent" prospective study used in the observation of a specially exposed group or industrial population starting from some date in the past. The initial exposures occurred 11-19, years ago and varied in intensity and duration from one RANCH HAND member to another. Access to employment, medical, or other types of records is an obvious requisite for such a study. The classical "case-control", retrospective study is not operative in this protocol due to the lack of defined clinical endpoints. The mortality study will be conducted in two phases; a review of past mortality, and a continuing assessment of the death rate in the exposed and control cohorts over the twenty year duration of the RANCH HAND II project. Based upon USA vital statistics, 8.6% of the study subjects are expected to have died between completion of their Vietnam tour and initiation of this study. Of these deaths in the control group, approximately 30% should have been due to cardiac causes, 24% to neoplasia, 13% to accidents, 5% to cirrhosis, and 0.1% to leukemia. (2) Data Collection Methods The mortality status of the exposed cohort and the randomly selected controls will be ascertained using multiple techniques including: payments of Veterans Administration Death Benefits, Social Security Administration Records, Air Force Accounting and Finance Center wage and retirement payments, and interviews with subjects or their families. Death certificates, autopsy reports, and medical records will be obtained for each deceased subject. The International Classification of Disease, Ninth Revision, 1978, will be used for coding. At the time of the first followup examination, all participants will be asked to allow an autopsy to be performed at government expense at the time of their death, and have the tissues forwarded to the Armed Forces Institute of Pathology, and the results sent to USAFSAM. (3 ) Analysis of^ Mortality Data Considering the basic groups R' and C 1 in Figure 4, individuals will be classified into three categories: alive, dead, or unaccounted. If a large number of individuals in each group are unaccounted for, the study can obviously be severely biased. Thus, significant effort will be expended to reduce the unaccounted category as much as possible. At most, 1 to 3 percent of both groups can be allowed to remain unaccounted, with a 1% rate 31 �being preferred. If for example, the mortality rate in C 1 is 0.10, then an unaccountability rate of 0,01 could alter the mortality rate by as much as 10%. Whatever the unaccountability rates, the pattern of unaccountability must also be compared between groups R 1 and C'. For example, the possibility of age differences must be examined, particularly if the unaccountability rates are high. The following paragraphs discuss the analysis of mortality under the assumption that low unaccountability rates have rendered the mortality analysis meaningful. Multiple mortality assessments will be accomplished during the course of this study, one at the beginning of 1 the study, using available mortality data on the basic mortality cohorts in C and R 1 (5:1 ratio), and others using mortality data on R 1 and all controls used in the study (both C 1 and replacements) as controls accumulate prospectively. The procedures described here will be used in all of these assessments. Henceforth, within the protocol, the term "mortality data" does not distinguish between that data collected initially and that data collected in the future. The mortality data will be analyzed using several different approaches. Crude age-specific death rates will first be calculated and tabulated. Age will be d-jvided into k strata, and person-years will be observed for each strata as will be the number of deaths in each strata. In this manner a tabular display will be developed as shown in Table 7. Table 7 STRATIFIED FORMAT OF AGE-SPECIFIC DEATH RATES Ranch Hand Person Years Deaths 1 Pl2 Person Years m 12 PIS Death Rate PH 2 Controls m Deaths P2i P21 22 m22 r m P !3 "Ilk Death Rate P23 23 22 •"ik Since the death rates TIJ and r2j are Poisson variables, they can be contrasted directly. If the relationship of rjj to r2j is found to be consistent between age strata (within statistical variability), a summary mortality index may be calculated. One summary index that will be calculated is the Standardized Mortality Ratio (SMR) which is (Armitage, 1971): 32 �SMR * M x 100 k I m i M » "Classical" standardized mortality ratios using national mortality data as the reference will not be calculated for RANCH HAND II due to the effects of the healthy worker phenomenon. The term I mn is the total number of deaths observed in the RANCH HAND group while I Py r2j is the number of deaths that would be expected were the age-specific RANCK HAND death rates the same as the age-specific control death rates. Thus the concern is for an SMR greater than 100%. If a crude death rate for controls, dc, is calculated as k I then the standardized crude rate for the RANCH HAND group d^^ is d RH = An approximate statistical test would regard d^ as a Poisson random variable with mean dr,. An alternative approach to the provision of a proportionate mortality ratio is that of Breslow and Day (1975). In this treatment, a multiplicative model is employed, for example: Mjk = 9 ifj*k where \\jk is bhe mortality rate, 0-j is the contribution due to population differences (RANCH HAND versus Control), <)>j is the contribution due to age 33 �group, and ^ is the contribution due to length of time in RVN, etc. statistical approach here is via maximum likelihood. The Logistic models (Walker and Duncan, 1967) have been extensively studied at USAFSAM for application in cardiovascular disease analysis. These models, in the herbicide context would have the form P = [1 + exp(a + 3iA + 3eT + 3sR + Bi»E + 05AE + ...J]- . where P A T R E = = = = = probability of death age in years length of time in RVN indicator variable for race exposure variable and where a\t 3i, i=l,2,... are coefficients to be estimated from the data. Testing for a group difference can be accomplished by estimating 3^ and the interaction coefficients such as 35. If all interaction coefficients involving the exposure variable E are zero and E is treated as a 0/1 variable, Cox (1958a, 1958b) has shown that thd most powerful test for non-zero 34, in the setting of matched pairs, is McNemar's test. This latter test makes full use of the paired design of the study. For McNemar's test, the data are cast into a 2 x 2 table as shown in Table 8. In this table, "a" is the number of pairs in which both members have died, "b" is the number of pairs in which only the RANCH HAND person has died, etc. Using McNemar's test, the test statistic 2 |b-c| 2 x =J L b +c is calculated and referred to the chi-square distribution with one degree of freedom. Cox (1966) and Meittinen (1969) provided extensions of McNemar's test for R controls per exposed (R-to-1 matching). Of course the above analyses will be accomplished considering all deaths, and deaths by specific cause. As previously discussed, RANCH HAND personnel may be characterized as risk takers. This risk taking behavior may be associated with increased mortality from a variety of causes. On the other hand, herbicide exposure has caused neuropathy in the RANCH HAND personnel, one could anticipate that this disability would increase the probability of accidental death. Therefore, 34 �Table 8 FORMAT OF McNEMAR'S TEST CONTROLS RANCH HAND PERSONNEL DEAD ALIVE TOTAL Dead a b a+b Alive c d c+d Total a+c b+d n accidental death rates among RANCH HAND participants will be corrected for risk taking. This can be accomplished by including assessment of risk taking behavior in the questionnaire, indepth interview, and psychological evaluation. Both control and RANCH HAND mortality could be corrected using these measures, with the resultant rates being less biased and, therefore, a better indicator of exposed versus control effect. (b) Mortality analysis without cov.a Mates. The first step in the statistical analysis of survival data is descriptive, i.e., the construction of summary measures which provide a basis for comparing different exposure groups without any allowance for the effects of possibly confounding variables (e.g., age) except perhaps for some limited stratification. Since one must expect many "losses to follow-up", only methods which take full cognizance of this complication will be considered. It should be pointed out that all the methods described below assume independence between censoring (e.g., loss to follow-up) and death or morbid event, although some techniques permit different patterns of censoring in different exposure groups. The life table method can be adapted to obtain a step-function approximation to survival distributions in the presence of censoring (Chiang, 1968, Gross and Clark, 1975). The failure time distribution is the function F°(t) which provides the probability of death at or before time t in the study. The Kaplan-Meier estimator of F°(t) is F°(t) where F-°(t) - 1 - n [1 - l/R(Ti)] ieD(t) In this equation, D(t) is the "death set" at time t, i.e., the set of all indices i of individuals who were observed to fail before time t. R(T^) is the number of individuals who were at risk just before time T^, the time of death (or morbid event) of the i^n study individual in D(t). A nonparametric approach to testing the equality of survival distributions in a matched 35 �pair study has been developed by Wei (1980). His statistic is a generalization of the Gehan (1965a) statistic. A second test for homogeneity of survival distributions for discretized failure data is the test for marginal homogeneity in a KxK table due to Stuart (1955). Thirdly, the McCullough Model and test may be used on the KxK array to test for marginal homogeneity and stochastic ordering. (c) Morta1 i ty ana lysis wi th _cgva r i ates. These methods allow adjustment of mortality rates or morbidity rates using covariates such as age, race, length of time in RVN, AFSC, risk taking score, etc. Kor the purposes of this discussion it will be assumed that the covariables are categorical, that there are only two such covariables and the covariables do not interact in affecting the hazard of death or morbidity. These assumptions can all be relaxed using available methods. The hazard function h-j(t) for the 1th individual in the study is the function which provides the conditional probability of death or morbid event in the time interval (t, t+dt) given his survival up to time t. The function H-j(t) where t Hi(t) = / hi(T)dT 0 is called the cumulative hazard for the ith individual. that the failure time distribution F?(t) is given by: It is readily shown F°(t) = 1 - exp(-H.(t)) From this last equation it follows that hj and F° are transforms of each other, hence the dependence of F° on covariables may be modeled via h-j. This may be accomplished as follows. Let X-j(t) and Y-j(t) denote discrete valued stochastic processes pertaining to the ith individual and describing two covariates of interest (e.g., one may be an exposure variable and the other may be covariate such as age or crew position). A basic model for hazard is: hi(t) = exp [?Xi(t) + nYi(t)] where ? and n are "log-relative risks". This model may be extended to allow for any number of possibly interacting factors. Inference about log-relative risks may be drawn using either an approach derived from D. R. Cox (1972) by E. Peritz and R. Ray (1978) or using an approach described by Frank (1977). Another model, termed the proportional hazards model, is given by 36 �[3Xi(t)] The proportional hazards model has been discussed, for the special case that Xi(t) does not change with time, by Cox (1972). A test for the equality of survival distributions in a matched pair study which incorporates the proportional hazard model has been given by Breslow (1975). A test of fit for the proportional hazards model is given by Schoenfeld (1980). E. Morbidity Study (1) General Consrderations A vigorous attempt to determine the morbidity experience of all exposed subjects and their primary controls will be undertaken using questionnaires, indepth personal interviews, and physical examinations. A waiver will be requested from the U.S. Attorney General so that medical information collected during the conduct of this study may be exempted from subpoena into Federal Court. Total confidentiality of medical information will be granted to subjects who are not on active duty, and partial confidentiality will be given to active duty subjects with release of information to the DOD only in instances where there is a public safety or national security risk. The schedule and method of contact with the study subjects is depicted in the Appendix Table A-7. (2) Questipnnaire Methods All living exposed subjects and their primary controls will be offered a comprehensive personal and family health questionnaire administered in the subject's home by a civilian contractor. In addition to subject interviews, a face-to-face interview will be conducted with the current spouses of the subjects to obtain a more accurate and complete assessment of fertility and reproductive function. Reproductive Information that will be collected includes but is not limited to the number of live births, the number of still births, the number of miscarriages, the number of children conceived, the number of abnormal offspring, and the total years of marriage. Previous spouses of divorced or remarried subjects w i l l also be interviewed to obtain similar data. Interviews with the first order next-of-kin of deceased subjects will provide morbidity data on thesubject prior to his death. Whenever subjects, their spouses or next-of-kin will not consent to participate in a face-to-face interview, attempts will be made to elicit the information by telephone. The questionnaire is an important part of this study because noncompliance rates for the physical examination and its face-to-face medical interview are expected to be substantially greater than non-compliance with the initial questionnaire. The questionnaire serves a four-fold purpose: (1) to capture baseline personal and medical data on subjects who might be noncompliant for subsequent physical examinations, (2) to serve as a cross-reference 37 �source for objective data obtained at the time of physical examination, (3) to obtain a targeted medical inventory, independent of the physical examination process, and (4) to obtain health perception data to serve as a foundation for the replacement strategy. As depicted in the Appendix, Figure A-2, only an estimated 40% of the RANCH HAND: population will participate in the examination, while at least 65% will respond to the questionnaire. The information collected by questionnaire from; these additional 309 individuals and their controls will provide valuable morbidity data which would otherwise be lost. The questionnaire (see Section XI) will emphasize identification data, RVN tour history, dermatologic conditions, neuropsychiatric conditions, fertility aberrations, genetic defects in offspring, sensory defects, and personality factors. A targeted medical inventory will be included in the questionnaire, and will inventory symptoms prior to, during, and after duty in RVN as well as those currently manifested. It will take approximately six months to complete all initial questionnaires on both groups. The questionnaire will be "fieldtested" by the contractor on former Air Force personnel with RVN experience. Specific questions on the questionnaire will be directed to verifiable information, wherever possible. Questionnaire development and refinement, including specific response verification procedures have been pursued through civilian contract. Questionnaire data will be cross-linked and integrated with medical record information and physical examination findings. Questionnaire data from individuals not completing all phases of the study will not be discarded, but will be incorporated within the entire data base where statistically appropriate. Each participant will be asked to sign release forms so that all civilian health records, including those of dependents, can be obtained and reviewed as necessary. Attempts will be made to obtain pathological reports and specimens following surgical procedures. Federal health records on all family members on file in the NPRC will be retrieved. For retired members, and separated members with VA privileges, all available VA medical records will be obtained. All retrieved medical records will be reviewed, scored, compared to questionnaire data for reliability, and then be entered into a repository system. I lantified participants who are nonresponsive to questionnaire will be pursued to determine status, disinterest, moribund state or death, etc. These individuals will be cross-referenced in other federal record systems in an attempt to achieve total ascertainment. Death certificates and autopsy sports will be retrieved on all dead exposed and matched control subjects for the mortality analysis. Birth/death certificates will be sought for all offspring. (3) Physical Examination A voluntary comprehensive physical examination will be offered to all individuals in both the exposed and primary control groups within one year of questionnaire administration. The condition for entry into the examination phase of the study will be the completion of the baseline questionnaire. In the event that the primary control does not complete both the questionnaire and the physical examination, a replacement will be selected from the control set [See Figure 3 and Section F(3)J. Statistical testing will be conducted by a variety of techniques on both questionnaire and examination findings. At the time of physical examination, an extensive physical examination, medical 38 �history, and review of symptoms will be conducted. A standardized protocol will be used to insure comparability of data. This will provide crossreference data to the initial questionnaire and to medical record data, if retrievable. Specific response verification and bias indicator questions will be included in this interview as well. (a) Examinati on Parameters A comprehensive physical examination will be conducted on all willing participants. The examination will be structured as outlined below and in Section XII and will be performed at the earliest practical time following the completion of the questionnaire. The close sequencing of these study components will limit the development of major symptoms in the interval between the questionnaire and the examination. Examinations will be performed under contract at a single civilian medical center haying dermatologic, neurologic and electromyogram/ nerve conduction capabilities. Informed consent forms will be obtained for all procedures. Physicians and technicians will handle all participants without a knowledge of exposed or control status, and will conduct the examinations by standardized protocols to minimize variability. Medical students, interns, and residents will not be allowed to perform these examinations, and specialty trained neurologists and dermatologists will perform the appropriate portions of the examination. An onsite monitor will insure that the examination protocol is followed. All laboratory tests will be subject to rigid quality control. Laboratory and physical examination data will be measured on a continuous scale whenever possible in order to improve statistical power in the analysis. Under special circumstances, additional testing will be accomplished. Karyotyping of the individual and his family members will be considered if clinical history or physical examination findings are suggestive of this need. Most well conducted studies have shown that, when present, chromosomal abnormalities due to TCDD are transient. If on detailed analysis of the baseline examination and questionnaire, reproductive areas are heavily affected, routine karyotyping may be included in the test battery for the followup phases of the study. TCDD analysis on blood and urine will be considered in the future provided that (1) strong cause and effect relationships can be ascribed to Herbicide Orange and (2) high resolution mass spectrometry technology achieves 10 femtogram sensitivity with high isomeric specificity. Serum, urine, and semen specimens will be obtained from all participants, aliquoted, and preserved at -70°C for possible analysis in the future. These serum and/or urine specimens will also be used for analysis of porphyrin metabolites if analytic techniques make this a feasible diagnositc procedure. Extensive immunologic function analyses will be conducted on a randomly selected group of subjects. Physical examination and laboratory data will be placed in the member's coded master file for detailed cross-analysis to questionnaire data. Information identifiable to the subject will not be released without his consent in accordance with the Privacy Act. However, in accordance with Air Force regulations, active duty flying personnel and active duty air traffic controllers found to have conditions which are disqualifying for flying duty will be temporarily "grounded" pending resolution of the medical condition. 39 �Physi cal Examination Prof i1e General Physical Examination FBS, 2 Hr Post Prandial Urinalysis BUN/Creatinine Cholesterol/HDL Triglycerides Serum Protein Electrophonesis Hemoglobin Hematocrit White Blood Cell Count and Differential Platelet Count RBC Indices Sedimentation Rate Prothrombin Time CPK ECG Chest X-Ray VDRL/FTA Cortisol Differential Thyroid Profile (RIA) Pulmonary Function Studies Blood Alcohol Dermatologic Examination Urine Porphyrins Urine Porphobilinogen Delta-aminolevulenic Acid Neuro-Psychiatric Examination General Neurologic Examination Psychological Battery: Nerve Conduction Velocities MMPI WAIS WRAT Halstead-Reitan Wechsler Memory Scale Subtests Cornell Index Reproductive Examination LH, FSH, Testosterone Semen Analysis Neoplastic/Hepatic Examination SGOT Alkaline Phosphatase SGPT LDH (Isoenzymes 1f elevated) GGTP Hepatitis B Antigens/Antibodies Bilirubin, Total and Direct Additional Studies (Individuals with abnormal history or examination) Karyotyping Immunoelectrophoresis Hepatitis A Antigens/ Bilateral profile and fullAntibodies face photographs Skin Biopsy Anti-Nuclear Antibody Quantitative Immunoglobulins Additional Consultations as Required Immunologic studies (conducted on a randomly selected group of subjects) Enumeration of B and T Cells B and T Cell Function Enumeration of Monocytes 40 �(4) Analysi s of Questi onnai re an^d Physi cal Exami nati on Data The Questionnaire and Physical Examination will produce data of three types: (1) dichotomous, (2) polytomous and (3) continuous. Dtchotomous (e.g., present/absent) rates will be evaluated using the tools described above for mortality analysis. For example, the questionnaire will provide data concerning the first occurrence of disease states by age, and standardized rates and relative risks may be calculated. The occurrence of such findings can be related to age, time spent in RVN, exposure, and other variables using logistic models followed by McNemar's test where appropriate. These tests will examine the presence or absence of group effect and allow assessment of the statistical significance on non-unity relative risks. Polytomous findings will occur in both questionnaire and physical examination responses. As an example consider retinal findings categorized into four grades, and studied as a function of age and exposure group as represented in Table 9. In this table the x-jjk's are counts of occurrence. In analyzing tables such as these, techniques as described by Bishop, Fienberg, and Holland (1975) will be used. Specifically, if m-jj^ is the expected value of x-jjk, general log-linear models of the form + u2(j) + u3(k) + u 13 (ik) + u23(Jk) + u123(ijk) will be used, where u:(i) is the effect of RANCH HAND membership alone on cell frequency, u12(ij) is the effect of an interaction on RANCH HAND membership with retinal grade, etc. This model can work with dichotomous as well as polytomous data. Under appropriate conditions on expected values of entries in Table 9, the pairing in the study design can be used with the data being organized as shown in Table 10. In Table 10, NJJ is the number of pairs such that the exposed person has retinal grade i, and the control person has retinal grade j. Appropriate tests for this setting are indicated by Fleiss (1973) and McCullough (1978). With regard to continuous variables, the intended method follows Carpenter (1977) who found substantial gains in analysis efficiency by matching cases, subsequently employing covariance analysis to remove non-controlled effects. The conditional logistic regression model for relative risk, Holford, White and Kelsey (1978), is also applicable and will be used. 41 �Table 9 FORMAT OF CATEGORICAL REPRESENTATION OF RETINAL CHANGES RANCH HAND PERSONNEL CONTROLS ""--vAge Category Retinal Category^*""**-^ 1 2 3 4 1 X i ; 1 X 11.2 X 113 X 2 X 121 X 122 X 123 3 X 131 X 132 X 133 4 X 1U1 i ^ X 1 2 3 4 m X 211 X 212 X 213 X 21»v X 12H X 221 X 222 X 223 X 224 X 13"+ X 231 X 232 X 233 X 234 u «/ w " 1 U 9. " 1 U' 3 ^ l A *L t U T" XTi XT O \f w y ** Table 10 FORMAT OF PAIRING FOR GRADES OF RETINAL FINDINGS ^Control Grade RANCH HAND Grade" 1 Nil N 12 N 13 N11+ 2 N21 N22 N23 N2(t 3 N31 N 32 N 33 N34 4 N N N N (5) Analysis of Fertl11ty/Reproduction Data. The herbicides under consideration in this study have been alleged to effect fertility and/or reproductive functioning. An attempt will be made to address these allegations by analyzing at least three primary variables: the total number of conceptions since exposure in RVN:, the number of miscarriages in spouses since exposure in RVN and, the number of abnormal offspring since exposure in RVN. The interview with current and former spouses will provide much more accurate information on fertility and reproductive functioning than if similar data were obtained from the male subjects themselves. The study questionnaire will provide the numbers of miscarriages, abnormal offspring and of live births. The sum of the number of miscarriages, still births, and live births will provide an estimate of the total number of conceptions. If differing divorce rates are found in the RANCH HAND and control groups, this may render the average number of years of marriage and the distribution of the years of marriage different in the two groups. This will be investigated and adjusted 42 �for if need be, either by analyzing total number of conceptions divided by (or normalized by) the number of years of marriage, or by using a more detailed covariance analysis. Further, the ratio of the number of miscarriages to adjusted total conceptions will be calculated and compared, as will be the ratio of the number of abnormal births and adjusted total conceptions. In summary, the following statistics relating to fertility will be calculated and analyzed at the very least: TOTAL CONCEPTIONS = #Live Births + #Still Births + #Miscarriages NORMALIZED FERTILITY INDEX MISCARRIAGE FRACTION ABNORMALITY FRACTION TOTAL CONCEPTIONS YEARS OF MARRIAGE # MISCARRIAGES TOTAL CONCEPTIONS # ABNORMAL OFFSPRING TOTAL CONCEPTIONS F. Foilpw - up S t udy (1) Study Adaptations Following complete data analysis of the initial mortality and morbidity studies, adaptive or restrictive health surveys will be developed and administered to all follow-up study subjects three, five, ten, fifteen and twenty years after the initial questionnaire. Similarly, a condensed physical examination profile that will achieve adequate sensitivity and specificity for prospective diagnosis will be developed. The adaptive physical examination will be offered to all follow-up participants, and will also be conducted in years three, five, ten, fifteen, and twenty (see Appendix, Table A-5). An interim examination in year three is essential in this study because the age group under study is approaching that portion of the mortality/illness incidence curve with the steepest slope. A lapse of five years between the first two examinations could easily miss significant development of disease in the intervening years. Ample precedent for interim examinations can be found in the Framingham cardiovascular disease study, and in the follow-up evaluation of West Point graduates being conducted by the Air Force. 43 �(2) Entry Criteria All exposed or control individuals completing the baseline questionnaire and physical examination will be entered into the follow-up; further continuation will depend upon the member's willingness/ability to participate in additional health surveys and condensed examinations. Specific study entry rules are detailed in Table A-6 and Figure A-3 of the Appendix. (3) Loss to Study; Key Issues Loss of participants over time adversely affects any epidemiologic study in two ways. Ar the sizes of the study groups decrease, statistical power also declines, and bias is injected into the study if losses are not randomly distributed in the study populations. It is reasonable to assume that in this study, losses will be non-random with greater non-compliance among individuals who perceive their health as "well," since there is less incentive for this group to continue participation. As shown in Figure 5, such a differential pattern of loss will alter the population, and skew the frequency distribution curve. Most previous epidemiologic studies have approached the problem of declining statistical power by beginning the study with multiple controls per exposed subject, and passively allowing attrition to occur throughout the study period. However, this approach does not address the problem of bias. This study will take an active approach to both of these problems by using a replacement concept. As a control is lost to study, a replacement will be chosen from the original set of ten matched controls. The replacement will be selected from the control set, and will have a perception of health similar to that of the lost control (Figure 6). The replacement strategy will maintain statistical power and the integrity of the matched design despite loss to study in the control group, and will correct anticipated bias while minimizing the number of required physical examinat'ons. At the initiation of the follow-up study, loss of an exposed member will not be cause to cease surveillance of his primary matched control. In the event of a control loss (for reasons other than death), another control from the set will be brought to study (Figure 7), the comprehensive questionnaire will be administered, and a baseline physical examination performed. If a control is noncompliant for one portion of the study and is replaced by another control, the noncompliant individual will be approached at the time of subsequent questionnaires and examinations, and encouraged to reenter the study. If he reenters, both he and the replacement will be included in the evaluation. Similarly, noncompliant exposed subjects will also be aggressively recruited for all subsequent study phases. 44 �FIGURE 5 EFFECT OF NON-RANDOM LOSS TO STUDY IN THE CONTROL POPULATION N WELL ILL HEALTH SPECTRUM IF CONTROL LOSSES ARE ILL, A SPURIOUS EFFECT IS ATTRIBUTED TO HERBICIDE EXPOSURE. IF CONTROL LOSSES ARE WELL, A TRUE/VALID HEALTH EFFECT IS DILUTED. �riGUKt THE REPLACEMENT STRATEGY EXPOSED PRIMARY CONTROLS LOSSES REPLACEMENTS MATCHED FOR HEALTH STATUS {DEAD CONTROLS NOT REPLACED 01 �FIGURE 7 CONTROL REPLACEMENT FOR THE MORBIDITY AND FOLLOW UP STUDIES EXPOSED CONTROL YEAR 0 YEAR 1 YEAR 2 YEAR 3 YEAR 4 YEAR 5 YEAR 6 • QUESTIONNAIRE DATA O RECONSTRUCTED DATA LOSS TO STUDY PHYSICAL EXAMINATION DATA �For exposed and control individuals who drop out of the study but subsequently re-enter, medical data for the intervening years will be reconstructed from questionnaire and interview responses. IN ALL CASES OF LOSSTO-STUDY, INTENSIVE EFFORTS WILL BE MADE TO DETERMINE THE SPECIFIC REASONS FOR NON-COMPLIANCE, AND DATA FROM REPLACEMENT CONTROLS WILL BE REVIEWED TO ASSESS COMPARABILITY WITH THE LOST INDIVIDUALS. Medical record reviews of new entrants will continue throughout the follow-up period, (4) Study Length The follow-up st"dy is initially planned for 20 consecutive years. Procedures, progress, anJ interim results of the study will be monitored by an independent scientific review group, responsible to the Office of Science and Technology Policy in the White House. G. Determination of "Disease" (1) Introduction Since this study is dealing with an unknown clinical endpoint with unknown latency, determination of a disease state by statistical methodology is a prime scientific thrust of the investigation. From the literature, chloracne is the only generally accepted chronic disease associated with high exposure to dioxin. The questions of primary interest are: (1) Does a history of chloracne invariably lead to future disease? and (2) In the absence of chloracne, is there emergence of other attributable diseases? Under a broad concept of "spectrum of illness", either or both of these conditions are possible. The clarification of their respective contributions to the natural history of past or of subsequent "disease" is of significant interest. (2) Discussion Inferences about a disease state from this study can be derived from several logical approaches. The^e approaches can be grouped into two categories: (1) those dealing with symptoms which can be used to construct a symptom complex that may represent disease, and (2) those dealing with physical signs which in themselves rep/esent disease. In the former, one can form a subset of individuals that have symptoms (e.g., infertility) and study them during the morbidity and follow-up studies. Focusing on the overall patterns of alleged symptoms and categorizing them into a symptom complex may identify those individuals with a disease syndrome, or those at higher risk of developing disease (e.g., genetic disorders, cancer). In the latter approach, data on abnormal physical signs (e.g., genetic defects in offspring) and laboratory results can be compared between exposed and non-exposed groups in an attempt to again establish the presence or absence of disease. By putting this array of data into a logical decision-making scheme, specific relative risks can be calculated in the follow-up study, and specific response patterns can be inferred as shown in Figure 8. 48 �FIGURE INTERPRETATION OF HORIZONTAL COMPARISONS OVERT EFFECT lYi D i\ SUBCLINICAL OVER-REPORTING M R = MQ i ' « f* u MR = MC _ Cf — o l> Q~ JR « - sc SR > S c n S t\ F F R * Fc c D C -^ •r f*C " uo F RS* F F CS F RS" F R - Fc r\o RS" F MORTALITY/SYMPTOM/ SIGN REGRESSION ON EXPOSURE F R = FC F CS ft! 5 - F C S F CS RS = F CS SIGN REGRESSION NO REGRESSION ON EXPOSURE ON EXPOSURE SEEN F R = F RS S R + F RS C - S R ) �Again referring to Figure 8, at least three clinical patterns can defined. These patterns are delineated using relative risks (mr/mc, sr/sc, fr/fc etc., between group or "vertical" comparisons, referencing Figure 4) and using within group ("horizontal" study) comparisons such as regressing symtoms and findings rates against an index of herbicide exposure, and other comparisons. Specifically, an overt clinical effect would be marked by: an increased mortality rate in the RANCH HAND group (mr > me), an increased rate of symptom formation in the RANCH HAND group (sr > sc), and an increased rate of objective medical findings in the RANCH HAND group as compared to the control group (fr > fc). Further, the occurrence of physical or objective medical findings would consistently relate to symptoms in the overt case (that is, frs > fcs and frs > fcs\ and finally, in the classic instance, mortality, and symptom and sign formation would be seen to be increased with increasing herbicide exposure. A subclinical pattern is indicated in the central column of Figure 8. In this setting, one expects no statistically significant differences in mortality or symptom reporting between the two groups, exposed versus control. However, one expects a consistent predominance of medical signs in the RANCH HAND group with regression of the signs on increasing herbicide exposure. A pattern strongly suggesting over-reporting is presented as the right column of Figure 8. In this setting, there is no difference between the groups as regards mortality or medical sign incidence; however, more symptoms are reported by the RANCH HAND group. While in this pattern the RANCH HAND subjects are reporting more symptoms, objective medical finding rates are not consistent with symptom reporting. When no regression of symptoms on exposure level is found, over-reporting is clearly and strongly suggested. This discussion of response patterns has used regression on an exposure index in a central way. Development of such an index is discussed below. It is noted, however, that a direct index of exposure can be confounded by other factors such as cellular repair mechanisms or bioaccumulation in adipose tissue with release over time upon weight loss. Use of other factors, such as time since exposure, should help to overcome these confounders. The strength of any inferences made from these analyses is dependent upon the statistical power inherent in the study. In addition, due to the possibility of latency being a factor in this study, a negative analysis at any time within the study does not categorically imply lack of disease, since sufficient time for emergence may not have passed. H. Exposure Indices (1) Exposure Concepts A major concern in conducting this study is the lack of accurate exposure data. Although most personnel assigned to RANCH HAND squadrons were undoubtedly exposed to Herbicide Orange and TCDD, the exposures within the 50 �group must have varied widely. Exposure to herbicides and TCDD by RANCH HAND personnel occurred almost daily. Anecdotal information suggests that many had direct skin contact which was repetitive over a long period of time (one-year tour for most individuals). Further, it is also suggested that most RANCH HAND personnel felt that the herbicides employed in the operations were not toxic to animals and man, and hence, they did not exercise the caution in handling these chemicals that is recommended today. From a historical review of RANCH HAND operations, it appears most individuals can be classified into one of three groups based on their likely potential for exposure to the herbicides: (1) Pilots, Co-pilots and Navigators: (2) Crew Chiefs, Aircraft Mechanic, and other Support Personnel: (3) Console Operators and Flight Engineers: low potential moderate potential high potential The "pilot" group received most of their exposure during preflight checks as well as during the actual dissemination missions. The crew chief group experienced contact with herbicides during dedrumming and aircraft loading operations, as well as during on-site repair of the aircraft and spray equipment. The console operator group was exposed while supervising the loading of the aircraft, during ground testing of equipment, and by tank leakage during dissemination missions. The available historical records on Operation RANCH HAND indicate that personnel assigned to the project seldom had a "routine" work schedule or environment, thus complicating estimates of the level of herbicide and dioxin exposure. Since actual exposure data (e.g., mg of herbicide/kg body wt) are not available, an exposure index will be used. The exposure indices will be calculated for each RANCH HAND individual to obtain frequency distribution, and will be calculated by evaluating the known factors that would have influenced exposure. These will include such factors as: (1) Date of tour with RANCH HAND in Vietnam. (2) Number and lengths of tours in Vietnam with RANCH HAND. (3) Number of herbicide dissemination missions (as reflected by flying hours and air medals). (4) Herbicides employed (records are available that reflect the amount oP each herbicide sprayed each month and year). (5) Crew position. (6) Routes of exposure (the major route of exposure for most RANCH HAND personnel was probably percutaneous, although exposure through inhalation may have also been significant). 51 �A crude exposure index which is applicable to the entire RANCH HAND cohort is expressed with the following formula: E. - q, X T. In this formula, E-,- is the calculated exposure for the iiil RANCH HAND member, qj is the quantity of TCDD-containing herbicide sprayed from aircraft assigned to the iJ^l subject's base during his assignment, and T-j is the length of the illl subject's assignment (tour length). However, great care must be exercised when applying the above index. For example, the index should be used as an independent regression variable against clinical findings only within occupational strata, to avoid confounding occupational effects with exposure effects. Different degrees of regression between clinical findings and the exposure index can be expected in differing occupational groups since: (a) modes of exposure are likely to be different in different occupational categories, (b) socioeconomic correlates within occupational category could confound an herbicide effect, and (c) other exposures which could synergistically or antagonistically interact with TCDD-containing herbicide may be correlated with occupational category. Another factor which must be considered when applying this crude exposure index is the problem on confounding a possible herbicide effect with an effect associated with tour length. Being in a comabt zone is a major psychophysiological stress, and time spent in such an area may be significantly associated with changes in long term morbidity and/or mortality. This crude exposure index, when used alone, could result in a positive regression with disease incidence or prevalence which is not due to the herbicide exposure. An approach that will correct for this potential confounding is to regress observed medical findings on both Ej and T-j to differentiate the independent effects of herbicide exposure and combat zone experience. The values of q-,- and T-j needed to calculate E-j are generally available from government records. Specifically, tour dates are available from military personnel records, and the quantity of herbicide sprayed is available for the period January 1965 through April 1970 from the "HERBS TAPES." These tapes are comprised of computerized data obtained from actual spray mission reports. This material provides the date, base of mission origin, amount and type of material sprayed (Herbicides Orange, Blue, or White) and location of the intended spray target. Estimates of the amount of herbicide sprayed prior to 1965 may be available from procurement records for Herbicides Purple, Pink, and Green, which were sprayed exclusively from Tan San Nhut Air Base from 1962 through 1964. Animal data imply that TCDD is the most toxic component in the herbicides used in RVN. By using q-j, the amount of herbicide sprayed, one is using a variable that roughly correlates with TCDD exposure. However, it would be highly desirable to be able to analyze observed health effects in terms of specific TCDD exposure. The material sprayed from 1965-1970 had significantly lower 52 �TCDD contamination then did those herbicides manufactured and purchased prior to 1962 and used from 1962 through 1964, but due to data limitations from a scarcity of Herbicide Purple, Pink, and Green samples, TCDD concentration profiles for those chemicals cannot be quantitatively determined. However, it may be feasible to develop estimates of the degree of contamination based upon the TCDD concentration from military and manufacturers' data. As another approach to examining the effect of TCDD itself, one might consider stratifying the exposed cohort by date of assignment in Vietnam, expecting that those assigned earlier were more heavily exposed to TCDD. While it may well be true that earlier assignees were exposed to higher TCDD concentrations, it is unlikely that differences between "early" and "late" assignees, if they occur, can be reliably attributed to TCDD concentration changes, since several potentially confounding variables exist: (a) volunteerism among early assignees, (b) differing assignment patterns between early and late RANCH HANDers (TOY vs long term pattern) and (c) different RVN living conditions. It is preferable to use an exposure index which is more closely tailored to the specific individual than the crude index discussed above. While T-j is subject specific, q-j is a value which refers to all individuals on the base during the period of time represented by T-j. A refined index for ground crew can be expressed as: E. = F1 X q. X C X T. where, FJ = Average flights per day served by the ii!l ground crew member. qi = Average quantity of herbicide dispensed by flights served by the illl ground crew member. C = Estimated TCDD concentration of the herbicides in use during the il!l subject's tour of duty. T-J = Time spent in TVN in days for the ilQ. ground crew member, The variable FJ can be estimated by dividing the number of RANCH HAND flights per day by the number of crew chiefs during the time period T-j. All other variables are estimated as with the crude index. A refined index is also possible for aircrew members and is expressed as fol1ows: Ei = M1 X D. X q. X C X P. where, Mi = total number of missions flown by the iJiil air crew member. Di = average duration of missions flown by the iJEill air crew member. qi = average quantity of herbicide dispensed per flight served by the \th. air crew member. C = estimated TCDD concentration of the herbicides in use. P< = a cr-w p o s i t i o n weight ing factor. 53 �As with the refined ground crew index, this refined aircrew index cannot be directly calculated in a strictly quantitative sense using available government records, since records to specifically link missions with particular individuals are not available to objectively determine M-j and Dj. However, reasonably accurate estimates of these parameters may be feasible using questionnaire data. Also air medal awards may allow an indirect estimate of Mi. The crew position parameter P-j must also rely upon estimations. While the specific crew duties of each subject are known, the differential exposures associated with the crew positions within the C-123 aircraft were not determined during RVN spray missions. The 355th TAS/Spray Branch, Rickenbacher AFB OH is presently using the C-123 aircraft, configured with the A/A 45 Y-l Internal Dispenser and attempts to assess Pi can be made. Air flow measurement and herbicide simulant deposition studies conducted by Meek are performed during the course of four C-123 flights. However, difficulties with the measurement equipment limit the validity of the value of the data in an exposure index. Further work along these lines could yield a more quantitative position weighting factor, P-j, for each individual. Refined ground crew and air crew exposure indices can be used singly or in combination with the crude exposure index first presented; however, as with the crude index, confounding must be avoided when the refined indices are used in statistical analyses. The exposure indices listed above are, of course, only applicable to the Ranch Hand cohort. As mentioned, a positive regression of disease incidence or prevalence with increasing exposure index will strongly support herbicide causation. We do not wish to minimize however the role of RANCH HAND versus control group disease incidence/prevalence differences as indicators of a herbicide effect. A major component differentiating the RANCH HANDers from the controls is the increased residence of RANCH HANDers in the RVN itself. If within country time does not correlate with disease incidence, RANCH HAND versus control disease incidence differences may be strongly related to herbicide. If in-country time is significant as a disease correlate, this in itself will be valuable information with regard to assessment of the RVN experience. 54 �V I . Specijl ratns The previous discussion has outlined the general statistical approach followed by this protocol, and has outlined planned analytical methods and inferential strategies for the mortality, questionnaire and physical examination study phases. This section provides an indepth consideration of some special statistical study aspects. A* False Report ing/Mis rep resentatiion Since concern for compensation could unconsciously or consciously influence symptom reporting, and since press reporting itself can stimulate anxiety-based symptom formation, a discussion of false reporting is indicated. A data pattern indicating overreporting has already been discussed in Section V. The goal here is to understand the effect of misrepresentation on estimates of relative risk and the odds ratio. Let S stand for presence of a symptom, and IT denote its absence. This false reporting may be represented as in Figure 9. Figure 9 FALSE REPORTING/MISREPRESENTATION TRUE STATUS Total A A+B REPORTED STATUS C+D B+D A+C The proportion of correctly classified positives is defined by A/(A+C) and is called the sensitivity of the classification scheme; the proportion of correctly classifled negati ves D/(B+D) is called the spec i fi city. When there is non-differential misrepresentation, that is, when the sensitivity and the specificity are the same among the exposed and nonexposed, the bias induced in the estimate of relative risk will be toward the null value. The situation is summarized by Figure 10. 55 �Figure 10 MISREPRESENTATION IN RANCH HAND II TRUE STATUS Exposed S Nonexposed **• S TOTAL S S TOTAL S a b a +b e f . e + f S REPORTED STATUS c d c +d g h a +c b +d n e +g f + h g +h n Using this representation, the true relative risk is (a+c)/n * (e+g)/n, and the apparent relative risk is (a+b)/n * (e+f)/n. Figure 11 provides a graphic representation of how apparent relative risk varies as a function of specificity. For this curve, the true relative risk is 2 with the exposed population having a symptom incidence of 0,1 and the nonexposed population having a symptom incidence of 0.05 (Copeland et. al. 1977). The effect of nondifferential false reporting on the odds ratio is nearly as severe as that shown in Figure 11 for relative risk. A technique does exist for correcting the estimate of relative risk to account for false reporting, but the technique requires knowledge of the sensitivity and specificity of the classification scheme; knowledge that may not exist in this study. It should be noted that since the above remarks are concerned with relative risk, the number n of subjects in each group is irrelevant, as the results shown are independent of n. If the false reporting is differential, an estimate of relative risk that is biased away from the null value can result. This will occur in situations in which the RANCH HAND personnel and controls do not misrepresent their symptoms in the same manner (Copeland et. al. 1977). Thus the "true" outcomes of herbicide exposure may be distorted depending upon the degree and direction of misrepresentation. B. Adequ acy of Samp1e Sizes (1) Overview The size of the RANCH HAND cohort is approximately 1000 individuals. It is clear that a lethal effect of herbicide which occurs in only 1 out of 2000 controls will be quite difficult to detect unless the herbicide effect is very strong. For example, at a rate of 1 in 2000, 0.5 affected controls are expected. If the basic rate is doubled by herbicide to 2 per 2000, one affected RANCH HAND individual would be expected. At a rate of 1 per 2000 for 56 �Figure 11 APPARENT RELATIVE RISK VERSUS SPECIFICITY 2.0 Sensitivity = .9 1.8 1.6 APPARENT RELATIVE RISK •1.4 1.2 1.0 50 55 60 70 75 80 85 90 95 100 SPECIFICITY controls and a rate of 2 per 2000 for RANCH HAND personnel, the probability of observing no affected individuals in both groups is (1 - 1/2000)1000 (1 - 2/2000)1000 = .22 or, in other words, "there is a 22% chance" that no affected individuals will be found in this study. In a population of 100,000 exposed individuals, 100 cases would be expected, 50 of which would be due to herbicide. In short, since the size of the RANCH HAND group is fixed, this study has limited statistical power to define the relationship of herbicide to the rarer diseases. The power (1-3) of a study design is the probability that a specified difference between populations will be detected if it in fact exists. In general, power is a direct function of sample size; that is, for a particular study design, the more subjects measured the larger the study power. It is understood that this protocol makes use of the entire known RANCH HAND population (and excludes ancillary exposed groups for reasons previously cited); the exposed sample size cannot be increased. Power augmentation, therefore, can only be accomplished by the less efficient procedure of increasing the control group size which has statistical limitations as well as staggering financial and logistic considerations. Hence, considerable effort has been made to correct loss to study issues (by replacement and other techniques to induce participation) and to use the most powerful statistical design concepts. 57 �Essentially all previous animal and human studies concerning herbicide suffer from a lack of adequate consideration of study power. The following presents a preliminary analysis of study power for the case of continuous and dichotomous variables expected from the study. Also reviewed are alternative studies involving Marine samples. (2) Power in Conti nuous Vari abl e Case Assume that blood cholesterol levels are being compared between RANCH HAND and control groups, and that the coefficient of variation for cholesterol in the control group is 0.1, where the coefficient of variation is the ratio oc/yc. Assume ORH = ac. The symbol ex is the probability that the study will indicate an effect where none exists, and 1-p is the power as defined before. Consider that the RANCH HAND mean cholesterol PRH is shifted from the control mean yc. A natural question is to inquire about the study power as a function of available pairs (n) and mean ratio y = Table 11 POWER CALCULATIONS ASSUMPTIONS: a=0.05, ac/pc=0.1, Y= Power = 1-3 n=180 n=450 .20 1.01 .20 .20 1.02 1.05 .20 .55 >.995 .38 .88 >.995 .70 .70 .70 1.01 1.02 1.05 .86 >.995 >.995 .995 >.995 >.995 Power calculations are displayed in Table 11. Study power in the case of a matched pair design is strongly dependent on the degree of positive correlation produced between the involved groups by the matching procedure. Of course, the degree of correlation can be expressed by the correlation coefficient r which can take values between -1 (negative correlation) and + 1 (positive correlation), and two values of r have been employed in Table 11. From this table it is seen that if only 450 pairs are studied a 1% shift in mean (= 1.01) will not be reliably detected, but a 2% shift will be detected with a probability of 0.88 if r = 0.2 at least. From this calculation one can infer the need to examine at least 450 pairs to obtain the 2% shift, and to strive for more if possible. 58 �(3) Power in the Pichotomous yajijble^ Case There is significant discussion in the mathematical statistics literature concerning the efficacy of paired designs in the setting of dichotomous responses (Billewicz, 1974; Dry, 1975; Miettinen, 1970; and several others). Table 12 shows a set of calculations which are applicable to the present study. Table 12 POWER CALCULATIONS FOR THE DICHOTOMOUS VARIABLE CASE AS A FUNCTION OF EFFICACY OF PAIRED DESIGNS POWER = 1 - 3 PI Rel. PZ Risk r n= 250 n= 350 n= 450 .05 .01 5 0 .77 .82 .92 .04 .01 4 0 .61 .75 .85 .03 .01 3 0 .40 .51 .59 .10 .05 2 0 .61 .75 .85 .20 .10 2 0 .87 .94 .97 .05 .01 5 .1 .89/. 029 .94/.032 .98/. 064 .04 .01 4 .1 .72/.033 .87/.038 .88/.041 .03 .01 3 .1 .387.020 .68/.046 .71/.077 .10 .05 2 .1 .76/.055 .85/.048 .88/.048 .20 .10 2 .1 .94/. 043 .98/.046 t *. .99/.057 * V i * ^ *« = .050 **a = as indicated In this table, r is again the correlation coefficient indicating the degree of correlation induced between the involved groups by the matching procedure. The probability of the disease among RANCH HAND personnel is symbolized as PI, while P2 is the probability of the disease among the controls. Relative risk is the ratio Pi7p?.. With r = 0.1, sign test power tables were used as an exact version of McNernar's test, and therefore different a levels are shown under each power number. Table 12 shows the positive influence of effective 59 �pairing in the higher power levels noted. Also, it appears that for p2 = 0.01 and P! = 0.03, physical examination of 450 pairs (900 examinations) will disclose the three-fold relative risk with probability less than the minimum target .80. In other words, there is a greater than "20% chance" that a three-fold relative risk on a 1/100 disease state will go undetected in this study if only 350 pairs are examined and if low correlations occur. Once again the need to examine the maximum numbers of pairs in the study is seen. To present these dichotomous power calculations more clearly, calculations in the context of actual disease states have been accomplished. The diseases considered are cardiovascular disease and cancer, corresponding to high and low rate illnesses for the age groups presently under investigation. (a) Card iovas cu1 ar Pi sea s e A logistic risk function was fitted to data from 17,455 autopsies gathered in a WHO collaborative study in Czechoslovakia, Sweden and the USSR. The function fitted has the form P = [1 + exp(a + 3(x-.5) + Yty-.B))]-1 where p = the probability of a complicated coronary lesion x = age scaled linearly so that x = 0 is equivalent to 30 years, and x = 1 is equivalent to 58 years (the age span of the current study) y = 1 or 0 if the subject is exposed or not and a and 3 were obtained from the data. The function represents a fairly high rate disease in that at 40 years of age 7% of the group had the lesion, and at 60 years of age 20% had the lesion. The coefficient y> represents the exposure effect. Power calculations for Y = 3 and Y = .83 are shown in Table 13. This table suggests that if, as a cell toxin, herbicide exposure accelerates cardiovascular disease, this study has a good chance of detecting that acceleration if the herbicide effect is comparable to the age effect. A slight beneficial effect of pairing is seen in this hypothetical example. (b) Cancer A logistic risk function was fitted to breast cancer data presented by Breslow and Day (1975). The function fitted represents a low rate disease in that at 35 years of age only .000336 of the group had the lesion while at 70 years of age .00676 of the group will have the lesion. 60 �Using pairing to achieve a power of 0.80 in this setting, 1312 pairs would be needed, when the exposure effect is equal to the age effect. This exceeds the size of our RANCH HAND cohort, and reinforces the fact that herbicide exposure effects on rarer diseases will not have a high likelihood of being detected by this study, and again supports an attempt to examine as many pairs as possible. Table 13 POWER CALCULATIONS AS A FUNCTION OF HERBICIDE EFFECT ASSUMPTION: a = 0.05 T = Y = Number of Pairs Power Neglecting Pairing Power With Pairing Power Neglecting Pairing Power With Pairing 100 .93 .93 .64 .53 (a = .036) 160 >.97 .98 .81 .82 200 >.99 >.995 .86 .87 250 >.99 >.995 .93 .95 300 >.99 >.995 .96 .97 350 >.99 >.995 ,97 .98 Alternatiye Studies Usi^ng Marine Cohorts The GAO and the National Academy of Sciences have referred to specific Marine cohorts as candidates for a Herbicide Orange epidemiological study. In one suggested study configuration, 5900 marines who were within one half kilometer of a herbicide spray track on the day of spraying are called the exposed group, while 212,100 marines are considered unexposed. In a second suggested study configuration, 21,900 marines within one half kilometer of a spray path within 4 weeks of spraying are considered exposed, while a remaining 196,100 marines are considered unexposed. A mortality study was proposed in both of these study configurations. The mortality phase of this protocol involves approximately 1200 exposed and 6000 control individuals, so that, on the surface, the Marine studies would appear to be more powerful in a statistical sense due to larger numbers. However, in fact, two factors couple to render the marine studies less powerful than the RANCH HAND study detailed in this protocol. First, calculations show that a soldier standing directly 61 �under a spray track at the exact time of spraying receives approximately 1/1000 the dose received by RANCH HAND individuals repeatedly disseminating the mixture throughout the usual RVN tour. Thus even if the unlikely event of being directly under a spray path were repeated 10 times during a marine's RVN tour, the marine's dose would still be only 1/100 that of the RANCH HANDERS. The second factor impacting the Marine study power is the difficulty imposed by the fact that troop positions are only very inexactly known. The available data provide only the battalion headquarter's position relative to herbicide spray paths. Thus troops considered to be exposed could be very far from spray paths, and in fact, be unexposed. On the other hand, troops deemed unexposed in terms of their battalion headquarter's position could in fact have been near spray paths on the day of spraying. Thus, the Marine studies are limited by the problem of misclassification in addition to the fact that the marines received a lesser herbicide exposure than RANCH HAND personnel. It is possible to compare the RANCH HAND study described in this protocol with the Marine studies in a quantitative way. Results of such an analysis are set out in Tables 14 thru 17. In Table 14, the Marine study using 5900 exposed soldiers is contrasted with the RANCH HAND study considering a disease with an incidence of 0.001 in the control groups, and 0,004 in the RANCH HAND exposed cohort. With a relative risk of 4 against a control disease incidence of 0.001, RANCH HAND power is 0.87 while the Marine study power is much less for several combinations of Marine exposure and misclassification. The misclassification figures shown refers to the percentage inclusion of unexposed individuals into the exposed Marine group. For the calculations, disease incidence in the marine exposed group was assumed to be linearly related to exposure. Table 15 is strictly analogous to Table 14 except that the disease state studied has an incidence of 0.01 in the control groups and 0,02 in the RANCH HAND exposed cohort. Again the RANCH HAND study is seen to be significantly more powerful than the Marine study. Tables 16 and 17 directly parallel Tables 14 and 15, respectively, except that the Marine exposed group is considered to consist of 21,900 soldiers. Here again RANCH HAND study power is seen to be significantly superior. Figure 12 shows the RANCH HAND mortality study power as a function of relative risk, and disease incidence in the control group. Figure 13 shows marine study power versus marine exposure for zero to 25% misclassification and a control disease incidence of 0.001 and RANCH HAND relative risk of 4. For this circumstance it is clear that the marine study becomes competitive with the RANCH HAND power only if one assumes that the marines received approximately one half of the RANCH HAND exposure dose. Figure 14 is the same as Figure 13 except that 21,900 marines are considered exposed. Again the Marine study becomes competitive with the RANCH HAND study only if one can assume the exposed marines received 0.2 or more of the RANCH HAND exposure, an assumption which is not supported by the available data. C. The Replacement Concept In the mortality analysis, a randomly selected group of control Individuals will be compared to the RANCH HAND group, and the data gathered will be analyzed for evidence of herbicide effect. In the questionnaire and 62 �MORTALITY ANALYSIS FABLE 14 POWER COMPARISON OF THE RANCH HAND STUDY TO THE MARINE POPULATION CONSIDERING MISCLASSIFICATION AND RELATIVE EXPOSURE POWER TABLE RANCH HAND POWER 1-B MARINE STUDY POWER EXPOSURE LEVELS RELATIVE TO RANCH HAND % MISCLASSIFICATION en us 1/10 .87 ASSUMPTIONS: 0 10 25 RH STUDY POP. 1,200: 6,000 (1:5) MARINE STUDY POP. 5,900: 212,100 NORMAL INCIDENCE OF DISEASE 0.001 DISEASE INCIDENCE IN RH 0.004 LINEAR DOSE - RESPONSE MISCLASS. Of MARINE CONTROLS EXCLUDED 1/20 1/100 .18 .16 .15 .10 .09 .09 .06 .06 .06 1/1000 .05 .05 .05 �MORTALITY ANALYSIS TABLE 15 POWER COMPARISON OF THE RANCH HAND STUDY TO THE MARINE POPULATION CONSIDERING MISCLASSIFICATION AND RELATIVE EXPOSURE POWER TABLE % MISCLASSIFiCATION RANCH HAND POWER n I-B MARINE STUDY POWER EXPOSURE LEVELS RELATIVE TO RANCH HAND 1/10 1/20 1/100 1/1000 CD .92 0 .10 .06 .05 10 .17 .10 .06 .05 25 ASSUMPTIONS: .19 .14 .09 .06 .05 RH STUDY POP. 1,200: 6,000 (1:5) MARINE STUDY POP. 5,900: 212,100 NORMAL INCIDENCE OF DISEASE = 0.01 DISEASE INCIDENCE IN RH = 0.02 LINEAR DOSE - RESPONSE MISCLASS. OF MARINE CONTROLS EXCLUDED �MORTALITY ANALYSIS .E 16 POWER COMPARISON OF THE RANCH HAND STUDY TO THE MARINE POPULATION CONSIDERING MISCLASSIFICATION AND RELATIVE EXPOSURE * POWER TABLE ANCH HAND POWER 1-B MARINE STUDY POWER % MISCLASSIFICATION EXPOSURE LEVELS RELATIVE TO RANCH HAND 1/10 1/20 1/100 1/1000 .87 0 10 25 ASSUMPTIONS: RH STURY POP. 1,200: 6,000(1:5) MARINE STUDY POP. 21,900: 196,100 NORMAL INCIDENCE OF DISEASE =0.001 DISEASE INCIDENCE IN RH= 0.004 LINEAR DOSE - RESPONSE MISCLASS OF MARINE CONTROLS EXCLUDED .38 .33 .26 .17 .15 .13 .07 .06 .06 .05 .05 .05 INCORRECT POPULATION NUMERICS BASED ON ENVIRONMENTAL FATE OF TCDD �TABLE 17 MORTALITY ANALYSIS POWER COMPARISON OF THE RANCH HAND STUDY TO THE MARINE POPULATION CONSIDERING MISCLASSIFICATION AND RELATIVE EXPOSURE * POWER TABLE RANCH HAND POWER 1-B MARINE STUDY POWER MISGLASSIFICATION 1/10 01 01 EXPOSURE LEVELS RELATIVE TO RANCH HAND 1/20 1/100 1/1000 0 .41 .17 .07 .05 10 .36 .16 .07 .05 25 .92 .28 .13 .06 .05 ASSUMPTIONS: RH STUDY POP. 1,200; 6,000 (V.5) MARINE STUDY POP. 21,900: 196,100 NORMAL INCIDENCE OF DISEASE = 0.01 DISEASE INCIDENCE IN RH = 0.02 LINEAR DOSE - RESPONSE MISCLASS. OF MARINE CONTROLS EXCLUDED * INCORRECT POPULATION NUMERICS BASED ON ENVIRONMENTAL FATE OF TCDD �FIGURE 12 CD POWER VERSUS RELATIVE RISK, 1:5 MORTALITY STUDY BY THREE DISEASE INCIDENCES RELATIVE RISK �POWER CURVES OF THE MARINE STUDY CONSIDERING RELATIVE EXPOSURE AND MISCLASSIFICATION OF THE STUDY POPULATION 1.0 r 0.8 CO NO MISCLASSIFICATION 0.6 CO CSL 0.4 5,900 EXPOSED 25 % MISCLASSIFICATION 212,100 CONTROL C3 a. RH RR = 4.0 0.2 0.0 .001 p ,=.001 p 2 = -004 • .01 i i i i i 111 .1 MARINE EXPOSURE/RANCH HAND EXPOSURE LI 1.0 �IGURE 14 POWER CURVES OF THE MARINE STUDY CONSIDERING RELATIVE EXPOSURE AND MISCLASSIFICATION OF THE STUDY POPULATION 1.0 r .8 j- INCORRECT POPULATION NUMERICS BASED ON EVIRONMENTAL FATE OF TCDD to CO uu NO MISCLASSIFICATION .6 25% MISCLASSIFICATION .4 21,900 EXPOSED 196,100 CONTROL RH RR = 4.0 .2 p 1 =.001 p 2 =-004 0.0 .001 J_ .01 I I I I 1 ill J .1 MARINE EXPOSURE/RANCH HAND EXPOSURE I 1.0 �physical examination phases of this study, one of the mortality controls will be randomly selected for each RANCH HAND individual. During the physical examination phase, we must anticipate a significant degree of unwillingness to participate, particularly on the part of control personnel. This loss to study can result in significant bias and loss in statistical power; thus the replacement concept has been developed to mitigate these consequences. In this replacement strategy, we make use of the control individuals matched with each RANCH HAND person. As previously noted, this is accomplished using computerized data files and the matching parameters of age, AFSC, and race. With each RANCH HAND individual Ri there will be associated ten controls C^, C-j2> C-j3, ..., C-j10' The first of these controls, Ci! will be employed in the questionnaire and physical examination phases of the study. If C^ is alive, but unwilling to participate in the study, he will be replaced by another randomly selected participant with similar perception of health status. In order to avoid bias in morbidity analyses, no dead control will be replaced. It is important to emphasize that all replacement controls will be carefully flagged so that they may be treated separately in the statistical analysis. These replacements will be carefully compared to the lost controls to develop indicators of comparability (e.g., morbidity and mortality experience). The initial analysis will be performed on the intact exposed/control pairs. Additional analysis will be conducted on all pairs, both those intact, and those with replaced controls. If we consider RANCH HAND individual R-j, with living control C-j1} we can calculate the probability that control C-jk will be available for the 1st, 2nd and 3rd physical examinations. To examine this question, a small computer Monte Carlo simulation was required. A short BASIC language computer program and glossary are included in Appendix Table A-8. This simulation examines the effect of non-participation expressed as two probabilities PI and P2. Figure A-2 displays the expected participation by the RANCH HAND population, and control group participation is expected to be somewhat less. PI is the probability that when first asked to attend a physical examination, the control individual will not comply. P2 is the probability that a control individual who has agreed once to a physical examination, will not comply for a subsequent examination. In general, PI may be greater than P2. Note that the probabilities P! and P2 must reflect all causes of non-compliance including morbidity and mortality. Table 18 displays a representative simulation run, which provides the number of controls required to find willing matches for 1000 RANCH HAND personnel. The potential bias introduced by non-willingness in controls can be analyzed statistically. If Pq(x) is thesame probability density function for compliant individuals and PNC(X) is the function for non-compliant individuals, we have 70 �Table 18 CONTROL DISTRIBUTIONS BY EXAMINATION MATCHING 1000 RANCH HAND PERSONNEL (Pi = .70, P 2 = .25) EXAMINATION NUMBER CONTROL COHORT 1 2 3 Ci 318 237 177 C2 211 188 156 C3 131 133 136 C4 96 101 97 C5 74 89 90 CG 49 68 77 C7 34 43 59 C8 25 39 52 C9 16 18 33 C 13 20 35 33 64 88 10 Number of Matching Failures p(x) = apc(x) where p(x) is the probability density function for the entire population and x is a vector of important health parameters available on each person. Since / p(x)dx = J pc(x)dx = / PNc(x)dx = 1 it follows that a + 3 = 1 71 �and a and 3 may be viewed as coefficients which "mix" the two subpopulations. If Mc and MNQ are the means of the compliant and noncompliant subpopulations respectively, it can be shown that M = aMn + where M is the mean of the entire population. From this last equation, it is clear that as noncompliant individuals are lost (i.e., 3 tends to zero, a tends to one), M tends to Mc. Thus the maximum bias is the quantity McM. In this study we propose to replace non-compliant control individuals with matched RANCH HAND control individuals, that is with individuals drawn from a population with density equal to or at least similar to PNC(X)' Tne resulting new density is P"(x) such that p"(x) = a"pn(x) + 3"PNC(X) where a" + 3" = 1 M" = a"Mn + 3"?NC and where PNC(X) approximates PNC(X)« If 3" is chosen to be close to or equal to 3 above, it appears that M" can well approximate M, the true population mean. The difficulty in this approach will be to assure that the replacements are representative of the non-compliant individuals in all respects other than logistic factors impacting willingness to participate in the program. Our proposed approach is to obtain sufficient data on the unwilling personnel so that a discrimination function of the form D = can be derived. This function is envisioned to have the following properties: 72 �(a) larger values of D correspond to decreasing probabilities of compliance with the physical examination, (b) the factors hj relate to the subjects' health status, while the factors 1-j relate to logistic difficulties (distance, job) which tend to preclude attendance at the physical. Factors to be considered in the formulation of this function are displayed in Table 19. (c) D is an increasing function of each hi and of each lj, Table 19 FACTORS AFFECTING COMPLIANCE Health Status (hj) Loglst1c Pifflailties (1 j) Subjective Health Assessment (good/poor) Time Away from Family Current Utilization of LongTerm Health Care (Yes/No) Time Away from Job Absenteeism Pattern (Greater Than/Less Than Ten Lost Days in Past Six Months) Distance to Examination Site Active Pilot Income (Greater than/Less than $17,000) In the replacement scheme, controls substituted for noncompliant controls, should have identical health factors (h-j) as those individuals they replace. The only significant differences should be in the logistic factors Oi)« The replacement method should permit correction of non-compliance bias given that health factors h-,- and logistic factors 1-j are actually distinct. The determination of these two classes of factors will be made using data from the study itself. Specifically, the logistic factors 1-j will be independent of health status to the degree testable by the quantity of data available in the study. This replacement strategy has two major advantages: selection bias reduction/estimation and cost reduction. Were replacements not employed, one would be compelled to start the morbidity study with a 4 to 1 or 5 to 1 design in order to insure an adequate number of participating controls on the third physical examination (see Table 18). Such a large control group for physical examination is very costly with little 73 �corresponding gain in study power and with no correction of the selection bias. D. Statistical Analysis of Large Data Sets A large amount of data will be collected on each subject in this study. Testing at the 0.05 a level means that in 5 out of 100 instances where there has actually been no herbicide effect, a herbicide effect will be falsely inferred. This is the inverse of the power question which concerns the probability of detecting an event when it actually occurs. If 100 independent measures are taken from subjects one should expect, testing at the 0.05 a level, that five measures will be positive on the average. This awareness itself should help prevent over reaction to isolated findings. Further, the present protocol does not in fact have one hundred independent measures. Rather the data gathered are grouped into correlated batteries or systems of data. Findings with any given measure will be related to the values of other correlated variables to provide substantiation indicating an authentic finding. E. Tiroe-In-Stu dy Effects The study outlined in this protocol is expected to involve up to six examinations extending over a period of twenty years. It could be anticipated that participation in the study, by increasing the health awareness of the subjects, would tend to improve the health of the cohorts. The possibility of differential participation in the study by the exposed and control groups could bias against finding a herbicide effect if one exists. The control group could be less willing to participate in the study than will the exposed RANCH HAND personnel. Thus, if on the average, controls spend less time in the study than RANCH HANDERS, and under the supposition that increased time in study will correlate with better health, increased RANCH HAND participation would counterbalance any adverse herbicide health effect. The corrector for this time-in-study effect is simply to study the relationship between health outcome and participation in the RANCH HAND study by regression or other analogous statistical methods. Participation can be quantitated by such metrics as (a) number of physical examinations attended (b) age at physical examinations attended or (c) pattern of physical examination attendance. Special study design features do not need to be incorporated to properly evaluate time-in-study effects on questionnaire and physical examination portions of the study. However, the effects of differential time-in-study on the mortality analysis must be carefully considered. In order to detect time-in-study effects on mortality, individuals whose mortality are being tracked should have been in the study for the same length of time (both exposed and control individuals), or the distribution of time spent in the study should be similar in both groups. Because of anticipated differential participation between the exposed and control groups, one cannot assume that both cohorts will have equal time in study distributions. Steps must be taken to insure that a proper time-in-study distribution occurs in the control mortality group. Control over this distribution is possible through placement of the mortality cohort in the structure of the control group with 74 �respect to the replacement strategy. The following five designs have been considered: I. mortality subjects randomized over all ten control positions, and therefore called into the study randomly. II. mortality subjects in the first five control positions, and therefore called into the study first. III. mortality subjects in positions #1 and #2, with the three remaining subjects randomized into positions #3 through #10. IV. mortality subjects in positions #1, #2, #9, and #10, with the one remaining subject randomized in positions #3 through #8. V. mortality subjects in the first four positions and position #10. For each of these five designs, certain quantities were calculated. For testing a physical examination effect on mortality, one would require adequate numbers of mortality subjects having had all six physical examinations, and adequate numbers having had none. Therefore, assuming 1200 RANCH HAND subjects, El = expected number of mortality subjects having all six physical examinations. E2 = expected number of mortality subjects never asked to take the physical examination. E3 = expected number of mortality subjects physical examinations. having taken no For testing or modeling time-in-study effects, one would want adequate numbers of mortality subjects having only one physical, having exactly two physicals, etc. Hence, we calculate, for J = 1, 2, 3, 4, 5, 6: NJ = expected number of mortality subjects taking exactly J physicals (for example N3 is the number of mortality subjects who will have taken three physicals by the end of the study). and MJ = expected number of mortality subjects which will actually have taken examination J. The values of El, E2, E3, NJ, and MJ have been calculated for the five study designs outlined above using an adaptation of the Monte Carlo program 75 �shown in Appendix Table A8. Best case and worst case situations were considered. In the worst case, it was assumed that when first asked to participate, 75% of the subjects refused, while when asked after having once participated, 50% of subjects refused further contact. In the best case, the first time refusal rate was assumed to be 50%, and the refusal rate for a subject who had participated in a prior examination was assumed to be only 15%. Table 20 shows the calculated results. In examining this table it is of interest to note that the calculated values are not strikingly dependent on study design configuration. However, for both the worst and best cases, design 2 where the mortality subjects are placed in the first five control positions, appears superior and will be used in this study. Table 20. TIME-IN-STUDY EFFECTS V DESIGN PARAMETERSi\ 1 WORST CASE 2 3 4 5 1 BEST CASE 2 3 4 El 18 29 25 22 27 267 E2 765 194 580 865 493 3953 2409 3137 3478 2690 E3 4691 4548 4645 4716 4623 Nl 700 751 713 681 714 227 370 284 239 331 N2 340 374 347 328 355 185 307 284 239 331 N3 163 188 168 157 177 146 249 189 161 225 N4 71 84 76 72 79 116 203 157 136 188 N5 33 43 36 31 39 94 171 129 110 160 • N6 18 29 25 22 27 267 521 454 428 504 Ml 18 29 267 521 M2 14 14 46 77 M3 24 17 53 83 M4 40 25 62 94 M5 54 28 76 107 M6 80 34 85 116 76 521 454 428 5 504 4977 4204 4569 4739 4345 �VII. Data Repository Throughout the period of this investigation, data collection methods will be integrated by use of computer systems. A data repository will be established at the USAFSAM. Master files will be formed for each exposed member and for his matched control/controls. The individual master files will be keyed to one or more identifiers. Confidentiality of data will be maintained by the use of computer generated code numbers. Addresses and telephone numbers of all study subjects will be continually updated to insure proper follow-up. Individual data items and their sources are as follows: (1) Questionnaire a. Initial b. Indepth interview (during physical examination) c. Follow-up (2) Psychological Battery a. b. Initial Follow-up (3) Physical Examination a. b. Initial Follow-up (4) Medical Records a. Active duty b. VA c. Civilian d. Dependent (5) Historical Data a. b. c. Military personnel files Flight records Military unit (6) Death Certificates and Autopsy Reports a. b. Study members Dependents (7) Birth Certificates a. Dependents Mortality data will be obtained from individual medical records, VA records, the screening of personnel records, contact with family or personel physicians, and other available information sources. Date of death (verified by death certificate and available autopsy reports) will be obtained. Cause of death will be expressed as an ICDA number or numbers. The reliability of the mortality data coding will be evaluated by using a dual coding system based on underlying cause of death criteria in use by the National Center for Health Statistics. This will assure that the results of this study are compatible with data based on US mortality statistics. In addition to standard coding for the underlying cause of death, all diagnoses entered on the death certificates will be coded so that multiple cause of death analyses can be conducted. 77 �The computer software for the data analysis phase will be prepared to assure proper data conversion, quality control and standardization of testmeasurements. Quality control areas will include verification of identification data, range checks, and identification/correction of ambiguous or conflicting data. 78 �VIII. Recogni zed Study Pi f f i cu 1 ties a n d C o r r e ct 1 ye Mea s u r es A - Medical P^recedence (1) Problem A departure from the ususal methodological approach characterizes this particular epidemiological investigation. Clearly there is no historical "roadmap of methodology" to conduct this study. Most occupational exposure studies use the presentation of an unusual disease to justify the initiation of a comprehensive study. A rare disease or a common disease in an uncommon site, or one with an unusual presentation appearing in space-time clusters, (often in an unusual population or age group) usually generates the requirement for a new study. In the case of Herbicide Orange, the evidence for long-term human effects is tenuous and controversial . Despite the unique problems that this study possesses, such as the lack of clinically defined endpoints, there are many problems that it shares with other occupational ly related exposure studies. For example, the question of a latent period in the development of symptoms/signs, the lack of accurate dose-response relationships, and the possibility of a synergistic effect with other toxins/ carcinogens are all operating in this study. Since most cohort studies of occupational mortality use the general population as a standard for deriving the expected number of deaths, preempl oyment selection ("healthy worker" bias) affects the comparative experience. Age-standardized mortality ratios (SMR's) in general are 60-90 percent of the standard in the working population. Similar conflicting results can occur using the matched cohort method proposed in this study design. Statistical verification of the validity of utilizing such a control for a summary mortality index (e.g., SMR) has been infrequently attempted in the past. Inability to verify the validity of the more classical methods of comparing mortality will necessitate the use of multiplicative and/or logistic models to obtain a valid standardized mortality ratio. (2 ) Correcti y e_ Measures Study approaches generated by unprecedented occurrences of occupational ly related medical complaints require novel approaches, and reorientation beyond standard methods. The success key to this study design is a series of effective, progressive, and helpful peer reviews (all of which have occurred to date and have been incorporated herein). Beyond even the immediacy of the current study, is the growing problem of a myriad of occupationally-related exposures, both in the military and civilian sector, which will require similar epidemiological studies in the future in order to make some judgment as to whether or not an association is of causal significance. (1) Problem The numerous media presentations on "Herbicide Orange" issues have focused attention on the RANCH HAND group. Several attempts have been 79 �made to construct lists of former members of this group, and thus, the RANCH HAND population should be somewhat easier to locate and contact than the control population. This difference will be particularly evident with respect to reported mortality experience. The incentives for cooperation and study participation are likely to be greater in the exposed group than in the controls. Also, the close knit reunion association of former RANCH HAND personnel will lead to a more precise reporting of morbidity and mortality in that group. Such group identity tends to decrease the degree of unaccountability in the exposed group while its absence in the controls may lead to under ascertainment of mortality. This could then lead to the attribution of excess mortality in the exposed population. (2) Corrective Measures Unaccountability bias will be minimized by keeping the percentages of unaccounted for study subjects below 1% in both exposed and control groups. The morbidity and mortality status of all individuals selected for the study will be strongly pursued utilizing a variety of techniques previously described in this document. C. "Risk Taking" Behavior Bias (1) Problem The early RANCH HAND aircrew population was an exclusively volunteer group; the C-130 control population, while volunteers in the Air Force, were not volunteers for special hazardous missions. RANCH HAND mission conditions were considered to be more dangerous than those encountered in the normal combat environment. This suggests that some differences may exist in the psychological profiles of the two groups. A sensation seeking or risk taking psychological orientation may have altered the accident mortality or morbidity patterns of the exposed group. In addition, an accident rate affected by peripheral neuropathy could be masked by undetected risk taking behavior bias. (2) Corrective Measures In an attempt to correct for the unique psychological factors that affect the choice of an aeronautical career, and to adjust for the effects of combat stress, transport aircrew members were matched with crewmembers of similar transport aircraft. However, the volunteer nature of the pre-1965 RANCH HAND operation suggests that this basic matching (as an attempt to control for the psychological effects of combat stress) is not totally ideal. The factors of volunteerism and risk-taking behavior must be considered from both the individual and group perspectives. The assessment of individual risk-taking behavior has been quantified by psychological instruments such as the Sensation Seeking Scale (SSS) of Zuckerman, et al . and the Life Experience Inventory (Torrance). The SSS has been demonstrated to have considerable validity in measuring a variety of phenomena including volunteerism and participation in risky activities and has been applied to naval 80 �aviation trainees (Waters). This study was unable to demonstrate an increased accident-related mortality in this group of individuals. D. Response Bias (1) Problem False positive response is anticipated as the primary bias operating in this study. Compensation issues arising from individual claims to the VA or from class action suits, heightened health concern generated by extensive publicity, disenchantment with military service, and the simple desire to please the interviewer may introduce positive responses that exceed the study's ability to correct or adjust. False negative response will also operate, and such bias is even more difficult to assess than the spurious response in a positive direction. Significant factors in this direction include: issues of patriotism and loyalty, personal conviction as to the propriety of the defoliation program and their participation in it, the strong virility orientation of the pilot/aircrew population (particularly with reference to questions of libido and fertility), personal inconvenience caused by study participation, errors of memory, and fear of the adverse effects on career goals that abnormal physical examination results could produce (a significant problem for active civilian and military pilots). (2) Pending Retirement Bias The military retirement system also creates a potential source of bias when personnel who are approaching the end of their careers exaggerate their symptoms so that they may become eligible for disability benefits. (3) Corrective Mea s ure s The primary correction technique for questionnaire response bias will be a carefully constructed and standardized physical examination. Multiple verification and bias indicator questions will be designed and included in the initial questionnaire. Memory verification will be conducted by cross-referencing responses to medical and personnel records. Detailed statistical correlations between the questionnaire responses and the physical examination results 'will be conducted. All interviews and physical examinations will be conducted on a "blind" basis to the maximum extent possible. Self-administered and group-administered questionnaires, which would allow for uncontrolled response changes, will not be conducted. The payment of a $100 per day stipend to all eligible participants will be arranged to increase participation rates. Medical data will not be released to agencies such as the Federal Aviation Administration, and therefore civilian flying activities will not be adversely affected by participation in this study. Models of anticipated biases and their estimated impact on the study will be attempted prior to the final analysis of any phase in order to justify the analytic methods used. Conclusions drawn from this study will be predicted and coupled to a bias estimate. 81 �E. Interviewer Bias (1) Problem Voice inflection, speed of interview, intonation and ethnicity are recognized factors which can affect positive or negative interview response. These factors will definitely operate in this study. (2) Corrective Measures The questionnaire itself will be developed and refined by a civilian contractor. This contractor will assure that the instrument will elicit sensitive personal and medical information in an accurate and efficient manner, while minimizing discomfort to both the subject and the interviewer. All questionnaires will be administered by well-trained and experienced personnel employed by an opinion research organization under contract to conduct this aspect of the study. F. Changes to the Protocol (1) Problem The question of adverse health effects due to Herbicide Orange exposure in Vietnam has evoked many strong emotions. The actions of consumer groups, environmentalists, and other special interest groups have generated defensive responses on the part of some governmental agencies, and reactive decisions by others. Frequently, these responses have been based on unsubstantiated claims and/or scientific evidence of questionable validity. As a result of these governmental actions, the impact on the planning of this study has been substantial. Suggestions to increase the scope of the effort to include other "exposed" individuals or poorly defined ancillary groups continue to surface. However, problems of group ascertainment, exposure validation, control group selection, and control of additional bias make the inclusion of such individuals undesirable from a sound scientific perspective. If such decisions are made without regard for their scientific impact, compromise of study validity is assured. (2) Corrective Measures The scientific groups participating in the extensive peer review process agreed with these concerns. The formation of an effective scientific monitoring group will insure that scientific issues will take precedence over emotional pressures to alter the study design when such changes will limit the scientific validity of the study. The dilution of the scientific credibility of this effort by unscientific decisions will be diplomatically resisted. While all suggested improvements will be considered, any alterations or corrections to the study protocol will be based on sound scientific assessments of the proposed changes. Alterations of the protocol will be made only after careful review and analysis by the principal investigators and the monitoring group. 82 �G- Loss to Study/Statistica l a n d Bias Considerat ions (1) Problem Losses to study in the RANCH HAND group pose a major problem to the validity of the inferences that can be made from any subsequent comparisons between or within groups. The avenues of loss will conceivably arise from individual apathy (volunteer bias), lack of appropriate financial reimbursement for loss of salary, the presence or absence of illness (perception of health), and the lack of a desire for "treatment". Losses of matched controls during the questionnaire and physical examination phases of the study, though predictably greater than in the exposed group, may be managed by replacement from the predetermined set of controls. The estimated participation of individuals is shown in Section XV, Figure A-2. It is estimated that the overall response rate of the exposed group will be 65% in the initial questionnaire and 40% in the physical examination phase of the study. These high non-compliance estimates are expected to occur despite great efforts to keep the questionnaire at an acceptable length, and to coordinate questionnaire administration and physical examination with the subject's personal schedule. Losses to study in either the exposed or control groups will obviously lead to decrements in statistical power, and will raise the possibility of severe bias. Losses from the control group are expected to be greater than losses from the exposed set. Such losses would skew the distribution of controls, (Figure 5) and thus alter the characteristics of the population available for study. If differential losses in the control group occur (i.e., "well" controls dropout more frequently than "ill" controls), a "true" herbicide effect would be diluted (Figure 15). Conversely, if "ill" controls are differentially lost, a spurious effect would be attributed to herbicide exposure. To a lesser extent, losses in the exposed group could create similar effects; however, loss to study in the RANCH HAND population should be much less of a problem then in controls, due to their vested interest. (2) Corrective Me as u res The USAF is committed to expending maximal effort to encourage participation. Loss to study problems in the study participants will be avoided as much as possible by detailed and exhaustive efforts to contact and followup each identified participant. NON-PARTICIPANTS WILL BE STRONGLY ENCOURAGED TO RECONSIDER THEIR INITIAL DECISIONS. Design considerations have been made to minimize loss to study in both the exposed arid control populations. Although the USAF can not fully compensate study subjects for lost wages during the physical examination, transportation costs, per diem, and lodging costs will be reimbursed, and a $100 per day stipend will be paid to all eligible participants. The replacement concept will help to counteract the decrement in statistical power, and offset the bias created by differential patterns of loss. The exposed group is already of maximum size and cannot be increased, but non-compliant controls can be replaced. This w i l l maximize the degree of pairing between the two study groups. If a non-compliant control is replaced by a control with a similar perception of �FIGURE 15 RATIONALE OF REPLACEMENT DILUTIONAL BIAS EXPOSED PRIMARY CONTROLS LOSSES CO P(L/WJ > PjL/1) CONDITIONAL PROBABILITIES: P(L/W)>» L - LOSS W = WELL I = ILL �his own state of health, the alteration of the control group distribution is offset; (i.6i, an " i l l " control is replaced with an "ill" individual, and a "well" control with another "well" individual.) This concept of replacement, coupled with the payment of stipends, and extensive efforts to encourage compliance will minimize losses to study and offset the adverse effects of those losses that do occur. H. Statistical Power Limitations (1) Problem As discussed in Section VI, statistical power considerations are heavily dependent on loss to study rates. Since the design of the study is also limited by the size of the exposed population, statistical power for identifying the relative risk of an uncommon disease or symptom-complex (<1/100) is very low (<.50), (See Section VI. B.). This study will, to a greater extent, be able to detect increased risks in common diseases or symptom-complexes (>1/100). (2) Discussion The "herald sign" of TCDD exposure, chloracrie, is expected to have the greatest likelihood of achieving adequate statistical power in this study. Recent findings from Seveso, Italy, support the importance of chloracne as the primary marker symptom. The incidence of chloracne has been reported by Regglani (personal communication) and Homberger, et al., to be 14.9 cases per 1000 residents in the region of highest contamination of Seveso (Zone A) and 6 to 12 cases per 1000 in the Seveso community as a whole. These rates vary by age group, with children being at highest risk. Only 1 to 5 cases per 1000 were seen in other regions of Northern Italy (Milan, Como, and Lecco). The incidence of adolescent acne in all of these populations varies between 21% and 30%. These incidence rates probably place chloracne at the lower limit of adequate statistical power of this study. In the Nitro, West Virginia studies, residuals of chloracne, as well as exacerbations of previously active disease, continue to be seen 10 years after the most recent exposures, and 30 years after the industrial accident. Thus, it is likely that any chloracne in the exposed population may be detected, despite the intervening years since RANCH HAND exposures. In addition to chloracne, other recently reported human effects of TCDD exposure at Seveso, Italy, appear to fall within the capabilities of this study design (e.g., peripheral neuropathy, neuropsychiatric effects, and liver dysfunction). In general, with respect to statistical power, continuous data (clinical or laboratory measurements) even from relatively small samples fair much better than either categorical or dichotomous data (presence or absence of a given condition). Consequently, a concerted effort will be made to obtain physical examination data in a scored and/or continuous manner. 85 �I. Variabi1ity of Procedu res (1) Problem The variation of physical examination findings from differences in technique and the random errors inherent in laboratory testing are items of concern, particularly if attributable health effects are subtle or of low magnitude. Nonstandardized procedures and techniques are major contributors to this variance. (2) Corrective Measures Variability in examination procedures will be minimized by the use of standardized procedures, examination protocols, on-site monitors, and training. All laboratory procedures will be conducted at the examination center and quality control will be stressed at all times. (See Section IX) J- Confounding Exposure Factors (1) Problem While virtually all of the media attention has been directed toward the 2,4,5-T-containing herbicide formulations, other herbicides were applied concurrently by the C-123 aircrews in Vietnam. Herbicide Blue (Cacodylic acid with 15.4% pentavalent arsenic) and Herbicide White (2,4-D and Picloram) were used throughout the 1962-1970 time period. Any long-term health effects from these additional compounds may confound the results of the study. Peripheral neuritis, tremors, skin and lung cancer, loss of hair and nails, skin rashes, and gastric symptoms have been alleged after exposure to arsenical pesticides. The organophosphate insecticide Malathion was also sprayed by some of these same aircrewmembers when RANCH HAND duties permitted their temporary assignment to mosquito/malaria control missions. Many of these individuals were involved in the aerial spray application of these and other pesticides both before, during, and after their Vietnam service. Longterm effects from these chemicals would confound the study results. The small size of the RANCH HAND population will allow very little opportunity for analytic stratification for these confounding variables. Differing patterns of exposure to aircraft fuels in the study populations have been suggested as confounding factors. The C-130 aircraft were powered by turbo-prop engines which used jet fuel (JP-4), while the C-123 and C-7 aircraft were powered by standard reciprocating engines which used leaded aviation fuel (AV-GAS). After June 1968, many C-123s were modified by the addition of auxilliary jet engine boosters for added power on takeoffs and in emergencies. (2) Discussion and Corrective Measures While the extent of confounding caused by exposure to these other pesticides is undetermined at this time, assessment of its magnitude must rely on responses of the subjects to that portion of the questionnaire dealing with other occupational exposures. For this reason, information 86 �concerning exposures to other herbicides/insecticides used in Vietnam will be collected. Whenever possible, stratification techniques will be used to adjust for these confounding variables during data analysis. Variations in fuel between C-130 and C-123 aircraft would be significant factors if individuals in the study were heavily and repetitively exposed. However, the normal duties of the study participants did not involve aircraft refueling or other fuel handling activities. Thus, fuel exposures can be minimized as significant confounding factors. 87 �IX. Quality Assurance and Management Considerations A. Quality Control (1) Overview As in any major scientific effort the quality of the data and the comparability of the data over time are key factors in achieving valid results. Quality assurance in both scientific and management aspects of this study are planned, and will be fully integrated into each phase of the study. (2) Sc i entif i c As pect s (a) Protocol Development The Air Force scientific protocol has been under development for more than one year. It has been subjected to an unprecedented five stage independent peer review process to insure the highest quality and validity of its science. (b) Blind Assessment Protocols The exposed or non-exposed status of each individual will not be revealed to any of the Health Examiners. Each aspect of the physical examination will be conducted by rigid adherence to the examination protocol. Past medical history and review of systems will be obtained by individuals not associated with the examining process. (c) Population Ascertainment Quality Control The study/control populations for this effort were ascertained through extensive computer, and hard copy record searches. The matching variables for each individual were entered and verified with a computer program to minimize transcription errors. Data collection for both exposed and control populations was conducted using identical techniques, thus avoiding systematic bias in population ascertainment. (d) _P reel si on Mate hi ng Computer techniques will permit extremely close matching of the control participants to the RANCH HAND participants for three distinct variables. This will substantially enhance the analytic flexibility and validity of the study. (e) Questionnaire Techniques Detailed questionnaire methods are under development to provide comprehensive crosschecks between objective and subjective health information. Particular emphasis will be placed upon techniques to ascertain false positive information which might impact the validity of the study. 88 �(f) Laboratory J[)ua1Jt,y Control The contractor for acquisition of health data mandatorily must have a detailed in-house laboratory quality control program coupled with enrollment into the "CLIA" or "CAP" laboratory survey. In addition, randomly selected duplicate specimens will be sent to a central Air Force reference laboratory for verification. (g) Single Physical Examination Site All physical examinations conducted by the contractor will be performed at a single site by dedicated teams of health professionals to insure that data variability is at an absolute minimum. The contractor will be a fully accredited medical institution, and must provide organizational evidence of national/international preeminence. (h) Re r son n el Qu a 1 i f i ca t i on s All examining physicians will be certified and .accredited by a Medical Specialty Board. Paramedics, medical students and interns will not participate as examiners in this study. (3) Management Aspects (a) Informed Consent All participants will be fully informed as to the nature and purpose of all medical diagnostic tests and examinatjpns, .and will certify their complete understanding by signing specially designed informed consent forms. Release of medical data will be in strict accordance with Privacy Act determinations, and Air Force policies. Total confidentiality will ;b.e granted to subjects who are not on active duty. Active duty sutej.ects will be given limited confidentiality with release of medical informatl<Hi fco the ;DOP only in instances in which there is a risk to public safety or national A monitoring group of scientists and p,er$pnn£l outside the USAF will regularly review and assess the con.d:WCt of the RANC.H :HA'N.P study* [his group will interact closely with the Air Force principal investigators, and will provide written commentary and recommendat!ioifi;S directly /to the .White i louse Office of Science and Technology Policy,. Apprpxi'Kist<6ily equal representation will be maintained between government scientists., ^C-ademic •.scientists, and scientific personnel nominated by veterans advocacy groups, (c) Consultants In addition to the $truct<ur.e£l Air Farpe ma:ntgerDgnt system, outside management and scientific consultants will -be utiiliz-ed fop .provide assistance to the principal investigators upon request. 89 �(d) Contract Performance All data acquisition contracts will contain highly detailed schedule performance requirements. All statements of work will be coordinated with two procurement levels, appropriate Air Force program coordinators, and the outside monitoring group. (e) On-Site Contract Monitor An Air Force Medical Service officer will be assigned to the physical examination site to: (1) provide visible Air Force representation to all participants, (2) conduct detailed entry and exit briefings with all participants, particularly ensuring that the health assessment was conducted on a "blind basis", (3J review all medical data for completeness and accuracy prior to computer entry, and (4) examine all relevant features of the data acquisition process, and insure absolute compliance to the contract specifications. (f) Data Security All medical information obtained on each participant will be entered into a computer data respository. Access to "these data will be limited to key scientific investigators by master code numbers. B. Management Structure (1) General Organization Standard Air Force Systems Command research and development concepts and organization will be used to manage this study and assure effective control of all phases of the investigation. The organizational structure is outlined in Figure 16. (2) Functions (a) Program Element Monitor (PEM) of the Program primary support the Air The tasks of the PEM will be preformed by a representative USAF Surgeon General's staff. The PEM will serve as the Air Staff Monitor, and as such, he will represent the needs and interests of the investigators to the Surgeon General and the Air Staff. He will the needs of the study to the Deputy Chiefs of Staff, the Secretary of Force, the Secretary of Defense, and Congress. 90 �Figure 16 MANAGEMENT STRUCTURE Program Element Monitor HQ USAF/SG Representative AFSC Systems Officer HQ AFSC/SG Representative Program Office USAFSAM AMD Representative USAFSAM Principal Investigators (Technical Contract Monitors) Det 1 AMD or TOY Rotation On-Site Contract Monitor (Quality Control-Physical EXAMS) (b) Systems Officer (SYSTO) The SYSTO will serve as the Program Manager at the Air Force Systems Command level. In this capacity, he will monitor program status, key issues, and problems. He will also serve as coordinator and expediter between the PEM and the primary investigators. Additionally, the SYSTO will prepare program documentation, coordinate all aspects of the program, monitor obligations and expenditures, and Initiate reprograrnming actions to support unfunded study requirements. (c) Prog rami J3ffice The Program Office will be staffed by a representative of the primary investigators and an Aerospace Medical Division (AMD) representative. This office is responsible for implementation of the complete program 91 �management plan on a day-by-day basis. Routine periodic management assessments and program status information will be provided to the SYSTO. The office will assure that all professional and technical aspects meet the stringent quality requirements outlined in the study protocol. It is the responsibility of this office to insure that all schedules, milestones, and financial requirements are met. This office also interfaces with, and provides guidance and support to the onsite contract monitor(s). (d) USAFSAM Principal Investigators/Scientists This team is the leading technical resource for this program. Members of this team are responsible for the faithful execution of the protocol, and as such, approve/disapprove all protocol changes, working in concert with the outside monitoring group. The principal investigators are the tecnhical monitors on all contracts under the protocol. They are responsible for the security of all data, for all data analysis, and for all interpretation of analyses subject to review by the outside monitoring group. These investigators provide summary data to Air Force management personnel on request, to enable proper contract billing and program resource analysis. The primary flow of data, data analyses, and analysis interpretation from the principal investigators/scientist directly to the monitoring group is designed to obviate any appearance of Air Force management bias. (e) Onsite Contract Monitor (Physical Examination Contractor) The onsite monitor will act as the Air Force representative at the examination site. He will monitor and assess the quality and timeliness of the contractor's performance, and will advise the Program Office of any performance decrements, as well as other problems encountered at the examination site. He will be responsible for the quality control of all aspects of the examination process (physical examination, laboratory procedures, and psychological and physiological testing). He will also welcome each study subject, review the results of the complete evaluation, and debrief each subject at the conclusion of the examination process. 92 �X. Repprti ng Procedures Interim synoptic progress reports will be provided to the Surgeon General through Quarterly Management Reviews conducted each January, April, July and October. Key data analyses will be displayed, but inferences and conclusions will await full data analysis at the conclusion of each phase. A formal report for each of the three phases will be completed with forecasted submission dates of: Mortality Study, June 1982; Morbidity Study, June 1983; and Follow-up Study, June 1985, 1987, 1992, 1997, 2002. Findings and conclusions of each phase will be published in a journal of stature. Total study design, findings, and conclusions will be published in the USAFSAM Aeromedical Reviews or Technical Reports. 93 �XI. QUESTIONNAIRE The release of the actual questions within the questionnaire could possibly result in irreparable damage to the study from an avoidable source of responder bias. Consequently, this section provides a summary of the general subjects to be covered on the questionnaire and a brief discussion of those specific areas that will receive particular emphasis. The questionnaire will, of necessity, be lengthy, but it will be administered at a time convenient to the subject. Subjects who refuse to participate in a face-to-face interview will be encouraged to cooperate with modified questionnaires given by telephone. The questionnaire will verify personal identification data such as name, SSAN/AFSN, date of birth, address, telephone numbers, race, military status, effective date of status, location of military medical records, and marital history information. RVN tour information will be rechecked and expanded to include specific data such as date of tour, tour end date, AFSC, organization of assignment, PCS and TOY status, combat missions, and whether or not the tour was a RANCH HAND affiliated tour. Pre- and Post-RVN exposure information, both occupational and avocational, to asbestos, radiation, herbicides, pesticides, and carcinogens will be elicited. Data concerning the frequency and duration of these exposures are very important. RVN exposure to these chemical and physical agents will also be collected. Medical information obtained during this interview will include a statement of general health, smoking history, alcohol consumption history and longterm medication/drug use. In addition, questions dealing with infertility, birth defects of offspring, as well as the wife's obstetrical history (i.e., total conceptions, live births, miscarriages, stillbirths and premature pregnancies) will be obtained. A family history emphasizing cancer, heart disease, liver disease and inherited disorders in both the subject's and spouse's families will be collected. A comprehensive medical inventory will be included emphasizing the neurologic, dermatologic, reproductive, and hepatic systems. At the time of the physical examinations, each subject will be given a comprehensive face-to-face medical history which will expand and verify the health information that was obtained in the initial questionnaire and records review. An extensive review of systems will be covered at that time, including an extensive occupational and avocational exposure history. Just prior to the time of follow-up adaptive physical examinations, a preliminary telephone contact will establish the subject's current health status and his willingness to continue participation in the study. Appointments for the follow-up examinations will also be arranged. Adaptive questionnaires will be given emphasizing those symptoms and systems that were found to be significantly associated with the exposed population on analysis of earlier study results. If the subject expresses a desire to cease participation at 94 �this time, he will be encouraged to reconsider his decision, and the reasons for dropping out of the study will be sought. At the time of subsequent followup evaluations, subjects who have left the study will be given the opportunity to rejoin the study. 95: �XII. Physical Examination Design A. General Instructijgns This phase of Project RANCH HAND II is a cross sectional study of the subject's health at the time of examination. The physical examination and all required laboratory procedures will be performed by physicians and technicians at a major civilian medical center under contract to the Air Force. It is important that examiners remain unaware of the subject's status as a RANCH HAND participant or as a control subject. The physician examiner is tasked to examine and objectively record his findings. The examining physician is not, and cannot be expected to arrive at any definitive diagnosis, as the full history and laboratory results will not be available to him. Medical history, laboratory results, and physical examination findings will be evaluated by an independent diagnostician employed by the contractor. This diagnostician will formulate diagnoses and differential diagnoses, if appropriate. In addition, he will present a detailed analysis and debriefing to the study subject, and provide a copy of the analysis to the subject's personal physician, if so requested. If, during the examination, the physician discovers evidence of serious illness requiring immediate treatment, the normal emergency or urgent care procedures of the medical facility would apply. Such care will be arranged by the diagnostician and will be supplied by the contractor at Air Force expense. If during the examination, evidence of illness requiring nonemergency medical attention is found, the diagnostician should infonn the subject and offer to have forwarded pertinent information to the subject's physician. A clear record of any such advice and treatment should be recorded. The ultimate value of the RANCH HAND II Study will lie in the collection of complete, accurate and, whenever possible, quantitiative data permitting the most stringent and powerful statistical analysis. For that reason, the physical examination protocol requires exact measurements in many instances, and the use of defined meanings of semiquantitative indicators in other places. These examinations will define the health status of the subjects at a point in time, and will establish the presence or absence of abnormal physical findings. After statistical review of the study groups, these findings may permit definition of a chronic effect due to exposure. An inaccurate examination may lead to falacious study results in two ways: a presumed syndrome may be defined which does not in fact exist, or a syndrome which in fact exists may not be defined with enough validity to warrant further actions. 96 �B. Conduct of the Examination SUBJECT HVMBRH SECTION PHYSICAL EXAMINATION t. OENF.HAL APPEARANCE a . Appearance/Stated Age f*$ Younger Than £70Tder Than ' jd Same As b'. f^J Well-nourished f~J Obese £7 Under-nourished £j Older Than C. Appearance of illness or distress / 7 Yes £7 No " d- Hair Distribution / / Normal / 7 abnormal " " SPECIFY: 2. HIIHHT SITTING BLOOD PRESSURE RIGHT AHM. AT HEART LEVEL WEIGHT fUn Cltl j. PULSE RATE R E G U L A R : [ _ | YES 3YSTOLIT . . . . . . . j -, 01ASTOUCDescribe any IrregulaHttet. Q] NO a. Irregular /*/ b. Irregularly irregular / 7 " c. VPBs per minute _ «. EYE GROUNDS f*"] NORMAL f~T_ABNORMAL ARCUSSENILIS 8. EN T T.l P«^NT f~ J NORMAL Describe any vascular loslons, hcmoirbagen, exudatea, £7 Hemorrhage's p«P»u«d«««. /"7 Exudates ^7 Papilledema f~J Disk Pallor f~J f> Cupping £2 A-V nicking" /~7 ^ light reflex f~~f Arteriolar spasm 5 QABMHT [~] ABNORMAL «- Describe any abnomi*llty. Tympanic membranes intact /~7 Yes /~7 No Nasal ulcerations /~7 No /~7 Yes 7. NECK ffi.p.ci.ili- (dvro/d «|««4 |_| NORMAL Thyroid gland palpable f~7 Enlarged 7y Nodules /V Tenderness 7 8. THORAX AND LUNGS 9. M E A N T ( " J NORMAL R £V | J ABNORMAL.^ L /"7 Describe any abnomalUy. f~~f Parotid gland enlargement /7 R £7 L . ["] NORMAL Asymmetrical expansion Hyperreconance Dullness Abnormal OciOar^igmentation Q] ABNORMAL f~7. Wieezes /""7 Rales ['^ABNORMAL Descrtb* «ny abtiowullty, sspuctnlly bulUr rolos. qircumferena^ at nipple level Expiration ,qm Inspiration _^ cm Describe sny enlargement, Irregularity of rat*, munmure, «t Ihrtllf. Displacement of apical impulse £J No f~J Yes Precordial thrust /^7 No /"7 Yes Heart sounds normal /"7 Yes /~7 No /~7Sl /^7Sg £783 jContinuof? in I too 18 on Reverse) 10. AOOOMPN PI NORMAL £7 Heptomegaly " cm Liver Span £7 Splenomegaly M. rxTn£MirifS I"*] NORMAL £7 Absence, specify: £7 Edema " "[^"J ABt*olMAL D*«ciibe at>y dbnotwaUty V»H*i special attentlon-lo th? £7 Other mass - tpi««« •bdiiYw. Record waist measurement Specify: on attached form. £7 Tenderness /"7 Liver £7 Spleen /7 Other, specify: [fj] ABNORMAL f~J Pitting /~7 Non-pitting /~7 Loss of hair on toes Describe any edema of signs of vascular insufficiency, £7 Clubbing of nails £7 Varicosities 97 �SECTION PHYSICAL EXAMINATIOH <C<x,tlm»<l) 2. P E R I P H E R A L P U L S E S RADIAL FEMORAL POPLITEAL 3 O R 5 A L I S PCDI3 POSTFnion TlfJIAU ; ABNORMAL /7 ~ /7 ~ /7 ~ [~J t~~t indicate type and location of lesions on the attached anatomical . fiaure £ Hyperpigmentation 7 ^-^I'almar Keratosi* /~7 Jaundice £7 Petechiae £7 Spider angiomata £7 Ecchymoses £7 Palmar erythema / / Soles of feet l)ormatoj>raphia Comedones Acneiforra lesions Acneiform scars Depigmentation Inclusion cysts Cunis Rhomboidalis Full-Face and Bilateral profile photos taken '~'J^,ilS i _ i NORMAL '^"ABNORMAL £7 Muscle - Specify: / 7 Spine ~ £7 Weakness / 7 Scoliosis ~ £7 Tenderness / 7 Abnormal Consistency ~ / 7 Tenderness, ~ /~7 Atrophy Level Decreased range of motion Biopsy Taken 14. M U S C U L O S K E L E T A L / 7 Pelvic tilt ~ ^ Straight Leg 7 • 15. GENITOURINARY - RECTAL - HERNIA £7 NORMAL f~7 Inguinal hernia /~7R /^/L /~7 Tastes Absent Enlarged Atrophic /I7PCJ rj rj /7 !L £7 £7 £7 £T ABNORMAL. /~7 Varicocele /~7 Epididymis £7 Scrotal Mass ^ dia / 7 Hemorrhoids ~ / 7 Prostatic ~ Enlargement /7 Rectal mass 16. IA'>yPH MODES - CHECK ALL AREAS. / 7 NORMAL' £7 ABNORMAL - SPECIFY CERVICAL, ~ OCCIPITAL, SUPRACLAVICULAR, AXILLARY, SPITRAaiLEAR, INGUINAL, FEMORAL / 7 Enlarged ~ £7 Tender £~7 :!ard / 7 Fixed ~ £V Confluent 17. NERVOUS SYSTEM - SEE'ATTACHED FORMS OBSERVATIONS 18. HEART -W (Continued from Item 9) Murmur / 7 No f~J Yes Area £7 ~ s-/s £7 Ao £ pu 7 £7 Z 7 APex I £7 Dia 98 �CLINICAL RECORD NEUROLOGICAL EXAMINATION HEAD AND NECK - Normal to Palpations/Inspection £7Y £7N Specify Scar £7 Asymmetry £7 Carotid Bruit £7No £JR £7L Neck Range of Motion £7 Normal or Decreased to £7 Left Depression £7 £7 Right £7 Forward £7 Backward TRUNK MOTOR SYSTEM - Handedness Right £7 Left £7 Gait £7 Normal or £7 Broad Based £7 Ataxic £7Small Stepped £70ther-Specify Associated Movements £7Arm Swing £7Normal or Abnormal ,£7R £7^ Muscle Status (strength, tone, volume, tenderness, fibrillations) Bulk £7 Normal £7 Abnormal Tone Upper Extremities £7N0rmal or £7Increased £7Decreased £7Right £jLeft Lower Extremities £7Normal or £7"Increased ,£7TJecreased £7Right £7Left Strength - Distal wrist extensors £7NontlJi'l £70ecreased Ankle/Toe Dors/Flexors £7Normal £7Decreased £JR £7L Proximal Deltoids £7Normal £7Decreased £7& Hip Flexors £7Normal £7Decreased £7L £7& £7L Abnormal Movements (tremors, tics, choreas, etc,) Fas 1cu lotions .£7N.o Tenderness £7No £7Yes (Ii4+) Tremor £7No £7Yes (1-4+) £JYes - Specify Upper Extremity £7R £7D £7Resting £7Essen:t1a1 r£7;Intention ther Lower Extremity £7R £7L/O° Coordination (a) EquiTibratory - Eyes Open Eyes Closed - Romberg £7Positive (Abnormal) Right Foot (b) (c) Left Foot Monequilibratory (F to N; F to 'F; H to K:) :F:inger-to-no.SB-to-ftnger £7Nort"a' £7 Abnormal £7R:ight ^ OLeft £7Both. . . „„. . Heel-Knee-Shin £7Normal £7«bnornial £7:RighT ,T7Le'ft £7Both Succession Movements (including check, rebound, posture-ho'lcnng) If indicated, check £7Normal £7Abnorma1 £J.R ,£7R Rapidly alternative movements £7Normal S k i l l e d Acts ( ) Handwriting. ( ) £7Nega:ti'Ve (Normal) If indicated, £7Norma1 £7;flbn.orma'l ,£7R .-£7'£7Abnorma1 Speech (articulation, aphasia, a.gnosia) Grossly £7Normal £7Abnormal - Specify Dysarthria ./~7 Aphasia .£7 •99 �Reflexes (0-absent; 1-sluggish; 2-active; 3-very active; 4-transient clonus; 5-susta1ned clonus) R Deep L Deep R R Other L L Abnormal Babinski R L Patellar Biceps Triceps Achilles Remarks MENINGEAL IRRITATION Straight Leg Raising £7Norma1 NERVE STATUS (tenderness, tumors, etc.) £7Abnormal £71 £7Both SENSORY SYSTEM (tactile, pain, vibration, position. If positive sensory signs are present, summarize below and indicate details on Anatomical Figure, Std. Form 531) Light Touch £7Normal Pin Prick £7Normal ^/Abnormal ^Abnormal (Map on Anatomical Figure) Vibration (at ankle, 128 hz tuning fork): £7Normal OAbnormal £7R Position (Great toe): £7Normal /^Abnormal £JR £7L £7Both CRANIAL NERVES I R Smell II III /^/Present /^Absent L Smell £JPresent £JAbsent Fundus R Normal £7' Abnormal /~7 Disk Pallor/atrophy £7Exudate £7Papi 11 edema Fundus L Normal £7 Abnormal £7 Disk pallor/atrophy £7Exudate £7 Papi 11 edema £7Hemorrna9e Fields (to confrontation) Right £7Normal /^Abnormal Left £7Normal ZI7Abnoninal Normal ~ Specify Unequal £7 Difference mm oth er £j /"/R 7~7L Abnormal £j Pupils-Size (mm) Equal Shape, position Round Light, Reaction Normal Position of Eyeballs Movements R Nystagmus Rotary £7 (Draw position) Horizontal £7 100 Vertical £7 �XI Ptosis R£7 L £7 • V Motor R Clench Jaw - Symmetric £7 Sensory R Normal f~J L Normal £7 Corneal Reflex Deviated £7 Abnormal /~7 Vi/~7 Abnormal £7 V R R/~7 L£J Vo L Yes No VII Motor R Normal smile £7 /I7 L Normal smile O Ves O'No Palpebral Fissure £7Y.es £JNo Palpebral Fissure OYes £7No IX Palate and Uvula X Movement Normal £J Palatal Reflex Deviation to OR R £7Normal /^Abnormal L £7Normal /~7 Abnormal XII Tongue-Protruded-Central £7 R £J L £7 Atrophy /^JNo £JYes MENTAL STATUS (alert, clear, cooperative, etc.) £JYes - Specify 10! Gross abnormalities: �DIAGNOSTIC SUMMARY SYNOPSIS OF POSITIVE FINDINGS Medical History: Physical Examination: General Dermatologic Neurological Psychological Laboratory Results: Diagnosis: Differential Diagnosis, if applicable: Date Signature of Diagnostician 102 �C. Spec i a1 P rocedu res (1) Nerve Conduction Velocities (NCV) These studies have been determined to be an important parameter in long-term follow-up studies of persons thought to have been exposed to Herbicide Orange components. The Nerve Conduction Velocities should be performed by a physician or by a specialty qualified technician under the supervision of a physician trained in neurophysiological methods. (a) Specific NCVs ( ) Ulnar Nerve (one side only) 1 (a) motor (above elbow, below elbow) (JD) values recorded (i) distal latency (ii) NCV (2) Peroneal Nerve (one side only) (a), motor (b) values recorded (i) distal latency (ii) NCV (1) Sural Nerve (one side only) (aj sensory: orthodromic (b) values recorded: NCV (b) Methods Standardized, published methods will be used (e.g., Smorto, Marcio P., and John V. Besmajian; Elecj:rod1jgnos1 S; Harper and Row; NY, 1977). (2) Psychological Test Battery (a) General This battery yields objective numerical da.ta, and is wellstandardised and clinically validated. The individual tests were chosen to insure an adequate analysis of one of the major alleged manifestations of 103 �Herbicide Orange toxicity. Each test either validates the other tests or is considered to be a "definitive" test for analysis of a suspected psycho-neuropathic effect under study. Compared to the general civilian population, characteristic response tendencies are observed on the MMPI and Cornell Index among active duty aircrewmen being evaluated in an aeromedical setting. It is also important to consider the effect that pending retirement has exerted on the reporting of medical history and symptomatology. This may also alter responses to psychological testing. (b) Specific Tests (D Nechsler Adult Intelligence Scale (NAIS) Individually-administered collection of verbal and nonverbal intellectual measures; also useful for clinical inferences when combined with the neuropsychological battery below. (2.) Reading subtest of the Wide jange Achievement Test (WAIT) Individually-administered measure of word recognition ability. Important to rule-out reading inefficiency should the response to the personality instruments below be of questionable validity (e.g., high F scale on MMPI). (1) Halstead-Reitan Neuropsychological Test Battery Individually-administered collection of brain behavior relationship measures for establishing the functional integrity of the cerebral hemispheres. The battery must include the following subtests: Category, Tactual performance, Speech-Sounds, Seashore Rhythm, Finger Tapping, Trail Making, and Grip Strengths. The Aphasia Screening and Sensory-Perceptual Exams are considered optional in view of their redundancy with the clinical neurologic exam included in this project. Individualized test debriefing is conducted to clarify test performances in the WAIS and Neuropsychological Battery. (D Three subtests of the Wechsler Memory Scale I (MIS I) Individually-administered measures of immediate and delayed recall of verbal and visual materials. The Logical Memory, Associate Learning and Visual Reproduction subtests are to be administered in the standard, immediate-recall fashion initially. After 30 minutes has elapsed, the examinee is asked, without prior alerting, to recall as much as he can about the Logical Memory and Visual Reproduction subtest stimuli. Standard scoring is used for both test-retest administrations. 104 �(5) Cornell Index (CD Self-administered and standardized neurppsychiatric symptom and complaint inventory, including items involving asthenia, depression, anxiety, fatigue, and GI symptoms in lay language. Endorsement of items are to be explored and clarified in test-debriefing, (6) Minnesota Multiphasic PersonalIty Inventory (MMPI) 60 to 90 minute self administered clinical psychiatric screening instrument; also capable of estimating response biases (e.g., "fake good," or "fake bad"). The shortened version of Form R (i.e., items 1 to 399) may be substituted for the 566-item Long Form. Standard scoring and Minnesota norms are to be used, with the possible exception of active duty examinees where USAFSAM aircrew norms may be applied. Clarification of profiles showing response biases, questionable validity, and/or unusual item endorsements will be conducted in individual test debriefing. (3) 12-Lead E1 ectrpeardlogram (a) Procedures A standard 12-lead scalar electrogram is required. If an arrhythmia is observed, a one minute rhythm strip will be obtained. The electrogram will be done following a minimum fast of fpur hours, (b) Interpretation The electrocardiograms will be interpreted logists at the examining center, and then forwarded to Brooks AFB cians in the USAF Central ECG Library will compare the tracing individual ECG records in the case of rated (pilot or navigator) by cardiowhere physi*to previous subjects. (c) Disposition (USAF Central |CG Library) (1) Pilots and Navigators The original tracings will permanent record established for each individual. (2) Enlisted Subjects The original tracings will permanent record established for each individual, (4) be micrqfisched and be microflsched antf a Radi ographi c Exami nati on A standard 14x17 in., standing* rpentgenograrn position using small nipple markers will be accomplished. 105 In the PA �(5) Pulmonary Function Studies Standard evaluation of vital capacity and forced expiratory volume at 1 second will be performed. (6) Laboratory Procedures (a) Specific Tests to be Performed on all Participants (1) Hematocrit (2) Hemoglobin (J3) RBC Indices (4) While Blood Cell Count and Differential (5) Platelet Count (6_) Erythrocyte Sedimentation Rate (7_) Urinalysis (8_) Semen Analysis (Number, % Abnormal, Volume) (9_) Blood Urea Nitrogen (10) Fasting Plasma Glucose (11.) Creatinine (12) 2-hour Post Prandial Plasma Glucose (13) Differential Cortisol (0730 and 0930 hours) (14) Cholesterol & HDL (J.5) Triglycerides (16) SGOT (J7) SGPT (18) GGTP (19) Bilirubin, Total and Direct (20) Alkaline Phosphatase (21) LDH 106 �(22) Serum Protein Electrophonesis (_2J3) CPK (24) VDRL (2^) LH (26) FSH (27) Testosterone (28) Thyroid Profile (RI.A) (13, 74, TSH.FTI) (_29) Delta-aminolevulinie Acid (30) Urine Porphyrins (31) Hepatitis B antigen/antibodies (32) Prothrombin time (33) Blood Alcohol (b) To be performed on selected subjects (1) autoimmune disorders Anti-nuclear Antibody on subjects with indications of (2) Hepatitis A Antigens/antibodies for those with current or past history of VTver disease (3) Karyotyping for those fathering children with birth (4) Skin photography aind skin biopsy on subjects with defects suspected chloracne (J5) To be performed if medical history indicates a subject has an increase in infectious diseases; (a) Immunoelectrophoresis (b) Quantitative Imngnoglobylin Determinations 107 �() 6 To be performed on a randomly selected group of subjects (a_) Enumeration of B and T cells (b) Enumeration of Monocytes (c_) B and T cell function tests (7) Rationale for laboratory procedures (a) Studies on the toxicity of TCDD in animals have shown that the following organ systems are damaged: (1) Liver: Hepatic necrosis, liver enzyme changes, hypoproteinemia, hypercholesterolemia, hypertriglyceridemia. (2) Reticuloendothelial System: cellular immunity, decreased lymphocyte counts. (J3) Hemopoietic leukopenia, pancytopenia. System: (4j Endocrine System: cortex, hypothyroidism. Thymic atrophy, altered Anemia, thrombocytopenia, Hemorrhage and atrophy of adrenal (5) Renal: Increase in blood urea nitrogen. (j>) In addition, statistically significant increases in hepatocellular carcinomas (liver) and squamocellular carcinomas of the lung were found. (b) Studies on the toxic effects of TCDD in man have shown that the following organ systems are damaged: (1) Skin: Chloracne, hirsutism. (2) Liver: Porphyria cutanea tarda. Increased levels of transaminase and of 6GTP. Enlarged, tender liver, hyperlipidemia. (_3) Renal: Hemorrhagic cystitis, focal Pyelonephritis. ( ) Neuromuscular System: 4 Asthenia, i.e., headache, apathy, fatigue, anorexia, weight loss, sleep disturbances, decreased learning ability, decreased memory, dyspepsia, sweating, muscle pain, joint pain and sexual dysfunction. (J5) Endocrine System: Hypothyroidism. 108 �(c) Based upon the reports of toxic effects in animal and human exposures, the following organ panels were thus recommended: (1) Hemopoietic (2) Reticuloendothelial (3) Renal (_4) Endocrine (J5) Neuromuscular (dj Hemopoietic screening should include: (1) Hematocrit (2) Hemoglobin (3) RBC indices ( ) Erythrocyte sedimentation rate 4 (J5) Platelet count (6) Prothrombin time (e) Reticuloendothelial system: (_!_) White blood cell count (2) Differential (J3) Serum protein electrophoresis (_4) Selective use quantitative immunoglobulin determination of immunoelectrophoresis (5) B cell and T cell counts and functions (f_) Hepatic screen: (1) SCOT (2) SGPT GGTP 109 and �(£) Bilirubin, Total and Direct (j>_) Alkaline phosphatase (6) LDH (2.) Cholesterol (8) HDL (9) Triglyceride (10) Urine prophyrins (11) Urine porphobilinogen (12) Hepatitis B antigens/antibodies (g) Renal screen: (_1) Urinal ysis (2) BUN (3) Creatinine (h) Endocrine screen: (_!) Differential cortisol (0730 and 0930 hours) (2) Thyroid profile (RIA) (3) Fasting plasma glucose (i) Neuromuscular system: (I) CPK (j) Elucidation of sympoms of asthenia: (1) Testosterone (2) LH FSH 110 �(k) The following tests should be peformed only as follow-up for abnormalities in the history or physical examination findings: (1) HAVAB (IgG and IgM) (2) ANA 111 �XIII. PRINCIPAL INVESTIGATORS, CO-INVESTIGATORS AND CONTRIBUTORS A. PRINCIPAL INVESTIGATORS George D. Lathrop, MD, MPH, PhD Colonel, USAF, MC Chief, Epidemiology Division USAF School of Aerospace Medicine Brooks AFB, TX 78235 William H. Wolfe, MD, MPH Lt Colonel, USAF, MC Chief, Disease Surveillance Branch Epidemiology Division USAF School of Aerospace Medicine Brooks AFB, TX 78235 Richard A. Albanese, MD, GS-15 Chief, Biomathematical Modeling Branch Data Sciences Division USAF School of Aerospace Medicine Brooks AFB, TX 78235 Patricia M. Moynahan, BSN, MS, Lt Colonel, USAF, NC Chief, Occupational Epidemiology Branch Epidemiology Division USAF School of Aerospace Medicine Brooks AFB, TX 78235 B. CO-INVESTIGATORS Alvin L. Young, BS, MS, PhD Major, USAF Special Assistant on Military Herbicides Department of Environmental Medicine Veterans Administration 810 Vermont Ave NW Washington DC, 20420 Clarence F. Watson, Jr., MD, MPH Colonel, USAF, MC Chief, Clinical Sciences Divsion USAF School of Aerospace Medicine Brooks AFB, TX 78235 112 �James A. Wright, MD, MPH Major, USAF, MC Assistant Chief, Disease Surveillance Branch Epidemiology Division USAF School of Aerospace Medicine Brooks AFB, TX 78235 Joel E. Michalek, PhD, GS-13 Mathematical Statistician Data Sciences Division USAF School of Aerospace Medicine Brooks AFB, TX 78235 Phelps P. Crump, PhD, GS-15 Chief, Consultation & Training Branch Data Sciences Division USAF School of Aerospace Medicine Brooks AFB, TX 78235 Richard C. McNee, MS, GS-14 Chief, Advanced Analysis Branch Data Sciences Division USAF School of Aerospace Medicine Brooks AFB, TX 78235 Alton J. Rahe, MS, GS-13 Mathematical Statistician Data Sciences Division USAF School of Aerospace Medicine Brooks AFB, TX 78235 Michael A. Sauri, MD, MPH & TM Major, US Army, MC Department of Internal Medicine Brook Army Medical Center Fort Sam Houston, TX 78234 Richie S. Dryden, MD, MPH Lt Colonel, USAF, MC Chief, Flight Medicine Branch Clinical Sciences Division USAF School of Aerospace Medicine Brooks AFB, TX 78235 113 �C. CONTRIBUTORS Thomas V. Murphy, MBA, GS-9 Statistician Disease Surveillance Branch Epidemiology Division USAF School of Aerospace Medicine Brooks AFB, TX 78235 Robert A. Bottenberg, PhD, GS-15 Chief, Computational Sciences Division AF Human Resources Laboratory Brooks AFB, TX 78235 Jimmy D. Souter, BA, 6S-14 Chief, Analysis & Programming Branch Computational Sciences Division AF Human Resources Laboratory Brooks AFB, Tx 78235 Calvin C. Fresney, GS-12 Chief, Data Base Management Section Computational Sciences Division AF Human Resources Laboratory Brooks AFB, TX 78235 Henry W. Clark, BA, GS-12 Supervisory Computer Systems Analysist Computational Sciences Division AF Human Resources Laboratory Brooks, AFB, TX 78235 Phillip G. Brown, BS, MS Major, USAF, BSC Assistant for Bioenvironmental Engineering Office of the USAF Surgeon General Boiling AFB, MD 20332 114 �xlv A. • SELECTED BIBLIOGRAPHY (Key References) GENERAL REFERENCES Meek, Stephen L., An estimate of the relative exposure of U.S. Air Force crewmembers to agent orange. Masters degree thesis, University of Washington, School of Public Health and Community Medicine, Seattle, 26 February 1981. Young, A. L., J. A. Calcagni, C. E. Thalken and J. W. Tremblay. 1978. The toxicology, environmental fate, and human risk of Herbicide Orange and its associated dioxin. USAF Occupational and Environmental Health Laboratory, Brooks Air Force Base, Texas. Technical Report OEHL-TR-78-92. 247 p. International Agency for Research on Cancer. 1978. IARC Internal Technical Report No. 78/001. Coordination of epidemiological studies on the longterm hazards of the chlorinated dibenzo-dioxins/chlorinated dibenzofurans. Joint NIEHS/IARC Working Group Report. Lyon, France. 44 p. Report by the Comptroller General of the United States. April 7, 1979. Health effects of exposure to Herbicide Orange in South Vietnam should be resolved. General Accounting Office Pub. CED-79-2. 38 p. B. PHARMACOKINETICS OF 2,4-D Berndt, W. 0. and F. Koschier. 1973. In vitro uptake of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) by renal cortical tissue of rabbits and rats. Toxicol. Appl. Pharmacol. 26:559-570. Clark, D. E., J. S. Palmer, R. D. Radeleff, H. R. Crookshank and F. M. Farr. 1975. Residues of chlorophenoxy acid herbicides and their phenolic metabolites in tissues of sheep and cattle. J. Agric. Food Chem. 23(3):573-578. hlo, H. and P. Ylitalo. 1977. Substantial increase in the levels of chlorophenoxyacetic acids in the CNS of rats as a result of severe intoxication. Acta Pharmacol. Toxicol. 41:280-256. .'i\:, U. 1966. Distribution and elimination of chlorinated phenoxyacetic acids in animals. Acta Vet. Scand. 7:264-271. urunow, W. and C. Bohme. 1974. Uber den stoffwechsel von 2,4,5-T and 2,4-D bei ratten und mausen. (Metabolism of 2,4,5-T and 2,4-D in rats and mice.) Arch. Toxicol. 32:217-225. (German) Khanna, S. and S. C. Fang. 1966. Metabolism of 14 C-labelled 2,4-dichlorophenoxyacetic acid in rats. J. Agric. Food Chem. 14(5):500-503. 115 �International Agency for Research on Cancer. 1977. 2,4-D and esters. P. 111-199. ln_ IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Vol. 15. Some Fumigants, the Herbicides 2,4-D and 2,4, 5-T, Chlorinated Dibenzodioxins, and Miscellaneous Industrial Chemicals. Lyon, France. C. PHARMACOKINETICS OF 2,4,5-T Bohme, C. and W. Grunow. 1974. Uber den stoffwechsel von 4-(2,4,5-trichlorophenoxy)-buttersaure bei ratten. (Metabolism of 4-(2,4,5-trichlorophenoxy)-butyric acid in rats.) Arch. Toxicol. 32:227-231. (German) Dencker, L. 1976. The herbicide 2,4,5-T: Early placental barrier and accelerated fetal uptake with advancing gestation. P. 59-79. In Tissue Localization of Some Teratogens at Early and Late Gestation RUTated to Fetal Effects. Acta Pharmacol. Toxicol. 39(Suppl 1): 131p. Ebron, M. And K. D. Courtney. 1976. Difference in 2,4,5-T distribution in fetal mice and guinea pigs. Toxicol. Appl. Pharmacol. 37:144-145. Fang, S. C., E. Fallin, M. L. Montgomery and V. H. Freed. 1973. The metabolism and distribution of 2,4,5-trichlorohenoxyacetic acid in female rats. Toxicol. Appl. Pharmacol. 24:555-563. Lindquist, N. G. and S. Ullberg. 1971. Distribution of the herbicides of 2,4,5-T and 2,4-D in pregnant mice: Accumulation in yolk sac epithelium. Experientia 27:1439-1441. Piper, W. N., J. Q. Rose, M. L. Leng and P. J. Gehring. 1973. The fate of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) following oral administration to rats and dogs. Toxicol. Appl. Pharmacol. 26:339-351. Sauerhoff, M. W., W. H. Braun, G. E. Blau and P. J. Gehring. 1976. The dosedependent pharmacokinetic profile of 2,4,5-trichlorophenoxy acetic acid following intravenous administration to rats. Toxicol. Appl. Pharmacol. 36:491-501. D. PHARMACOKINETICS OF TCDD Allen, J. R., J. P. Van Miller and D. H. Norback. 1975, Tissue distribution, excretion and biological effects of [^C] tetrachlorodibenzo-p-dioxin in rats. Food Cosmet. Toxicol. 13:501-505. Piper, W. N., J. Q. Rose and P. J. Gehring. 1973. Excretion and tissue distribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat. Advan. Chem. Sen. 120:85-91. Reggiani, G. 1978. The estimation of TCDD's toxic potential in the light of the Seveso accident. 20th Congress of the European Society of Toxicology, Berlin (West), June 25-28. 20p. 116 �Rose, J. Q., J. C. Ramsey, T. H. Wintzler, R. A. Hummel, and P. J. Gehring. 1976. The Fate of 2,3,7,8-tetrachlorodibenzo-p-dioxin following single and repeated oral doses to the rats. Toxicol. Appl. Pharmacol. 36:209226. Vinopal, J. H. and J. E. Casida. 1973. Metabolic stability of 2,3,7,8tetrachlorodibenzo-p-dioxin in mammalian liver microsomal systems and in living mice. Arch. Environ. Contam. Toxicol. 1(2):122-133. E. PHARMACOKINETICS OF 2,4-D and 2.4,5-T IN MAN Coutselinis, A., R. Kentarchou and D. Boukis. 1977. Concentration levels of 2,4-D and 2,4,5-T in forensic material. Forensic Sci. 10:203-204. Gehring, P. J., C. G. Kramer, B. A. Schwetz, J. Q. Rose and V. K. Rowe. 1973. The fate of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) following oral administration to man. Toxicol. Appl. Pharmacol. 26:352-361. Kohli, J. 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D. and J. A. Moore. 1971. Teratology studies with 2,4,5trichlorophenoxyacetic acid and 2,3,7,8-tetrachlorodibenzo-p-dioxin. T o x i c o l . Appl. Pharmacol. 20:396-403. 117 �Green, S. 1977. Cytogentio By-Lines 7(6):292. effects of TCDD on rat bone marrow cells. FDA Hussain, S., L. Ehrenberg, G. Lofroth, and T. Gejvall. 1972. effects of TCDD on bacterial systems. Ambio 1 (1):32-33. Mutagenic Poland, A. and A. Kende. 1976. 2,3,7,8-Tetrochlorodibenzo-p-dioxin: enviromental contaminant and molecular probe. Fed. Proc. 35(12):2404-2411. Poland, A., W. Greenlee, and A. Kende, 1979. Studies on the mechanism of action of the chlorinated dibenyo-P-dioxins and related compounds. P. 214-230. _I_n Health Effects of Halogenated Aromatic Hydrocarbons. The New York Academy of Science. Vos, J. G. and 0. A. Moore. 1974. Suppression of cellular immunity in rats and mice by maternal treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Int. Arch. Allergy 47:777-794. Wasson, J. S., J. E. Huff and N. 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APPENDIX TABLE A-l SUMMARY OF 2,4-D, AND TCDD ANIMAL STUDIES TABLE A-2 "SYMPTOM COMPLEX" DERIVED FROM LITERATURE REVIEW OF CASE STUDIES EXPOSED TO 2,4-D, 2,4,5-T AND/OR TCDD TABLE A-3 DETAILED LISTING OF SYMPTOMS/ SIGNS BY MAJOR CATEGORY FROM LITERATURE REVIEW OF CASE STUDIES EXPOSED TO 2,4-D, 2,4,5-T AND/OR TCDD TABLE A-4 AGE COMPARISON OF EXPOSED SUBJECTS AND THEIR MATCHED CONTROLS TABLE A-5 STATISTICAL DESCRIPTION MATCHING PROCESS TABLE A-6 SPECIFIC STUDY ENTRY RULES TABLE A-7 SCHEDULE AND MODE OF CONTACTS WITH STUDY SUBJECTS TABLE A-8 MONTE CARLO SIMULATION FIGURE A-l 2,3,7,8-TETRACHLORODIBENZO-PDIOXIN (TCDD) FIGURE A-2 ESTIMATED PARTICIPATION POPULATION FIGURE A-3 OF STUDY DESIGN FORMAT 125 2,4,5-T OF THE IDENTIFICATION/ RANCH HAND �TABLE A-l SUMMARY OF 2,4-D, 2,4,5-T, AND TCDD ANIMAL STUDIES 2.4-D 2,4.5-T TCDD LD50 RANGE (ACUTE) 100-1000 mg/kg 100-1000 mg/kg 1-1000 g/kg CHRONIC TOXIC OOSE APPROACHES ACUTE LEVEL RAPID CLEARANCE 1/2 ACUTE LEVEL; VARIABLE CLEARANCE MARKEDLY LOWER LEVEL BIOACCUMULATION SIGNS OF ACUTE/ CHRONIC TOXICITY ANOREXIA ANOREXIA WEIGHT LOSS WEIGHT LOSS ATAXIA INVOLUTION OF THYMUS MUSCULAR WEAKNESS G.I. INJURY ALOPECIA IRRITATED G.I. TRACT LIVER CONGESTION EPITHELIAL CHANGES MINOR LIVER INJURY KIDNEY CONGESTION LIVER LESIONS (VARIABLE) ro CTl MINOR KIDNEY INJURY HYPOTHYROIDISM MINOR LUNG CONGESTION EMBRYOTOXIC DOSE APPROACHES TOXIC LEVEL APPROACHES TOXIC LEVEL MARKEDLY BELOW TOXIC MATERNAL LEVELS TERATOGENICITY QUESTIONABLE; WEAK AT BEST *LOW INCIDENCE ONLY IN MICE (CLEFT PALATES DILATED RENAL PELVIS) SPECIES VARIATIONS: YES MICE NO RATS CARCINOGENICITY QUESTIONABLE; WEAK AT BEST ONE STUDY: YES NUMEROUS STUDIES: NO EPITHELIAL CHANGES IN PRIMATES: YES IN RATS �TABLE A-2 "SYMPTOM COMPLEX" DERIVED FROM LITERATURE REVIEW OF CASE STUDIES EXPOSED TO 2,4-0; 2,4,5-T WD/OR TCDO 2.4,5-T (+ TCDO) TCDO CHLORACME CHLORACNE PORPHYRIA PORPHYRIA HYPERPiGMENTATIOD HYPERP^G^eNTATION ASTHENIA ASTHENIA ASTHENIA PERIPHERAL NEUROPATHY PERIPHERAL fBURQPATHY PERIPHERAL NEUROPATHY CARDIAC .CARDIAC DISTURBANCE 2.4-D SWEATING/FEVER CARDIAC ^DISTURBANCE R£mL OYSPUHCJIfiH UV£R DYSR»CII€« fii HVEft DYSFUNCTION GI DISTURBANCE GI OISTtKBANCE JtfAOACHjE CSf H¥POTHYROIOIS« CO»VULSiONS «EARIHffi/SJ»ELL OISTURBAHCES �TABLE A-3 DETAILED LISTING OF SYMPTOMS/SIGNS BY MAJOR CATEGORY FROM LITbRATURE REVIEW OF CASE STUDIES EXPOSED TO 2,4-D; 2,4,5-T AND/OR TCDD NEURO-PSYCHIATRIC ABNORMALITIES AESTHENIA PERIPHERAL NEUROPATHY ANXIETY HYPOREFLEXIA DEPRESSION WEAKNESS FATIGUE PARESTHESIAS APATHY EXTREMITY NUMBNESS LOSS OF DRIVE MYALGIA DECREASED LIBIDO GAIT DISTURBANCE IMPOTENCY "MILD" PARESIS SLEEPLESSNESS EMOTIONAL INSTABILITY ANOREXIA DIZZINESS DECREASED LEARNING ABILITY �TABLE A-3 (CONTINUED) DETAILED LISTING OF SYMPTOMS/SIGNS BY MAJOR CATEGORY FROM LITERATURE REVIEW OF CASE STUDIES EXPOSED TO 2,4-D, 2,4,5-T AND/OR TCOD DERMATOLOGIC DISEASE CHLORACNE PORPHYRIA CUTANEA TARDA HYPERPIGMENTATION HIRSUITISM (B005f) ALOPECIA OF THE SCALP OTHER DISORDERS HEPATIC DYSFUNCTION SEMAL DYSFUNCTION INCREASED CHOLESTEROL AW TRHa.*CERIO£ PROTEINURIA ItCREASES IN LIVES TESTS IBStlLAR fiiOMERULAR DEGENERATION RENAL GLUO)SORIA 61 PtSTORBANCE OUaiAC 01STUR6AMCE •NAHSEA B8ADYCARDIA VOMITING TACHYCARDIA DIARRHEA ATRIAL FIBRILLATION GASTRITIS ABDOMINAL PAIN �TABLE A-4 AGE COMPARISON OF EXPOSED SUBJECTS AND THEIR MATCHED CONTROLS AFSC/Race Strata Officer: Pi lot /Caucasian /Black Number of Exposed Subjects Mean Number of Matched Controls 349 6 9.5 2.7 Age Differenc 0-60 0-57 Nonpilot /Caucasian /Black CO 10.0 10.0 0-07 0-36 Other/Caucasian /Black o 78 2 25 1 10.0 5.0 0-27 0-54 187 15 10.0 9.8 0-35 0-58 528 51 10.0 10.0 0-48 0-06 Enlisted: Flying/Caucasian /Black Nonf lying/Caucasian /Black Killed in Action Of fleers /Caucasian /Black 14 1 ~ Enlisted/Caucasian /Black 7 0 — — — �TABLE A-5 STATISTICAL DESCRIPTION OF THE MATCHING DIST IN MONTHS - 1 - 2 «. "^ - 4 « 5 - 6 - 7 •• ft - 9 -10 -11 -12 -13 -14 -15 -16 -17 -18 -19 -20 -21 -22 -23 -24 -25 -26 -27 -28 -29 -30 -31 -32 -33 -34 -35 -36 -37 -38 -39 -40 -41 -42 -43 -44 -45 -46 -47 -48 -49 -50 -51 -52 -53 -54 -55 -56 -57 -58 -59 -60 COUNT 847 231 114 92 88 41 33 28 27 10 18 17 9 23 11 20 16 4 6 11 10 4 4 4 3 6 2 6 2 2 2 1 6 3 5 4 3 4 2 3 5 4 2 6 9 3 0 0 3 4 2 0 4 6 3 4 3 5 5 3 DIST IN MONTHS 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 COUNT 828 231 121 91 67 47 39 22 23 21 18 22 18 11 8 15 11 6 6 3 9 6 13 5 4 7 8 8 9 4 5 5 2 3 7 3 3 11 5 5 2 6 2 9 4 6 4 3 1 4 2 0 4 2 3 0 2 3 1 4 PROCESS 0 1 2 3 4 5 6 7 6 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 COUNT % 8612 1675 462 235 183 ABSOLUTE DIST IN MONTHS 70.6 13.7 n 3.8 1.9 1.5 1.3 0.7 0.6 0,4 0.4 0.3 0.3 39 27 0.3 15$ 88 $0 50 31 36 34 19 35 27 10 12 14 19 10 17 9 7 13 10 14 11 6 7 6 8 6 12 7 6 1? 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 7 8 7 10 4 IB 13 9 4 3 4 8 4 0 8 8 6 4 5 8 6 7 131 0.2 0.3 0.2 0.3 0,2 0.1 0.1 o.i 0.2 0.1 0. 0. 0. 0. 0. 0. 0.1 0.0 0.1 0.0 0.1 o.o 0. 0. 0.0 0. 0. 0. 0. 0. 0.0 0.1 0.1 0.1 0.0 0.0 0.0 0.) 0.0 0.0 0.1 0.1 0.0 0.0 0.0 0.1 0.0 0.1 CUMULATIVE TOTAL 8612 10287 10749 10984 11167 11322 11410 11482 11532 11582 11613 11649 11688 11715 11749 11768 11803 11830 11840 11852 11866 11885 11895 11912 11921 11928 11941 11951 11965 11976 11982 11989 11995 12003 12009 12021 12026 12034 12049 12056 12064 12071 12081 12085 12100 12113 12122 12126 12129 12133 12141 1214S 12143 12153 12161 12V67 12171 12176 12184 12190 12197 70.6 64.3 88,1 90.1 91.6 92.8 93,5 94,1 94.5 95.0 95.2 95.5 95.8 96.0 96.3 96.5 96.8 97,0 97.1 97.2 $7.3 97.4 97.5 97.7 97.7 0.8 97.9 98.0 98.1 $8.2 $8.2 98.3 98.3 96.4 §1.5 98.6 98.6 98.7 99,8 99.8 99.9 99.0 9,9.0 99! 2 99.3 99.4 99.4 99.4 99.5 0.5 99.6 99.6 99.6 99.7 99.8 99.8 99.8 99.9 99.9 100,0 �Table A-6 SPECIFIC RULES FOR ENTRY INTO THE MORBIDITY STUDY RULES CIRCUMSTANCES RANCH HANDER (RH) DIES FOLLOWING INITIAL DATA COLLECTION CONTROL FOLLOWED THROUGHOUT AND REPLACED AS NECESSARY RH DIES OF COMBAT CAUSE MEDICAL RECORDS REVIEWED; NO CONTROL SET.FORMED RH DIES OF NONCOMBAT CAUSE PRIOR TO INITIAL DATA COLLECTION 1ST ORDER SURROGATE INTERVIEW ACCOMPLISHED; CONTROL SELECTED AND FOLLOWED THROUGHOUT; AS NECESSARY RH NONCOMPLIANT FOR BASELINE QUESTIONNAIRE AND PHYSICAL CONTROL FOLLOWED THROUGHOUT THE STUDY; REPLACED AS NECESSARY RH COMPLIANT FOR QUESTIONNAIRE; NONCOMPLIANT FOR BASELINE PHYSICAL EXAMINATION CONTROL FOLLOWED THROUGHOUT THE STUDY; REPLACED AS NECESSARY RH NONCOMPLIANT DURING FOLLOWUP CONTROL FOLLOWED THOUGHOUT THE STUDY; REPLACED AS NECESSARY CONTROL DIES FOLLOWING INITIAL DATA COLLECTION NOT REPLACED IN THE PROSPECTIVE STUDY OF MORBIDITY CONTROL DIES OF COMBAT CAUSE MEDICAL RECORDS REVIEWED; EXCLUDED FROM FURTHER STUDY CONTROL DIES OF NONCOMBAT CAUSE PRIOR TO INITAL DATA COLLECTION INCLUDED IN MORTALITY AND RETROSPECTIVE MORBIDITY STUDIES; SURROGATE INTERVIEW ACCOMPLISHED. NOT INCLUDED IN PROSPECTIVE MORBIDITY STUDY AND REPLACED BY A LIVING COMPLIANT CONTROL. CONTROL NONCOMPLIANT FOR BASELINE PHYSICAL EXAMINATION CONTROL FOLLOWED THROUGHOUT STUDY REPLACE AS NECESSARY CONTROL NONCOMPLIANT DURING FOLLOWUP CONTROL FOLLOWED THROUGHOUT STUDY REPLACE AS NECESSARY NONCOMPLIANT CONTROL RETURNS TO STUDY BOTH PRIMARY AND REPLACEMENT CONTROLS WILL BE CONTINUED IN STUDY 132 �Table A-7 SCHEDULE AND MODE OF CONTACTS WITH STUDY SUBJECTS STUDY PHASE CONTACT MADE Morbidity Study Introductory Letters Morbidity Study Comprehensive Questionnaire Oct .81 -Mar 82 Baseline Physical Exam Dec 81-Sep 82 Adaptive Questionnaire Adaptive Physical Examination Oct 83-Mar 84 Dec 84-Jun 85 Adaptive Questionnaire Adaptive Physical Exarnlnation Oct 86-Mar 87 Dec 86-Jun 87 Adaptive Questionnaire Adaptive Physical Examination Oct 91-Mar 92 Dec 91-Juri 92 Adaptive Questionnaire Adaptive Physical Examination Oct 96-Mar 97 Dec 96-Jun 97 Adaptive Questionnaire Adaptive Physical Examination Oct 2001-Mar 2002 Dec 2001-Jun 2002 Follow-up Study 133 Oct 81 �Table A-8 MONTE CARLO SIMULATION PROGRAM 210 220 230 240 250 260 270 280 290 300 310 320 330 340 10 DIM C(10,3) 20 DIM A(10,3) 30 P2=.25 40 D1-.45 50 M=0 60 N=0 70 FOR 1=1 TO 10 80 FOR 0=1 TO 3 90 A(I,J)=0 100 C(I,JH 110 NEXT J 120 NEXT I 130 M=M+1 140 PRINT M 150 IF M=1001 THEN 330 160 F=l 170 1=1 180 J=l 190 C(I,J)=RND(1) 200 X=P2+F*D1 IF C(IJ) > X THEN 270 1=1+1: F=l IF I > 10 THEN 250 GOTO 190 N=N+1 GOTO 130 A(IJJ)=A(I,J)+1 J=J+1 IF J>3 THEN 320 F=0 GOTO 190 GOTO 130 STOP SELECT PRINT 215 350 FOR 1=1 TO 10 360 370 380 390 400 410 420 PRINT A(I,1), A(I,2), NEXT I PRINT PRINT "N(l)", N(l) PRINT "N(2)", N(2) PRINT "N(3)M, N(3) END GLOSSARY I = Control individual index J = Examination number index A(I,J) = Attendance array = number of times the ith control was used for the jth examination C(I,J) = Testing variable array N = number of times no control was available M = number of matches attempted of = preselected probabilities. Pj = Dl + P2 and Pg = P2 P2 RND = Random DIM = Dimension F = Flag 134 �Figure A-l 2, 3, 7, 8-TETRACHLORODIBENZp-p-DIOXIN (TCDD) • WOlECUkAR WEIGHT • MELWN& POINT g 321.8935 303-305 °C • DECOMPOSITION POH*T 980-lr0000C ORittQ-IWCHLOiOffENZENE 1.40 CHtW?OBENZENE 0.72 HERBICIDE o.58 CttL(MOFORM ACETONE METOANOL WATER 0.37 ft 11 Q.m 2*1Q~7 �l\-2 ESTIMATED IDENTIFICATION/PARTICIPATION OF THE RANCH HAND POPULATION RESPONSE ESTIMATE RANCH HAND POPULATION ESTIMATED NUMBER OF PARTICIPANTS 1200 ^-^^^-^_ CO en UNACCOUNTABLE < 1% ACCOUNTABLE _-^— — -—-' NON-PARTICIPANTS QUESTIONNAIRE DEAD/MORIBUND 10% PARTICIPANTS UNWILLING 25% ' ' ,. • BASELINE EXAM NON-PARTICIPANTS 40% PARTICIPANTS — 1 „ • NON-PARTICIPANTS 1st FOLLOW-UP 20% EXAM PARTICIPANTS . — 2nd FOLLOW-UP NON-PARTICIPANTS EXAM PARTICIPANTS 20% 99% 1188 65% 772 60% 463 80% 371 80% 297 �S - i j u r e A-3 STUDY DESIGN FORMAT MORTALITY STUDY 1:5, RETROSPECTIVE MORBIDITY STUDY 1:1, Rr l Ci 1 — t " I* 1 -1 lj|,2 Ci T Cl,4 f» - 1*1,5 * R . 2 L,,,. . + -i > •4- *?o < . C2 3 C° 4 /*-> tto '•7 R * cV,- .—>• nc " •>,£ -1 C-? 3-!J • "OiJ 4- T C-3 A /*, "3^9 * ~ 1 • P , Cj 5 V4,^ Ci 3 - nc CA A CAT, I/ 4jU !._!_ I * C4,8 1 ] 1 l 1962 1965 1970 . SPRAY I-*-OPERATIONS R = RANCH HAND c = CONTROL l t l f 1 l 1 i i 1 , 1381 1984 1986 1996 1991 BASELINE QUEST. | ADAPTIVE QUESTS. AND EXAMS AND EXAM nc = NONCOMPLIANT t = DECEASED L_L_L_ 2001 * = 5 OTHER REPLACEMENT CONTROLS �XVI. Examiner's Handbook A. General Instructions Project RANCH HAND II is a multiyear effort to determine whether or not C-123 aircrew members who were engaged in the aerial spraying of herbicides in Vietnam have developed significant adverse health effects from that exposure. Detailed surveys of the world's literature have been used in designing the history questionnaires, physical examination protocol, and laboratory procedures. This phase of Project RANCH HAND II involves a cross .sectional study of the subject's health at the time of examination. It is important that examiners remain unaware of the subject's status as a RANCH HAND participant or as a control subject. The physician examiner is tasked to examine and objectively record his findings. The examining physician is not, and cannot be expected to arrive at any definitive diagnosis as the full history and laboratory results will not be available to him. Medical history, laboratory results and physical examination findings will be evaluated by an independent diagnostician employed by the contractor. This diagnostician will formulate diagnoses and differential diagnoses, if appropriate. Additional procedures to treat or evaluate emergency or urgent medical conditions will be directed only by this physician. In addition, he will present a detailed analysis and debreifing to the study subject and provide a copy of the analysis to the subject's personal physician, if so requested. The physicians performing examinations fpr Project RANCH HAND II should be aware that the report of examination will become a permanent record. This report will be referred to not only in the near future as the cross sectional study is analyzed, but also at the time of the next review of the subject in the follow-up phases of Project RANCH HAND. These examinations will define the health status of the subjects at a point in time, and will establish the presence or absence of abnormal physical findings. After statistical review of the study groups, these findings may permit definition of a chronic effect due to exposure. An inaccurate examination may lead to falacious study results in two ways: a presumed syndrome may be defined which does not in fact exist, or a syndrome which in fact exists may not be defined with enough validity to warrant further actions. The examining physician is responsible for recording a complete and detailed report of the physical examination. In this role, the examining physician is tasked with collecting evidence of the presence or absence of physical signs of abnormality only. TheTformulation of diagnostic impressions by individual examiners is not requested nor desired. All items on the physical examination report form must be completed. It is imperative that the physician make such additional remarks as may be required to adequately describe existing physical and mental impairments. Since clinical endpoints have not been well defined following chronic exposure to Herbicide Orange, the examining physician and the diagnostician must not definitively ascribe abnormalities to herbicide exposure during the course of the examination or during the patient's debriefing. If, during the examination, the physician 138 �discovers evidence of acute serious illness requiring immediate treatment, the normal emergency or urgent care procedures of the medical facility would apply. Such care will be supplied at Air Force expense. If during the examination, there is evidence of illness requiring non-emergency medical attention, the diagnostician should inform the subject and offer to forward or have forwarded pertinent information to the subject's physician. A clear record of any such advice and treatment should be recorded. The ultimate value of the RANCH HAND II Study will lie 1n the collection of complete, accurate and, whenever possible, quantitative data permitting the most stringent arid ppwerful statistical analysis. For that reason, the physical examination protocol requires exact measurements in many Instances, and the use of defined meanings of semiquantitative indicators in other places, B. Conduct of the Examination (1) Upon arrival at the examining facility, the subject should be briefed by the on-site monitor on the appolntjjieflts which have been arranged, their times, and locations. (2) Collation and: forwarding of 0xam|nat1pn rejiiltft The monitor will complete a checklist fpr each study subject and review all medical information for quality and' completeness before forwarding to USAFSAM/EK, Brooks AFB, TX 7B235." 139 �C. ..Examination. Format_ PHYSICAL E X A M I N A T I O N SECTION 1. G E N E R A L A P P E A R A N C E . £3 Same As a . Appearance/Stated Age '/*y Younger Than £701der Than bi £7 Well-nourished £7 obese £7 Under-nourished £7 Older Than C. Appearance of illness or distress f~7 Yes £7 NO d- Hair Distribution /~7 Normal f~7 Abnormal e. Temperature SPECIFY: 2. Mf I « H T cm i 3. PULSE H A T E W E I G H T ;-lMdr..«.d) REGULAR: !_JYE5 SITTING BLOOD PRESSURE RfOHT ARM A T H E A R T L E V t L kg Describe any irregularities. [~J NO a. Irregular £^7" b. Irregularly irregular f~J c. VPBs per minute 4, EYE GROUNDS [~] NORMAL [~"; ABNORMAL £7 A-V nicking" £7 f light reflex /~~J Arteriolar spasm J. ARCUS SENILIS 6. CNT T<1[7J PRESENT f" j NORMAL Describe any vascular lesions, hemorrhages, exudates, £7 Hemorrhage*! p«pi»ed«n.. f~7 Exudates £7 Papilledema £7 Disk Pallor £J /• Cupping Q A8S«NT ^3. T~] ABNORMAL Abnormal Ocular Pigmentation /~7 Yes ^7 No Describe any abnonnality. Tympanic membranes intact £7 Yes £7 No Nasal ulcerations £7 No £7 Yes R £7 L £T 7. NECK (F.,p.ci,iir ihrntld timnd) '_J NORMAL !__• ABNORMAL, Describe any abnormality. Thyroid gland palpable £7 £7 Parotid gland enlargement Enlarged £*^ £7 R £7 L Nodules /~7 Tenderness 8. T H O B A X A N D L U N G S £7 Carotid pulses [~; NORMAL /™7 Asymmetrical expans'ion £7 Hyperresonance /"7 Dullness 9, H E A R T ' ~ ' NORMAL [ Q] ABNORMAL £7 Wheezes /~7 Rales 1 ABNORMAL Describe anv abnormality, especially basilar rales. Circumference at nipple level Expiration cm Inspiration cm Describe any enlargement irregularity of rate, murmur?;, or t h n l l s . Displacement of apical impulse £7 No £7 Yes Precordial thrust £7 No £7 Heart sounds normal £J Yes £J No £7Sl £JS2 £7S3 £734 Yes (Continued in Item 10 on Reverse) 10. ABDOMEN { ] NORMAL /~7 Heptomegaly ' cm Liver Span /~~7 Splenomegaly II. '-XTREMITIFS ;""! NORMAL ' ~j ] ABMOtMAL Deecribe any *«normality Vn«i special attention to the £7 Other mass - »pi««> •»<< liver. Record waist measurement Specify: on attached form. f~7 Tenderness >leen /"7 Other, specify: rj Liver n S£ Describe a n y ederna or signs of vascular insufficiency. \ ] ABNORMAL £7 Absence, specify: £7 Edema £7 Pitting /~7 Non-pitting £7 Loss of hair on toes £72 £7L £7 Clubbing of nails £7 Varicosities 140 �PHYSICAL EXAMINATION 56CTIOM io AM XL' PULSSS 6IMIN, H»D|*lFEMOftAL POPLITEAL OOKSALIS I}. SKIN i I NORMAL fndiS^ts ty|5S! and loeatidn of lesions on the / / OormatQgf'aphia /~7 Comedones /~7 Acneiforirt lesions f~7 Acneiform scars' /~7 Depigmentation C7 Inclusion cysts C3. Cutis Rhofflboidalis f k'ofatosis Futt-PaCe _....,.,. . p^'dfitfe phQtOS .«Mll. '.'-/ffiV. A7 Muscle - Specify: £7 weakness £7 Tenderness / Abnormal Consistency 7 £7 Atrophy tilt Inguinal hernia ,/yR Testes Absent Enlaorged /~7R /7 /^ ^ ^ Hemorrhoids £7 Prdstatic AtrO^hifc /^ effi 16. occipftAt, *7 Enlarged 17 7'^ERvo'Js' T?eri4e:r tem Pu Did OF ^_fiA» s..; itx». rrtass Confluent sVglffiM -"SEE ATTAfiMb '?!&" (Continued from ftectal �CLINICAL RECORD NEUROLOGICAL EXAMINATION HEAD AND NECK - Normal to Palpations/Inspection £JY £JN Specify Scar £7 Asymmetry £7 Carotid Bruit £7No £7R £7L Neck Range of Motion £7 Normal or Decreased to £7 Left Depression £7 £7 Right £7 Forward £7 Backward TRUNK MOTOR SYSTEM - Handedness Right £7 Left £7 Gait £7 Normal or £7 Broad Based £7 Ataxic £7Small Stepped £70ther-Specify Associated Movements £7An)1 Swing £7Normal or Abnormal £7R £JL Muscle Status (strength, tone, volume, tenderness, fibrillations) Bulk £7 Normal £7Abnormal Tone Upper Extremities £7Normal or £7Increased £7Decreased £7Right £7Left Lower Extremities £7Normal or /"/Increased £7Decreased£7Right £7Left Strength - Distal wrist extensors £7Normal £7Decreased Ankle/Toe Dors/Flexors £7Normal £7Decreased £JR £7L Proximal Deltoids £7Normal £7Pecreased £7& Hip Flexors £7Normal £7Decreased £7L £7R £7L Abnormal Movements (tremors, tics, choreas, etc.) Fasiculations £7N° Tenderness £7No £7Yes (1~^+) Tremor £7No /^JYes - Specify Upper Extremity £7R £7L>£7Resting : £7Essential Right Foot (c) £7Negative (Normal) Left Foot NonequiHbratory (F to N; F to F; H to K) Finger-to-nose-to-finger Normal £7Abnormal £7Right £7Left £7Both Knee-Shin £7Normal £7Abnormal"^£7Right £7Left /JBoth Succession Movements (including check, rebound, posture-holding) If indicated, check £7Normal £7Abnormal £JR £7R £ Rapidly alternative movements £7Normal Skilled Acts (a) Handwriting. (b) £7Intention tner Lower Extremity £7 R'£7y/I70 Coordination (a) Equilibratory - Eyes Open Eyes Closed - Romberg £7Positive (Abnormal) (b) £7Yes H-4-i-) If indicated, £7Normal ^Abnormal £7R £7L £7Botl1 £7Abnormal Speech (articulation, aphasia, agnosia) Grossly £7Normal £7Abnormal - Specify Dysarthria £7 Aphasia £7 142 �Reflexes (0-absent; 1-sluggtsh; 2-active; 1 . 3-very active; 4-translent clonus; 5-sustained clonus) R L R L Other L Abnormal L Deep ;R Deep : R. Babinskt Patellar Biceps Triceps Cremasteric Achilles Remarks MENINGEAL IRRITATION Straight Leg Raising ^Normal £7AbnormaT £7R £Jl NERVE STATUS (tenderness, tumors, etc.) SENSORY SYSTEM (tactile, pain, vibration, position. If positive sensory signs are present, summarize below and indicate details on Anatomical Figure, Std. Form 53T) Light Touch £7Normal £7Abnormal . , __,. . ,—,., ,, /Map on AnatpmlcaT Figure); n. Pin n Prick £7Normal £7Abnormal v ^ T ..T 3 -/ . Vibration (at ankle, 128 hz tuning fork:): ^NopnifT QAbnormal £3* Norma1 Position (Great toe): £7 Abnorma:1 £7 CRANIAL NERVES £7Absent I R Smell L II Smell £7Present Fundus R Normal r^Exudats [_ £7 Absent Abnormal £7 Disk. Pallor/atrophy i T1 edema £7Hemorrhag:e Fundus L Normal £7 Abnormal £7 Disk ., £7Exuc!ate £7 Papi 11 edema £7Hemorrhage Fields (to confrontation) Right £7Normal £7Abnormal I I Monnal £7 I l £7Abnorrnal: Left ^Abnormal - Specify Pupils-Size (mm) Equal £7 Unequal /~7 Difference mm Shape, position Round £7_ Other ff rjK n\. Light, Reaction Nprmal^_7 Abnormal £j £JK Position of Eyeballs Movements R Nystagmus Rotary rj (Draw position) L Horizontal £7 143 Vertical £7^ �XI Ptosis R£7 L £7 V Motor R Clench Jaw - Symmetric £7 Deviated £7 Sensory R Normal £7 Abnormal £7 V]£7 R V] L Normal £J Abnormal £7 V-| Corneal Reflex R L VII Motor R Normal smile £7Yes £JNo L Normal smile £7Yes £7No R£7 L£J V2£7 Palpebral Fissure £7Yes £7No Pa lPebfal Fissure £7Yes £7No IX Palate and Uvula X Movement Normal £7 Deviation to £7R £7L Palatal Reflex R £JNormal /^Abnormal XII • L ^Normal- /"/Abnormal Tongue-Protruded-Central £7 R £7 L £7 Atrophy £7No £7Yes MENTAL STATUS (alert, clear, cooperative, etc.) Gross abnormalities: £7No £7Yes - Specify 144 �DIAGNOSTIC SUMMARY SYNOPSIS OF POSITIVE FINDINGS' Medical History: Physical Examination: General Dermatologic Neurological Psychological Laboratory Results: Diagnosis: Differential Diagnosis, if applicable: Date Signature of Diagnostician 145 �D. Special Procedures (1) Nerve Conduct1 on Velocities (a) These studies have been determined to be an important parameter in long-term follow-up studies of persons thought to have been exposed to Herbicide Orange components. (b) The Nerve Conduction Velocities should be performed by a physician or by a specialty qualified technician under the supervision of a physician trained in neurophysiological methods. (c) Specific NCVs (See form included in F. Below) (1) Ulnar Nerve (one side only) (a) motor (above elbow, below elbow) (b) values recorded (i) distal latency (11.) NCV (2) Peroneal Nerve (one side only) (aj motor (b>) values recorded (i) distal latency (ii) NCV (1) Sural Nerve (one side only) (a) (b) (d) sensory: orthodromic values recorded: NCV Methods 146 �PERONEAL NERVE (_!) Active electrode is placed over the extensor digitorum brevis and reference over the little toe. Stimulating electrodes are placed over anterior distal leg 8 cm proximal to active electrode. Proximal site is distal to head of fibula. If entrapment is suspected at fibular head use a stimulation site of 12-18 cm more proximal to the fibular head. Anomalous innervation to the extensor digitorum brevis occurs in 1/5 patients (at least partially). Identified by inability to evoke a muscle action potential when stimulating at anterior ankle or a different shape (smaller) potential when stimulating here. This accessory nerve causes posterior to lateral malleolus so cathode should be placed here. NORMAL VALUES 49.9 ± 5.9 M/sec Distal latency: 4.5 ± .8 ms Proximal latencies have been determined for use in below the knee amputees, and neuromuscular diseases where extensor digitorum brevis action potential cannot be elicited. Active electrode is placed 1/2 way down leg over middle of dorsiflexor muscle group and stimulation at fibular head. NORMAL VALUES 5.5 - 7.2 ms (N = 217) 147 �SURAL NERVE (2) Active and recording electrodes are placed under lateral malleolus on lateral aspect of ankle. Sural nerve is stimulated as it pierces the gastrocnemius fascia just lateral to the midline of posterior distal calf, 10-18 cm proximal to active electrode, If leg is cold - a clue is prolonged latency of peroneal nerve - determine temperature. Subtract .1 ms (latency of activation) from the observed latency and divide into the distance. NORMAL VALUES (after LaFratta) (To Peak) Age 20-29 30-39 40-49 50-59 60 & over 44 38.80 36.70 37.20 35.00 ± ± ± ± ± 2.5 3.3 3.7 3.0 3.8 M/sec M/sec M/sec M/sec M/sec UJ > cc UJ 2 148 �ULNAR NERVE MOTOR CONDUCTION (3) Active erence radial trode. and 18 electrode is placed over center of abductor digiti quinti; refover proximal phalanx fifth digit. Stimulation (cathode) just to tendon of flexor carpi ulnaris 8 cm proximal to active elecProximal site of stimulation should be just below ulnar groove cm proximal to ulnar groove on medial aspect of humerus. N. B.: Elbow should be flexed to 70 degrees during procedure of stimulation and measurement to make more precise the actual length of ulnar nerve. More proximal stimulation sites include supraclavicular and C-8 root (see median nerve). SENSORY CONDUCTION Antidromic - ring electrodes over fifth digit separated by 4 cm. N.B. motor artifact may be interfering. Stimulate 14 cm proximal to active electrode at same site as motor stimulation. Orthodromic - reverse stimulation and recording electrodes. More proximal sites of stimulation may also be done. NORMAL VALUES 57 ± 62.7 56.7 54.9 4.7 M/sec ± 5.5 M/sec ± 4.2 M/sec ± 3.9 M/sec motor forearm segment - motor across elbow segment - sensory orthodromic (to peak) - sensory antidromic (to peak) Distal Latency: Motor: 3.7 ± .3 Sensory: 3.0 ± .25 Antidromic (peak) 3.0 ± .25 Orthodromic (peak) Muscle AP 8-20 mV Sensory AP 15-50 mV ADDENDUM For deep branch surface recording electrode should be over adductor pollicus (i.e. just medial to thenar eminence on palmar surface of web space). Additional latency is .5 ms. 149 �ACT REF \\ i ULNAH NERVE ! V4 REF 150 �(e) Disposition Forward the recorded results on the form attached to the examination package to the diagnostician. (2) Psychological Battery (a) General (1) This battery yields objective numerical data, and is well-standardized and clinically validated. The individual tests were chosen to insure an adequate analysis of one of the major alleged manifestations of herbicide toxicity. Each test either validates one of the other tests, or is considered to be a "definitive" test for analyis of a suspected psycho/ neuropathic effect. (2.) Compared to the general civilian population, characteristic response tendencies are observed on the MMPI and Cornell Index among active duty aircrewmen being evaluated in an aeromedical setting. It is also important to consider the effect that pending retirement has exerted on the reporting of medical history and symptomatology. This may also alter responses to psychological testing. (3) The battery requires approximately 5-1/2 to 6-3/4 hours to administer, depending on the speed of the examinee. An additional 1 to 2 hours of scoring and other clerical tasks will be required. Si rice test debriefing to clarify unusual performances, response biases, etc., is a crucial part of the psychologic evaluation, it is recommended that testing begin and be completed as early as possible during each examinee's stay at his respective evaluative facility. (b) Specific Tests (!) Nechsler Adult Intelligence Scale (MAIS): 60-75 minute individually-administered collection of verbal and nonverbal intellectual measures; also useful for clinical inferences when combined with the neuropsychological battery below. (2) Reading subtest of the Wide Range Achievement Test (WRAT): 10-minute individually-administered measure of word recognition ability. Important to rule-out reading inefficiency should response to personality instruments below be of questionable validity (e.g., high F Scale on MMPI). (3_) Halstead-Reitan Neuropsychological Test Battery: 150-180 minute individually-administered collection of brain behaviorrelationship measures for establishing the functional integrity of the cerebral hemispheres. The battery must include the following subtests: Category, Tactual performance, Speech-Sounds, Seashore Rhythm, Finger Tapping, Trail 151 �Making, and Grip Strengths. The Aphasia Screening and Sensory-Perceptual Exams are considered optional in view of their redundancy with the clinical neurologic exarn included in this project. Individualized test debriefing is conducted to clarify test performances in the WAIS and Neuropsychological Battery. (4) Three subtests of the Uechsler Memory. Scale I (HMS I): 30-minute individually-administered measures of immecRate and delayed recall of verbal and visual materials. The Logical Memory, Associate Learning and Visual Reproduction subtests are to be administered in the standard, immediate-recall fashion initially. After 30 minutes has elapsed, the examinee is asked, without prior alerting, to recall as much as he can about the Logical Memory and Visual Reproduction subtest stimuli. Standard scoring is used for both test-retest administrations. (5) Cornell Index (CI); 10-15 minute selfadministered and standardized neuropsychiatric symptom and complaint inventory, including items involving asthenia, depression, anxiety, fatigue, and GI symptoms in lay language. Endorsement of items are to be explored and clarified in testdebriefing. (6) Minnesota Multiphasic Personality Inventory (MMPI): 60 to 90 minute selT administered clinical psychiatric screening instrument; also capable of estimating response biases (e.g., "fake good," or "fake bad"). The shortened version of Form R (i.e., items 1 to 399) may be substituted for the 566-item Long Form. Standard scoring and Minnesota norms are to be used, with the possible exception of active duty examinees where USAFSAM aircrew norms may be applied. Clarification of profiles showing response biases, questionable validity, and/or unusual item endorsements will be conducted in individual test debriefing. (c) Examination Results Forward all test materials as scored with annotations, interpretations, and impressions to the diagnostician for inclusion in the subject's examination file. (d) Psychometric?; Special Instructions (1) For the Cornell Index and MMPI, each subject is instructed: (a) to answer carefully every item; and (b) that wherever applicable, his responses should reflect personal experiences, beliefs, preferences, etc., only for the time period between his combat tour in SEA and the date of testing. These instruments are not to be group administered and a reasonable amount of privacy should be provided. These instruments should not be completed at the subject's overnight quarters nor anywhere else outside the supervised confines of the evaluative facility. 152 �(2) If a subject's measured word recognition falls below the 6.5 Grade Level (Raw Score=40, Level H) according to the WRAT Reading subtest, the Cornell Index and MMPI are read aloud or administered via tape recording. In such cases, the subject retains the right to mark his answer sheet outside the view of the examiner or of others within hearing distance. (jB) All eleven subtests of the WAIS are administered, i.e., pro-rating of subtests is not allowed. The scoring of WAI$ subtest items, and the operations of summing, transferring, and finding Raw Scores, Scaled Scores, and Tabled IQ values are double-checked for accuracy by the Psychologist in charge (or his/her appointed representative) before the raw data are forwarded to the diagnostician. (4) Precautions similar to those in #3 above are exercised in the scoring and other clerical tasks associated with the Halstead-Reitan, WMS I, WRAT, Cornell, and MMPI. (5i) For the Halstead-Reftanj use as the preferred, or dominant, hand the one which the subject uses most in writing. If 1n doubt, administer a "Name Writing Test", where the subject Is simply asked to write his name in a normal manner as though sighing a personal check. The examiner measures the time for each hand to perform, (without alerting the subject to the timing), and assigns dominance to the quickest hand. (6) For the grip strength measure, report the average, 1n kilograms, of 3 brief, but maximum, squeetls of the dynamometer for the preferred and the non-preferred hands. Alternate hands between trials. (7) The Psychologist in charge will conduct a one-to-one test debriefing with" each subject to estimate the test-by-test and overall accuracy and validity of the test results. A prepared form is provided for this purpose, and should be filled out completely before forwarding, with the subject's raw data, to the diagnostician* If applicable, input from the testing technician utilized is encouraged. (3) Elect roca rd i og ram (a) A standard 12-lead scalar eleetrogram is required. If an arrhythmia is observed, a one minute rhythm strip 1s requested, in addition. The eleetrogram will be done following a minimum fast of four hours. Mounting; ' Mount the tracing in the usual manner of the laboratory for the recorded used. ( c ) Pis posit ion: Forward the mounted tracing and rhythm strip, if obtained, to the diagnostician. 153 �(d) Interpretation: The electrocardiograms will be interpreted by cardiologists at the examination center, and forwarded to USAFSAM/NG where physicians in the USAF Central ECG Library will compare the tracing to previous individual ECG records in the case of rated (pilot or navigator) subjects. (e) Disposition (USAF Central ECG Library); (1) Pilots and Navigators - The original tracings will be microfisched and added to the individual s permanent record. (2) Enlisted Subjects - The original tracings will be microfisched and a permanent record established for each individual. (4) Radiographic Exami nation (a) Examination A standard 14x17 in,, standing, roentgenogram in the PA position using small nipple markers will be accomplished. (b) Interpretation A board-certified radiologist at the examination center will interpret the roentgenogram and record the results and forward them to the diagnostician. (5) Pulmonary Function Studies Standard evaluation of vital volume at 1 second will be performed. (6) capacity and forced expiratory ""' • . Laboratory Procedures (a) General Instructions; First Day (I) The patient should report in the morning in a fasting state having had water only after midnight. The patient will have been requested to eat approximately 150 gms of carbohydrate each of the three preceding days and to consume no alcoholic beverages. Non-compliance is not a contraindication to drawing the blood specimens. However, a notation of extent of noncompliance should be made by the examining physician to aid in the interpretation of the results. (b) General Instructions; Second Day Serum hormone levels should be determined from specimens collected on the morning of the second day. Hormonal levels appear to oscillate rapidly in a random fashion. Distributions drift with time suggesting 154 �diurnal variations and some are affected by nonfasting state. Therefore, patients should be fasting prior to drawing blood for hormone analysis. (c) Specific Tests.to be Perforrned, on a11_ Participants (I) Hematocrit (2!) Hemoglobin (3) RBC Indices (4) While Blood Cell Count and Differential (5) Platelet Count (6) Erythrocyte Sedimentation Rate (7J Urinalysis (<3) Semen Analysis (Number, $ Abnormal, Volume) (9J Blood Urea Nitrogen (10) Fasting Plasma Glucose (jU) Creatinlne (J.2^) 2-hour Post Prandial! Plasma Glucose (_13) Differential Cortisol (0730 and 0930 hours) Q4) Cholesterol & HDL (15) Trlglycerides (JL6) Bilirubin, Total and Direct (17.) SGOT (18) SGPT Q9) GGTP Alkaline Phosphatase LDH Serum Protein Electrophoresls (23) CPK 155 �( 4 VDRL 2) •f.*' (25) • ' ' " ' ' ' ' LH FSH Testosterone (28) Thyroid Profile (RIA) (T 3 , T4, TSH.FTI) (29) Delta-aminolevulinic Acid .-> . (30) Urine Porphyrins (ID ," Hepatitis B antigen/antibodies (HBsAg, anti HBcAg, anti HBsAg) Prothrombin time • (33) * *• , . . ' . . Blood Alcohol ' ' • •'''••''. (d) Tests to be performed on selected subjects (1) Anti-nuclear Antibody on subjects with evidence of autoimmune disorders ;-, (2) Hepatitis A Anti gens /anti bodies for those with current or past liver disease Karyotyping for those fathering children with birth defects ~ (4) Skin photography and skin biopsy on subjects with suspected chloracne (5) For those whose medical history indicates an increase in infectious diseases (aj Immunoelectrophoresis (b^) Quantitative Immunoglobulin Determinations (6) To be performed on a randomly selected group of study subjects (a) Enumeration of B and T cells (b) Enumeration of Monocytes (c) B and T cell function tests 156 �(e) Rat i ona 1 e .for. 1 a borat ftry (I) studies on the toxicity of TCDD in animals have shown that the following organ systems are damaged: (a) Liver: Hepatic necrosis, Mver enzyme changes, •hypoprotelnemia, hypercho1esterd1em1a, hy pe rt r i g 1 y ce r 1 dertii a , (jb) Reticuloendothflial System: altered cellular immunltyT decreased lymphocyte; counts,. (c) leukopenia, pancytopenia."" Hemopoletic (d) Endocrine adrenal cortex, hypothyroTdisiti. (e) Renah Sy$tenii Systet; Thyiwfc IfropHy, Anemia, throiiibocytopenla, Hemorrhage lncr§a§6 |n blood urta andatrophy of nftrogen. (f) in addition, statistically significant increases in hepatocellular carcinomas (liver) and s4tJamd;Celtylar eareinomas of the lung were found. (2) Studies on the t0^|| effects of 1P00 In man hwe shown that the following ofgan §y§teffls are skin: Chloracne, hlrsutisffi. (b) Liver: PorpHyfia cutanea tarda,, levels of transamlnase and" of GGTP. Eftl a rpd, tender liver, hyperlipiderttia. (£) Renal i Hewof^aflc cystitis* foeal tis. (dj Neurornuscular Systetn: Asthenia, i*e., headache, apathy, fatigue, anorexia, weight loss* sl&ep disturbances, decreased learning ability, decreased memory, dyspepsia, sw&atirljj, muscle pain, Joint pain and sexual dysfunction. (ej Endocrine Systertl: (3) Based upon the repor^f-of toxic effects in animal and human exposures, the following organ panels ari* recommended: (a_) Heiiiopoietic (b_) Reticuloeridothelial �(cj Renal (d) Endocrine (e) Neuromuscular Hemopoietic screening should include: (aj Hematocrit (b) Hemoglobin (cj RBC indices (c[) Erythrocyte sedimentation rate (e) Platelet count (_f) Prothrombin time (5) Reticuloendothelial system: (a_) White blood cell count (b) Differential (c) Serum protein electrophonesis (d) Selective use of immunoelectrophoresis and quantitative immunoglobulin determination (e) (6J B cell and T cell counts and functions Hepatic screen: S60T SGPT (£) G6TP (d^) Bilirubin, Total and Direct (e) Alkaline phosphatase (f) LDH (£) Cholesterol 158 �(hi) HDL ( j Triglyceride j ( j Urine prophyrins j (kj Urine porphobilinogen (_]_) Hepatitis B antigens/antibodies (HB^Ag, anti1 HBCAG, anti HBsAg3) (7_) Renal screen: (a) Urinal ysis (b^) BUN (c_) Creatinine (8) Endocrine screen (a) Differential cortisol (0730 and 0930 hours) (b) Thyroid profile (RIA) (c) Fasting plasnif glucose Neuromuscular system: CPK Elucidation of sympoms of asthenia: (a) Testosterone ( ) FSH £ (11) The following tests should be pefprmed only as followup for abnormalities in the history or physical examination findings: (aj HAVAB (IgG and IgM) (b) ANA 159 �E. Forms Anatomical Figure (Anterior) Anatomical Figure (Posterior) Nerve Conduction Velocities Psychometric De-Briefing Form 160 �;AL RECORD ANATOMICAL FIGURE 161 �162 �NERVE CONDUCTION VELOCITIES SOCIAL S E C U R I T Y NUMBER GRADE NAME il.nsi, First. All C,ASg NR, :?A fr 0^" E X A M I N A T I O N MONTH DAY TEMP: DATE: £Z7L • Elbow 1. Ulnar (one side only) £ 7 Above ^ /**"7Below Nonnal Values for Laboratofy Latency / / /./ Distance I N.C.V. /___ I Stm. Curr. 2. I I / ms I mm I.I I m/s / / .../.. / mV /......LJ......-J Peroneal (one side only) /""'/R Normal Values for Laboratory Latency / / . / . / / ms /..,/,/,/,_ ,/ Distance / / / / mm /. /.... 7.... J N.C.V. I / / /./.../ m/s Stm. Curr. 3. I I I I. ../,/. / I m. V Sural (one side only) (If unobtainable, Median or Ulnar Sensdty recommend) / "/R Normal Values for Laboratory Latency / / Ld-—L ms /...../ . . y . ./ .. Distance / I I I m m N.C.V. / Stm. Curr. /.././ / / / m/s / / mi / / 163 LJ �Ranch Hand II: Psychometric De-Briefing Form _______„ R L Test Date EvaT FacTTity Handedness Subject: Name Psychologist/ De-Briefer : Title Name Degree Yes No Clin/Couns Cert/Lie Testing Technician: Name Same as above Degree Test/Experience (Yrs) jnstructions In the appropriate column below, indicate the test-by-test validity of the psychometric results based upon the Examiner's observations of the subject during testing and upon the Psychologist's evaluation of the data in test debriefing with the subject. Use the numbered factors below to indicate the reason(s) for questionable validity among any of the data. For datum thought to be of questionable validity, also provide an estimate of the subject's "true" score or result. Forward the completed form with the subject's raw data. Reasons for Questionable Validity 1. Poor reading comprehension 2. Fatigue 3. Neg attitude, angry, marginal cooperator 4. Careless, hurried responses 5. Examiner Error Test Score 6. Exaggeration of complaints ("fake bad") 7. Minimizing complaints ("fake good") 8. Disorganized personality (Psychotic) 9. Physically ill (flu, venipuncture effects, etc) 10. Other (Specify ) Valid Results WAIS VIQ PIQ FSIQ 2, WRAT Reading 3, Halstead-Reitan Category Test 164 Reason(s) for Questionably Valid Results Est of "True" Score/Result �Ranch Hand II: Test Score Psychometric De-Briefing Form Continued Valid Results Reason(s) for Questionably Valid Results Est of "True" Score/Result Tactual Performance Test Preferred Hand Non-Preferred Hand Both Hands Memory Localization Speech-Sounds Perception Seashore Rhythm Finger Tapping Preferred Hand Non-Preferred Hand Trail Making Test Part A Part B Grip Strengths Preferred Hand Non-Preferred Hand WMS I Logical Mem (immed) Visual Repro (immed) Associate Lrng Logical Mem (delayed) Visual Repro (delayed) 5. Cornell Index 6. MMPI (overall rating of protocol) WNL or ONL 165 �XVII. ANNEX 1 - EXPOSURE INDEX CONSTRUCTION When exposure concepts were Intlally discussed, the principal investigators were optimistic about the feasibility of developing an exposure estimate or index which was specific to the individual study subject. However, as the investigators became more familiar with the operational environment of the Vietnam War and the limitations of the personnel records system, it became obvious that a validated individual-specific exposure index could not be developed. This specific index was dependent on the availability of operational records containing individual flying time data and aircraft maintenance records containing the names of ground support crew members. Because this data was unobtainable, a less specific exposure concept was then developed. This index was to be base-specific rather than individual-specific, and is the index presented in the protocol in this technical report. However, further inquiry disappointingly showed once again that available data sources would not provide adequate information to support the construction of this index. The base-specific index relied upon records to provide a quantitative measurement of the number of missions and amount and type of herbicides sprayed by air crews from each base. This Index assumed that all personnel at a given base shared equally in the workload. Unfortunately, the "Herbs tapes" did not specify the base to which spray aircraft were assigned, and the military personnel records did not definitively specify the exact duty locations of all personnel. Thus, a still more generalized exposure concept was necessary. Although the more refined indices could not be validly applied, it was feasible to develop an exposure index for this study which can be validated, fulfills the requirements of the study design, and is fully supported by available data sources. A crude index can be developed and applied universally to all exposed subjects, regardless of their assigned duties in Vietnam. This index is based solely on the amount of dioxin disseminated throughout Vietnam each month from January 1962 through April 1970. The data to support this index are based on a comprehensive listing of herbicide missions, being developed by the Department of Defense, and estimates of the TCDD content of 2,4,5-T over time. These estimates are being developed and refined at USAFSAM at the present time. A refined exposure index for ground crew members is also feasible and is under development. This index builds on the crude index and takes the experience of ground crew members into account. It also assumes that each individual assigned to these duties in the Vietnam theater carried out his share of the workload in his specialty. This "experience factor" is constructed by dividing the total number of herbicide spray sorties flown during a subject's tour of duty by the number of individuals performing the subject's duties during the period of his tour. Similarly, a refined air crew index can be constructed. This index expands the concept of the ground crew index by including a factor reflecting the variable levels of exposure within the C-123 aircraft. Simulant studies to quantify these differences were conducted, and plans are underway to repeat these studies to revalidate the conclusions. 166 �Symbolic representations of these indices are shown below: Crude Exposure Index: WTT «-*L ( TCDD E l = sprayed in the / Vietnam Theater during) the 1th subject's tourl •u. *r Refined Ground Crew Exposure Index: GND Herbicide sorties performed in the Vietnam theater during the ltn subject's tour TCDD sprayed in the Vietnam theater during the 1th subject's tour • > Number of ground crew personnel (job specified) in the Vietnam theater I during the 1th subject's \ "our _J Refined Air Crew Exposure Index: /— AIR \ Herbicide sorties performed \ in the Vietnam theater during the 3*" subject's J tour H \TCDD sprayed in / I the Vietnam I {theater during V the 1th subject's /tour \ Number of airmen with subject's duties in the Vietnam theater during the ltn subject's tour ««-«/ V™, r X \Crew positioni <weight of the] /1th subject L. (total amount) X (experience) X (intensity) The data required to support these indices are either currently available or are in the final stages of development. These indices are feasible and will adequately support the analytic strategy of the study design. 1.67 �XVIII. ANNEX 2 - COMPARISON GROUP ^ELIGIBILITY A central element of epidemiologic research is study population ascertainment. Incomplete population ascertainment always carries with it the possibility of serious selection bias which cannot be corrected using statistical procedures. Complete ascertainment of the exposed and comparison populations occurred through a manual review of military personnel records from 1962-1964, combined with a computer tape generated by the Air Force Human Resources Laboratory (AFHRL). This computer tape was based on retrieval parameters identified to AFHRL by the United States Air Force School of Aerospace Medicine (USAFSAM) principal investigators. The retrieval process required computer searches of multiple Air Force Military Personnel Center tapes spanning the time period of January 1965 through December 1971. In November of 1980, AFHRL delivered to USAFSAM a tape that was thought to contain the total eligible study population. The study match was completed and the selected individuals were contacted to participate in the study. In December of 1981, Louis Harris and Associates, the questionnaire administration contractor, notified the USAFSAM investigators that several of the participants had reported no experience in Southeast Asia, suggesting that there had been overselection. Review of these participants' military personnel records clearly revealed that they were comparison subjects who had not had Southeast Asia experience. In order to maintain the integrity of the questionnaire implementation and the physical examination contract, it was necessary to implement a modification of the replacement strategy which had been originally designed for use with control subjects who refused to, participate in the study. It had been intended that the noncompliance questionnaire be given to both the replacement and the refusing subjects, and that they would be matched for equivalent health perception prior to implementing this strategy. However, the early requirement to replace these ineligible individuals did not allow the use of the noncompliant instrument. The eligibility of replacement candidates was verified and these valid subjects were entered into the study. Inappropriate subjects were informed of this selection error and excluded from further participation in the effort. Two hundred eleven inappropriate subjects had been interviewed, and 26 had been examined. This situation also necessitated an immediate manual review of the personnel records of all individuals for th.e comparison group. The review of records was completed in March of 1982 and the verification of this process was initiated. The objective of this quality control effort was to verify the eligibility of the comparison group by subsampling techniques and to insure that errors in excess of one percent ineligibility did not exist. The estimated error rate was found to be 0.00748% with confidence bounds of 0.00340% and 0.0312%. To further reduce this error rate, each replacement candidate's personnel records were re-evaluated prior to forwarding his name to the questionnaire contractor, thereby assuring that all replacements were absolutely eligible for the study. The overall review demonstrated that 18% of the 12,193 individuals in the original control population were erroneously included. These ineligible subjects were randomly distributed throughout the C1-C10 matrix. Two percent of this error was due to inaccurate data on the USAF personnel tape and 16% due to incorrect cohort selection specification and/or computer search implementation. All errors were in the direction of overselection, due to the inclusion of non-Southeast Asia C-130 units in the specifications. 168 �Following the removal of the ineligible subjects from the cohort matrix, the empty positions were then filled by valid comparison subjects with higher cohort numbers, thus constituting a leftward shift of the matrix. This process was reviewed by the subcommittee of the Advisory Committee on Special Studies Relating to the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants and members of one of the other peer review groups prior to implementation, and its use was found to be totally acceptable. Its use resulted in a reduction of the study from 1:10 to a 1:8 design. Monte Carlo studies using current physical examination compliance rates showed this collapse to have not significant impact on statistical power in the followup phase of the study. Although the shift-left process constituted an unplanned use of the replacement strategy, it permitted the continuation of both the questionnaire and physical examination contracts without disruption and with total validity. 169 �XIX. ANNEX 3 - SUPPLEMENTAL ANALYSES '*• ' ' " ' : • • • . - : • The study is of distinct benefit to the herbicide-exposed group since it may provide the individuals with an early warning of herbicide effects if they are occurring; or if no herbicide effects are uncovered, the study can provide some peace of mind by contributing to settlement of the public controversy. The study, however, is also of very significant benefit to unexposed individuals participating in the effort as comparison subjects. These additional returns occur because of the nature of the study design and the analytic flexibility inherent in that design. Except for the skin condition called chloracne, none of the disease entities that have been related to herbicide exposure are unique to that exposure. Processes such as peripheral neuropathy, teratogenesis, and carcinogenesis have been reported in laboratory studies with animals or in epidemiologic studies of herbicide; but these processes also occur somewhat commonly in general populations without herbicide exposure. Thus, to determine the occurrence of a true herbicide effect, this epidemiologic study is gathering data on other factors known or suspected to produce disease, and which could obscure herbicide effects. Among these potentially confounding factors are several military and civilian occupational exposures to chemical, physical, and biologic agents including: asbestos, x-ray or nuclear radiation, industrial chemicals, insecticides or pesticides, and prior infectious disease processes. By studying possible correlations between these factors and disease processes, benefits accrue to both the herbicide-exposed and unexposed subjects. Correlations between disease incidences and other potentially causative factors will be sought using statistical data-processing techniques such as multivariate regression or analysis of variance. This approach will identify herbicide effects in a fair and equitable manner as described in the protocol, but it will also provide additional medical data of significant direct interest in its own right. 170 �Glossary of Abbreviations ABBREVIATION AFSC ALK PHOS AMD AV-GAS BUN C-7 C-123 C-130 CBC CPK CSF Det 1 AMD DNA DOD 2,4-D ECG EPA FBS FSH G.I. GAO GGTP HDL Herbicide Orange Herbicide Pink Purple Green JP-4 LDH LD50 LH NCI MMPI PACER HO PACER IVY RANCH HAND DEFINITION Air Force Specialty Code Alkaline Phosphatase Aerospace Medical Division, Brooks AFB Texas supervises all medical research activities within the Air Force Systems Command Leaded Aviation Fuel (Reciprocating Engine) Blood Urea Nitrogen USAF Cargo Aircraft 2 engine, Propeller, Reciprocating USAF Cargo Aircraft, 2 engine, Propeller, Reciprocating USAF Cargo Aircraft, 4 engines, Turbo-Propeller Complete Blood Count Creatine Phosphoktnase CerebTOSpinal Fluid Onslte physical examination contract monitor Deoxyrlbonuclefc add Department of Defense 2,4-dlicftlorophenoxyacetic actd Electrocardiogram Eiwironmefttal Protection Agency Fasting Blood Sugar Fol1 tele Stlmu1 at1ng Hormone Gastrointestinal General Accounting Office Glutaryl-glutamic Transpeptidase High Density Lfpid Mixture of 2,,4-B and 2,,4,,5-T contaminated with TCDD Other 2,4,5-T/TCDD-conta1n1ng herbicides Jet Fuel Lactose Dehydrogenase (Median) Lethal Dose for 50% of Tested Animals Luteinlztng Hormone National Cancer Institute Minnesota Multiphasic Personality Inventory Code Name for the Herbicide Incineration Project Code Name for the Movement and Storage of Herbicides at Johnston Island USAF Organizational Code Name for the Defoliation Operations in Vietnam 171 �ABBREVIATION DEFINITION RBC RIA RVN SEA SGOT SGPT SMR SSS SYSTO TCDD TOY TLV 2,4,5-T USAF USAFSAM Red Blood Cell Radio-immune Assay Republic of Vietnam Southeast Asia Serum Glutamic Oxaloacetic Transaminase Serum Glutamic Pyruvic Transaminase Standardized Mortality Ratio Sensation Seeking Scale Systems Officer 2,3,7,8-tetrachl orodi benzo-p-di oxi n Temporary Duty Threshold Limit Value 2,4,5-trichlorophenoxyacetic acid United States Air Force United States Air Force School of Aerospace USSR VA VDRL/FTA WAIS WRAT ; Medicine Union of Soviet Socialist Republics Veterans Administration Serdlogical Tests for Syphilis Wechsler Adult Intelligence Scale Wide Range Achievement Test 172 �trr Special i rjjjCw iiia.f (1020 �USoF SCVOOL OF AEROSPACE MEDICINE AEROSPACE MEDSCAL DIVISION (AFSCJ BROOKS AFB IX 78235 PEN/ THIRD-CLASS SULK RATc MAIL POSTAGE & FEES PAID USAF PERMIT NO. G-l � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 058 Folder The folder containing the original item. 1570 Series The series number of the original item. Series III Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Lathrop, George D. Patricia M. Moynahan Richard A. Albanese William H. Wolfe Description An account of the resource <strong>Corporate Author: </strong>United States Air Force School of Aerospace Medicine, Aerospace Medical Division (AFSC), Brooks AFB, Texas Date A point or period of time associated with an event in the lifecycle of the resource 1982-12-01 Title A name given to the resource Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides: Study Protocol Subject The topic of the resource Air Force Health Study ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/6647a4ccc4bb3f04be3584b6842a41b3.pdf e50578ba488ff84f65b68f969f4f9a74 PDF Text Text Item ID Number 01557 Lathrop, George D. United States Air Force School of Aerospace Medicine, Report/Article TitlB Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides: Baseline Questionnaires Journal/Book Title Year 1982 Month/Day November Color CI NumDeroflniaQ.es 289 Descplpton Notes Wednesday, May 23, 2001 Page 1568 of 1608 �Report SAM-TR- 82-42 EPIDEMIOLOGIC INVESTIGATION OF HEALTH EFFECTS IN AIR FORCE PERSONNEL FOLLOWING EXPOSURE TO HERBICIDES: BASELINE QUESTIONNAIRES George D. Lathrop, Colonel, USAF, MC Patricia M. Moynahan, Colonel, USAF, NC Richard A. Albanese, M.D. William H. Wolfe, Lieutenant Colonel, USAF, MC November 1982 Initial Report for Period September 1981 — November 1982 Approved for public release; distribution unlimited. Prepared for: The Surgeon General United States Air Force Washington, D.C. 20314 USAF SCHOOL OF AEROSPACE MEDICINE Aerospace Medical Division (AFSC) Brooks Air Force Base, Texas 78235 �NOTICES This initial report was submitted by personnel of the Epidemiology Division and the Data Sciences Division, USAF School of Aerospace Medicine, Aerospace Medical Division, AFSC, Brooks Air Force Base, Texas, under job order 2767-00-01. When Government drawings, specifications, or other data are used for any purpose other than in connection with a definitely Government-related procurement, the United States Government incurs no responsibility or any obligation whatsoever. The fact that the Government may have formulated or in any way supplied the said drawings, specifications, or other data, is not to be regarded by implication, or otherwise in any manner construed,, as licensing the holder, or any other person or corporation; or as conveying any rights or permission to manufacture, use, or sell any patented invention that may 1n any way be related thereto. The Office of Public Affairs has reviewed this report, and it is releasable to the National Technical Information Service, where it will be available to the general public, including foreign nationals. This report has been reviewed and is approved for publication. 5 ATRICIA M. MO^AHAN, Colonel, USAF, NC Project Scientist ROY L. DEHART Colonel, USAF, MC Commander GEORGE D.TATHROP, Colonel, USAF, MC Supervisor �: UNCLASSIFIED SECURITY CLASSIFICATION "Of THIS PAGE (When Dale Entered) READ INSTRUCTIONS BEFORE COMPLETING FORM REPORT DOCUMENTATION PAGE 1. REPORT NUMBER •2. GOVT ACCESSION NO 3. RECIPIENT'S C A T A L O G NUMBER SAM-TR-32-42 ». TITLE (*** subtin*) EPIDEmCnrOinr INVESTIGATION OF HEALTH EFFECTS IN AIR FORCE PERSONNEL FOLLOWING EXPOSURE TO HERBICIDES: BASELINE QUESTIONNAIRES 5. TYPE OF REPORT & PERIOD COVERED Initial report Sen 1981-Nov 1982 6. PERFORMING O^G. REPORT NUMBER 3. CONTRACT OR G R A N T NUMBERS) George b. Lathrop, Colonel, USAF, MC Patricia M, Moynahan, Colonel, USAF, NC Richard A. Albanese. M.D. William H. Wolfe. Lieutenant Colonel. USAF, MC 9. PERFORMING ORGANIZATION NAME AND ADDRESS USAF School of Aerospace Medicine '(EKO) Aerospace Medical Division (AFSC) Brooks Air Force Base, Texas 78235 H. 10. PROGRAM ELEMENT, PROJECT. TASK AREA 4 WORK UNIT NUMBERS 65306F 2767-00-01 CONTROLLING OFFICE NAME AND ADDRESS 12. REPORT DATS November 1982 USAF School of Aerospace Medicine (EKO) Aerospace Medical Division (AFSC) rQnk'siin Air Force S.ranks' A j.,r FQt Base. Taxas 78235 . 13. NUMBER OF PAGES I*. . MONITORING AGENCY NAME 4 AOORESSf*/ diUerent titan Controlling Office) MONITORING AGE: 284 IS. SECURITY CLASS, (at this report) Unclassified l!«. OECLASSIPICATtON/DOWNGRADING SCHEDUUE is. DISTRIBUTION STATEMENT (at M* Approved for public release; distribution,unlimited. 17. DISTRIBUTION STATEMENT (oi ttiu tbetrlxt ontfred In Slock 30, It different from Report) ie. SUPPLEMENTARY NOTES 19. KEY WORDS (ConHnuv on reverse aide il neceiifty and identity by block number) Questionnaires Baseline Data Collection Herbicides Herbicide Orange Study Subject Questionnaire Spouse Questionnaire Dioxin Next-of-Kin Questionnaire Epidemiologic InvesMiniquestionnaire tigation Morbidity Phenoxy Herbicides 20. ABSTRACT (Continue on reverse aide II neceetery end Identity by block number) In 1979 the United States Air Force (USAF) made the commitment to Congress and to the White House to conduct an epidemiologic study of the possible health effects from chemical exposure in Air Force personnel who conducted aerial herbicide dissemination missions in Vietnam (Operation RANCH HAND). The purpose of this epidemiologic investigation is to determine whether long-term health effects exist and can be attributed to occupational 00 FORM 1 JAN 73 1473 EDITION OF 1 NOV SS IS OBSOLETE UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PAGE (Whm Data Entered) �UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PAOEfHTien Dmta Entantt) 20. ABSTRACT (continued) exposure to herbicides. The morbidity portion of this epidemiologic investigation includes a questionnaire and a physical examination. The questionnaires presented in this technical report are the field instruments used for the baseline data collection effort of 1981-1982. UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PAGE (When Dftt Enttrad) �QUESTIONNAIRE PREFACE In 1979 the United States Air Force (USAF) made the commitment to Congress and to the White House to conduct an epidemiologic study of the possible health effects from chemical exposure in Air Force personnel who conducted aerial herbicide dissemination missions in Vietnam (operation RANCH HAND). The purpose of this epidemiologic investigation is to determine whether longterm health effects exist and can be attributed to occupational exposure to herbicides. The study protocol for this effort incorporates a matched-cohort design placed in a nonconcurrent prospective setting. The study approach includes mortality, morbidity, and follow-up elements. The morbidity portion of the study consists of an in-home interview of the study subject and his spouse, as well as a unique physical examination of the study subject and his matched comparison. The choice of the in-home interviewing method, as well as refinement of the unique physical examination, was significantly aided by extensive peer review of the scientific study protocol. The peer review agencies included: The University of Texas School of Public Health, Houston, Texas, the USAF Scientific Advisory Board, the Armed Forces Epidemiologic Board, and the National Academy of Sciences. In 1980 the Science Panel of the Agent Orange Working Group was created as an additional peer review agency. This group, redesignated the Advisory Committee on Special Studies Relating to the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants* continues to monitor the conduct of this epidemiologic investigation. The questionnaires presented in this technical report are the field instruments used for the baseline data collection effort of 1981-1982. They are the result of a maturation process which began in 1979. In that year, contract number F41689-80-M-0174 was awarded to Research Statistics, Inc. of Houston, Texas. The purpose of this contract was to develop a Statement of Work (SOW) which would describe, in survey research terms, the requirement for the questionnaires necessary to support the epidemiologic study. Following refinement by the USAF principal investigators (PI'S) and management personnel, this SOW was used as the basis for a contract no. F41689-80-C-0059, with the National Opinion Research Center (NORC) of New York, New York. In this contract the USAF required the development of questionnaire instruments, procedures, forms, field manuals, training programs, and a pretest of developed instruments. At the core of the required questionnaires was a foundational questionnaire targeted at in-person administration to study subjects and their wives. It also had to be adaptable for use with the next of kin of deceased subjects. A brief noncompliance instrument was also required for use with those study subjects who declined participation. This miniquestionnaire was to contain questions concerning general health status and noncompliance factors. All questionnaires (study subject, spouse, proxy, and noncomplaint) were required to be adaptable to telephone as well as in-person administration methods. The NORC staff worked very closely with the USAF PI'S as well as their consultant staff to develop questionnaire instruments that would collect �quality health data that could be analyzed for health effects due to herbicides and that would capture data that could be lost through low compliance to the physical examination. Questions concerning specific health effects of phenoxy herbicides and dioxin were defined from the known human and animal effects found in the literature, as well as hypothetical effects found in biochemical and other biological systems. Additionally, veterans' complaints and the public's perception of the health effects of these chemicals were included. Wherever possible, portions of the questionnaire were taken from instruments NORC and other survey groups had previously field tested, thus maximizing instrument validity and reliability. Following an interviewer training program, NORC conducted an acceptability pretest in May 1981. Twenty-two study subjects, eighteen spouses, and two proxy subjects were interviewed. The questionnaires were found to be acceptable. Following modifications that resulted from the pretest the statement of work was developed for the implementation of the questionnaires. A competitive bidding process resulted in the award of the questionnaire implementation contract, No. F41689-81-C-0060, to Louis Harris and Associates, Inc. (LHA) of New York in September 1981. The purpose of this contract was to collect baseline data on the health, medical, demographic, social, and psychological conditions of the study population through the use of the developed questionnaires. Participation of the study subjects was to be on a completely voluntary basis. Letters from the Secretary of the Air Force and USAF Surgeon General were sent to each participant prior to the start of the interviewing process to encourage participation and to provide a brief overview of the general purpose and nature of the study. Louis Harris and Associates initially reviewed the NORC products and reformatted the instruments from a horizontal to a longitudinal format to better suit their interviewing style. The reformatting process allowed the addition of medical questions generated from recently published studies, as well as the inclusion of behavioral measurements not previously identified. Following the reformatting process, LHA trained 86 executive interviewers in a series of 11 training.sessions held throughout the United States and Europe. All LHA interviewers were required to have a minimum of one year prior experience in interviewing, with at least one experience in health data collection. Addresses of the study population were forwarded to LHA from the USAF and a locate algorithm was developed. During the approximately two-hour interview with the study subjects, the interviewers obtained written permission for government access to medical, hospital, personnel, and other records necessary to validate the questionnaire data. A Privacy Act Statement was signed as well. LHA was required to comply with the letter and intent of the Privacy Act of 1974 in collecting, storing, processing, and transferring personal and medical data. All questionnaire data were and continue to be treated with complete confidentiality. In September 1982, the LHA contract was extended to 15 November 1982 to permit the collection of baseline questionnaire data on the entire study population. 11 �ACKNOWLEDGMENTS The services of many staff members and consultants of the United States Air Force School of Aerospace Medicine are acknowledged. Special acknowledgement is made to the following co-investigators: Clarence F. Watson, Jr., M.D., M.P.H.; Alvin L. Young, B.S., M.S., Ph.D.; Joel E. Michalek, Ph.D.; Phelps P. Crump, Ph.D.; Richard C. McNee, M.S.; Alton J. Rahe, M.S.; Michael A. Sairi, M.D., M.P.H. & T.M.; Richie S. Dryden, M.D., M.P.H.; James A. Wright, M.D., M.P.H., who consulted and coordinated on questionnaire development. In addition, special acknowledgement is made to the United States Air Force School of Aerospace Medicine, Management and Air Training Command Procurement Personnel: Hugh F. Mulligan, Colonel, USAF, BSC, Chief, Program Acquisition Division; Charles T. Fuller, Major, USAF, Deputy, Program Acquisition Division; Donald F. Norville, Air Training Command Contracting Officer, Randolph AFB, TX, who coordinated the requirements for the questionnaire implementation contract. 111 ��CONTENTS CHAPTER I STUDY SUBJECT QUESTIONNAIRE Page I. INTRODUCTION 1-1 II. DEMOGRAPHIC 1-2 III. EMPLOYMENT HISTORY 1-4 IV. MARITAL/REPRODUCTIVE HISTORY 1-12 V. MEDICAL HISTORY 1-26 VI. SUBSTANCE USE HISTORY 1-40 VII. PSYCHOLOGICAL HISTORY 1-45 VIII. EXPOSURE TO TOXIC SUBSTANCES 1-77 IX. INCOME 1-83 X. SUPPLEMENTAL RECORDING BOOK XI. 1-85 ATTACHMENTS: 1. Introductory Letters: a. Secretary of the United States Air Force 1-135 b. Surgeon General United States Air Force 1-136 c. Louis Harris and Associates, Inc 1-140 2. Privacy Act Statement 1-141 3. Life Events Chart 1-142 4. Show Cards: a. Show Card "A": Academic Classification 1-143 b. Show Card "B": Industrial Classification 1-144 c. Show Card "C": Birth Control Techniques 1-145 d. Show Card "D": 1-146 Infertility History �Page e. Show Card "E", Anatomical Illustration 1-147 f. Show Card "F": Frequency Chart 1-148 g. Show Card "G": Chemical/Toxic Substances 1-149 h. Show Card "H": Protective Equipment/ Decontamination 1-150 i. Show Card "I": Income Table 1-151 5. Self-administered Form 1-152 6. Medical Provider Permission Form 1-154 7. Former Wife Introduction Letter 1-155 8. Interview Evaluation 1-156 9. Mailing Transmittal Form 1-157 CHAPTER II SPOUSE QUESTIONNAIRE I. INTRODUCTION 11-158 II. DEMOGRAPHIC 11-159 III. REPRODUCTIVE HISTORY 11-160 IV. SUBSTANCE USE HISTORY 11-169 SUPPLEMENTAL RECORDING BOOK 11-171 V. VI. ATTACHMENTS: 1. Introductory Letter, Former Wife 11-194 2. Privacy Act Statement 11-196 3. Show Cards: a. Show Card "C": Birth Control Techniques b. Show Card "D-l": 11-197 Infertility History 11-198 4. Medical Provider Permission Form 11-199 5. Interview Evaluation 11-200 6. Mailing Transmittal Form 11-201 vi �CHAPTER III NEXT OF KIN (PROXY) QUESTIONNAIRE I. INTRODUCTION 111-202 II. DEMOGRAPHIC III-203 III. EMPLOYMENT HISTORY 111-205 IV. MARITAL/REPRODUCTIVE HISTORY I11-212 V. MEDICAL HISTORY III-217 VI. SUBSTANCE USE HISTORY II1-228 VII. LEISURE ACTIVITIES III-230 VIII. MORTALITY DATA II1-231 IX. SUPPLEMENTAL RECORDING BOOK X. III-232 ATTACHMENTS: 1. Introductory Letter: Chief, Epidemiology Division, USAFSAM II1-266 2. Privacy Act Statement III-267 3. Life Events Chart III-268 4. Show Cards: a. Show Card "B": Industrial Classification III-269 b. Show Card "E": Anatomical Illustration IH-270 5. Medical Provider Permission Form II1-271 6. Interview Evaluation III-272 7. Mailing Transmittal Form 111-273 CHAPTER IV NON-COMPLIANT QUESTIONNAIRE I. INTRODUCTION IV-274 II. DEMOGRAPHIC IV-275 III. HEALTH IV-275 vii �IV. V. INCOME IV-276 PHYSICAL EXAMINATION IV-276 �CHAPTER I STUDY SUBJECT QUESTIONNAIRE The following Study Subject Questionnaire was used to collect baseline data for the Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicide Orange. This data was collected during 1981-1982. The questionnaire and supplemental recording book are the actual field instruments. They have been photocopyed and reduced for the purpose of this report. Additional field documents, such as show cards, are included as attachments to the questionnaire. In total, these documents demonstrate complete data collection methods for the Study Subject Questionnaire. Additional questions regarding reproductive experiences were added following the initial publication of the Study Subject Questionnaire. These questions are inserted where applicable in this instrument. Additional attachments include: Introductory Letters, Privacy Act Statement, Life Events Chart, Self-administered Sheet, Medical Provider Permission Form, Interview Evaluation, and Mailing Transmittal Form. The Study Subject Questionnaire, as used in the field, follows. �LOUIS HARRIS AND ASSOCIATES, INC. 630 Fifth Avenue New York, New York 10111 FOR OFFICE USE ONLY: O.M.B. NUMBER 0701-0033 Approval Expires 11/30/82 Case No. (12^17) Study No. 812039 Respondent #: (5-8) CONFIDENTIAL STUDY SUBJECT QUESTIONNAIRE This study is being conducted to collect information on the health of current and former Air Force personnel and their families. Since I will be asking you questions about your health, career, and personal history, we have prepared a Life Events Chart to help you remember when various events in your life occurred. The best way to use the Life Events Chart .is to first record when you were born in the Age Column, or how old you were in 1930, if you were born before 1930. Then, record your age at subsequent 5-year intervals in the Age Column. Next, note the year you graduated from high school and/or college in the next column. You can enter the year you joined the military in the next column. There are other columns to record any marriages or children you may have had, as well as other major events in your life. I will be asking you questions about each of these areas during the interview. If you will take a few moments to fill out Che Life Events Chart now, it will help you to recall dates and ages during the interview. First, I have a few background questions to ask you. 1. CARD 001 What is your date of birth? (WRITE IN DATE) DAY MONTH YEAR I I I I <22 ) (23) T (18) (19) 2. (20 ) (21) In what city and state were you born? I RECORD IN SUPPLEMENTARY RECORDING BOOK ON PAGE ll 3. What is your religious preference — religion, or no religion? Protestant Catholic is it Protestant, Catholic, Jewish, some other „ _-l ~-2 Jewish Other (SPECIFY) None. -5 What is the highest grade or year in high school that you completed? Less than 1 year of H.S...(j25( 1st year H.S. (9th Grade) 2nd year H.S. (10th Grade).... 3rd year H.S. (llth Grade).... 4th year H.S. (12th Grade) ~" -1 -2 -3 -A �812039 CARD 001 JHAND REgPONPENT CARD "A"I 5a. Please look at this card and tell, me yhich of these .regular academic school certificates, diplomas, or degrees you have obtained? .JMULTIP^E RECORD _BELOWT .(26( High school diploma. YEAR I -1 ' 3 ) (37) (6 YEAR High school equivalency diploma..... ( ( _... . -1 (38) ,2( (8 Associate of Arts (A.A.). Bachelor of Arts (B.A.) or Bachelor of Science (B.S.) Masters..... Doctorate. * * -1 (3Q( • ••• «1 ...-».(31 ( -1 wl (39) YEAR T T~" T 1 . 1 I (40) fair Ti YEAR ir ni ) (43) YfiAR T I I, . J T 1. T I YEAR I T -I .... I (47) Others (SPECIFY) YEAR -1 (1) YEAR (2) .(33( -1 YEAR (3) -1 YEAR No certificate, diploma, or degree (volunteered)....(35( •f 1 TEW"EACH t)ESBEE. PIPLOMA. OR CERTIFICATE.''ASjC Q . b 'j] Jb. In what year did you receive"your (CERTIFICATE/ ST17D1PLOHA/DEGREE)? (5 5T iRECORD AB"5vET �812039 CARD QQ6 6a. I am interested in training programs which prepared you for a major change in your occupation. First, I will ask about civilian job training programs. Besides the formal schooling you told me about, have you participated in any civilian job training programs that prepared you for a major change in your occupation? Yes.-.t1^ (ASK Q.6 b) Mo 13-1 A -1 -2 (SKIP TO Q.7) 1st Program b. 2nd Program For what kind of work was your f i r s t civilian training program preparing you? f. 3rd Program For what kind of work was your next civilian training program preparing you? j. For what kind of work was your next civilian training program preparing you? 05 ( (16( (16 ( (17( (17 ( (17 ( net (18( O8( (19( c. (16( (19( U9( In what month and year did you s t a r t this training? g. MONTH MONTH YEAR 1 1 I I 1 1 1 ' | l-l 1 1 (20) (21) (22) (23) d. In what month and year did you complete this training? I I e. 1 I I 1 l l I l l (20) (2H (22) (23) h. In what month and year did you complete this training? MONTH 1 1 -1 (ASK Q . 6 f ) L. I I l-l (24) (25) 1 1 MONTH YEAR 1 I I 1 1 1 l-l 1 1 (20) (21) (22) (23) In what month and year did you complete this training? YEAR 1 1 L. In what month and year did you start this training? 1 1 1 MONTH 1 1 1 1 Have you participated in any other civilian job training program that prepared you for a major change in your occupation? Yes.(28( ..j ( ASK Q.6j) 1 1 l-l m. 1 1 1 1 (26) (27) Have you participated in any other civilian job training program that prepared you for a major change in your occupation? —3 f <IK T P *m O 7 ^ .. YEAR 1 1 (24) (25) (26) (27) No. . Yes.(28( k. YEAR 1 I MONTH YEAR I I I I I l l I l l (24) (25) (26) (27) Have you participated in any other civilian job training program that prepared you for a major change in your occupation? In what month and year did you start this training? Ye«.(28( -l (fkeCOhP AbjHTfhMif fSitHINC PROGRAMS IN S.R.B, ON Pfit I*> -7 iOO TO 0.7) No 01 79-80 02 79-80 03 79-80 �CARD 007 812039 7a. Now, let's talk about military technical and specialized training programs that prepared you for a major change in your occupation. Besides the formal schooling (and the job training programs) you've told me about, have you participated in any military technical or specialized training programs that prepared you for a major change in your occupation? Yes...U2< (ASK Q.7b) No 13-14 -1 -2 (SKIP TO Q.8) 1st Program b. 2nd Program g. For what kind of work was your first military training program preparing you? 3rd Program For what kind of work was your next military training program preparing you? L. For what kind of work was your next military training program preparing you? ( 15( (15( (16( (16( (16( (17 ( (17 ( (17 ( (18( (18( (18( (19( (19( (19( ••: (IX c. What is the AFSC for that job? h. What is the AFSC for that job? (20 ( d. MONTH ! 1 l-l (21) ( 2 2) e. 1 1 1 1 ' j. M 1 1 l-l 1 1 <25) ( 6 2 ) (27) ( 8 2) Have you participated in any other military job training program that prepared you for a major change in your occupation? , -1 (ASK Q.7g) -2 (SKIP TO 0.8) 1 I k. MONTH 1 1 ' I I l-l (21) ( 2 2) YEAR 1 1 ( 3 (24) 2) (20 ( n. 1 1 In what month and year did you complete this training? YEAR 1 1 Yeg.(29( No In what month and year did you start this training? (3 (4 2) 2) MONTH f. 1 1 In what month and year did you complete this training? 1 1 i. YEAR 1 1 What is the AFSC for that job? (20 ( In what month and year did you start this training? 1 1 m. 1 1 o. MONTH YEAR 1 1 1 1 1 l l I l l (25) ( 6 2) (27) ( 8 2) Have you participated in any other military job training program that prepared you for a major change in your occupation? Yes.(29( No... -1 (ASK Q.7L) -2 (SKIP TO Q 8) In what month and year did you start this training? In what month and year did you complete this training? 1 I p. MONTH YEAR 1 I I 1 1 1 l-l 1 1 (21 ) (22 ) (23 ) (24 ) MONTH YEAR 1 M 1 1 l l I l l ( 5 (26) 2) (7 (8 2) 2) Have you participated in any other military job training program that prepared you for a major change in your occupation? 79-8(1 02 y<7-Kfi -1 (RECORD ADDI- No .,J .° Yes.(29( ING PROGRAMS IN S.R.B. ON PG. 15) -2 (GO TO Q 8) 0!) 7<I-RO �CARD 008 812039 8. Now I have some questions about working. Please tell me about all your jobs that lasted three months or longer since the first time you stopped going to school full time. Count changes of jobs for the same employer as separate jobs. Do not include jobs in the military. 13-U Second Job First Job 8a. In what month and year did you start your first job that lasted three months or longer? MONTH 1 1 In what month and year did you start your next job that lasted three months or longer? YEAR III 1 1 1 H 1 1 (15) (16) (17) (18) 8b. What (is/was) the name of your employer? IRECORD IN S.R.B. - PG i ] 8c. 9a. (Is/Was) the job fulltime or part-time? Full time..(19( Third Job 1 1 MONTH YEAR 1 1 1 1 1 1 l-l 1 1 (15) (16) (17) (18) lOa. In what month and year did you start your next job that lasted three months or longer? MONTH 1 1 YEAR 1 1 T i l 1 l-l 1 1 (15) (16) (f7) (16) 9b. What (is/was) the name of your employer? lOb. What (is/was) the name of your employer? 9c. 10c. (Is/Was) the job fulltime or part-time? IRECORD IN S.R.B. - PG i 1 (Is/Was) the job fulltime or part-time? -1 Full time..(19( IRECORD IN S.R.B. - PG i 1 Full time..(19( -1 -1 8d. What kind of business is that —• what (do/ did) they make or do there? 9d. What kind of business is that — what (do/ did) they make or do there? lOd. What kind of business is that — what (do/ did) they make or do there? 8e. What ally what your 9e. What ally what your lOe. What ally what your IRECORD (do/did) you actudo on the job -.(are/were) some of main duties? IRECORD'IN S.R.B. - PG 1 I (do/did) you actudo on the job — (are/were) some of main duties? (RECORD IN S.R.B. - PG i I (do/did) you actudo on the job — (are/were) some of main duties? IN S.R.B. - PG 1 1 [HAND RESPONDENT CARD "B"| (HAND RESPONDENT CARD ^B" 1 (HAND RESPONDENT CARD "B"l 8f. Please look at this card and tell me the number which best describes the kind of industry you (work/ worked) in. 9f. lOf. Please look at this card and tell me the number which best describes the kind of industry you (work/ worked) in. (WRITE IN NUMBER) (WRITE IN NUMBER) 8g. 1 I I 1 1 1 (20) (21) In what month and year did this job end? 9g. MONTH YEAR 1 ' 1 I I 1 1 1 1 l-l 1 1 (23) (24) (25) (26) Current job..(27( (SKIP TO -1 Q.Ha) Please look at this card and tell me the number which best describes the kind of industry you (work/ worked) in. I I In what month and year did this job end? 1 I MONTH YEAR 1 1 1 1 1 I l - l 1 1 (23) (24) (25) (26) Current job..(27( 8h. What was the main reason you stopped working on your job? 9h. I 1 I 1 (20) (21) -1 (SKIP TO Q.lAa) What was the main reason you stopped working on your job? <28( 01 79-80 1 1 I 1 I 1 (20 ) (21 ) lOg. In what month and year did this job end? 1 i MONTH 1 11 YEAR 1 1 r__i-i._i__JL (23) (2/, ) Current iob..(27( <2S ) (2f-> (SKIP TO -1 Q.lAa) lOh. What was the main reason you stopped working on your job? (28 ( (8 2( (29( (ASK 0.9a) (WRITE IN NUMBER) (2<> ( (29 ( (ASK Q.I la) (ASK 0. lOa) o? 79-HO ( H 7'i-HO �• ' . . . ' cARD 008 Fifth Job Fourth Job lla. In what month and year did you start your next job that lasted three months or longer? 8120.39 Sixtt) Job 12a. In what month and year did you start your next job that lasted three months or longer? 13a. In what month and year did you Start your next job that lasted three months or longer? 13-11 MONTH i 1 YEAR 1 1 1 1 H 05 ) ( 16) 1 I 1 I 1 1 ( 17) ( 18) MONTH 1 I I 1 .1-1 ( 15) ( 16) YEAR MONTH YEAR f 1 1 1 I I 1 1 1 1 I l l I l l (17) (IB) ( 17) ( 18) (15) (16) lib. What (is/was) the name of your employer? 12b. What (is/was) the name of your employer? [RECORD IN S.R.B. - PG 1 1 13b. What (is/was) the name of your employer? lie. (Is/Was) the job fulltime or part-time? 12c. (Is/Was) the job fulltime or part-time? 13c. (Is/Was) the job fulltime or part-time? Full time..( 19( Full time..(19( TRECORD IN S.R.B. - PG i 1 Full time..( 19( ...._-! Part time -2 IRECORD IN S.R.B. - PG i 1 -1 -1 lid. What kind of business is that — what (do/ did) they make or do there? 12d. What kind of business is that — what (do/ did) they make of do there? 13d. What kind of business is that — what (do/ did) they make or do there? lie. What ally what your 12e. What ally what your (do/did) you actudo on the job — (a re /were) some of main duties? 13e. What (do/did) you aetu• ally do on the job — what (are/were) some of your main duties? Please look at this card and tell me the number which best describes the kind of industry you (work/ worked) in. 13f. Please look at this card and tell me the number which best describes the kind of industry you (work/ worked) in. (do/did) you actudo on the job — (are/were) some of main duties? IRECORD IN S.R.B. - PG i | (RECORD IN S.R.B. - PG i 1 IRECORD IN S.R.B. - PG i 1 IHAND RESPONDENT CARD 1(B"T THAND RESPONDENT CARD ''B"| IHAND RESPONDENT CARD "B"| llf. Please look at this card and tell me the number which best describes the kind of industry you (work/ worked) in. 12f. (WRITE IN NUMBER) (WRITE IN NUMBER) I I 1 (20) 1 1 ( 21) llg. In what month and year did this job end? MONTH 1 1 I I 1 l-l. (23 5 (24 > I I 1 (25 ) ( 26) I 1 I 1 (20) (21) 12g. In what month and year did this job end? YEAR 1 1 I 1 1 1 MONTH YEAR 1 I I 1 1 1 H 1 1 (23 ) (24) C>5 ) ( 26) Current (SKIP TO job.. (27 ( -1 Q.14a) Current job..(2X llh. What was the main reason you stopped working on your job? 12h. What was the main reason you stopped working on your job? -1 (SKIP TO Q.14a) (28 ( (28 ( (29 < '7"~"""(AS$: 6Vi2a) " M; • VV~R?) (29 ( (ASK Q.lSa} Oc> 79"-8.(i (WRITE IN NUMBER) 1 1 <20) (£l) 13g. In what month and year did this job end? 1 1 MONTH 1 1 1 1 l-l 63 ) ( 24) Current job..(27( -1 YEAR 1 1 I . I ( 25) ( 26) (SKIP TO Q.14a) 13h. What was the main reason you stopped working on your job? <28( - $?[- ' (RECORD ADDITIONAL JOBS IS S.R.B. - PG 16 ATO 17) 06 Y'T-SO �CARD OU 812039 14a. During the past six months, did illness or injury keep you from work, not counting work around the house? Yes 02 (_. No _ Retired (vol.). -1 (ASK Q.Ub) _~2\(SKIP TO Q.15) lAb. . Altogether, how many days did illness or injury keep you from work during the past six months? (REFERS if) "WORKING DAYS" OW.Y) (WRITE IN NUMBER) ; __, „ days (1'S) (15) 14c. What illnesses or injuries caused you to miss work? I L S (22 124 (. (25( (26( (27( -128 T29 (30 (31( X32 (33( �812039 CARP 015 15. Now I am going to ask y<>u about your years in the mili tarya. —rr I 1 MONTH YEAR I I I 1 1 l-l 1 ( 14) (15 ) (lb ) (17) b. What branch of the military was that? Air Force. (18 ( -1 Ndvv -5 MONTH YEAR I 1 1 1 1 1 l-l 1 1 1 (14) (15) U6) (IT ) MONTH YEAR 1 I I 1 1 1 l-l 1 1 04 ) ( 15) (16) ( 17) 1 1 g. What branch of the mili- L. What branch of the military was that? tary was that? -2 Coast Guard... k. In what month and year did you next enter the Armed Forces? f . In what month and year did you next enter the Armed Forces? In what month and year did you first enter the Armed Forces? c. Were you discharged or separated from the (BRANCH OF SERVICE)? Air Force. ( 18( Coast Guard... Air Force. 08 ( -1 -5 h. Were you discharged or separated from the (BRANCH OF SERVICE)? Coast Guard... -1 ~ -5 m. Were you discharged or separated from the (BRANCH OF SERVICE)? Discharged/ Discharged/ Discharged/ separated. (19 ( -1 (ASK separated.( 1% -1 (ASK separated. (19( -1 (ASK Q.15d) Q.lSn) Still in Still in Still in (MILITARY) -2 (SKIP TO (MILITARY)..... -2 (SKIP TO (MILITARY)..... -2 (SKIP TO ~ Q.16) ~ . Q.16) Q.16) d. In what month and year were you discharged/ separated from the (BRANCH OF MILITARY)? MONTH YEAR 1 I I I 1 1 I I l-l 1 1 (20) (21 > <22) ^23) i. In what month and year were you discharged/ separated from the (BRANCH OF MILITARY)? 1 1 n. MONTH YEAR 1 I I 1 1 1 l-l 1 1 (20) (21) (22) (23) In what month and year were you discharged/ separated from the (BRANCH OF MILITARY)? MONTH 1 I I 1 1 l-l (20 ) (21 ) YEAR I I 1 1 (22 ) (23 ) e. Following your separation j. Following your separation o. Following your separation or discharge in (DATE IN or discharge in (DATE IN or discharge in (DATE IN "d"), did you reenter the "i"), did you reenter the "n"), did you reenter the Armed Forces? Armed Forces? Armed Forces? Yes..(24( -1 79^80 (ASK Q.15f) Yes..(24( -1 (ASK Q.15k) Yes..(24( -1 No.. . . — 2 (SKIP TO Q 16) 02 79-80 No --2 03 79-80 (RECORD ADDITIONAL SERVICE PERIODS IN S.R.E. PG 18) (SKIP TO Q 16) �CARD pie. 812039 16. I would like .to ask you the names of all the countries you have been stationed in while on active duty in the Armed Forces. First Country Second Country Third Country a. Starting with induction, g. What was the next country m. What was the next country in what country were you that you were stationed that you were stationed first stationed while on in for more than 90 days in for more than 90 days active duty? Include while on active duty? while on active duty? 12-13 temporary duties of (14-15) (14-15) greater than 90 days. (14-15) ^ RECORD COUNTRY HERE AND IN S.R.B. PG 2 AND CONTINUE) (RECORD COUNTRY HERE AND IN S.R.B. PG 2 AND CONTINUE) No others. ( 16( /T57 b. (RECORD COUNTRY HERE AND IN S.R.B. PG 2 AND CONTINUE) -1 (SKIP TO No others. (16 ( -1 (SKIP TO Q.18) . Q.18) In what month and year h. In what month and year n. In what month and year did you begin and end acdid you begin and end acdid you begin and end active duty in (COUNTRY)? tive duty in (COUNTRY)? tive duty in (COUNTRY)? BEGIN BEGIN YEAR MONTH YEAR 1 M i l I I I I 1 1 1 l - l I I 1 1 l-l I . I ( 17) ( 18) ( 19) ( 20) ( 17) ( 1© . 09 )( 20) END END MONTH YEAR MONTH YEAR 1 I I 1 1 1 I I I 1 1 1 l-l 1 1 1 .1 l-l 1 1 ( 2J) (22) ( 235 (24) (21 ) ( 22) (23 )( 24) BEGIN MONTH YEAR 1 1 1 1 1 1 1 1 l-l 1 1 (17)08) ( 19) ( 20) END MONTH YEAR MONTH Cur rent... (25 ( -1 Current..'. (25 ( 1 I 1 1 1 1 1 1 H I 1 ( 21) ( 22) G>3 ) ( 24) Current... ( 25( -1 -1 c. What specific job assign- i. What specific job assign- o. What specific job assignments (do/did) you have ments (do/did) you have ments (do/did) you have in (COUNTRY)? Can you in (COUNTRY)? Can you in (COUNTRY)? Can you give me the AFSC? give me the AFSC? give me the AFSC? 1. ( 26-28)1. 66-28) 1. C6-28) 2. £9-31) 2. C9-31) 2. (29-31) 3. (32-3<M 3. 02-34) 3. 02-34) (Do/Did) your duties in j. (Do/Did) your duties in p. (COUNTRY) include flying? (COUNTRY) include flying? (Do/Did) your duties in (COUNTRY) include flying? d. Yes.( 33( No . . Yes.(35( e. How many flight hours did you log while in (COUNTRY)? 1 1 1 | 1 1 Hours 06 ) (37) (38) Other (SPEC1FYJ -1 Yes.(35( -1 No -1 -2 -2 No -2 k. How many flight hours did you log while in (COUNTRY)? 1 1 I I 1 1 1 1 Hours ( 36) ( 37) ( 38) Other (SPECIFY) q. How many flight hours did you log while in (COUNTRY)? 1 1 I I 1 Hours ( 36) ( 37) ( 38T Other (SPECIFY) . 3 ( -1 (9 .(39( -1 1 | 1 . 3 ( -1 (9 f. What specific letter and L. What specific letter and r. What specific letter and numerical ^Utoigniltionfs) numerical designation^ ) numerical designation^) did each aircraft have? did each aircraft have? did each aircraft have? 1. f4,0-43) 1. (40-43) 1. (40-43) 2. (44-47) 2. (44-47) 2. <4ft-4.7) 3. f48-5]V 3. (48-51) 3. (48-51) (52-55) 4. (52-55) 4. *• (ASK Q.16p) 02 79-80 01 79-80 1U (52-55) (ASK Q.17a) (ASK Q.16m) 0) 79-HO �CARD_Q16 812039 Question 17 iT3 Fourth Country Fifth Country Sixth Country a. What was the next country g. What was the next country m. What was the next country that you were stationed that you were stationed that you were stationed in for more than 90 days in for more than 90 days in for more than 90 days tfhit« Oil active duty? while on active duty? while on active duty? (14-15) \ RECORD COUNTRY HERE AND IN 6,R,». PC J AND CONTINUE) (RECORD COUNTRY HERE AND" IN S.R.B. PC 2 AND CONTINUE) (14-15) (RECORD COUNTRY HERE AND IN S.R.B. PC 2 AND CONTINUE) No others. (16 ( -1 (SKIP TO Q.18) No others. (16 ( -1 (SKIP TO Q.18) No others. (16 ( -1 (SKIP TO Q.18) b. (14-15) In what month and year h. did you begin and end active duty in (COUNTRY)? BEGIN BEGIN MONTH YEAR 1 1 I I 1 1 1 1 l-l 1 1 (17) (18) (19) (20 r MONTH YEAR 1 1 1 1 f 1 l-l . 1 1 1 ( l7> lit ) (19) (20 !> END MONTH YEAR 1 M i 1 . . , -1 1 (21) (22) (23) (24) -1 Current.. .(25 ( In what month and year did you begin and end active duty in (COUNTRY)? BEGIN 1 II MONTH 1 1 1 l-l YEAR 1 " t 1 1 (n ) as ) fly ) po ) END MONTH YEAR I I I 1 1 1 -1 i (21) (22) (23) (24) l 1 Current . , . (25 ( In what month and year n. did you begin and end active duty in (COUNTRY)? END' MONTH 1 1 YEAR I I l-l (21). (22) (23) (24) Current . . . (25 ( -1 -1 c. What specific job assign- i. What specific job assign- o. What specific job assign, merits (do/did) you have ments (do/did) you have ments (do/did) you have in (COUNTRY)? Can you in (COUNTRY)? Can you in (COUNTRY)? Can you give me the AFSC? give me the AFSC? give me the AFSC? (26-28) 1. O6-28) 1. (26.- 28) 2. U9-31) 2. (29-31) 2. (29-31) 3. (32-34) 3. (32-34) 3. (32-34) 1. • d. (Do/Did) your duties in j. (COUNTRY) include flying? (Do/Did) your duties in p. (COUNTRY) include flying? Yes. ( 5 ( 3 No e. How many flight hours did you log while in (COUNTRY)? 1 L Other (SPECIFY) Yes. (35 ( No -1 -2 k. How many flight hours did you log while in (COUNTRY)? 1 1 I I I I Hours (36) (37) (38) 1 1 1 1 Hours (36) (37) (38) Other (SPECIFY) 1 1 1 1 1 1 J J Hours (36 5 (37 ) (38 ) Other (SPECIFY) . 3 ( -1 (9 f. What specific letter and t. numerical designation(s) did each aircraft have? -1 -2 q. How many flight hours did you log while in (COUNTRY)? 1 1 . 3 ( -1 (9 (Do/Did) your duties in (COUNTRY) include flying? .(39; -l What specific letter and r. What specific letter and numerical designation(s) numerical designation(s) did each aircraft have? did each aircraft have? 1. (40-43) 1. (40-43) 1. (40-43) 2. (44-47) 2. (44-47) 2, (44-47) 3. (48-51) 3. (48-51) 3. (48-51) fll'-W 4. 4. (ASK Q.17g5 04 79-80 (52-55) (52- IS) 4. (RECORP ADDITIONAL COUNTRIES IN S.R.B. PC 19 AND 20) ftt 05 7 "' 0 9:8 (ASK Q. 17ml 11 �812039 . CARD 020 Now I would like to ask you about your marital history. 18. Have you ever been legally married? -1 (ASK Q.19) -2 (SKIP TO Q.24) 19. How many times have you been legally married? I T (WRITE IN NUMBER) I times 43 ) (14) FIRST/ONLY MARRIAGE 20a. In what month and year did you get married (th f i r s t time)? 1 I SECOND MARRIAGE 21a. MONTH YEAR 1 1 1 ! 1 l l I l l ^5 )" (16 ) ( 17) ( 18) THIRD MARRIAGE In what month and year did you get married the second time? 1 1 MONTH 1 I I 1 • .1-1 (15 > ( 16) YEAR I 1 22a. In what month and year did you get married the third time? MONTH I 1 YEAR I I 47 T (18) 45) (16F (17 ) ( 18) 20b. What (is/was) her current full name? 1 RECORD IN S.R.B. PG 2 f 21b. 20c. 21c. 22c. 20d. What is her date of birth? 21d. What is her date of birth? 22d. What is her date of birth? What was her maiden name? 1 RECORD IN S.R.B. PG 2 I MONTH (19 ) (20 ) 1 1 MONTH 1 1 1 1 ( 21) ( 2'J) -1 -2 21e. 1st 1 1 r 2 n dI 3rd 4 t What was her maiden name? IRECORD IN S.R.B. PG 2 [ YEAR 1 1 ( 21) ( 22) MONTH Yes...(_2| Ho YEAR I (19 ) (20 ) Gl ) ( 22) Have you ever had any children by (your/thin) wife? 22e. Have you ever had any children by (your/this) wife? -I -2 -1 Yes...(23( No... Did your wife ever have 22f. Did your wife ever have any pregnancies by you any pregnancies by you which ended in a miscarwhich ended in a miscarriage? riage? -1 (ASK Q.21g) Yes...(24( -1 (ASK Q.20g) Yes...(24( -i) V (SKIP TO Don't know -3J Q.20L) 20g. When was that? (PROBE: Any others?) No 1 1(19 ) ( 20) 20f. Did your wife ever have 21 f . any pregnancies by you which ended in a miscarriage? Yes... (24 ( 22b. What (is/was) her current full name? I RECORD IN S.R.g. PG 2 I What was her maiden name? (RECORD IN S.R.B. PG 2 1 20e. Have you ever had any children by (your/this) wife? Yen...(23( No cur- 1 RECORD IN S.R.B: PG 2 1 YEAR 1 1- What (is/was) her rent full name? -2) I (SKIP TO Don't know -3J Q.21D 21g. When was that? (PROBE: Any others?) No MONTH YEAR 1 I I 1 1 1 |-| | | 1st < 2 5 ) (26) (27) (28) MONTH YKAfl (SKIP TO -3j Q.22L) Don't know 22g. When was that? (PROBE: Any others?) MONTH YEAR 1 I I I 1 | |-| | I 1st (25) (26) (27) (28) MONTH _VM!L_ YEAR 1 T MONTH 1 | i 11 T"~~I . T™ T---TT r i l l I l l 2 n dI l l I l l 2nd (29) (30) (31) (32) (29) (30) (317T3ST' MONTH YEAR MONTH YEAR 1 1 1 1 " 1 I I 1 1 1" 1 ' 1 I 1 |-| | 1 3rd | I |-| | | 3rd (33) ( 3 4 ) (35) (36) (33) (34) (35) (36) MONTH YEAR MONTH YEAR 1 I I I 1 T 1 1 I I I 1 hI l l I l l 4 t hI l l I l l 4th ( 3 7 ) (38) (39) (40) ( 37) ( 38) ( 39> ( 40) (GO TO Q.20h) (GO TO Q . 2 1 h ) 12 I r T I I-1 (29) I (TO <2HT YKAIl (25) <Z6) (30) MONTH (31) I (J^ YEAR T (33TT34) MONTH (35) YEAR i—i—r1-1i—ii ri i (37) i (38) (39) (411) (GO TO Q.22h) �.-.-.i'.-. ,.V; FIRST/ONLY MARRIAGE I J. 1 1 1 1 Months (41 ) (42 ) Hssn't trying ( 43S 1 1 1 t 1 1 Weeks <44 > ( 4# 1 1: 1 1 812039 THIRD MARRIAGE 22h. How many months did it take your wife to become pregnant this time? 1 1 Months <41 ) (42> Wasn't trying (_A3C -1 20 i. How many weeks had your 21 i. wife been pregnant when, the (1st, etc.) miscarriage occurred? 1st cARC '020 21h. How many mpnths did it take your wife to become pregnant this time? 20h. How many months did it take your wife to become pregnant this time? I t .. . SECOND MARRIAGE 1 1 (41) (42) Wasn't trying ( 4X -I How many weeks had your wife been pregnant when the (1st, etc.) miscarriage occurred? 1st I 1 2nd l l 1 1 Weeks (44) <45) 1 1 Weeks ( 4.4) (45 ) let 2nd 1 1 1 Weeks <46 ) (47 ^ 3rd 1 1 1 1 I 1 Weeks (48) (49> 3rd 4th 1 1 1 'I 1 1 Weeks (50 J ( 55) 4th 1 1 I 1 2nd; 1 1 I I I | Weeks (48 ) ( 49) 20 j. Did a doctor tell you why this (1st, etc,) miscarriage might have occurred? -1 22i. Mow many, weeks had your wife been pregnant when the (1st, etc.) miscarriage occurred? I I I I | | Weeks <46 ) ( 47} I 1 1 Months I 1 " t 1 | Weeks <46) (47) 1 3 r dI 1 1 1 I Weeks (50 ) ( 51) 4th 21 j. Did a doctor tell you why this (1st, etc,) miscarriage might have occurred? 1 1 1 1 I | Weeks ft»8 ) ( 49) 1 I Weeks (50 ) ( 51) 22 j. Did a doctor tell you why this (1st, etc.) miscarriage might have occurred? Yes. (52 ( -1 (ASK Q.22k) Yes. (52 ( -1 (ASK Q.21k) Yes. (52 ( -1 (ASK Q.20k) No -2 (SKIP TO Q.20L) No.i.... -2 (SKIP TO Q.21L) No -2 (SKIP TO Q 22L) 20k. What did the doctor say .21k. What did the doctor Say caused the miscarriage? caused the miscarriage? 22k. What did the doctor say caused the miscarriage? 1st 1st 1st 2nd 2nd 2nd 3rd 3rd 3rd 4th 4th 4th 20L. Rid your wife have any 211.. Did your wife have any 22L. Pid your wife have any pregnancies by you, which pregnancies by you which pregnancies by you which ended in a stillbirth? ended in a stillbirth? ended in a stillbirth? Yes... (53 ( No ,. ~~ 5 -1 (ASK Q,20ti)> Yes... ( 3 (T -2 (SKIP TO Q. No 1.'' ' " ' 20q) 20m. When was that? Any others?) MONTH (PROBE: MONTH YEAR V" 1 1 2nd MONTH YEAR 1 ' 1 1 I 1 1 1 1 l-l 1 1 2nd (58) (59) (60) (61) MONXH YEAR 1 1 3rd 1 1 4t>t». I' |.X ( 1 (& (3 6 , 6 ) ( 4 ' "(6$) 6) MONTH YEAR " '1; l - l 1 7 ' 'I l-l 1 "1 1 4th YEAR "\ " ' M " ' 1 1 l-l . 1: MONTH 1 \ i t 1 1 1 1; I I l-l (58) (59> MOUTH 1 ~ '1 1 1st 1. 1 2nd ( 0 (61) 6) YE&R [: f l-l I' 1 3rd (62). ' 6 ) ' ( 4 "ftftf (3 6J MQNTH YMR, 1- i r i; ' • i 1 \-\ ! 79-80" 13 YEAR 1 i 1 l 1 l-l \ 1 (5« ) PS ) (36F<;57) " MONTH TJ6AR i ~n r • f r l-l 1 1 ( 8 (59 >' (60) £61 ) 5) MONTH YiEAR, F" 1 i; """I : l-t ' 6 ) (6i> (2 MO>ITR r 1 ' I, ( 6 « •' 'U-3J, ,') YEftR r I r ' i i- ' ' f 1 4th ( l-li 1: 1: (fef)');,' (67=) " » : (:6»> (») (GQ TO Q,Hft)i (.6ft? ( ( . . • ?§) (GO TO Q.2ln) (?ROBE; \ v •• '\ \--\-- -\ 156 > <5T) YEAR (6(>5 (f>7): '/GO to, Q.20n) 22m. When vas that? Any others?) (PROflE: (59 ( 5 ) 5' MONTH 1 1' -1. (ASK q.22m) 22q) 21m. When was that? Any others?) F ' T" '1 T~ "i "T 1 (54 )1 (55 ) (56 ) (57 Ut '"I 1, 1 ) 3r4 -1 (ASK Q.Hm)*e.»,.«(53l "-2 (SKIP TO Q. t: �ADDITIONAL RECORDING SHEET FOR NON-LIVE-BIRTHS FIRST/ONLY MARRIAGE MISCARRIAGES - Q.20h I 2nd I Months (12) (13) Wasn't trying (14( Don't know -1 SECOND MARRIAGE MISCARRIAGES - Q.21h 2nd r T I 3rd I I I Months (12) (13) Wasn't trying (14( -1 Don't know -2 T I 3rd 1 I I I Months (15) (16) Wasn't trying (17( Don't know -1 -2 THIRD MARRIAGE MISCARRIAGES - Q.22h 2nd I I Months '(12) (13) Wasn't trying (14( -1 Don't know -2 T I I I Months (15) (16) Wasn't trying (17( Don't know -1 -2 3rd I I Months " (18) (19) Wasn't trying ( 0 2( -1 Don't know -2 4th I 1 [ Months (18) (19) Wasn't trying ( 0 2( Don't know (GO TO Q.20i) [ Months (15) (16) Wasn't trying (17( Don't know I I 4th 812039 CARD 143 -1 -2 4th I -1 -2 T I Months (18) (19) Wasn't trying ( 0 2( -1 Don't know -2 (GO TO Q.2H) I (GO TO Q.22i) [AFTER Q.20k/21k/22k ASK FOR EACH MISCARRIAGE:f Were either of you using birth control at the time she bedame pregnant? IFOR ANY "YES" ASKTT IHAND RESPONDENT CARD "C"| Please look at this card nnd tell me all the numbers that apply to the types of birth control you used. 1st: J21-22) 1st: J21-22) 1st: J21-22) 2nd: _(23-24) 2nd: _(23-24) J23-24) 3rd: _<25-26) 3rd: J25-26) 3rd: (GO TO Q.21L) (GO TO Q.20L) mST/ONLY MARRIAGE STILLBIRTHS - Q.20n \ I I Months (32) (33) Wasn't trying (34( -1 Don't know -2 (35) (36) Wasn't trying (37( Don't know Months -1 -2 2 n d I T I I Months (29) (30) -1 Wasn't trying (31( Don't know I I r 4th I i I I Months (32) (33) Wasn't trying (34( -1 Don't know ~2 I I Months (35) (36) Wasn't trying <37( -1 Don't know -2 I I T T I 3rd Months (32) (33) Wasn't trying ( 4 3 ( -1 Don't know... -2 T I Months (35) ( 6 3) Wasn't trying (37( -1 Don't know "2 4th (GO TO Q.21o) (GO TO Q.20o) r I Months (29) (30) Wasn't trying (31( -1 Don't know -2 2nd 1 3rd T -1 -2 I J 4th THIRD MARRIAGE STILLTBIRTHS - Q.22n I Months (29) (30) Wasn't trying (31( Don't know 3rd (27-28) (GO TO Q.22L) SECOND MARRIAGE STILLBIRTHS - Q.21n T 2nd _(25-26) (27-28) 4th: (27-28) 4th: 4th: 2nd: I I I ! (GO TO Q.22o) I AFTER Q. 2Qp/ 21 p/22p; ASK ^FOR EACH STILLBIRTHjj_ Were either of you using birth control «t"the' lime sh« became pregnant? IFOR ANY "YES" ASK~ IHAND RESPONDENT CARD "c"| Please look at this card and tell me all the numbers that apply to the types of birth control you used. _(38-39) J38-39) 1st: 1st: _(40-41) (40-41) 2nd: (40-4)) 2nd: 2nd: J38-39) 1st: _(42-43) 3rd: (44-45) (44-45) 4th: 4th: (GO TO Q.20q) (GO TO Q.21q) . 14 (44-45) 4th: (GO TO Q.22q) �RECORpiNO SHgfc'T FQR 1 2nd 1 1 Months (46 ) (47) Wilsn't trying (48( Don't 1 -1 2nd Wa»n' I tryjrifi (51( Don't I -1 1 I 1 1 Months (46) (47) W a s n ' t trying (4_8J -1 3rd 1 I I 1 1 1 Months W a s n ' t trying (51( -1 . 1 1 Months 1 1 I ABORTIONS - 9.225 2nd I I I I I | Months (46) (47) W a s n ' t trying (48( -1 3rd I I '2 r i( i1 Months 4th •ri.ii^.1) SKCQNIt MAjMjACiK ABORTIONS - Q.21s 1 3rd 812039 CARP 143 KIRST/Oftl.Y MAHRtACE 'ABORTIONS - Q.20s 'ft 2") (555 Wasn't trying (56( Don't I -1 4th 1 1 1 I (G() TO Q.20t) 1 I Months W a s n ' t trying ( 5 l ( -1 -2 1 [ Months (52) (53) Wasn't trying (54( I I -1 -2 4th 1 1 I 1 I 1 Months (52) (53) Wasn't trying (54( (GO TO Q . 2 1 t ) -1 (GO TO Q.22t) 1 AFf^R §,20t/21t/22t ASK FOR EACtf ABORTION;! Were e Lttief of you using birth control at the time she became pregnant? IFOR 1 A W .''YES" ASK: 1 :'\ ..":. • ".' IHAN^ iUSjPbNDENT •' •' : CAfo "C'M Please look at this card and tell roe all the numbers that apply to the types of birth 1st: (55-56) 1st: (55-56) 1st: (55-56) 2nd: (57-58) 2nd: (57-58) 2nd: (57-58) 3rd: <59-60) 3rd: (59-60) 3rd: (59-60) (61-62) 4th; 4th: (61-62) 4th: (GO TO Q.20u) 01 79^80 (61-62) (GO TO Q.Zlu) (GO TO Q.22u) 02 W%& 79^15 15 �CARD FIRST/ONLY MARRIAGE 20n. How many months did it take your wife to become pregnant this time? 1 1 1 1 Months (U) U3) Wasn't trying (14( -1 (12) (13) Wasn't trying (14( 20o. Did a doctor tell you why this stillbirth might have occurred? 21o. Did a doctor tell you why this stillbirth might have occurred? Yes.(i5( No . . 220 2 In. How many months did it take your wife to become pregnant this time? I I 1 1 1 1 Months -1 (ASK Q.20p) Yes.(l5( No -2 (SKIP TO Q.20q) -1 -2 -1 (ASK Q.21p) (SKIP TO ( 21 q) ) 812039 THIRD MARRIAGE SECOND MARRIAGE 22n. How many months did it take your wife to become pregnant this time? 1 I I 1 I I Months (i/) (U) Wasn't trying O*( -1 22o. Did a doctor tell you why this stillbirth might have occurred? Yes.(15( -1 (ASK Q.22p) No -2 (SKIP TO Q 22q) 20p. What did the doctor say 21p, What did the doctor say 22p. What did the doctor say caused the (1st, etc.) caused the (1st, etc.) caused the (1st, etc.) stillbirth? stillbirth? stillbirth? 1st 1st 1st 2nd 2nd 2nd 3rd 3rd 3rd 4th 4th 4th 20q. Did your wife ever have 21q. Did your wife ever have 22q. Did your wife ever have any pregnancies by you any pregnancies by you any pregnancies by you which ended in abortion? which ended in abortion? which ended in abortion? Yes...(lft ( No , -1 (ASK Q.20r) Yes... 06 ( -2 (SKIP TO Q. No 20u) 20r- When was that? Any others?) 1st 2nd 3rd 4th -1 (ASK Q.21r) Yes...(16( -2 (SKIP TO 0. No 21u) (PROBE: 21r. When was that? Any others'?) (PROBE: 22r. When was that? (PROBE: Any others?) MONTH YEAR MONTH YEAR 1 I I I I I I I I I| | 1st 1 -1 1 1 1st (17) (18) (19) (20) (17) ( Id (19) (20) MONTH YEAR MONTH YEAR 1 1 11 1 1 I I I I 1 1 I 1 1-1 I I 2nd 1 l-l 1 1 2nd <21 ) (22) (23) (24 ^> <21> (22> ^23) (24) MONTH YEAR MONTH YEAR 1 1 1 ! 1 1 1 1 1 1 1 I l l - I l 3 rl d 1 1 l-l 1 1 3 r d (25) (26) (27) (28) < 25 > (26J (27) (28> MONTH YEAR MONTH YEAR 1 1 1 I I 1 1 1 1 4th 1 l-l 1 I 4th <29> (30) (31) (32) < 29 > (30 > (31) (32> 20s. How many months did it take your wife to become pregnant this time? 1 1 1 1 (33) (34) Wasn't trying <35( 21s. How many months did it t-ke your wife to become pregnant this time? 1 1 Months -1 1 1 Months (33) (34) Wasn't trying (35( -1 (ASK Q.22r) -2 (SKIP TO Q. 22u) -1 MONTH YEAR 1 I I 1 1 1 - I I I (I/) ( i»> (19) (20) MONTH YEAR 1 I I I 1 1 1 1 - I I I ( 2J> (22 ) (23 ) (24 ) MONTH YEAR I I I I I 1 1 - I I I (25 ) ( 20 (27 ) ( 29 MONTH YEAR 1 1 I I 1 1 1 1 l-l 1 1 (29) (30) (31) (32) 1 1 22s. How many months did it take your wi fe to become pregnant this time? T~ f 1 1 ' Mofctfift (33) (34) Wasn't trying (35( -I 20t. What was the main reason 21 1. What was the main reason 22t. What was the main reason for the (1st, etc.) for the (1st, etc.) for the (1st, etc.) abortion? abortion? abortion? 1st 1st 1st 2nd 2nd 2nd 3rd 3rd 3rd 4th 4th (CO TO Q.20v ) 4th (GO TO Q.21v) 10 (GO TO Q.22v) �.CARP 220 FIRST/ONLY MARRIAGE 20u. (IF ANY CONCEPTIONS ~ 21u. CHILD, MISCARRIAGE, STILLBIRTH, OR ABORTION: SKIP TO q.iOw THIRD MARRIAGE (IF ANY CONCEPTIONS — 22u. (IF ANY CONCEPTIONS — CHILD, MISCARRIAGE, CHILD, MISCARRIAGE, STILLBIRTH, OR ABORSTILLBIRTH, OR ABORTION: SKIP TO Q.2lw TION: SKIP TO Q.22W ALL OTHERS: ASK Q.2lu ALL OTHERS: ASK Q.22u) Did either you or your Did either you or your wife use birth control wife use birth control techniqueB regularly? techniques regularly? ALL OTHERS: ASK Q.20" Did either you or your Vif* U8e birth control techniques regularly? Veg..( 36( -1 (ASK <J.20v) No __-2 <ASK Q.20x) 812039 SECOND -MARRIAGE Yes..(36( -1 (ASK Q.Zlv) No _^-2 (ASK Q.21x) Y«»..(_36(- -1 (ASK Q.22v) NO -2 (ASK Q.22x) I HAND BESPOMPENT I HAN Cv. Please look at this car 21v. Please look et this car 22v. and tell me all the numand tell me all the nui berS that apply to the bers that apply to the types of birth control types of birth control you or your wife normal you or your wife normal ly used. ly used. Please look at this card and tell me all the numbers that apply to the types of birth control you or your wife normally used. 06. ( 42(_-l 01. (M -i Q7.C4f""-l oz.daT^-i 08.(44(,. -1 03.(_39( -1 0.tT9 ( 5 ~ l OA.(40(. -1 io.(M_ -i OS.(4l( '1 02. ( a l -1 O3.(j?9( .-1 OA.(40( .-1 OS.(4i( -1 12 (SPECIFY) 12 (SPECIFY) n.csn-1 12 (SPECIFY) 01.(M -1 06. (421 07. Q8.(44(" -1 Q9.(45( • -1 10.(46( • Ug _ -1 (SKIP TO Q.20x) (SKIP TO Q.20x) (SktP TO Q.20x) 20w. Did any of these preg- 21w. Did any of these preg- 22w. Did any of these pregnancies occur while nancies occur while nancies occur while either you or your wife either you or your wife either you or your wife wire practicing birth were practicing birth were practicing birth control? control? control? Yes....(49( No Yes....(49( No -1 20x. During this marriage, how many times were you living apart from your wife for more than moti.thg? 1 I I Times (50 ) (51 ) -1 -1 "-2 21x. During this marriage, 22x. During this marriage, how many times were you how many times were you living apart from your living apart from your wife for more than threi wife for more than three months? tfionths? T Never.. (52 { (9 4( Yes No -1 I T I . I Time* (So) pi ) (SKIP TO Never..(53 Q.20aa/bb .-1 (SKIP TO Q.21aa/bb I I I I I ^ I Times po ) (51) Never..(53( -1 (SKIP TO Q.22aa/bb) 20y. How many months did you 21y. How many months did you 22y. How many months did you live apart the (first/ live apart the (first/ live apart the (first/ next) time? next) time? next) time? I I I ].... L Months (53) (54] I "~'~"i 2nd 3rd J III T I I Months (55) (56) I I I !„„- , Months 2nd 3rd Months 4 t h I t 16:0 ( I t I I I | Months (39 ) (60) i—n—r 5Jh I 6tli (57) (58) I 6th i (GO TO 0.20?.5 Months (55) (So)' I I T L . ,l . . J Months ..r,.. (61) (62) i,^,-] (53 I I .1 1 Months (55) ( 50 3rd 1 Months l.s.t Months 2nd Months L .. J (57) (58) I 1. .....I . .J Months (53 ) (54) ! J. L . . . Months ..-[ ((,:)) (64) (GO TO 0. 17 t 2th I <S'9) I I I Months "' v......i r \ I I,^..L, T ,,,.I. Months I I .._.!_.....I Months ( h J ) (r()4"5" (GO TO Q . 2 2 z ) �812039 CARD 220 SECOND MARRIAGE FIRST/ONLY MARRIAGE 20z. As a result of (this/ these) separations, did you and your wife have fewer children than you wanted to have? Yes....(65( No... 21i. As a result of (this/ these) separations, did you and your wife have fewer children than you wanted to have? -1 -2 Yes,...65( THIRD MARRIAGE 22z. As a result of (this/ these) separations, did you and your wife have fewer children than you wanted to have? Yes....(65( No -1 IIF LAST MARRIAGE! IIF LAST MARRIAGE! llF ONLY MARRIAGE] -1 -2 20aa.Are you currently married and living with your wife, or are you divorced, widowed, or separated? 21aa.Are you currently married and living with your wife, or are you divorced, widowed, or separated? 22aa.Are you currently married and living with your wife, or are you divorced, widowed, or separated? Living with wife...(66( Living with (SKIP TO wife...fe_6( -1 Q.23) Living with (SKIP TO wife...fe6( -1 Q.23) Separated.... -3f Q.20cc) Widowed -4J Divorced -2) (SKIP TO Separated..,. ~"3f Q-Zlcc) Widowed . . . -4j ... (RECORD IN S.R.B. PO 2 1 I RECORD IN S.R.B. PG 2 I Divorced -m SKIP TO Separated,... -3f Q.22cc) Widowed -4| ~"°" J (RECORD IN S.R.B. PG 2 1 -1 (SKIP TO Q.23) (IF OTHER MARRIAGES! (IF OTHER MARRIAGES] IIF OTHER MARRIAGES | 21bb.How did that marriage 22bb.How did that marriage 20bb.How did that marriage end -- were you divorced end — were you divorced end — were you divorced or were you widowed? or were you widowed? or were you widowed? Divorced<67( Widowed ~J.[(ASK Q.20cc) Divorced(.67[ -A (ASK Q.2f:c) Divorced ^7j_j_- 1 ( ASK Q . 2l.c c ) | -21 Widowed -2l Widowed....'. -21 ~"~ j "*"— J (RECORD IN S.R.B. PC 2, 1 (RECORD IN S.R.B. PG 2 1 (RECORD IN S.R.B. PG 2 1 20cc.In what month and year were you (divorced/ widowed/separated)? 21cc.In what month and year were you (divorced/ widowed/separated)? 22cc.In what month and year were you (divorced/ widowed/separated)? MONTH YEAR 1 1 1 1 1 l l I l l (68) (69) (70) (71) (IF A SECOND MARRIAGE GO TO Q.21a) 01 79-80 T I MONTH YEAR 1 I I 1 1 1 l-l 1 1 (68) (69) (?6) (71) (IF A THIRD MARRIAGE GO TO Q.22a) 02 79-80 1 1 18 MONTH YEAR 1 I I 1 ] l l I l l (68) (b9) (70) (71) (RECORD OTHER MARRIAGES IN S.R.B. PG 21-25) 03 79-80 1 I �812039 CARD Q2 3 23a. Have you ever lived together as a partner for 3 month s or more with someone other than your ( w i f e / w i v e s ) ? Yes ( 12C -1 (ASK ().23b) _-) Refused -3 f j 23b. How many times di 1 you live as a partner with someone fo c 3 months or more? TO Q.25) I (WRITE I 1 NUMBER) 1 I 1 I I times 03 ) ( 14) FIRST PARTNER SECOND PARTNER 24n. In what month and year t1 Ml yon b e g i n l i v i n g w i t h a partner (the f i r s t time)? 1 1 24h. In what month and year i l i d ynn liegin 1 i v l n g w i t h a partner the second time? MONTH YEAR 1 I I 1 1 1 l-l 1 1 (15) 116) (17) (18) 1 1 24b. How old was she at that time? (WRITE IN AGE) 1 I 1 1 1 (WRITE IN AGE) | 1 I (WRITE IN AGE) 1 I Yes.( 26( -1 (ASK Q.24e) -2 (SKIP TO Q.24g) No 24L. 24e. When was that? 1st YEAR 1 1 1 1 ) (30 ) 1st MONTH YEAR 1 I I 1 1 2 n d I l l I l (31 ) (32 ) (33 ) (34 ) -1 (ASK Q.24L) -2 (SKIP TO Q.24n) When was that? 1 1 MONTH YEAR 1 1 1 1 1 1 l-l 1 1 (27 ) (28 ) (29 ) (30 ) MONTH YEAR 1 I I 1 1 l l I l l2 n d I (31 ) ( 32) (33 )( 34) 1 1 I 1 I 24q. In what month and year did this relationship end? 1 I -1 24k. Did this partner ever become pregnant by you? 1 I ( 19) GO ) MONTH YEAR 1 1 1 1 1 l l I l l (21 ) (22 ) (23 ) (24 ) Current . . ( 25( ~1 MONTH 1 I I . 1 l-l (27 ) (28 ) (29 1 1 I | (19 ) ( 20) 24 j . In what month and year did this relationship end? 24d. Did this partner ever become pregnant by you? 1 1 MONTH YEAR 1 1 1 1 1 I l - l 1 1 ( 15) (16 ) (17 ) ( Ib) 24p. How old was she at that time? MONTH YEAR 1 I I 1 1 l l I l l (21 ) (22 ) (23 ) (24 ) Yes. (26 ( No . .. 1 I 241. How old was she at that time? 24c. In what month and year did this relationship end? Current . . (_£^ 24o. In what month and year diil you b « g i n l i v i n g with a partner the third time? MONTH YEAR 1 I I 1 1 1 l-l 1 1 (15) (16) ( 17) (18) (19 ) ( 2(J 1 I THIRD PARTNER MONTH YEAR 1 1 1 1 1 l l I l l (21 ) C22 ) G3 ) ( 24) Current.. ( 25( 24r. -1 Did this partner ever become pregnant by you? Yes. (26 ( -1 (ASK Q.24s) No -2 (SKIP TO Q.24u) 24s. When was that? 1st 1 1 MONTH YEAR 1 1 1 1 1 1 l-l 1 1 (27 ) (28 ) (29 ) ( 30) l 2nd 1 1 MONTH YEAR 1 I I 1 1 1 l-l 1 1 01 ) ( 32) ~63 ) ( 34) 1 24m. What was the outcome of 24t. What was the outcome of that pregnancy? (What that pregnancy? (What was the outcome of the was the outcome of the second pregnancy?) second pregnancy?) First 1 Second First 1 Second 1 1 Live birth. (35 ( - l i < 3 6 ( -1 Live birth. ( 33C -ll(36 ( -1 Live birth. (35 ( - l | 0 6 ( -1 -2 Miscarriage... -2 1 -2 Miscarriage... -21 -2 Miscarriage... -2| 1 -3| __-3 Stillbirth.... -3| -3 Stillbirth. ...~-3l ~-3 Stillbirth 24f. What was the outcome of that pregnancy? (What was the outcome of the second pregnancy?) First 1 Second Abortion...... -4 1 -4 24g. Did you or your partner use b i r t h control regul a r l y to a v o i d pregnancy? 24n. Did you or your partner use b i r t h control regul a r l y to avoid pregnancy? 24u. Did you or your partner use birth control regul a r l y to avoid pregnancy? Yes.<'J7( No ... Yes. (37 < No Yes(37 ( No -l"l (CO TO NEXT -if PARTNER ~ J Q - 2 4 h ) 0, -1~) <GO TO NEXT -2 r PARTNER -J Q . 2 4 o ) cp 19 -1\ (RECORD ADDITION-2| AL PARTNERS IN J S . R . B . PC; 26) ( 79 �CARP 025 812039 25a. Do you know of any other pregnancies, in addition to those we have already discussed, that you have caused? Yes.(12( (ASK Q.25b) No 2Sb. -1 -2 (SKIP TO Q.26a) 2Sd. When was that? When was that? SECOND FIRST MONTH (13) (14) MONTH YEAR (15) (16) r ii 1-1 n 25f. ri ii Live birth. ( 7 1( 25e. What was the outcome of that pregnancy? -1 Miscarriage.... Stillbirth,,,., -2 -3 PROBE: Were there any others? (IF YES, ASK Q.25d) THIRD MONTH YEAR 1 1 I I 1 1 1 1 l-l 1 1 (23) (24) (25) (26) YEAR ii ii r1-1i ii (18) (19) (20) (21) 25c. What was the outcome of that pregnancy? Live birth. ( 2 2( Miscarriage.... Stillbirth 25g. What was the outcome of that pregnancy? _i -2 —3 PROBE : Were there any others? (IF YES, ASK Q.25f) When was that? Live birth. ( 7 ( 2 Miscarriage. . . ._ Stillbirth -i -2 -3 PROBE: Were there any others? (IF YES, GO TO S.R.B. PAGE 27 Q.156) 26a. Did you ever try for a period of a year or more to conceive a child without being able to? Yes.(28( • No,...,. 26b. When was that? -2 (PROBE: First time (ASK Q.26b) . (SKIP TO Q.27) Were there any other times?) Second time FROM Third time 1 I MONTH C9 ) ( 30) ( 31) ( 32) (49) (50) (51) (52) (39) (40) MONTH 65 ) (36) YEAR I i I I F^T («') <«°) TO YEAR I 63 ) (3A) YEAR 1 MONTH I YEAR (37) (3B) TO MONTH FROM MONTH 1 T l I l-l FROM 1AR MONTH TO YEAR T 1 I 1 ~ I I l-l I (41) (42) (43) (44) 26c. During (this period/any of these periods) did either you or your partner see a doctor to discuss any difficulties in conceiving children? Yes.(53( No...777" -1 "-2 �CARD 027 812039 I ASK ETORYONET I HAND RESPONDENT CARD "D" j 2 7 a . T h e r e are many reasons that some couples find it difficult or impossible to conceive a child. Please read this card and tell me the letter for each reason which ever applied to you or a spouse or partner. Any other reason? TASK Q.27b AND Q.27c FOR EACH REASON IN Q.27a7| 27b. Did reason (LETTER) apply to you or your spouse? 27c. I MULTIPLE RECORD BELOW I In what year did this occur or become known to you? _ Q.27c Q.27b Year (28) Q.27a (29 ) A. Respondent.... (_18( Sterility due to surgery......(12 ( -1 -1 I l._ . 1 f'31)I . 00 ) Sr>ouse/partner(19 B. Respondent.... (20 ( -1 C33) 021 Sterility due to injury, accident, or illness (SPECIFY) I I -1 Spouse/partnerfel ( -1 I I (4 3) T I f35) C. Re sponden t.... (22 ( Sterility due to unknown causes 1 06)(37) Spouse/pa rtner(23(__-l (385 (39) D. Impotence (15 ( -1 <40 E. Respondent....(24 ( -1 Other known medical or physical conditions (SPECIFY) -1 Spouse/partner (25_(_-l F. Respondent.... g6 ( -1 Some other reason (SPECIFY) -1 Spouse/partner(27 2] I I �812039 CARD 028 28. How many children have you had — that is, of how many children are you the natural father? Please include children who live with you, those who live elsewhere, and those who may no longer be living. T I children (WRITE IN NUMBER) (ASK Q.29) da ) ( 13) No children A ( -1 (SKIP TO Q.33) 29. Starting with your first child, what is the first and last name of the child as it appears on the birth certificate? RECORD FIRST AND LAST NAMES OF ALL CHILDREN IN S.R.B. - PAGE 3-4. WRITE IN THE FIRST NAME ONLY AT THE TOP OF THE APPROPRIATE COLUMN(S). THIRD CHILD SECOND CHILD FIRST CHILD NAME: NAME: 30a. How old is (CHILD) now? 31a. How old is (CHILD) now? 1 1 1 1 1 1 I 1 Age (15 ) (16 ) Child died. . ( I X -1 ( I? Male 1 1 -1 I I 1 1 1 1 Age (15 ) ( 16) Child died..(17( -1 (18 ( Male (18 ( -1 32c. How much did (CHILD) weigh at birth? • POUNDS OUNCES I I I 1 j l l I l l (19 ) fcb ) Cl ) ( 22) Don't know...(23( -1 32b. (Is/Was) (CHILD) male or female? -1 31c. How much did (CHILD) weigh at birth?. POUNDS OUNCES I I I I I 1 l-l 1 1 (19 ) (20 ) (21 ) ( 22) Don't know... (23 ( as ) <i6 ) 32a. How old is (CHILD) now? l 1 Age 31b. (Is/Was) (CHILD) male or female? -1 -2 30c. How much did (CHILD) weigh at bir?h? I 1 l 1 Child died..( IX 30b. (Is/Was) (CHILD) male or female? Male Female... NAME: -1 1 1 POUNDS OUNCES I I I 1 1 1 l-l 1 1 09 ) CO ) (21 )( 22) Don't know...( 23( -1 30d. What is (CHILD) 's birth- 31d. What is (CHILD) 's birth- 32d. What is (CHILD) 's birthdate? date? date? MONTH DAY YEAR MONTH DAY YEAR MONTH DAY YEAR 1 I I 1 I I 1 1 1 1 1T I I I I I 1 1 1 1 1 1 1 1 1 1 l-l 1 l-l 1 1 1 1 l-l 1 l-l 1 1 124) (25) ( 2d (27) £>8 ) (29 ) l2t> ) (25 ) ( 2Q (27 ) *28 ) (29 ) *24 ) (25 ) ( 2 © ( 2 7 ) (28) (29 ) 1 1 l-l ALSO RECORD IN S.R.B. -PC 3l 1 l-l 1 1 lALSO KECORD IN S.R.B. -PC 3| lALSO RECORD IN S.R.B. -PC 3| >0e. Was the child premature, 31e. Was the child premature, 32e. Was the child premature, f u l l term, or overdue? full term, or overdue? full term, or overdue? Premature. OO ( -1 Overdue -3 (CO TO Q.30f) Premature.( 3Q[ Full term (GO TO Q.3H) -1 -2 Premature. ( 30^ Full term.. . (GO TO Q . 3 2 f ) -1 —2 �CARP 026 91203J. SECOND CHILD FIRST CHILD THIRD CHILD 30f. Where are f (CHILD) 's birth registration records located? In what city and state is that? 1 RECORD IN S.R.B. PG 3 | 3lf. Where are (CHILD) 's birth registration records located? In what city and state is that? 32f. Where are (CHILD) 's birth registration records located? In what city and state is that? IRECORD IN S.R.B. PG 3 1 30g. Where ate (CHILD) 's current medical records located' I" wnat city and ptafe is that? (RECORD IK S.'R'.B. PG 3 1 31g. Where are (CHILD) 's current medical records located? In what city and state is that? ] RECORD IN S.R.B. PG 3 1 32g. Where are (CHILD) 's current medical records located? In what city and state is that? 30h. What was (CHILD) 's mother's full name? 1 RECORD IN S.R.B. PG 3 1 31h. What was (CHILD) 's mother's full name? [RECORD IN S.R.B. PG 3 f 32h. What was (CHILD) 's mother's full name? (RECORD IN S.R.B. PG 3 1 30i. How old was the mother when (CHILD) was born? 31 i. How old was the mother when (CHILD) was born? 32i. How old was the mother when (CHILD) was born? 1 1 1 1 1 1 (31) (35) TRECORD IN S.R.B. PG 3 I 1 1 Age 1 1 Age 1 1 (31) (32) 30 j. Were either of you usin: 31 j. birth control at the time she became pregnant with (CHILD)? Yes. (33(^-1 (ASK Q.30k) No 1 I IRECORD IN S.R.B. PG 3 1 1 1 1 1 Age (31 ) ( 33 Were either of you using 32 j. Were either of you using birth control at the birth control at the time she became pregnant time she Became pregnant with (CHILD)? with (CHILD)? Yes.(33( -2 (SKIP TO Q.301) No, Yes.(33j -1 (ASK 0-32k) . -1 (ASK Q.31k) -2 (SKIP TO Q.31L) No -2 (SKIP TO Q.32L) IHAND RESP^NDEST CARD' "c'M 30k. IHAND RESPONDENT' CARD "c"l IHAND RESPONDENT CARD "C"l Please look at this 31k. Please look at this 32k. Please look at this card and tell me all o1 card and tell me all of card and tell me all of the numbers that apply the numbers that apply the numbers that apply to the types of birth to the types of birth to the types of birth control you or your control you or your control you or your partner were practicpartner were practicpartner were practicing? ing? ing? 31.(34( 32.(35( 33. ( R 3 ).3{ 4C7 35.(38( -1 -1 -1 -1 -1 06.(39( 07.(TO~( O8.(4ir 09.CS2T 1.« 0(( 11. 0 5 -i -1 -1 -1 -1 -1 12 (SPECIFY) Ol.(34( 02. (35? 0.3( 3(5 04. ( 7 37 05. ( 5 3? -1 -1 -1 -1 -i 06.(39( -1 07. (Z67 -1 08. ( T 3 ( -1 09. ( 2 7 1 -1 10. ( ^ -i " 11. (W -i 12 (SPECIFY) .5 U( (GO TO Q.30L) .« (( -1 (GO TO Q.31D 23 -1 01,(34( 02.(55( 03. ("351 04. ( 7 3? 05.(3B( -1 -1 -1 -i -i " 12 (SPECIFY) 06.(39( -1 01. (KR -1 08. ( ^ -1 O9.(72l -1 10.(43( -1 11. (W -1 • UM (GO TO Q.32L) -1 �CARD 028 812039 THIRD CHILD SECOND CHILD FIRST CHILD 30L. How many months did it 31L. How many months did it 32L. How many months did it cake her to become pregtake her to become pregtake her to become pregnant with this child? nant with this child? nant with this child? 1 1 1 I Months (46) (47) (46) (47) Less than 1 month. (48 ( ( 1 1 1 Months "1 Leas than 1 month. (48 ( Wasn't trying .,,.... 1 1 Months (46) (47) 4 -1 Less than 1 month. ( 8 ( -2 Wasn't trying 30m. Did (CHILD) have any birth defects? 31m. Did (CHILD) have any birth defects? 32m. Did (CHILD) have any birth defects? Yes. (49 ( -1 (ASK Q.SOn) Yes. (49 ( -1 (ASK Q.31n) -1 -2 Yes. ( 9 ( - 1 (ASK Q.32n) 4 No,..,.. -2 (SKIP TO Q,30o) No -2 (SKIP TO Q.31o) 30n. What kind of birth defects did (s)he have? Any others? 31n. What kind of birth defects did (s)he have? Any others? 32n. What kind of birth defects did (s)he have? Any others? 30o. Was (CHILD1) ever diagnosed as having cancer? 31o. Was (CHILD) ever diagnosed as having cancer? 32o. Was (CHILD) ever diagnosed as having cancer? Yes.(50( Yes.(50( Yes.(50( -1 (ASK Q.30p) -1 (ASK Q.31p) No,...,. -2 (SKIP TO Q.31r) No 30p. In what month and year 31p. was the diagnosis made? MONTH , YEAR 1 1 1 . 1. I I (51) f52) (53) (54) -1 (ASK Q.32p) -2 (SKIP TO Q.32r) In what month and year 32p. In what month and year was the diagnosis made? was the diagnosis made? MONTH 1 1 (51) (52) YEAR I I 1 1 (53) (54) MONTH YEAR 1 -1 (51) (52) (53) (54) 30q. What kind of cancer was diagnosed? 31q. What kind of cancer was diagnosed? 32q. What kind of cancer was diagnosed? (55-56) (55-56) (55-56) Not sure.,( 5X (GO TO Q.30r) -1 Not sure..(57( (GO TO Q.31r) -1 Not sure..(57( (GO TO Q.32r> _i �812039 . CARD ,028 SECOND CHILD FIRST CHILD THIRD CHILD 30r. (Does/Did) (CHILD) have a 31r. (Does/Did)(CHILD) have a 32r. (Does/Did) (CHILD) have i diagnosed learning disdiagnosed learning disdiagnosed learning disability? ability? ability? Yes.(5g.(,. -1 (ASK Q.30s) Yes. (58 ( -1 (ASK Q.31s) No 30s. What kind of learning disability (does/did) (s)he have? Yes.(58( -2 (SKIP TO Q.31t) No 31s. What kind of learning disability (does/did) (s)he have? -1 (ASK Q.32s) -2 (SKIP TO Q 32t) 32s. What kind of learning disability (does/did) (s)he have? 30t. (Does/Did) (CHILD) have 31t. (Does/DidMCHILD) have 32t. (Does/Did) (CHILD) have any physical, mental, or any physical, mental, or any physical, mental, 01 motor impairments? motor impairments? motor impairments? Yes.(52J__-l (ASK Q.30\i) No Yes. ( 9 ( -1 (ASK Q.31u) 5 -2 (SKIP TO Q.30v) No...... » 30u. What kind of impairment (does/did) (s)he have? Yes.(59( -2 (SKIP TO Q.31v) No...... 31u. What kind of impairment (does/did) (s)he have? "1 (ASK Q.32u) -2 (SKIP TO Q 32v) 32u. What kind of impairment (does/did) (s)he have? V IF CHILD IS DEAD: CONTINUE OTHERWISE: SKIP TO NEXT CHILD 30*v. On what date did (CHILD) die? IF CHILD IS DEAD: CONTINUE OTHERWISE: SKIP TO NEXT CHILD 31v. On what date did (CHILD) die? IF CHILD IS DEAD: CONTINUE OTHERWISE: SKIP TO NEXT CHILD 32v. On what date did (CHILD) die? ) MONTH DAY YEAR MONTH DAY YEAR MONTH DAY YEAR 1 I I 1 I I 1 1 I I V I I I I 1 1 l-l 1 1 1-1 .1.1-1 1 , 1 1 -1 -1 1 6) 60) (61) (62) (63) (64) (65) (60) (61 ) (62) (63) (64) (65)( 0 (61) (62) (63) (64) (65) iOw, What was the cause of death? 31w. What was the cause of death? 32w. What was the cause of death? (Ox. Where ie (CHILD) 's death registered? In what city and state is that? RECORD IN S.R.B. PC 3 1 31x. Where is (CHILD) 's death registered? In what city and state is that? (RECORD IN S.R.B. PG 3 I 32x. Where is (CHILD) 's death registered? In what city and state is that? (RECORD IN S.R.B. FG 3 (GO TO NEXT CHILD Q.31a) _ _ 79-80 (GO TO NEXT CHILD Q.32a) J32 79-80 (RECORD ADDITIONAL CHILDREN IN S.R.B. - PC 28-39) J)3 7<J-80 �812039 CARD 033 33. Now let's talk about your health. Compared to other people your age, would you say that your health is excellent, good, fair, or poor? Excel lent.... (12( Good ............. -1 -2 -3 Poor. 34a. Did a doctor ever tell you that you had pneumonia? Yes. (13 ( -1 No......___ _-2 34b. (ASK Q.34b) (SKIP TO Q.36a) How many times have you had pneumonia? (WRITE IN NUMBER) i I _ r J I times 04 ) ( 15) 35a. During what month? and years did you have pneumonia (the first time)? [RECORD IN S.R.B. PcTT IF BEFORE 1961, SKIP TO Q.35f. 35f. During what months and years did you have pneumonia (the second time)? IRECORD IN S.R.B. PC 5 1 IF BEFORE 1961, SKIP TO Q.35k. 35b. What is the full name 35g. What is the full name of the doctor who made of the doctor who made the diagnosis or the the diagnosis or the medical facility where medical facility where the diagnosis was made? the diagnosis was made? IRECORD IN S.R.B. PC 5 I 35c. What prescribed medicine did you take for the pneumonia you had that time? Third Time Second Time First Time [RECORD in S.R.B. PC 5 I 35k. During what months and years did you have pneumonia (the third time)? IRECORD IN S.R.B. PC 5 I IF BEFORE 1961, SKIP TO 35L. What is the full name of the doctor who made the diagnosis or the medical facility where the diagnosis was made? I RECORD IM S.R.B. PG 5 I 35h. What prescribed medicine did you take for the pneumonia you had that time? 35m. What prescribed medicine did you take for the pneumonia you had that time? 35i. Were you hospitalized for the pneumonia you had that time? 35n. Were you hospitalized for the pneumonia you had that time? 1. 2. 3. 35d. Were you hospitalized for the pneumonia you had that time? Yes.(l6( No 35e. -1 (ASK Q.35e) Yes.OJJ^-l (ASK Q.35i) Yes.(18( -1 (ASK Q.35o) -2 (SKIP TO Q.35f) No -2 (SKIP TO Q.35k) No _-2 (SKIP TO Q.36a) What was the full name of that hospital? IRECORD IN S.R.B. PG 5 I 35j. What was the full name of that hospital? IRECORD IN S.R.B. PC 5 I 35o. What was the full name of that hospital? I RECORD IN S.R.B. PG 5 I �036 36a. 812039 Did a doctor ever tell you that you had cancer? Yes..(;2( -1 (ASK Q.36b) No -2 (SKIP TO Q.37) 13-14 36b. In which parts of your body was cancer located? LIST EACH BODY PART BELOW. IF MORE THAN THREE BODY PARTS, USE S.R.B. - PACE 46 FOR ADDITIONAL PARTS. Part 1 Part 1 J6c. In what month and year 36i. vet cancer of the (BODY PART) first diagnosed? Part 3 In what month and year 36o. was cancer of the (BODY PART) first diagnosed? IRECORD IN S.R.B. PG 5 I RECORD IN S.R.B. PC 5 1 in what month and year was cancer of the (BODY PART) first diagnosed? (RECORD IN S.R.B. PG 5 j 36 j. What is the full name 36p. What is the full name 36d. What is the full name of the doctor or the of the doctor or the of the doctor or the medical facility where medical facility where medical facility where the diagnosis was made? the diagnosis was made? the diagnosis was made? IRECORD IN S.R.B. PC 5 | RECORD IN S.R.B. PC 5 1 IRECORD IN S.R.B. PG 5 1 I6e. What is the full name of, the doctor or the medical facility you last consulted about Cancer of the (BODY PART)? RECORD IN S.R.B. PG 5 | 36k. What is the full name of the doctor or the medical facility you last consulted about cancer of the (BODY PART)? IRECORD IN S.R.B. PG i" 36L. 6f. During what month and year did you last consult (NAME FROM Q.36e)? What is the full name of the doctor or the medical facility you last consulted about cancer of the (BODY PART)? IRECORD IN S.R.B. PC 5 I 36 r. During what month and During what month and year did you last conyear did you last consult (NAME FROM Q.36q)7 sult (NAME FROM Q.36k)? [RECORD IN S.R.B. PG 5 1 IRECORD IN S.R.B. PC 5 RECORD IN S.R.B. $ 5 1 36q. 36s. What treatments or 36m. What treatments or What treatments or medicines did you take medicines did you take medicines did you take for cancer of the (BODH for cancer of the (BODY for cancer of the (BODY PART)? PART)? PART)? (MULTIPLE RECOR6 BELOW I (MULTIPLE RECORD BELOW | [MULTIPLE RECORD BELOW 1 )6g. Radiation .^ ( ( -1 Chemotherapy. . . ( ° * ( -1 Radiation (15( -1 Chemotherapy. . . (16( -l Radiation (15( -1 Chemotherapy. . . (16( -1 Other (SPECIFY) Other (SPECIFY) ' Other (SPECIFY) .(18( .(18( -1 6h. During what month and year did you first receive (EACH TREATMENT CODED IN Q.36g) for cancer of the (BODY PART)? 36n. ~ -1 During what month and year did you first receive (EACH TREATMENT CODED IN Q.36m) for cancer of the (BODY PART)? .U8( -1 36t. During what month and year did you first receive (EACH TREATMENT CODED IN Q.36s) for cancer of the (BODY PART)? MONTH YEAR MONTH . YEAR MONTH YEAR adia1 i 1 T 1 1 RadiaT i l l RadiaI I 1 1 1 tion.... 1 1 l-i 1 I tion.... 1 1 1-1 1 1 tion.... 1 |. ... 1 J fl9> T20) hi!) (22> < 19) ( 20) ( 2 ) 62 ) : (19)( 20> < 21> < 22> MONTH YEAR MONTH YEAR MONTH YEAR hemo1 1 1 1 1 Chemo1 I 1 1 i Ch emoI 1 therapy. . 1 - 1 1 1 therapy. 1 1 1-1 1 therapy. 1 „ 1 (23) (24) (23) (56) ( 23) ( 24) ( 25) i 265 (23 ) ( 24> ( 25) ( 26) MONTH YEAR MONTH YEAR MONTH YEAR 1 1 1 1 1 1 1 1 1 1 ( 1 1 f 1 T uraery.. 1 1 1-1 1 1 Surgery.. 1 | I- I 1 | Surgery.. 1 1 1J | ( f 27) 66 ) ( H) ( 30) ( 27) ( 28) C29 ) ( 30) 27 > (28 > V29 > (30 > MONTH YEAR MONTH YEAR MONTH YEAR . 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 ther.... 1 l-l I I Other.... | | 1-| Other.... 1 1 H I . .1 ( 3lH J2) H3) ( 34) <3l ) (32 > (31 5 ~<J4 ) <-3! * <3!>> l 33> <34> (00 TO NKXT BODY PART) (GO TO NEXT BODY PART) (GO TO NEXT BODY PART IN 01 7'i-R() S.R.B. PACE 40) 02 03 7 9"- 80 79- HO 27 �CARD 037 812039 IIF LEUKEMIA NOT PREVIOUSLY MENTIONED. ASK:I 37a. Has a doctor ever told you that you had leukemia? Yes.l'(12( . -1 No 37b. -2 (ASK Q.37b) (SKIP TO Q.38) In what month and, year was your leukemia first diagnosed? I RECORD IN S.R.B. - PC 6 I 37c. What is the full name of the doctor or the medical facility where the diagnosis was made? TRECORD IN S.R.B. - PC 6 1 37d. P, What treatments or medicines have you taken for leukemia? I RECORD BELOW I MEDICINE/TREATMENT i. , _ E. FIRST'RECEIVED ,.^._..-_ ^____ r MONTH YEAR i Ii i-i Ii Ir n l4) (15) (16) MONTH 2. YEAR I J, I-I I, I (17) (18) (1?) (20) :YEAR 3. _ . . 1 1 T I I I I I, I-I I, I (21f ( 2 (23) 2) (24) 37e. During what month and year did you first receive (EACH TREATMENT OR MEDICINE IN Q.37d)? I RECORD ABOVE] 37f. What is the full name of the doctor or medical facility you last consulted about your leukemia? JRECORD IN S.R.B. - PC 6 j 37g. During what month and year did you last consult (NAME IN Q.37O? JJECORD IV S.R.B. - PC 6 I /25-60/ 28 �38a, had. I; yogld like to ask you some questions about other medical conditions you may have 1. Did you ever have diabetes? Yes No ( 1 ;_ 6( -I ("X" BOX ON PAGE 26) "-2' ' 2. Did you ever have thyroid problems? Yes (SPECIFY) .<62( No..,....., -1 T-r-,,.-,-,. "2 ( X BOX ON PAGE "" 3, Did you ever have anemia? Ye No (3 £( -1 -I ("X" BOX ON PAGE 26) A. Did you ever have a heart condition? Yes (SPECIFY) -I ("X" BOX ON PAGE 26) No...... . . . . ..... 5. Did you ever have an enlarged liver? Yea........<£5(_ No .......... -1 -2 <"X" BOX ON PAGE 2 . 6) 6. Did you ever have jaundice? Yea ........ ( , ( 66 , -1 No ............. -2 ( X BOX ON PAGE 27) "" 7. Did you ever have hepatitis? Yes ........ (67( -1 No .......... . . _ ; _..' -2 .. ("X" BOX ON PAGE 27) 8. Did .you ever have cirrhosis of the liver? Yes........( 6ft No......, ...... "1 -2 ("X" BOX ON PAGE 27) 9. Did you ever have intestinal parasites? Yes No, (9 $( -1 ("X" BOX ON PAGE 27) -2 10. Did you ever have gall bladder problems? Yes., No ( 7QL -1 ("X" BOX ON PAGE 27) '"™™.2 '_^*" 11. Did you ever have eny other liver condition? Yes (SPECIFY) .1 ("X" COX ON PAGE 2?) No 12. Did you ever have a respiratory condition other than pneumonia? Yes (SPECIFY) NO ,,, .7( (2 ~1 ("x11 BOX ON PACE 28) -1 <"X" 8PX ON PACE 28) ,..,,, .„,,;,.__•• 2 13. Did you ever have any other major condition' Yes (SPECIFY) ,<73J N o , , , , . , . , , . , , , , , , , ; , , , , , -_____-2 �CARD DIABETES I ASK Q.38b THROUGH Q . 3 8 h 1 IFOR EACH BOX "X"ED ON I IFF. 26-28 1 38b. 38c. When did a doctor first tell you that you had (CONDITION)? What is the full name of the doctor who made the diagnosis or the medical facility where the diag38d. 1 I THYROID PROBLEMS A HEART CONDITION ANEMIA I AN ENLARGED LIVER I IRECORD IN S.R.B.I IPAGE 7 1 (RECORD IN S.R.B.I (PAGE 7 1 IRECORD IN S.R.B.I IPAGE 7 1 IRECORD IN S.R.B.I IRECORD IN S.R.B.I IPAGE 7 1 IRECORD IN S.R.B.I IPAGE 7 1 I RECORD IN S.R.B.I IPAGE 7 1 IRECORD IN S.R.B.I IPAGE 7 I 1 PAGE 7 1 RECORD IN S.R.B.I IPAGE 7 1 1 1 RECORD IN S.R.B.I IPAGE 7 1 Do you have (CONDITION) -Yes.(l2( -1 (ASK Q.38e) Yes.( 12( No -2 (SKIP TO Q. No ~ 38g) 38e. I I 812039 038 Are you currently talcing any prescribed medicines for your (CONDITION) -Yes.(13( -1 (ASK Q.38f) Yes.( 13( -1 (ASK Q.38e) Yes.(12( -2 (SKIP TO Q. 38g) -1 (ASK Q.38e) Yes.(12( -1 (ASK Q.38e) Yes.(12( Uo -2 (SKIP TO Q. No. 38g) ~ 38g) -1 (ASK Q.36e) -2 (SKIP TO Q. -1 (ASK Q.38e) Yes.(13( -1 (ASK Q.38f) Yes.O3( (ASK Q.38f) -2 (SKIP TO Q. 38g) -1 (ASK Q.38f) No 38g) 38f. 38g. When did you last consult a doctor for (CONDITION)? 38g) 38g) 38g) What are the names of the medicines you are taking for (CONDITION)? 38h. What is the full name cf the doctor or medical facility you Last consulted about your (CONDITION)? - IRECORD IN S.R.B.I IPAGE 7 1 (RECORD IN S.R.B.I IRECORD IN S.R.B.I IPAGE 7 1 IRECORD IN S.R.B.I IPAGE 7 1 IRECORD IN S.R.B.I IPAGE 7 1 (RECORD IN S.R.B. | IRECORD IN S.R.B. I (PAGE 7 j IPAGE 7 1 (GO TO NEXT CONDITION "X"ED) (GO TO NEXT CONDITION "X"ED) (GO TO NEXT CONDITION "X"ED) 61 IPAGE 7 62 79-80 I 79-80 IRECORD IN S.R.B.I IPAGE 7 1 (GO TO NEXT CONDITIOt< "X"ED) 79-80 1 RECORD IN S.R.B. 1 IPAGE 7 1 1 RECORD IN S.R.B. ! IPAGE 7 1 (GO TO NIEXT CONDITION "X"ED) 65 �CARDO38 JAUNDICE IFOR EACH BOX "X^ED ON 1 1 1 1 ! 1 (PP. 26-28 I 1 1 1 "i.ASK O..38b THROUGH Q,38h I When did 8 doctor first tell yeu that you had (CONDITION)?, 38c. 38d, HEPATITIS 1 1 1 1 1 CIRRHOSIS OF THE LIVER 1 INTESTINAL PARASITES ! 1 1 1 1 t 1 1 ' ! 1 1 1 1 1 jRECOJtD IN S.R.B.1 What is the full name of the doctor vho made the diagnosis or the medical facility where the diag- (RECORD IN S. R.B.I IPAGE 7 IPAGE 8 I 1 RECORD IN S.R.B.1 IPAGE 7 1 I (RECORD IN S.R.B.1 IPAGE 8 I 1 RECORD IH S.R.B.1 IPAGE 8 1 1 RECORD IN S.R.B.1 IPAGE 8 1 J 1 1 1 1 RECORD IN S.R.B.1 IPAGE s 1 I RECORD IN S.R.B.1 IPAGE s 1 GALL BLADDER PROBLEMS 1 I i I IRECOR& IN s. R.B.I (PAGE S I (RECORD IN S.R.B. 1 IPAGE s 1 Po you have (CONDITION) .Yes! (12 ( -1 (ASK Q,38e) Yes. 02 ( -1 (ASK Q.38e) Yes. (12 ( -1 (ASK Q,38e) Yes.02 ( -1 (ASK Q.38e) Yes.Q2 ( -1 (ASK Q.38e) {jo -2 (SKIP TO Q. No -2 (SKIP TO Q. No. ... -2 (SKIP TO Q. -2 (SKIP TO* Q. Ho -2 (SKIP TO Q. No 38g) 38g) ~~ 38g) 38g) 38g) 38e. Are you currently taking X any prescribed medicines for your (COHWnOU) .Yes. (13 ( -1 (ASK Q.38f) Yes. ( 3 ( -1 (ASK Q.38e) Yes. (13 ( -1 (ASK Q.38f) 1 Yes. 03 ( -1 (ASK Q.38f) Yes. (13 ( -1 (ASK Q.38f) -2 (SKIP TO Q. No... -2 (SKIP TO Q. Ho -2 (SKIP TO Q. H . . 7 7 -2 (SKIP TO 0 . Ho o. 7 . -2 (SKIP TO Q No 38g) 38g) 38g) 38g) What are the names of the medicines you are taking for (CDtTOtTIOD)? When did you last consult a doctor for (CONDITION)? What is the full name of the doctor or medical facility you last consulted about your [RECORD IN S.R.B.} (PAGE 7 1 I RECORD IN S.R.B.1 IPAGE 8 1 (RECORD IN S.R.B.1 IPAGE 7 1 (RECORD IN S.R.B. I (GO TO NEXT CONDITION «X"EO) 66 79-HQ' IPAGE s 1 (GO TO NEXT CONDITION -X"ED) 67 79-BO (RECORD IN S. R.B.I IPAGE s 1 (RECORD IN S.R.B.1 (PAGE 8 1 (GO TO NEXT CONDITION "X"ED) 68 79-80' (RECORD IN S.R.B.1 (PAGE 8 1 (RECORD IB s. R.B.I (PAGE s 1 1 RECORD IN S.R.B.1 (RECORD IN S.R.B.T IPAGE 8 1 IPAGE s I (GO TO NEXT CONDITIOh "X"ED) 69 79-SU (GO TO NEXT CONDITION "X"ED) 70 79-80 �CARD 038 ANY OTHER LIVER CONDITION _____ I I I I (ASK Q.38b THROUGH Q.38h IFOR EACH BOX "X"ED ON IFF. 26-28 38b. When did a doctor first tell you that you had (CONDITION)? A RESPIRATORY CONDITION I OTHER. THAN PNEUMONIA I I I I I I I (RECORD IN s. R.B.I IPAGE 8 ! IRECORD IN s. R.B.I IPAGE 8 1 IRECORD IN s. R.B.I IPAGE 9 1 1 RECORD IN S. R.B.I 38c. What is the full name of the doctor who made the diagnosis or the medical facility where the diagnosis was made? IRECORD IN S.R.B. I IRECORD IN S.R.B.I IPAGE 9 1 (PAGE s 1 (PAGE 8 ( 12( -1 '(ASK Q.38e)Yes.( 12( No. . . -2 (SKIP TO Q. No .. 38g) 38e. I I I I ANY OTHER . MAJOR CONDITION 1 -1 (ASK Q.38e) Yes. 02 ( -1 (ASK Q.38e) -2 (SKIP TO Q. No...... -2 (SKIP TO Q. 38g) , 38g) Are you currently taking any prescribed medicines (13 < -1 (ASK Q.38f)Yes.( 13J -1 (ASK Q.38e) Yes. (13 ( -1 (ASK Q.38f) -2 (SKIP TO Q. No. . . -2 (SKIP TO Q. No -2 (SKIP TO Q. No .. 38g) ~ 38g) .8> 'g 38f. What are the names of the medicines you are taking for (CONDITION)? Any others? 38g. When did you last consult a doctor for (CONDITION)?. 38h, What is the f u l l nave, of the doctor or aedicat f a c i l i t y you last consulted about your (CONDITION)?.. 1 RECORD IN S.R.B. 1 IPAGE 8 1 IRECORD IN S.R.B. I IPAGE 8 1 IRECORD IN S.R.B.I IPAGE 9 1 (RECORD IN S.R.B. 1 IPAGE 8 1 IRECORD IN s. R.B.I IPAGE 8 1 IRECORD IN S.R.B.I TO NEXT CONDITION "X"E :D) 71 79-80 (GO TO NEXT CONDITIO •"X"ED) „ f 79-80 IPACE 9 I 73 79-80 812039 �812039 CARD 039 39. Have you ever had acne on your face':1 Yes..(12( _-l -2 No 40a. (ASK Q.40a) (SKIP TO Q.42) During what year did you last have acne on your face? I Year (WRITE IN YEAR) Before 1961 . .(15( _____.(ASK Q.40b) ~T13) TT4T Second Period First Period 40b. Think about the first time you had acne on your face **• when did it start? MONTH T~7T~-f T I l-l I I 06 )(17)( 18) (19) 40c. Until when did that last? •MONTH YEAR i n r (20) 22) (23) AOf. Think about the second time you had acne on your face -— when did it start? MONTH MONTH YEAR I I L (48) (49) (50) (51) I I (32) (33) (3A) (35) MONTH Third Period AOj. Think about the third time you had acne on your face — when did it start? YEAR AOg. Until when did that last? -1 (SKIP TO Q.A2) 40k. Until when did that last? YEAR I I MONTH YEAR I I (52) (537 ( 5 ( 5 5) 5) I I (36) (37) ( 8 ^ l ) 3 )t 9 40d. Please show me on this diagram where the acne was located (the first time). AOh. Please show me on this diagram where the acne was located. AOL. Please show me on this diagram where the acne was located. I HAND RESPONDENT CARD "E"l I HAND RESPONDENT CARD "E" I I HAND RESPONDENT CARD "E" I MULTIPLE RECORD BELOWT [MULTIPLE RECORD BELOW| [MULTIPLE REQORD BELQWJ templet;'. .'.... QA'r ^T Byes or eyelids. (25 ( ~-l Ears ............ (26( -1 Cheeks . .V(7 ( . ..2 -1 Nc.se Forehead ........ (29 ( Jaw, Chin, Other(30" Temples .TgiO( -1 Eyes or eyelids.(41 ( . -1 Ears (42 ( -1 Temples..» 66 ^ -1 Eyes or eyelids.(57 ( -1 Ears. Cheeks.......... $9 ( -1 Nose* .ftb ( -1 Forehead (ft3• ( . -1 Jaw, Chin, Otherl^T -1 AOe. Did you ever have another period of acne on your face? Yes.Ojj ( -1 (ASK Q . A O f ) No ...... _j-2 (SKIP TO Q.41a) :..:.M Cheeks -1 Nose Forehead........(45 (......-1 Jaw, Chin, Other(4T( -1 AOi. Did you ever have another period of acne on your face? 40m. Did you ever have another period of ache on your face? Yes.(63 ( -1 Yes. (47 ( -1 (ASK Q.AOj) -2 No _ -2 (SKIP TO Q.Ala) No. IF ANY" "Yls" TO TEMPLE, EYES, EYELIDS, OR EARS IN Q.AOd.AOh, OR AOL ABOVE: ASK Q.Ala. ALk OTHERS,! SKIi' TQ Q.42. Ala. Did you ever consult a doctor or medical facility about the acne on your (temples/eyes Of eyelids/ears)? -1 (ASK Q.Alb) -2 (SKIP TO 0.42) 4lb. When did you last consult a doctor about the aene on your (temples/eyes Or eyelids/ears)? s.R.ft. .7" Ale. What was the name of the doctor or medical facility y&u Consulted at the time? S.R.B. r.PC..9 33 �-29a- CARD 135 Aid. When you had this acne on your face did you also have it on your chest, back, shoulders, arms, or legs? Yes ..... (26( (ASK Q.Ale) No.........._ Ale. -1 -2 (SKIP TO Q.A2) Where was that? I CODE ALL THAT APPLY! Chest........(27<_ ,-1 Back ......... (T6( '''"'"'-! _ Shoulders. . . . 2 K_ (j .-1 Arms----.----( 30( _ -1 Legs ......... (3JT -1 Alf. When was that? FROM .MONTH YEAR "~I~ r r~~ T r i Ii I I nrr OAI TSFT TO MONTH (36) (37) YEAR (38) (39) �CARD 039 42a. 812039 Have you ever had (READ EACH COLUMN HEADING)? TlF "YES" TO ANY COLUMN HEADING. ASK Q.42b-h FOR THAT COLUMN I A. B. . Patches Of. .you*,Sfrifl. change color? Easier bruising of the skin than usual? Ycs.»v^( —1 J No ''~_ 2 C. Skin that was extra sensitive or seemed to hurt for no reason? Yes..(67(._-i Yes..(A9( . -1 No -2 Ir. On wlml p a r t of your body did you have (CONDITION)? Any other part? b. On what part 01 your body did you have (CONDITION)? Any other part? b. On what part of your body did you have (CONDITION)? Any other part? C. Did you discuss (CONDITION) with a doctor? c. Did you discuss (CONDITION) with a doctor? c. Did you discuss (CONDITION) with a doctor? Yes.( 66( -1 (ASK Q.42d) Yes.(68( No...... -2 (GO TO NEXT ~ CONDITION) No d. What was the diagnosis? d. e. e. What is the name of the doctor who made the diagnosis or the medical facility where the diagnosis was m?de? -2 (GO TO NEXT ~~ CONDITION) IRECORD IN S.R.B. - PG iol f. During what month and year was the diagnosis made? What is the name of the doctor or medical facility you last consulted about (CONDITION)? f. During what month and year did you last consult (NAME IN Q.42g)? IRECORD I'N S.R.B. - PG iol -1 (ASK Q.42d) No -2 (GO TO NEXT CONDITION) d. What was the diagnosis? e. What is the name of the doctor who made the diagnosis or the medical facility where the diagnosis was made? What is the name of the doctor who made the diagnosis or the medical facility where the diagnosis was made? IRECORD IN S.R.B. - PG iol During what month and year was the diagnosis made? f. IRECORD IN S.R.B. - PG iol g. IRECORD IN S.R.B. - PG iol h. What was the diagnosis? Yes.( 7 ( 0 IRECORD IN S.R.B. - PG 101 IRECORD IN S.R.B. - PG iol g. -1 (ASK Q.42d) What is the name of the doctor or medical facility you last consulted about (CONDITION)? IRECORD IN S.R.B. - PG idl g. IRECORD IN S.R.B. - PG iol h. During what month and year did you last consult (NAME IN Q.42g)? IRECORD IN S.R.B. - PG iol 35 During what month and year was the diagnosis made? What is the name of the doctor or medical facility you last consulted about (CONDITION)? IRECORD IN s.jt.B. - PG iol h. During what month and year did you last consult (NAME IN Q.42g)? IRECORD IN S.R.B. - PG iol �CARD 039 42a. Have you ever had (READ EACH COLUMN HEADING)? I IF "YES" TO ANY COLUMN HEADING. ASK Q.A2b-h FOR THAT COLUMN! D. A rash on your back caused by lower back pain? £. A short period of excessive hair growth caused by lower back pain? f i Yes.. ( 3 ( -1 7 No -2 Yes.. (71 ( -1 No, -2 On what part of your body did you have (CONDITION)? Any other part? b. On what part of your body did you have (CONDITION)? Any other part? c. Did you discuss. (CONDITION) with a doctor? c. Did you discuss (CONDITION) with a doctor? Ye s. (72 ( -1 (ASK Q.42d) Yes. ( 4 (^-1 (ASK Q.42d) 7 No No »•»••• b. -2 (GO TO NEXT ~~ CONDITION) d. What was the diagnosis? *2 d. What wa« the diagnosis? ' e. What is the name of the e. What is the name of the doctor who made the diagdoctor who made the diagnosis Or the medical nosis or the, medical facility where the diagfacility where the diagnosis was made? nosis was made? IRECORDJti S.R.B. - PG 101 (RECORD IN S.R.B. - PG 10| f. During what month and year was the diagnosis made? f. During what month and year was the diagnosis made? RECORD IN S.R.B. - PG 101 h. What is the name of the doctor or medical facility you last consulted about (CONDITION)? g. What is the name of the doctor or medical facility you last consulted about (CONDITION)? I RECORD IN S.R.B. - PG 10J g. IRECORD IN i.R.B. - PG 101 IRECORD IN S.R.B. - PG 10| During what month and year did you last consult (NAME IN Q.42g)? RECORD IN S.R.B. - PG 10| n. During what month and year did you last consult (NAME IN Q.42g)? IRECORD IN S.R.B. - PG 10! 812039 �CARD 812039 043 43a, Aside from injury, has there ever been a period of time when you had (READ EACH " COLUMN HEADING)? j: _ , ___ flF "YES" TO ANY COLUMN HEADING, ASK Q.43b-K FOR THAT COLUMNT B. Persistent tingling sensations in anv of your limbs? A. Persistent numbness in any of your limbs? b. When did you first notice (CONDITION)? When did you first notice (CONDITION)? MONTH YEAR ( 1 1 1 1 1 1 . H 1 1. c. Which limbs or muscles were affected? (CONDITION)? Any other part? c. Which limbs or muscles were affected? (CONDITION)? Any other part? Do you still have (CON- d. Do you still have (CONDITION)? DITION)? f. b. When did you first notice (CONDITION)? MONTH YEAR t 1 1 1 1 1 1 1 l-l 1 1 (43'. (443 ( 5 (16) 41 c. Which limbs or muscles were affected? (CONDITION)? Any • other part? d. Do you still have (CONDITION)? Yes.{47( Yes. (32 ( -1 No -2 Yes.(LZ!_-l No. . . . -2 .. e. NO....VTI '-2 MONTH YEAR 1 ! 1 1 1 1 1 1 l-l 1 'I (28 ) (29 > ( 30) (31 ) 1 ( 1} (14) (15) (16) d. Yes..^2( -! Yes.. (27 ( -1 Yes.. (12(^-1 b. C. Persistent deep burning sensations in any of your limbs? -i During what period was the (CONDITION) most intense? FROM MONTR YEAR 1 1 1 f 1 1 I I H 1 1 (18) <ig) <2Q) <21> TO MONTH YEAR 1 1 1 1 1 1 1 1 H I . I <22> <23) (24) (25) e. During what period was the (CONDITION) most intense? FROM MONTH YEAR 1 1 1 1 1 1 I l l - I l l (33) <34> ( 33 (36) TO MONTH YEAR 1 1 1 1 1 1 1 1 l-l 1 1 (37) (38) (39) (40) e. During what period was the (CONDITION) most intense? FROM MONTH YEAR 1 1 1 1 1 1 I I l-l 1, 1 &b ) 69 ) t 5d) I 51) TO MONTH YEAR 1 1 1 1 1 1 1 1 .1-1. 1 . 1 Did you see a doctor for (CONDITION)? f. Did you see a doctor for (CONDITION)? f. Did you see a doctor for (CONDITION)? CJ2') ('S3) (54) (55) V«t><_a6trJ-l (I* NO, GO TO Yes. ( 6 (_^1 (IF NO, CO TO 5 Yes.(u( -1 (IP NO, GO TO No...... -2 NEXT CONDITION) No...... -2 NEXT CONDITION) g. What was the diagnosis? g. What was the diagnosis? g. What was the diagnosis? h. What is the name of the doctor who made the diagnosis or the medical facility where . .the diagnosis was, made? 1 RECORD IN S.R.6. - PC 111 _ _...........______ _ [RECORD IV g.R.B. - PC 111 i . During what month and, year was the diagnosis made?. [RECORD IK S.R.jB. - "PC "ill' [RECORD IN S.R.B...'.- PC 111 - - _____ | RECORD IN S.R.B. - PC 111 I RECORD IN £.RJB. - PG 1.1 1 j. What is the name of the doctor Or medical facility you last consulted about (CONDITION ) ? TJEGOfiD IN ,.Sr^.,BA3^ k. . IN . S.R.B, - I)u^ri : n£_wh«t itiontVi apd ...year did you l a s t consult (NAME IN Q.4Jjg)? .............. .' j>j .;S»A ;.»•,,- PptllT .iRECOBi) JN .S.R.B. .-. PC ITT ' ' ' �CARD 443 812039 43a. Aside from injury, has there ever been a period of time when you had (READ EACH COLUMN HEADING)? ^ . I IF "YES" TO ANY COLUMN HEADING. ASK Q.A3b-K FOR THAT COLUMN I E. A reduction in grip strength? Persistent aches and pains in any of your limbs? Yes..( 1 2 < No., b. -1 -2 When did you first notice (CONDITION)? Yes..(j7( No b. MONTH YEAiR ! I I 1 1 1 H 1 1 (13) (14) (15) (16) -1 -2 When did you f i r s t notice (CONDITION)? MONTH YEAR 1 I I I I I C8 ) ( W, ( 30) ( 31) 1 1 c. Which limbs or muscles were affected? (CONDITION)? Any other part? c. Which limbs or muscles were affected? (CONDITION)? Any other part? d. Do you s t i l l have (CONDITION)? d. Do you still have (CONDITION)? Yes.G2 J Yes.(l7( i -1 No -2 e. During what period was the (CONDITION) roost intense? FROM MONTH YEAR ,1 I I I 1 :i e. l-l i i as ) (19 : GO ) ( 2i) TO MONTH YEAR 1 1 I I I 1 1 1 l-l 1 1 • , (22 > <23 •) (24 1 ( '251 f. Did you see a doctor fpr (CONDITION)? Yet,.C'-26< No g- During what period was the (CONDITION) most intense? FROM MONTH YEAR 1 1 1 1 1 1 1 1 l-l 1 1 (33) (34) (35) (36) TO MONTH YEAR 1 I I I 1 1 I l l - I l l (37) (38) (39) ftOJ f . Did you see a doctor for (CONDITION)? Yes.(41( -1 (IF NO, GO TO -2 NEXT CONDITION) What was the diagnosis? -1 NO...TTT -2 g. -1 What was the diagnosis? h. What is the name of the doctor who made the diagnosis or the medical facility where the diagnosis was made? 1 RECORD IN 'S.R.B . - PC 111 T ^RECORD IN S.IUB. - PC 11] i. During what month and year was the diagnosis made? |RECORD IN S.R.B. - PC llj I RECORD IN S.R.B. - PC UI j. What is the name of the doctor or medical facility you last consulted about (CONDITION)? • I RECORD IN S.R.B7 - PC YlT I RECORD IN S.R.B. - PC 111 k. During what month and year did you last consult (NAME IN Q.62g)? ' [RECORD IN E.IR,.¥. - PC 1 1 1 IRECORD ~IN S . K . B . - PC 111 38 �__; r_^.: ^ CARD Q4A 812039 44a. (Besides the prescribed medicines you told me about), are you currently taking any (other) medicines prescribed by a doctor? Yes (2 ( ^ No.,, "1 (ASK Q.44b) -2 (SKIP TO Q.45) 44b. For what conditions were the medicines prescribed? Any other conditions? (15C. 3:) �..CARP 045 45a. Have you ever smoked cigarettes regularly for a period of at least one month? Yes (12( -1 (SKIP TO Q.48a) In what month and year did you start smoking cigarettes on a fairly regular basis? MONTH YfAg"" .(13) ,(J4) 45c, (ASK Q.45b) -2 No 45b. 812039, Tl.5) In what month .and year did you ^aat smoke cigarettes on a fairly regular basis? MONTH YEAR 1 T I I (17) (18) (19) (20) 46a. When you started smoking cigarettes on a fairly regular basis in (START DATE), about how many packs per week did you smoke'? By "pack" we mean 20 cigarettes. I packs per week (22) (21) 46b. Until what month and year did you continue to smoke (NUMBER) packs per week on a regular basis? MONTH YEAR 1 | T 1 I T (IF DATE IS THE SAME AS Q.45c: SKIP TO Q.47a. I J J-l I | ALL OTHERS: CONTINUE) (23) (24) (25) (26) 46c, After that, about how many packs per week did you smoke? ~ P I I | I packs per week (27) (28) 46d. Until what month and year did you continue to smoke (NUMBER) packs per week on a regular basis? MONTH YEAR T | TT I "T (IF DATE IS THE SAME AS Q.45c: SKIP TO Q.47a. I j j-l || ALL OTHERS: CONTINUE) (29) (30) 731)132) 46e. After that, about how many packs per week did you smoke? ~ I I I I I packs per week (33) (34) 46f. Until what month and year did you continue to smoke (NUMBER) packs per week on a regular basis? MONTH YEAR I I TT I T (IF DATE IS THE SAME AS Q.45c: ASK Q.47a. I I J-l I I ALL OTHERS: RECORD ADDITIONAL PERIODS IN (35) (36> (37) (38) S.R.B. PAGE 41) 47a. You said Chat you (last smoked cigarettes/are currently smoking cigarettes) on a fairly regular basis (in DATE). On Yirj many days did you smoke cigarettes during the last three months (that you smoked on a fairly regular basis)? I I T I I I days (39) -(40) 47b. On the days that you smoked, about how many packs did you smoke per day? T J \ \ j \_ packs per day (41) ( 2 4) 47c. In general, did you inhale the smoke? Yes...(43(. No -1 -2 �. 48a. CARD 045 Have you ever smoked a pipe regularly for a period of at least one month? -2 No, A8b. 812039 (SKIP TO 0- 51a) In what month ami year did you start smoking a pipe on a fairly regular basis? MONTH YEAR 1 1 T T 1 1 1 1 1 1 (47) 48c. In what month and year did you last smoke a pipe on a fairly regular basis? MONTH YEAR 1 I I T l I 149) (50) I-1 I I T I (51) (52) 49a. When you started smoking a pipe on a fairly regular basis in (START DATE), about how many pipefuls per week did you smoke? F I I | I I pipefuls per week (53) (54) 49b. Until what month and year did you continue to smoke (NUMBER) pipefuls per week on a regular basis? MONTH YEAR 1 T^ T1 H T (IF DATE IS THE SAME AS Q.ASc: SKIP TO Q.SOa. J[ | |-j__ J I ALL OTHERS: CONTINUE) (55) (56) (57) (58) 49c. After that, about how many pipefuls per week did you smoke? iI r \ | I pipefuls per week "759 ) (60) A9d. Until what month and year did you continue to smoke (NUMBER) pipefuls per week on e regular basis? MONTH YEAR .1 [ T T1 I T (IF DATE IS THE SAME AS Q.ASc: SKI-P TO Q.SOa. j J I-| I j ALL OTHERS: CONTINUE) (61) (62) (63) (64) A9e. After that, about how many pipefuls per week did you smoke? I I T I (65) T [ pipefuls per week (66) 49f. Until what month and year did you continue to smoke (NUMBER) pipefule per week on a regular basis? MONTH YEAR 1 1 T1 1 T ( I F DATE I S T H E SAME A S Q.ASc: A S K Q.SOa. J L H I... I ALL OTHERS: RECORD ADDITIONAL PERIODS IN (67) (68) (69) (70) S.R.B. PAGE Al) 50a. You said that you (last smoked a pipe/are currently smoking a pipe) on a fairly regular basis (in DATE). On how many days did you smoke a pipe during the last three months (that you smoked on a fairly regular basis)? I I . I I I I days (71) (72) 50b. On the days that you smoked, about how many pipefuls did you smoke per day? T I 50c. I I I I pipefuls per (73) "(74) day In general, did you inhale the smoke? Yes... (/'-,( No -1 V T " -2 . �CARD 051 51a. Have you ever smoked cigars regularly for a period of at least one month? : Yes .(12( -1 (ASK Q.51b) , -2 (SKIP TO Q.54a) No Sib. In what month and year did you start smoking cigars on a fairly regular basis? MONTH YEAR "(13) (14) 51c. 812039 (15) (16) In what month and year did you last smoke cigars on a fairly regular basis? MONTH YEAR (17) (18) (19)(20> 52a. When you started smoking cigars on a fairly regular basis in (START DATE), about how many cigars per week did you smoke? iI I r I I cigars p e r week (21 ) (22) 52b, Until what month and year did you continue to smoke (NUMBER) cigars per week on a regular basis? MONTH YEAR I I TT I T (IF DATE IS THE SAME AS Q.Slc: SKIP TO Q.53a. I I . I-I I I A L L OTHERS: CONTINUE) (23) (24) (25) (26) 52c. After that, about how many cigars per week did you smoke? J j I cigars per week (27) (28) S2d. Until what month and year did you continue to smoke (NUMBER) cigars per week on a regular basis? MONTH YEAR T - | T1 I T ( I F DATE I S T H E SAME A S Q.Slc: SKIP T O Q.53a. I I I-J I I ALL OTHERS: CONTINUE) (29) (30) (31) (32) S2e. After that, about how many cigars per week did you smoke? I j I cigars per week (33) (34) 52f. Until what month and year did you continue to smoke (NUMBER) cigars per week on a regular basis? MONTH YEAR T IT1 1 T (IF DATE IS THE SAME AS Q.Slc: ASK Q.53a. J^ I l-j [_ j ALL OTHERS: RECORD ADDITIONAL PERIODS IN (35) (36) (37) (38) S.R.B. PAGE 42) 53a, You said that you (last smoked cigars/are currently smoking cigars) on a fairly regular basis (in DATE). On how many days did you smoke cigars during the last three months (that you smoked on a fairly rp'_,ular basis)? I 1 53b. I T \. I days (39) ( 0 4) On the days that you smoked, about how many cigars did you smoke per day? 1 I I I I I cigars per day (41) (42) 53c. In general, did you inhale the smoke? Ves...(43( No _-l -2 .12 �CARD 051 812039 54a. Now let's talk about drinking alcoholic beverages, that is, beer, wine, or hard liquor. Did you ever drink alcoholic beverages on a fairly regular basis? Yes (44 ( (ASK Q.54b) -2 No -1 (SKIP TO Q.57 ) 54b. In what month and year did you start drinking alcoholic beverages on a fairly regular basis? MONTH YEAR T I I I T l-l "(45) (46) 54c. T I T l - l (47) (48) In what month and year did you last drink on a fairly regular basis? MONTH YEAR I l-l I (49) (50) (51) (52) 55a. When you started drinking alcoholic beverages on a fairly regular basii in (START DATE), about how many drinks per week did you have? T I drinks per week (54) (53) 55b. Until what month and year did you continue to drink (NUMBER) drinks per week on a regular basis? MONTH YEAR T I T T 1 T ( I F DATE I S T H E SAME A S Q.SAc: SKIP T O Q.56a. I. I l-l I I ALL OTHERS: CONTINUE) (55) (56) (57) (58) S5c. After that, about how many drinks per week did you have? 1 J I I (59) I | drinks per week (60) 55d. • Until what month and year did you continue to drink (NUMBER) drinks per week on a regular basis? MONTH YEAR I T I I I ( I F DATE I S T H E SAME A S Q.54c: SKIP T O Q.56a. I ALL OTHERS: CONTINUE) (61) (62) (63) (64) 55e. After that, about how many drinks per week did you have? I J T I j [ drinks per week (65) ( 6 6) S5f. Until what month and year did you continue to drink (NUMBER) drinks per week on a regular basis? MONTH YEAR T I TT ~\ T (IF DATE IS THE SAME AS 0.54c: ASK Q.56a. I I ,1-1 I I ALL OTHERS: RECORD ADDlfldNAL PE'SIODS IN T67) (68) (69) (70) s.R.B. PAGE 43) 56a. You said that you (last drank/are currently drinking) alcoholic beverages 6H a fairly regular basis (in (END DATE)). On how many days did yo'u drink during the last months (that you drank on a fairly regular basis)? 1 566. I J_ days (71) (72) On the days that you drank, about how many drinks did you have per day? J I |_ drinks per ( 73) T74) day 53c. During these months which one of the following beverdges did you drink most -hard liquor, beer or ale, or wine or champagne? Hard liquor.. ( 5 7j Beer or ale Wine or champagne Combination 43 _-l -2 L-3 -4 �CARD 057 57. Have you ever tried smoking marihuana? Yes (12 ( Vb.'.....'..'... 57a. -2 (i3(. (SKIP TO Q.60) . -1 (ASK Q,57b) -2 No (SKIP TO Q.60) In what month and year did you start smoking marihuana on a fairly regular basis? MONTH YEAR 1 I T T 1 I l-l (14) (15) 57c. -1 (ASK Q.57a) Have you ever smoked marihuana regularly for a period of at least one month? Yes 57b. 812039 T ~T I I (16) (17) In what month and year did you last smoke marihuana on a fairly regular basis? MONTH YEAR T i T l I T <18> (19) (20) (21) 58a. When you started smoking marihuana on a fairly regular basis in (START DATE), about how many joints per week did you smoke? T I I | T I joints per week "(22) (23) 58b. Until what month and year did you continue to smoke (NUMBER) joints per week on a regular basis? MONTH YEAR T 1 T1 I T ( I F DATE IS T H E SAME A S Q.57c; SKIP T O Q.59a. I I hi I I ALL OTHERS: CONTINUE) (24) (25)(26) (27) 58c. After that, about how many joints per week did you smoke? I I T I I I joints per week (28) (29) 58d. Until what month and year did you continue to smoke (NUMBER) joints per week on a regular basis? MONTH YEAR 1 1 T1 T T (IF DATE IS THE SAME AS Q.57c: SKIP TO Q.59a. I I j-l | I ALL OTHERS: CONTINUE) "(30)01) (32) (33) 58e. After that, about how many joints per week did you smoke? I I r \ I \_ joints per week T34) (35) 58f. Until what month and year did you continue to smoke (NUMBER) joints per week on a regular basis? MONTH YEAR T ~] T1 T T (IF DATE IS THE SAME AS Q.S7c: ASK Q.59a. 1 I l-l I I ALL OTHERS: RECORD ADDITIONAL PERIODS IN (36) (37) (38) (39) S.R.B. PAGE 43) 59a, You said that you (last smoked marihuana/are currently smoking marihuana) on a fairly regular basis (in DATE). On how many days did you smoke marihuana during the last three months (that you smoked on a fairly regular basis)? T days (40) (41) 59b. On the days that you smoked, about how many joints did you smoke per day? I I I I I I joints per ~(42) (43)~ day 44 �CARD 057 812039 60. In your lifetime, have you ever had two weeks or more during which you felt sad, blue, depressed, or when you lost all interest and pleasure in things that you usually cared about or enjoyed? Yes No UA( ^-iV (ALSO RECORD ON S.R.B. PAGE 12) -2J 61a. Have you had two years or more in your life when you felt depressed or sad almost all the time even if you felt O.K. sometimes? Yes (45(__ (ASK Q.61b) -2 No -1 (SKIP TO Q.62) 61b. Did you tell a medical doctor about feeling depressed during this period? The term "medical doctor" includes psychiatrists, osteopaths, and medical students. Yes (6 4( (SKIP TO Q.62) -2 No -1 (ASK Q.61e) 61c. Did you tell any other professional about feeling depressed during this period? The term "other professional" includes psychologists, counselors, members of the clergy, and chiropractors? Yes (7 4( (SKIP TO Q.62) -2 No -1 (ASK Q.61d) 61d. Did you take medication more than once, either prescribed or nonprescribed, for feeling depressed during this period? Yes (8 4( (SKIP TO Q.62) -2 No -1 (ASK Q.61e) 61e. Did being depressed during this period interfere with your life and activities a lot? Yes No (4<j( 45 -1 -2 �812039 CARD 057 62a. Has there ever been a period of two weeks or longer when you lost your appetite? Yes (Q j( 62b. (ASK Q.62b) -2 No -1 (SKIP TO Q.63 a) Did you tell a doctor about your loss of appetite? Yes..'....($!_( No.. 62c. ,-* -2 (ASK Q-62cy (SKIP TO Q.62d) When, you told the doctor, what was his diagnosis? IF "NERVES, STRESS, ANXIETY": CIRCLE "5" BELOW AND SKIP TO Q.feyT IF "NOTHING DEFINiTE"/"DON'T KNOW": ASK IF DOCTOR'S EXAMINATION OR TESTS INDICATED ANY PHYSICAL ILLNESS. IF "NO": CIRCLE "5" BELOW AND SKIP TO Q.63a. IF "PHYSICAL ILLNESS OR INJURY," SKIP TO Q.62e. IF "MEDICATION, DRUGS, OR ALCOHOL," SKIP TO Q.62e. 62d. What was the cause of your loss of appetite? IF "NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE" OR "DON'T KNOW": CIRCLE "5" BELOW AND SKIP TO Q.63a. IF "PHYSICAL ILLNESS OR INJURY" OR "MEDICATION, DRUGS, OR ALCOHOL": ASK Q.62e. 62e. Has there ever been a period when you lost your appetite for two weeks or longer for any reason other than (READ'RESPONSE FROM Q.62c OR Q.62d)? Yes. -1 (ASK Q.62f) No 62f. .5( (2 ,...._ -2 (SKIP TO What was the cause of your loss of appetite in that period? IF "NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE'^OR "DON'T KNOW": CIRCLE "5" BELOW AND GO TO Q.63 a. ALL OTHERS: GO TO Q.63 a. FOR OFFICE USE ONLY 1 2 3 A (53) . 5 IF "5" CIRCLED RECORD IN S.R.B. �CARD 057 63a. Have you ever lost weight without trying to — several weeks (or as much as 10 pounds altogether)? as much as two pounds a week for Yes -1 (ASK Q.63b) No 63b. -2 (SKIP TO Q.64a) Did you tell a doctor about your weight loss? Yes (5 5( -1 (ASK Q.63c) -2 No 63c. (II ? ) ' (!) (SKIP TO Q.63d) When you told the doctor, what was his diagnosis? IF "NERVES, STRESS, ANXIETY"": CIRCLE "5" BELOW AND SKIP TO Q.64. IF "NOTHING DEFINITE"/"DON!T KNOW": ASK IF DOCTOR'S EXAMINATION OR TESTS INDICATED ANY PHYSICAL ILLNESS. IF "NO": CIRCLE "5" BELOW AND SKIP TO Q.64a. IF "PHYSICAL ILLNESS OR INJURY," SKIP TO Q.63e. IF "MEDICATION, DRUGS, OR ALCOHOL," SKIP TO Q.63e. 63d. What was the cause of your weight loss? IF "NERVES, STRESS, ANXIETY11 OR ^'NOTHING DEFINITE" OR "DON'T KNOW": CIRCLE "5" BELOW AND SKIP TO Q.64a. IF "PHYSICAL ILLNESS OR INJURY" OR "MEDICATION, DRUGS, OR ALCOHOL": ASK Q.63e. 63e. Has there evfer been a period when you lost weight without trying to — as much as two pounds a week for several weeks (or as much as 10 pounds altogether) for any reason other than (READ RESPONSE FROM Q.63c OR Q.63d)? Yes. .5( (6 -2 No.. 63f. _-l (ASK Q.63f) (SKIP TO Q.64a) What was the cause of your loss of weight in that period? IF ''NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE" OR "DON'T KNOW": CIRCLE "5" BELOW AND GO TO Q.64a. ALL OTHERS: GO TO Q.64a. FOR OFFICE USE ONLY 1 2 3 A (57) . 47 5 IF "V CIRCLED RECORD IN S.R.B. �CARD 057 812039 6Aa. Have you ever had a period when your eating increased so much Chat you gained as much as two pounds a week for several weeks (or 10 pounds altogether)? Yes. .5( (8 _-l -2 No.. 64b. (SKIP TO Q.65a) Pid you tell a doctor about your increased appetite and weight gain? Yes <5gL -1 (ASK Q.64c) No 64c. (ASK Q.64b) -2 (SKIP TO Q.64d) When you told the doctor, what was his diagnosis? IF "NERVES, STRESS, ANXIETY": CIRCLE "5" BELOW AND SKIP TO Q.65. IF "NOTHING DEFINITE'V'DON'T KNOW": ASK IF DOCTOR'S EXAMINATION OR TESTS INDICATED ANY PHYSICAL -ILLNESS. IF "NO": CIRCLE "5" BELOW AND SKIP TO Q.65a. IF "PHYSICAL ILLNESS OR INJURY," SKIP TO q.64e. IF "MEDICATION, DRUGS, OR ALCOHOL," SKIP TO Q.64e. 64d. What was the cause of your increased appetite and weight gain? IF "NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE'^OR n'DO(rT KNOW": CIRCLE "5" BELOW AND SKIP TP Q.65a. IF "PHYSICAL ILLNESS OR INJURY" OR "MEDICATION, DRUGS, OR ALCOHOL": ASK Q.64e. 64e. Has there ever been a period when your eating increased so much that you gained as much as two pounds a week for several weeks (or 10 pounds altogether) for any reason other than (READ RESPONSE FROM Q.64c OR 64d)? Yes. No., -1 (ASK Q.64f) -2 (SKIP TO Q.65fl) .6( (0 64f. What was the cause of your increased appetite and weight gain in that period? IF "NERVES, STRESS, ANXIETY" irOR "NOTHING DEFINITE'^W "DON'T KNOW": CIRCLE "5 "BELOW AND GO TO p.65a. ALL OTHERS: CO TO Q.65 a. FOR OFFICE USE ONLY 1 2 3 4 (61) . 5 IF "5" CIRCLED RECORD IN S.R.B. DA^F 1 1 �812039 CARD 057 65a. Have you ever had a period of two weeks or yore when you had trouble falling asleep, staying asleep, or with waking up too early? Yes. No 6M». (ASK Q.65b) .6( (2 _ -2 (SKIP TO Q.66a) Did you tell a doctor about your trouble sleeping? Ves ...... ( 3 6( (ASK Q.65c) No..........._ 65c. -1 -2 (SKIP TO Q.65d) When you told the doctor, what was his diagnosis? IF "NERVES, STRESS, ANXIETY": CIRCLE "5" BELOW AND SKIP TO Q.66. IF "NOTHING DEFINITE'V'DON'T KNOW": ASK IF DOCTOR'S EXAMINATION OR TESTS INDICATED ANY PHYSICAL ILLNESS. IF "NO": CIRCLE "5" BELOW AND SKIP TO Q.66a. IF "PHYSICAL ILLNESS OR INJURY," SKIP TO Q.65e. IF "MEDICATION, DRUGS, OR ALCOHOL," SKIP TO Q.65e. 65d. What was the cause of your sleeping problem? IF "NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE" OR "DON'T KNOW": CIRCLE "5" BELOW AND SKIP TO Q.66a. IF "PHYSICAL ILLNESS OR INJURY" OR "MEDICATION, DRUGS, OR ALCOHOL": ASK Q.65e. 65e. Has there ever been a period of two weeks or more when you had trouble falling asleep, staying asleep, or with waking up too early for any reason other than (READ RESPONSE FROM Q.6Sc OR Q.65d)? Yes. (ASK Q.65f) No.. 65f. -1 -2 (SKIP TO Q.66a) What was the cause of your 'Sleeping problem in that period? IF "NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE" OR "DON'T KNOW": CIRCLE "S^ELOW AND GO TO Q.66e. ALL OTHERS: GO TO Q.66a. FOR OFFICE USE ONLY 1 2 3 4 (65) . 5 IF "5" CIRCLED RECORD IN S.R.B. Dirr i o �812039 CARP 057 66a. Have you ever had a period of two weeks or longer when you were sleeping too .much? Yes. (6 6( No 66b. ...: -2 (ASK Q.66b) (SKIP TO Q.67 a) Did you tell a doctor about your sleeping too much? Yes No 66c, "I (67( ,. -1 _-2 (ASK Q.66c) (SKIP TO Q.66d) When you told the doctor, what was his diagnosis? It "NERVES, STRESS. ANXIETY": CIRCLE "5"'BEtOW AHt) SKIP T6 6..fe7.a. IF "NOTHING DEFINITE"/"DON'T KNOW": ASK IF DOCTOR'S EXAMINATION OR TESTS INDICATED ANY PHYSICAL ILLNESS. IF "NO": CIRCLE "5" BELOW AND SKIP TO Q.67 a. IF "PHYSICAL ILLNESS OR INJURY," SKIP TO Q.66e. IF "MEDICATIQN, DRUGS, OR ALCOH6L," SKIP TO Q.66e. 66d. What was the cause of your sleeping too much? IF "NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE11 OR "DON'T KNOW": CIRCLE "5" BELOW AND SKIP TO Q.67 a. IF "PHYSICAL ILLNESS OR INJURY" OR "MEDICATION, DRUGS, OR ALCOHOL": ASK Q.66e. •* 66e. Has there ever been a period when you were sleeping too much for two weeks or longer for any reason other than (READ RESPONSE FROM Q.66c OR Q.66d)7 Yes. No.. 66f. .6( (8 _-i (ASK Q.66fj -2 (SKIP TO Q.6?a) What was the cause of your sleeping too much in that period? IF "NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE" OR "DON'T KNOW": CIRCLE "S^BELOW AND GO TO Q.67 a. ALL OTHERS: GO TO Q.67 a. FOR OFFICE USE ONLY 1 2 3 4 (69) 5 IF "5" CIRCLED RECORP IN S.R.B. rAQfe } / �812039 CARD 057 67a. Have you ever had a period lasting two weeks or more when you felt tired all the time? Yes (70( -1 -2 No 67b. (SKIP TO Q.68a> Did you tell a doctor about your feeling tired out all the tine? Yes (?1( No 67c. (ASK Q.67b) -1 ,.,,..ro.3i-2 j (ASK Q.67c) (SKIP TO Q.67d) When you told the doctor, what was his diagnosis? IP" "NERVES, STRESS, ANXIETYtr: CIRCLE "5" BELOW AND SKIP TO Q.689IF "HOTHING DEFINITE"/"DON'T KNOW": ASK IF DOCTOR'S EXAMINATION OR TESTS INDICATED ANY PHYSICAL ILLNESS. IF "NO": CIRCLE "5" BELOW AND SKIP TO Q.68aIF "PHYSICAL ILLNESS OR INJURY," SKIP TO Q.67e. IF "MEDICATION, DRUGS, OR ALCOHOL," SKIP TO Q.67e. 67d. What was the cause of your feeling tired out all the time? IF "NERVES, STRESS, ANXIETY" OR NOTHING DEFINITE" OR^'DON'T KNOW": CIRCLE "5" BELOW AND SKIP TO Q.68a. IF "PHYSICAL ILLNESS OR INJURY" OR "MEDICATION, DRUGS, OR ALCOHOL": ASK Q.66e. 67e. Has there ever been a period when you felt tired out all the time for two weeks or longer for any reason other than (READ-RESPONSE FROM Q.67c OR Q.67d)? .(72( Yes. No.. 67f. (ASK Q.67f) -2 , -1 (SKIP TO Q.68a) What was the cause of your feeling tired out in that period? IF "NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE" OR "DON'T KNOW": CIRCLE "5" BELOW AND GO TO Q.&8a. ALL OTHERS: GO TO Q.68 a. FOR OFFICE USE ONLY 1 2 3 A (73) . 51 5 IF "5" CIRCLED RECORD IN S.R.B. PARF 1? �812039 -CARP 057 689- Has there ever Veen a period of two weeks or more when you talked or moved more Blowly than is normal for you? ""*" ' ' '. " "'' • Ye6,M.-.(Zi< "l (ASK Q.68b) No..........._ -2 (SKIP TO Q.69 a) 68b. Did you tell a doctor about your slowed speech or movement? Yes......(7$( -1 USK Q.68c) N...... o....._ -2 (SKIP TO Q.68d) 68c. When you told the doctor, what was his diagnosis? IF "NERVES, STRESS, ANXIETY": CIRCLE "5" BELOW AND SKIP TO Q.699. IF "NOTHING DEFlNiTE"/"pQNlT KNOW": ASK IF DOCTOR'S EXAMINATION OR TESTS INDICATED ANY PHYSICAL ILLNESS. IF "NO": CIRCLE "V BELOW AND SKIP TO Q.69 a. IF "PHYSICAL lUNESS OR INJURY," SKIP TO Q.68e. IF "MEDICATION, DRUGS, OR ALCOHOL," SKIP" TO Q.68e. 68d. What was the cause of your slowed speech or movement? IF "NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE^ OR "DON'T KNOW": CIRCLE "5" BELOW AND SKIP TO Q.69 a. IF "PHYSICAL ILLNESS OR INJURY" £R "MEDICATION, DRUGS, OR ALCOHOL": ASK Q.68e. 68e., Has there ever been a period when you talked or moved more slowly than is normal for you for two weeks or longer for any reason other than (READ RESPONSE FROM Q.68c OR Q.68d)T ' Yes. .7( (6 -V (ASK p.68f) -2 (SKIP TO Q.698) No.. 68f. What was the cause of your slowed speech or movement in that period? IF "NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE" OR "DON'T KNOW"; CIRCLE "S^BELOW AND GO TO Q,69a. ALL OTHERS: CO TO Q.69a. FOR OFFICE USE ONLY 1 2 3 4 (77) 52 S IF "5" CIRCLBP RECORD IN S.R.B. �812039 CARD 069 69a. Hap there ever been a period of two weeks or more when you had to be moving all the time — that is, you couldn't stand still and paced up and down? Ye No 69b. _-l -2 (SKIP TO Q.7CO Did you tell a doctor about your need to be moving all the time? Yes No 69c. (ASK Q.69b) (13 ( -1 (ASK Q.69c) -2 (SKIP TO Q.69d) When you told the doctor, what was hi* diagnosis? IF "NERVES, STRESS, ANXIETY": CIRCLE *5" BELOW AND SKIP TO Q.70S. IF "NOTHING DEFINITE"/"DON'T KNOW": ASK IF DOCTOR'S EXAMINATION OR TESTS INDICATED ANY PHYSICAL ILLNESS. IF "NO": CIRCLE "5" BELOW AND SKIP TO Q.7CaIF "PHYSICAL ILLNESS OR INJURY," SKIP TO Q.69e. IF "MEDICATION, DRUGS, OR ALCOHOL," SKIP TO Q.69e. 69d. What was the cause of your moving all the time? IF "NERVES, STRESS, ANXIETY11 OR "NOTHING DEFINITETrOR "DON'T KNOW1': CIRCLE "5" BELOW AND SKIP TO Q.70a. IF "PHYSICAL ILLNESS OR INJURY" OR "MEDICATION, DRUGS, OR ALCOHOL": ASK Q.69e. 69e. Has there evej: been a period for two weeks or longer when you had to be moving all the time — couldnT stand still and paced up and down for any reason other than (READ RESPONSE FROM Q.69c OR Q.69d)? Yes. (ASK Q.69f) No.. 69f. -1 -1 (SKIP TO Q.70a> What was the cause of your moving all the time in that period? IF "NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE" OR "DON'T KNOW": CIRCLE "57r~BELOW AND GO TO Q.70a. ALL OTHERS: GO TO Q.70a FOR OFFICE USE ONLY 1 2 3 4 (15.) . 5 IF "5" CIRCLED RECORD IN S.R.B. �CARD Q69 81203_9_ 70a. Was there ever a period of several weeks when your interest in sex was a lot than usual? . Yes (16(r -1 (ASK Q.70b) No -2 (SKIP TO Q.71a) 7Ob. Did you tell a doctor about your diminished interest in sex? Yes (17( No -1 (ASK Q.70c) ^-2 (SKIP TO Q.70d) 70c. When you told the doctor, what was his diagnosis? IF "NERVES, STRESS, ANXIETY": CIRCLE "5" BELOW AND SKIP TO Q.71a. IF "NOTHING DEFIN1TE"/"DON'T KNOW": ASK IF DOCTOR'S EXAMINATION OR TESTS INDICATED ANY PHYSICAL ILLNESS. IF "NO": CIRCLE "5" BELOW AND SKIP TO Q.71»IF "PHYSICAL ILLNESS OR INJURY," SKIP TO 9.70h. IF "MEDICATIQN .DRUGS, ORfltCOHOL'," SKIP TO Q.70h. 70d. Did you consult with any other professional, such as a psychologist, marriage counselor, minister, or nurse abput your diminished interest in sex? Yes....,.(jfl( -1 (SKIP TO Q.70g) No.,.,, -2 ._ (ASK Q.70e) 70e. Did you take medication more than once for your diminished interest in sex? Yes U9( No...... -1 (SKIP TO Q.70g) -2 (ASK Q.70f) 70f. Did your diminished interest in sex interfere with your life or activities a lot? Yeg......(20( , (ASK Q.70g) No 70g. -1 -2 (SKIP TO Q.71 a) What was the cause of your diminished interest in sex? IF "NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE" OR "DON'T KNOW": CIRCLE "5" BELOW AND SKIP TO Q.71 «•• IF "PHYSICAL ILLNESS OR INJURY" OR "MEDICATION, DRUGS, OR ALCOHOL": ASK Q.70h. "*" 70h. Has tl ere gver been a period when your interest in sex was diminished for two weeks or longer for any reason other than (READ RESPONSE FROM Q.70c OR Q.70d)? Ye (21t( (ASK Q.70i) -2 No.... -1 (SKIP TO Q.7U) 70i. What was the cause of your diminished interest in sex in that period? IF "NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE" OR "DON'T KNOW": CIRCLE "S^BELOW AND GO TO Q.71a. ALL OTHERS: GO TO Q.7U. FOR OFFICE USE ONLY 1 2 3 4 (22) 54 5 IF "5" CIRCLED RECORD I N S . R . 8 . �CARD 069 812039 71a. Has there ever been a period of two weeks or more when you had a lot more trouble concentrating than is normal for you? Yes. No.. 71b. (ASK Q.71b) (SKIP TO Q.72 a) Did you tell a doctor about your trouble concentrating? Yes (4 2( -1 (ASK Q.71c) -2 No /!<:. _-l _-2 .(23( (SKIP TO Q.71d) Wlmn you told Che doctor, what wag hie diagnosis? IF "NERVES. STRESS, ANXIETY": CIRCLE "5" BELOW AND SKIP TO Q.72a. IF "NOTHING DEFINITE"/"DON'T KNOW": ASK IF DOCTOR'S EXAMINATION OR TESTS INDICATED ANY PHYSICAL ILLNESS. IF "NO": CIRCLE "5" BELOW AND SKIP TO Q.72a. IF "PHYSICAL ILLNESS OR INJURY," SKIP TO Q.71e. IF "MEDICATION, DRUGS, OR ALCOHOL," SKIP TO Q.71e. 71d. What was the cause of your trouble concentrating? IF "NERVES, STRESS, ANXIETY" OR "NOTHiNG'DEFINITE11 OR "DON'T KNOW1': CIRCLE "5" BELOW AND SKIP TO Q.72 a. IF "PHYSICAL ILLNESS OR INJURY" OR "MEDICATION, DRUGS, OR ALCOHOL": ASK Q.71e. 71e. Has there ever been a period when you had more trouble concentrating than is normal for you for two weeks or longer for any reason other than (READ RESPONSE FROM Q.71c OR Q.71d)? Yes. .2( (5 71f. (ASK Q.71f) -2 No.. -1 (SKIP TO Q.72a) What was the cause of your trouble concentrating in that period? IF "NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE" OR "DON'T KNOW": CIRCLE "5" BELOW AND GO TO Q.72a. ALL OTHERS: GO TO Q.72a. FOR OFFICE USE ONLY 1 2 3 A (26) S5 5 IF "5" CIRCLED RECORD IN S.R.B. �CARD 069 812039 72a. Has there ever been a period of two weeks or more when your thoughts came much glower than usual or seemed mixed up? Yes. .(27< -1 (ASK Q.72b) -2 (SKIP TO Q.73) No.. 72b. Did you tell a doctor about your thoughts coming much slower than usual or seeming mixed up? Yes. .(2g( No -1 (ASK Q.72c) _-2 (SKIP TO Q.72d) Tic.. When you told the doctor, what was his diagnosis? IF "NERVES, STRESS, ANXIETY":CIRCLE "5" BELOW AND SKIP TO Q.73. IF "NOTHING DEFINITE"/"DON'T KNOW": ASK IF DOCTOR'S EXAMINATION OR TESTS INDICATED ANY PHYSICAL ILLNESS, IF "NO": CIRCLE "5" BELOW AND SKIP TO Q.73. IF "PHYSICAL ILLNESS OR INJURY," SKIP TO Q.72e. IF "MEDICATION, DRUGS, OR ALCOHOL," SKIP TO Q.72e. 72d. What was the cause of your your thoughts coming much slower than usual or seeming mixed up? • IF "NERVES, STRESS, ANXIETY" QR "NOTHING DEFINITE" OR "DON'T KNOW": CIRCLE "5" BELOW AND SKIP TO Q.73. IF "PHYSICAL ILLNESS OR INJURY" OR "MEDICATION, DRUGS, OR ALCOHOL": ASK Q.72e. 72e. Has there, ever been a period when your thoughts came much slower than usual or seemed mixed up for two weeks or longer for any reason other than (READ RESPONSE FROM Q.72c OR Q.72d)? Yes. .2( (9 No. -1 (ASK Q.72f) -2 (SKIP TO Q.73) 72f. What was the cause of your your thoughts coming much slower than usual or seeming mixed up in that period? IP "NERVES, STRESS. AHXIETV" OR "NOTHING DEFINITE" OK "DON'T KNOW": CIRCLE "5" BELOW AND GO TO Q.73. ALL OTHERS: GO TO Q.73. FOR OFFICE USE ONLY 1 2 3 4 (30) 56 . 5 IF "5" CIRCLED RECORD IN S.R.B. Dir.f 1 1 �CARD 069 . 812039 "'YES IN p. 73 THROUGH o.77 IN"S.R".¥". PAGE 12 1 73. Has there ever been a period of two weeks or more when you felt worthless, sinful, or guilty? Yes ...... (31( No..........._ -1 -2 Ik. Has there ever been a period of two weeks or more when you thought a lot about death — either your own, someone else's, or death in general? . No...........__ -2 75. Has there ever been a period of two weeks or more when you felt like you wanted to die? Yes ...... (33( No..........._ -1 -2 76. Have you ever felt so low you thought of committing suicide? Yes ...... ( 4 3 ( ._.-! No..........._ -2 77. Have you ever attempted suicide? Yes ...... (35(________-1 No ........... -2 INTERVIEWER INSTRUCTIONS: IF LESS THAN THREE BOXES CHECKED IN S.R.B. PAGE 12 FOR Q.62-77: SKIP TO Q.88a. IF THREE OR MORE BOXES CHECKED IN S.R.B. PAGE 12 AND "YES" IN Q.60, ASK Q.78a. IP THREE OR.MORE. BOXES CHECKED IN S.R.B. PAGE 12 AND "NO" IN Q.60, SKIP TO Q.79a. �. ^CARD.069 812039 78a. You said you've had a period of feeling (depressed or blue/OWN EQUIVALENT) and also said you've had some other problems like (LIST ALL ITEMS CHECKED IN S.R.B. PAGE 12). Has there ever been a tine when the feelings of depression and some of these other problems occurred together — that is, within the same month? Yes (6 3( (SKIP TO Q.80) -2 No -1 (ASK Q.78b) 78b, So there's never been a period when you felt sad, blue, or depressed at the same time you were having some of these other problems? Has been a period..(3_7j -1 (ASK Q.80) Never been a period -2 (SKIP TO Q.88a, PAGE 57) 79a. You said you have had periods when (LIST ALL ITEMS CHECKED IN S.R.6. PAGE 12). Was there ever a time when several of these problems occurred together — t h a t is, within the same month? Yes (g 3( (ASK Q.79b) -2 No -1 (SKIP TO Q.88a, PAGE 57) 79b. When you were having some of these problems at about the same time, were you feeling okay, or were you feeling low, gloomy, blue, or uninterested in everything? Gloomy, low, etc..(39( Okay -1 -2 (ASK Q.80) (SKIP TO Q.88a, PAGE 57) 80. What's the longest spell you've ever had when you felt blue and had several of these other problems at the same time — that is, how many weeks did it last? IF "WHOLE LIFE" OR MORE THAN 19 YEARS, ENTER "996" AND CONTINUE. IF LESS THAN 2 WEEKS, CODE "001" AND SKIP TO Q.88a, PAGE 57. iI . l1 1l .... rI ( 0 (41) 4) weeks (42) 81. Now, I'd like to ask about spells when you felt both (depressed/OWN EQUIVALENT) and had some of these other problems like (LIST 3 ITEMS CHECKED ON S.R.B. PAGE 12). In your lifetime, how many spells like that have you had that lasted two weeks or more? JIF MORE THAN 90 SPELLS, ENTER "907*7 I I I ( 44) spells 58 �CARD 069 82a. 812039 Did you tell a doctor about (that spell/any of those spells)? Yes (j 4( 82b. (SKIP TO Q.83) -2 No -1 (ASK Q.82b) Did you tell any other professional about (it/any of them)? Yes (6 4( (SKIP TO Q.83) -2 No -1 (ASK Q.82c) 82c. Did you take medicine more than once becaune of (that »p*ll/»ny of those «pellt)7 Yes U?( (SKIP TO Q.83) -2 No -I (ASK Q.82d) 82d. Did (that spell/those spells) interfere with your life or activities a lot? Ves...:...<48< No -1 -2 (ASK Q.83) 83. How old were you the first time you had a spell for two weeks or more where you felt sad and had some of these other problems such as (PROBLEMS CHECKED IN S.R.B. PAGE 12)? AGE: I I l I l I (49) (50) years 8Aa. Did (this spell/any of those spells) occur just after someone close to you died? Yes ' . (5_l( No -1 (ASK Q.SAb) ' -2 (SKIP TO Q.85) 84b. Have you had any spell of depression along with these other problems such as (PROBLEMS CHECKED IN S.R.B. PAGE 12) at times when it wasn't due to a death? No, only due to death (52( Yes, other times not due to death... -1 -1 85. Are you now in one of these spells of feeling low or disinterested and having some of these other problems? Yes (53( 85b. (SKIP TO Q.85d) -2 No -1 (ASK Q.85b) When did your last spell like that end? •^ Within last Between two Between one Between six two weeks (54( ,4( weeks and one month ago... month and six months ago.. months and one year ago... More than one year ago 85c. How old were you then? AGE: I I I years C>.r>) (56) 59 -1 -2 •(SKIP TO Q.BSd) -3 -I* -5 (ASK Q.85c) �CARD 069 812039 INTERVIEWER: DO NOT READ Q.85d AND Q.85e TO RESPONDENT. 85d. IS MORE THAN ONE SPELL CODED IN Q.81? Ys...(7 e....5( No 85e. -1 -2 (SKIP TO Q.86) (ANSWER Q.85e) ARE 52 OR MORE WEEKS CODED IN Q.80? Yes. No.. .51 (8 -1 ~-2 (ASK Q.86) (SKIP TO Q.87) 86. Now I'd like to know, about the time when you were feeling depressed for at least two weeks and had the largest'number of these other problems at the same time. (IF CAN'T CHOOSE: Then pick one bad spell.) How old were you at that time? I AGE: years (59) (0 6) 60 (ASK Q.87) �CARD 069 812039 fl flEin"X BELOW ALLlPROBLfiMS RECORDED ON S.R.B. PAGE 12, AND ASK Q.87 FOR THOSE CONDITIONS. 87. During this spell of depression when you were (AGE IN Q.86) years old ... IASK ONLY FOR CHECKED CONDITIONS I 1 .. j t>id you lose your appetite?.............................(61(_ -1 _ Did you lose weight without trying to — as much as ten pounds altogether?......................................(62< -2 -1 _ -2 II 111 Ytiiii "sling irirt-oKiso an rolKli that you B«ined ten pounds altogether'/.. .................................... (6ft( «t _ __ __-2 Did you have trouble falling asleep, staying asleep, or waking up too early?................................ . 6 (_ (4 -1 _ -2 V I Were you sleeping too much?.............................(6ft(_ -1 _ -2 ] ' I Did you feel tired out all the time?................. . . 6 ( .(6 -1 _ -2 j ] Did you talk or move more slowly than is usual for you? . ( 67 (_ j _ | Did you have to be moving all the time — that is, you couldn't sit still and paced up and down?...............( 8 _ 6( | | Was your interest in sex a lot less than usual?.........( 9 _ 6( I I Did you have a lot more trouble concentrating than ia usual for you?..........................................( 0 _ 7( -1 _ -2 I I Did your thoughts come much slower than usual or seem mixed up?..........................„......................( j _ 7( -1 _ -2 ] | Did you feel worthless, sinful, or guilty?..............( 2 7( -1 _ -2 I I Did you think a lot about death — either your own, someone else's, or death in general?....................( 3 7( y°u fee * like you wanted to die? .................... ( 4 7( T ~"[ '' Did you feel so low you thought of committing suicide?. . (_7jj( I Did you attempt suicide? I (7A( -1 _ -1 _ -2 -1 _ -1 _ -1 -1 -1 -2 -2 -2 -1 -2 -2 �CARD 088 88a. Have you ever considered yourself a nervous person? Yes (12 ( Ho 88b. _-2 (ASK Q.88b) (SKIP TO Q.89a) At what age did this nervousness begin? AGE: 1 I Whole life.. \ I I | years (13) (14) (15 ( (SKIP TO Q.89a) -1 (SKIP TO Q.89a) -2 Not sure 88c. -1 (ASK Q.88c) Do you think it began before or after you were 30? Before 3 . . ( 6 0..1J After 30 -1 -2 Still not sure... -3 812039 �CARD 088 812039 8$a. Have you ever had a spell or attack when all of a sudden you felt frightened, anxious, or very uneasy in situations when most people would not be frightened? Yes..( 17( -1 (ASK Q.89b) No -2 (SKIP TO SELF-ADMINISTERED SHEET AFTER Q.94b, PAGE 60) 89b. Did you tell a doctor about your feeling frightened, anxious, or uneasy? Yes de( No 89c. -1 (ASK Q.89c) -2 (SKIP TO Q.89d) When you told the doctor, what was his diagnosis? IF "NERVES, STRESS, ANXIETY": CIRCLE "511 BELOW AND SKIP TO Q.90. IF "NOTHING DEFINITE'VDON'T KNOW": ASK IF DOCTOR'S EXAMINATION OR TESTS INDICATED ANY PHYSICAL ILLNESS. IF "NO": CIRCLE "5" BELOW AND SKIP TO Q.90. IF "PHYSICAL ILLNESS OR INJURY," SKIP TO Q.89H. IF "MEDICATION, DRUGS, OR ALCOHOL," SKIP TO Q,89h. 89d. Did you consult with any other professional, such as a psychologist, marriage counselor, minister, or nurse about your feeling frightened, anxious, or Uneasy? Yes. _-l No.. -2 (SKIP TO Q.89g) (ASK Q.89e) 89e. Did you take medication more than once for your fear, anxiety, or uneasiness? Yes. .(20C j-1 -2 No.. (SKIP TO Q.89g) (ASK Q.89f) 89f. Did your fear, anxiety, or uneasiness interfere with your life or activities a lot? Yes.(21( No 89g. -1 (ASK Q.89g) -1 (SKIP TO SELF-ADMINISTERED SHEET AFTER Q.94b, PAGE 60) What Was the cause of your fear, anxiety, or uneasiness? IF "NERVES, STRESS, ANXIETY" OR "NOTHING DEFINITE" OR CIRCLE "5" BELOW AND SKIP TO Q.90. IF "PHYSICAL ILLNESS OR INJURY" OR "MEDICATION, DRUGS ALCOHOL": ASK Q.89h. , i - . .. . - - . i i—i ..- ''DON'T KNOW": , ob ' .....if. ..»•.»•• 89h. Have you ever had a period of fear, anxiety, or uneasiness for two weeks or longer for any reason other than (READ RESPONSE FROM Q.89c OR 89g)? Yes ( 2% 89i. (ASK Q.89i) -2 No -1 (SKIP TO Q.90) What was the cause of your fear, anxiety, or uneasiness in that period? IF "NERVEFrSTlES^AMiT;TTr1r'W~ItNOTrifiG"' DEFINITE""OK "DON'T KNOW": CIRCLE "5" BELOW AND GO TO Q.90. ALL OTHERS: GO TO Q.90. FOR OFFICE USE ONLY 1 2 3 4 63 �CARD 088 812039 90. During one of the worst spells of suddenly feeling frightened or anxious or uneasy, did you ever notice that you had any of the following. During this spell... Yes No A. Were you short of breath — having trouble catching your breath?.(24( ~1 ~2 B. Did your heart pound? ( 25( -1 -2 C. Were you dizzy or light-headed? (26( -1 -2 D. Did your fingers or feet tingle? ( 27( -1 -2 -1 -2 E. Did you have tightness or pain in your chest? . . . ?R( ..( F. Did you feel like you were choking or smothering? (29( -1 -2 G. Did you feel faint? (JQ( -1 -2 H. Did you sweat?.. (31( -1 -2 1. Did you tremble or shake? (32( -1 -2 J. (33( -1 -2 (" •( -1 -2 -1 -2 Did you feel hot or cold flashes? K. Did things around you seem unreal? L. Were you afraid either that you might die or that you might act in a crazy way? . (35( 91a. How old were you the first time you had one of these sudden spells of feeling frightened or anxious? I AGE: I T I I I years (36) (37) Whole life....!.... (T&(_ Not sure..............._ 91b. (SKIP TO Q.92) -1 -2 (SKIP TO Q.92) • (IF RESPONDENT IS UNDER AO, CODE "01" IN AGE BOX AND GO TO Q.92. IF RESPONDENT IS AO OR OVER, ASK Q.91b) Would you say it was before or after you were AO? Before 40,(3_9j_ -1 After AO ...... __ -2 Not sure ...... -3 92. Have you ever had three or more spells like this close together — three-week period? Yes......( 0 _ 4( No ........... say, within a -1 -2 93, Have spelts like this occurred at least nix different weeks of your life? Yes......(41 < _ -1 No..........._ -2 �CARD 088 94a. 812039 When did you last have a spell like this? Within last Between two Between one Between six two weeks or current..(42( weeks and one month ago... month and six months ago.. months and one year ago... ~ More than one year ago 94b. -2 I (SKIP TO SELF-3 J ADMINISTERED SHEET -4 I AFTER Q.94b) J -5 (ASK Q.94b) How old were you then? AGE: I I I (43) (44) years HAND SELF-ADMINISTERED SHEET TO RESPONDENnWDSAY: "The next questions are about how you have felt during the last three months. For each question, please circle the number corresponding to the answer that comes closest to the way you have been feeling. AFTER RESPONDENT COMPLETES SELF-ADMINISTERED SHEET, COLLECT SHEET AND RETURN TO Q.95. You will need to refer to Card "F" for many of these questions. I HAND RESPONDENT CARD "F"l 95a.In the last 3 months, how often have you kept losing your train of thought — would you say very often, fairly often, sometimes, almost never, or never? Very often..(45( Fairly often.... Sometimes Almost never "'_ -ij.(ASK Q.95b) -4 h(SKIP TO Q.96a) Never 95b. During what month and year did you begin losing your train of thought? i MONTH r i YEAR r i i i (46)i (47)i-i (48)i (49)i Don't remember (50 ( -1 | C ONT INUE _ VflTH C ARD~lnF'T 9 6 a . I n the last 3 months, how often have you felt unable to get things done? Very often..(5l( Fairly often.... Sometimes Almost never Never 96b. -l"l (ASK Q.96b) -4}.(SKIP TO Q.97a) During what month and year did you first feel unable to get things done? MONTH (52) (53) YEAR | T I I ( 54) ( 55) Don't remember CS ( 56( -1 �CARD 088 812039 I CONTINUE. WITH CARD " T T 97a. In the last 3 months, how often have you had trouble concentrating or keeping your mind on what you were doing? Very often. .(5T( Fairly often.... Sometimes Almost never.... Never 97b. -ll (ASK Q.97b) -2j -3 1 4 Vl -A V(SKIP TO Q.98a) -5J During what month and year did you first have trouble concentrating? 1 I MONTH YEAR 1 T l I T I l-l I I (58) ( 59) ( 0 (61) 6) Don't remember. . 6 ( (2 -i [CONTINUE WITH CARDi"F"T 98a. In the last 3 months, how often have you found yourself having to redo work that you had already done? Very often..fegj Fairly often.... -l) (ASK Q.98b) -2j Sometimes.. Almost never.... Never -3] -41 (SKIP TO Q.99a) -5j 98b. During what month and year did you begin having to redo work you had already done? MONTH J (65 . ) YEAR toeT ( 67) Don't remember. . 6 8 (.; -1 I CONTINUE WITH CARD "F"I 99a. In the last 3 months, how often have you found yourself unable to handle a task which at one time you could perform with little difficulty? Very, of ten.. ( J , 6): Fairly often.... -1\(ASK Q.99b) -21 Sometimes Almost never.... Never -3) -4V(SKIP TO Q.lOOa) -5J 99b. During what month and year did you first find yourself unable to handle such tasks? MONTH YEAR T i l l I I I I l-l I I "(70) (71) (72) (73) Don't remember. . 7 ( (4 -1 jCONTINUE UITH CARD "F"T lOOa. In the last 3 months, how often have you had trouble remembering things? Very often..(75j Fairly rften.... -l\ -2J (ASK Q.i00b) Sometimes -3 J Almost never.... -AMSKIP TO Q.10U) Nave r _»^_m~ -1 1 lOOb. During what month and year did you first have trouble remembering things? MONTH I YEAR l l I l l (70) (77) (78) (79) Don't remember..( 8<l__- 1 �...... .. •; ., CARD 101 812039 .'.CARD. "F" I 101 a. In the last 3 months, how often have you found yourself unable to handle large tasks efficiently? Very often..(.12( Fairly often.... -A. (ASK Q.iOlb) -2J Some t ime s Almost never.... Never -3 J -4l(SKIP TO Q.102a) -5j lOlb. During what month and year were you first unable to handle large tasks efficiently? MONTH YEAR (13) (14) (15) (16) I Don't remember. .(17( -1 1 CONTINUE WITH CARD " T F 102a. In the last 3 months, how often have you experienced difficulties when trying to solve some type of problem? Very often..O8( Fairly often.... -1\. (ASK Q.102b) -2| Sometimes -3 j Almost never.... -4V (SKIP TO Q.103a) Never -5J 102b. During what month and year did you begin having difficulty solving problems? MONTH YEAR I (19) (20) I (21) (22) Don't remember..(23( -1 TCONTINUE WITH CARD "FT 103a. In the last 3 months, how often have you felt confused and had trouble thinking? Very often..(24( Fairly often.... - \ (AgK Q.103b) ] -2J Sometimes....... Almost never.... Never -3| -4V (SKIP TO Q.104a) -Sj 103b. During what month and year did you first feel confused and have trouble thinking? MONTH YEAR (25) (26) (27) (28) Don't remember..(29( -1 [CONTINUE WITH CARD "F"I 104a. In the last 3 months, how often have you found yourself unable to perform tasks as quickly as you wanted to? ..(3pJ_____-lL (ASK Q.iQ4b) (0 -1\ Very often. . 3 ( Fairly often... en.... -2j Sometimes Almost never.... Never -31 -4>(SK1P TO Q.lOSa) -51 104b. During what month and year did you first have trouble performing tasks as quickly as you wanted to? MONTH T" 1 I t YEAR 1 I Til) 02) fn) O4 ) 67 Don't remember. . 0_5j____-l �CARD 101 812039 I CONTINUE WITH CARD " ' FT 105a. In the last 3 months, how often have you had a hard time getting going when you wake up? Very often..(36< -11 (ASK Q.lOSb) Fairly often... -0 Sometimes Almost never Never 105b. -3) -4y(SKIP TO Q.106a) -5 I During what month and year did you begin having a hard time getting I 1 Don't MONTH 1 I (37) (38) 1 1- •V YEAR 1 1 1 1 • (ASK Q.lOSc) (39) (40) (41( Within the last 12 months... -1 . -2 (SKIP TO Q.106a) 105c. During what period in your life was this most serious? MONTH YEAR MONTH YEAR (42) (A3) I I ( 4 (45) 4) TO I 1 1 - 1 1 . I (46) (47}(48) (49) (50( No period Not sure -1 __-2 TCONTINUE WITH CARD "F"! 106a.In the last 3 months, how often have you had uncontrollable feelings of anger? Very often..(.5l( Fairly often.... -1 J.(ASK Q.106b) -2J Sometimes Almost never Never -3 | -4 \- (SKIP TO Q.107a) -5J 106b. During what month and year did you first have uncontrollable feelings of anger? MONTH YEAR ^, 1 I I l T l (52) (53) Don't remember l - I I T l l (54) (55) (56( Within the last 12 months.. V (ASK Q.106c) -U -2 (SKIP TO Q.107a) 106c. During what period in your life was this most serious? MONTH YEAR MONTH YEAR 1 I T T T T T I Tl I T I I l-l I I TO I I l-l I I ( 57) (58) (59) (60) (61) (62) (63) (64) No period Not sure ( 65( 68 -1 -2 �...CARD. .107 812039 TCONTINUE WITH ...CARD :rVl 10 7«. In the last 3 months, how often have you been bothered by tiring out easily? Very often..(_12(_ Fairly often.... _ -l"l (ASK Q.io7b) -2J Sometimes......._ Almost never----_ Never ........... -3| -AY (SKIP TO Q.108a) -5j lt)7b. During what month and year did you begin tiring out easily? MONTH __ YEAR 1 I TT T T -I ....,.(. I-L , 1 . J >-(ASK Q.107c) (13) (i'i) ?15) (16) Don' t retnambei. .... , ...... « ( jf / ( i -1 • ~ •-'•"---- *J Within the last 12 months.. _ _-2 (SKIP TO Q.108a) 10.7c. During what period in your life was this most serious? MOMTH, YEAR MONTH __ YEAR .j u-p j. ^ | p ^ J..J ^. j. 1 I I l-l I I TO I I l-l I _ I (18) (19) (20) (21) ( 2 2 ) (23) (24) (25) No period.. ..... (26( Not sure ............ -1 -2 , WITH CARD. "F" I 108'i.In the last 3 months, how often has tiredness caused ydu to cut back your hobbies ot leisure activities? v Very often..(.22( -* V (ASK Q.lOSb) Fa,irly often.... "2J Sometimes Almost never Never -31 -AW (SKIP TO Q.109a) -Sj 108b. During what month and year did you begin cutting back your hobbies or leisure activities because of tiredness? MONTH YEAR \ I HT l-l (28) (29) Don't remember I .. I I (30) (31) ( 32( Within the last 12 months.. V (ASK Q.108C) -1 _-2 (SKIP TO Q.109a) 108c. During what period in your life was this most serious? MptlTH, YEAR MONTH YEAR T I T] I T I . I l-l I I (33) (34) (35) (36) T I I I"! I TO (37) (38) (39) (40) No pefiod.......(41(- . _-l Not sure -2 �CARD 107 812039 ]CONTINUE WITH CARD "F" | 109s. In the last 3 months, how often have you felt like a powder keg ready to explode? Very often..(.42( Fairly often.••• -ll(ASK Q.109b) ~2J Sometimes Almost never.... Never . . . -3 | -4 4-(SKIP TO Q.HOa) -5J 109b. During what month and year did you first feel like a powder keg ready to explode? 1 1 1 I I 1 1 1 l-l 1 1 (43) (44) (45) (46) • (ASK Q.109c) ( 47( Within the last 12 months.. -1 -2 (SKIP TO Q.llOa) 109c. During what perioc in your life was this most serious? MONTH YEAR MONTH YEAR 1 1 1 I I I I 1 1 1 I I 1 1 l-l 1 1 1 TO 1 1 1 l-l (52) (53) (54) < 55) (48) (49) (50) (51) No period ( 56( -1 JCONTINUE WITH CARD "F"| UOa.In the last 3 months, how often have you been troubled by feeling tired all the time? •> yery_often..(.57( Fairly often...._ -1 L (ASK Q.llOb) Sometimes......._ Almost never----_ Never...........~__ -4 M >H SKIP TO -5j Q.llla) llOb. During what month and year did you begin feeling tired all the time? MONTH YEAR I I I I1 I • H (58) (59) Don't remember (60) I I I I (ASK Q.flOc) (61) ( 62( ~1 Within the last 12 months.. _ -2 (SKIP TO Q.llla) llOc. During what period in your life was this most serious? MONTH __ YEAR MONTH __ YEAR 1 ^p ^ | j. j . | p ( 1 1 I I l-l I I TO I I . 1-1 . 1 . I ( 63) ( 64) ( 65) ( 66) ( 67) ( 68) ( 69) ( 70} No period ....... (71(_ Not sure............_ 70 -1 -2 �CARD HI 812039 I CONTINUE WITH CARP "F"I Ilia. In the last 3 months, how often have you felt too tired to walk up a flight of stairs? Very often..( 12(_ _-1 I (ASK Q.lllb) Fairly often.... Sometimes Almost never.... Never (SKIP TO Q.112a) lllb. During what month and year did you begin feeling too tired to walk up a flight of stairs? MONTH i I YEAH T.T~ T""~r T-l (ASK Q.lllc) ( 13) ( 14) ( 15) (16) Don't remember ( -2 Within the last 12 months.. (SKIP TO Q.112a) lllc. During what period in your life was this most serious? MONTH YEAR MONTH YEAR I (22) (23) I l-l ( 18) ( 19) (20) (21) (24) (25) No period Not sure.. -2 I CONTINUE WITH CARD "F"I 112a. In the last 3 months, how often have you found yourself powerless to control your temper? Very often..(27( -1 L(ASK Q.ll2b) Fairly often.... -21 Sometimes _ Almost never. . . ." Never (SKIP TO Q.113a) 112b. During what month and year did you first find yourself powerless to control your temper? I MONTH i YEAR Ti i r r(ASK (28) (29) Don't remember Q.112c) (30) (31) (. -2 (SKIP TO Q.113a) Within the last 12 months.. 112c. During what period in your life was this most serious? MONTH YEAR MONTH YEAR T I I (33) ( 34) I (35) ( 36) ( 37) '( 38) ( 39) (40) No period (_< l(_ Not sure 71 -1 �CARD 111 812039 IgONTlNUE WITH CARD 'Tfw\ 113a. In the last 3 months, how often have you felt too exhausted to perform your usual duties at work or at home in a competent manner? Very often..(42< Fairly often.... -1 I (ASK Q.U3b) -2j Sometimes Almost never.... Never -3 J -4 t(SKIP TO Q.114a) -5J 113b. During what month and year did you begin to feel too exhausted to perform your duties competently? MONTH YEAR 1 I I V(ASK Q.113c) (A3) (44) (45) (46) Don' t remember. ( 47( Within the last 12 months.. -2 (SKIP TO Q.114a) 113c. During what period in your life was this most serious? MONTH YEAR MONTH YEAR '_ T I T T 1 T I I l-l I I TO (48) (4$) (50) (51) (52) (53) (54) (55) No period Not sure. ( In the next series of questions, we are no longer referring specifically to the last three months. 114a. In general, do you speak to close friends — either in person or on the phone — much more often, somewhat more often, just as often, somewhat less often, or much less often than you used to? Much more often. Somewhat more often... Just as often. -2 f>(SKIP TO Q.llSa) Somewhat less often... Much less often -4 |(AgK Q.114b) ' *" 114b. During what month and year did you begin speaking less often to your close friends? MONTH YEAR 1 I T l I T I I 1-1 I I (58) (59) (60) (61) Don't remember..(62( -1 72 �CARD 111 811039 THAND RESPONDENT CARD "F"| 115a. How often has losing your temper created strains in your family relationships? Very often..(63j Fairly often. ... Sometimes Almost never.... Never 115b. -l~l (ASK Q.llSb) ~^J -3 J -it (SKIP TO Q.116) -5 I During what month and year did losing your temper begin creating in your family relationships? MONTH I I YEAR I I I I I I l-l .1 I (64) ( S 6 T (66) (67) Don't remember (8 6( (ASK Q.llSc) -1 ~2 Within the last 12 months.. _ 115c. (SKIP TO Q.116a) During what period in your life was this most serious? MONTH .. ^—-^I. I (70) __ ^- ^ l l YEAR ! I ___ ^ I (71) (72) TO MONTH ^I YEAR | -^ ^ ^ 1 1 1 I I 73) (741 (75) (76) No period.......(77 ( __-! Not sure ............ -2 116. In choosing your friends, how important to you are things like their religious or political beliefs. Would you say they are always very important, usually important, sometimes important, hardly ever important, or not important at all? Always very important. (78 (_ -1 Usually important......... _ -2 Sometimes important......._ -3 Hardly ever important....._ -A Not important at all......_ -5 [HAND; RESPONDENT CARD"F" I 117. How often have you deliberately said something that hurt someone's feelings? Very often..(79( Fairly often.... Sometimes Almost never.... Never.... -1 -2 -3 -4 -5 .KITH. CARD "F" I 118. of? How often have you done something of a sexual nature that society does not approve Very often.. (8_pJ __ Fairly often.... _ Sometimes. ......_ Almost never.... _ Never........ . .. 73 -1 -2 -3 -4 -5 �CARD 119 812039 119a. Do yon confide in close friends and relatives much more often, somewhat more often, just as often, somewhat less often, or much less often than you used to? Much more often...(12( Somewhat more often... Just as often/no difference -1 -2 Somewhat less often... Much less often -*\ (ASK Q.119b) (SKIP TO Q.120) -3 119b. During what month and year did you begin confiding less often in close friends and relatives? 1 I MONTH YEAR 1 F 1 I I I l-l I I (13) U 4 ) ( 1 5 ) (16) Don't remember.. (17( -1 120. Are your table manners at home just as good as they are when you are invited out to dinner? Would you say your table manners are always just as good at home, usually as good, usually not as good, or never as good at home? Always just as good at home...(18( Usually as good Usually not as good Never as good at home -1 -2 _-3 -4 121a. Do you find your current involvement in community activities to be much greater than it used to be, somewhat greater, just as great, somewhat less, or much less than it used to be? Much greater than it used to be Somewhat greater Just as great/no difference (19( -2 f (SKIP TO Q.122a) Somewhat less... Much less than it used to be "^(ASK Q.121b) 121b. During what month and year did you begin involving yourself less in community activities? MONTH YEAR I T (20) ( 2 l 5 ( 2 2 ) (23) Don't remember. . 2 ( (4 I HAND RESPONDENT CARD "F"I 122a. How often do you find you have trouble keeping track of bills — very often, fairly often, sometimes, almost never, or never? -1 would you say Very often..(_25< Fairly often.... -1 1 (ASK Q.122b) -2 J Sometimes Almost never Never -3 | -4 L(SKIP TO Q.123a) -5 ] I22h. During what month and year did you begin having trouble ket-pinp. truck of hills? MONTH YEAR T—i—n—i—r I _ L. l -(28) (29)I l. (275 I Don't remember. . (30( -1 �CARD 119 812039 TCONTINUE WITH CARD "F"I • 12.3a, How often do you find that you are unable to balance your checkbook? Very often..(3l( Fairly often.... .... \ (ASK Q.123b) ...l -2 J Sometimes Almost never Never -3[ -4V (SKIP TO Q.124) -5J 123b. During what month and year were you first unable to balance your checkbook? MONTH YEAR (3r2) (33) (34) (35) Don't remember. . 3 ( (6 I CONTINUE WITH CARD "rT 124. How often do you eat too much? Very often. ,(_37( Fairly often..... Sometimes Almost never.... Never -1 -2 "-3 -4 -5 125. In general, would you say your morals have been definitely above reproach, probably above reproach, probably not above reproach, or definitely not above reproach? Definitely above reproach Probably above reproach Probably not above reproach Definitely not above reproach (38 ( -1 -2 -3 -4 THAND RESPONDENT CARD "F"T 126a. How often has losing your temper created problems for you at work? Very often..(39 ( Fairly often..«._< Sometimes Almost never Never. -1 J. (^v Q.i26b) ______ -4^(SKIP TO Q.127a) 126b. During what month and year did losing your temper begin creating problems for you at work? MONTH YEAR rI i I \ l-lT I\ \I 140) (41) Don't remember (42) (43) . . . 4/j( ,.( Within the last 12 months.. 126c. • (ASK Q.126c) -1 -2 (SKIP TO Q.127a) During what period in your life was this most serious? T MONTH i ri __ YEAR i r I ~ I l-l I I U5) ( 6 4r (47) ( 8 4) i TO MONTH I I i ri YEAR i (49> (SO) ~T5i>" (52) No period.......(53( _ ^ -I Not sure ............ -2 75 r �CARD 119 812039 [CONTINUE WITH CARD "F"T 127a. How often has losing your temper resulted in a friendship breaking up? Very often..(j^J Fairly often.... -ll(ASK Q.127b) -2J Sometimes Almost never Never -3 | -4V (SKIP TO Q.128) -5J 127b. During what month and year did losing your temper first result in a friendship breaking up? MONTH YEAR 1 I I I l-j I I (ASK Q.127c) (55) (56) (57) (58) Don't remember ............. ( 9 5( -1 Within the last 12 months.. _ 127c. iI (60) (SKIP TO Q.128a) During what period in your life was this most serious? MONTH _ -2 i 1 YEAR 1 (61) n 1 1i - MONTH __ YEAR r i I ' n Ii i M I TO I (62) ( 3 6) (bit) (65) No period ....... (fj8( Not sure............_ I r ( 6 (67) 0) -1 -2 — — — — — — — — - • — • — • — - — — — - — — • " — — — — — ' — * — " " — • — - • - » . • * . . • • - • - * • • • • . • ! • • • . . • • » • . . • . . — —•. • • » • •• • • » • • — • — - • • • • — - . • • - • • « • • « •••—.••«.—.••• Now I'm going to ask you a few questions about recreation and leisure activities. 128. What are some of the hobbies and sports you participate in on a regular basis? Any others? 3. A,. 5. 6. 129. Have you participated three or more times in (READ EACH ITEM)? ANY ITEM MENTIONED IN Q.128 AND DO NOT READ THAT ITEM) (CODE "YES" FOR _ 1. _ No Scuba diving 2. Auto, boat, or motorcycle racing..............................(70 ( A. Mountain climbing..........................................•••'i2-i_ 5. Hang gliding..................................................(73 ( 6. Plane racing or plane acrobatics, not including flight training or any assignments for the Armed Forces..............(74 (_ 76 -1 _ "2 �ITISTESTtU-EMJLOVEaS AMD' DUTIES'TROH S.R.B. - ?ACE 1 AT tut TOE> 6F THE JOB cOUMiS OTT PACES 72" AND 73. IF So JgBffeNTEREp"lN S ^ IF MOKE THAN SIX JOBS ON S.R.B. PAGE 1, RECORD ADDITIONAL EMPLOYERS AND DUTIES AT TOP OF COLUMNS ON PAGES 44-45 IN S . R . B . ! - . PAcn'r'SK'iP TO Q . U T . T . 130. I would like Co asfc you about your experience with certain chemicals or toxic su bstances. m i li tarv . FIRST JOB 1'H'AND RESPONDENT CARD "G" 1 130a. While working at (EMPLOYER) as (DUTIES), d o / d i d you come in contact with any of the subs tances on t h i s card? By c o n t a c t , I mean that you inha led, t a s t e d , had s k i n contact w i t h , or were radiates by any of these substances? I MULTIPLE RECORD I Ol..(12( 02. .( 13( 03.. (TS -1 -1 -1 05. (1« 06. ( 17( O7.(l8( 04.. ( iy. -i SECOND JOB 01..(12( O2..(l3( 04.. ( 15( (IF "07," -1 -1 O5.(l6( 06.(T7( -1 1 1 ! 1 1 THIRD JOB -1 -.1 C1..(12( O2..(13( -1 -1 O4..(15( (IF "07," SKIP TO NEXT JOB) SKIP TO NEXT JOB) TASK Q.i30b FOR EACH SUBSTANCE CODED IN q.i30a.T 130b. tn general, how many days a month ( d o / d i d ) you come in contact with (SUBSTANCE)? -1 -1 -1 1 First, l e t ' s talk about your employment outside of the -1 05.(16( O6.(i7( -1 -1 (IF "07," SKIP TO NEXT JOB) 01..! I I (19H20) 1 1 1 1 1 1 01.. 1 1 1 04.. I I 1 (19K20) (21K22) I I I I I 01. .1 1 1 04.. I I (19)(20) (21M22) I I I 02. .1 1 1 (23X24) I I I 05. .1 1 1 (25) (26) 1 1 I I I I 02. .1 1 1 05. .1 1 1 (23) (24) '.25) (26) I I I I I 02. .t 1 1 05.. 1 1 (23) (24) (25) (26) I I I 03.. I I I (27)(28> !lF ANY SUBSTANCE CODED IN Q.130b, ASK Q.130cl 13Gc. While you were on that job, how o f t e n di d you wash to remove the (SUBSTANCES) or use pro" tective gear —> would you say all of the time, some of the time, or never? 04. .1 I (21H22) I I I 06.. 1 1 1 (29) (30> I I I I I I 03.. I 1 1 06..! 1 I (27) (28) (29) (30) I I I 1 1 03.. 1 1 1 06.. 1 1 (27) (28) (29X30) All the time(3l( Some of -IKASK Q. f 130d) [HAND RESPONDENT CARD "H'M 130d. Which of the following did you use on that job? [MULTIPLE RECORD IF NECESSARY 1 Air f i l t e r ( 32( -l\ Goggles (_33(__~1 (GO TO Face shield ( 34( -1 NEXT JOB) Special clothing. .(_3<__-l Washing f acilitiesC 3ft -1 01 79-80 -ll(ASK Q. \ 130d) All the t i m e . ( 3 l ( Some of -l) (ASK Q. > 130d) Never JOB) All the time.(3l( Some of -3 (GO TO NEXT JOB) Never -3 (CO TO NEXT JOB) Air f i l t e r ( 32( Goggles • . •• ( 33( Face shield (~34( Special clothing.. ( 35( Washing faelllties( 36( Air f i l t e r (32( -l| ( 33( — 1 (GO TO Goggles Face shield (~34( -1 ' N E X T -1 JOB) Special clothing. .( 3s( -1 Washing £acilities( 36( 02 79-80 -1 -t (GO TO -1- NEXT JOB) -1 -1 03 79-80 �CARD 130 FOURTH JOB I HAND RESPONDENT CARD ''c'1 1 130a. W h i l e working at (EMPLOYER) as (DUTIES), d o / d i d vou come in contact with any of the substances on t h i s card? By contact, I wan that you i n h a l e d , t a s t e d , had skin contact with, or were radiated by any of these substances? IMULTIPLE RECORDl IASK Q.130b FOR EACH SUBSTANCE CODED IN Q.130a.| 130b. In general, how many days a month ( d o / d i d ) you come in contact vith (SUBSTANCE)? Ol..(12( 02. . ( J 3 ( 03..(T31 O4..(15( -1 -1 -1 -1 SIXTH JOB FIFTH JOB 05-(16( -1 O 6 . ( l 7 ( -1 O7.(18( -1 (IF "07," SKIP TO NEXT JOB) 01..(12( -1 05.(16( -1 03.. (TT( O4..(15( -5 -1 01..(12( O2..(l3( 03..U4C Q6..(15( 07. (T8T -1 (IF "07," SKIP TO NEXT J O B ) -1 -' -1 -1 05. ( I f , I -1 06. (j 7', -1 O 7 . ( 1 8 ( -1 (IF " 0 7 , " S K I P TO NEXT J O B ) 1 . 1 04.. 1 1 (21M22) 1 1 1 I I I 01. .1 1 I 04. .1 I 1 (19) (20) .(21) (22) I I I i i ! 01. .1 1 1 04..! ! i (19 ) ( 2 0 ) (21 )(22 i 1 1 1 02. .1 1 I (23K24) 1 1 1 05. .1 1 1 (25)(26) I I I I I I 02.. 1 I I 05.. 1 1 1 (23) (24) (25) (26) I I I 1 i 1 02. .1 1 1 05. .1 1 1 (23) (24) (25) (26) I I I 03.. 1 I I (27)(28) I I F ANY SUBSTANCE CODED IN Q.ljOb, ASK Q.130cl 130c. While you were on that job, how o f t e n di d you wash to remove the (SUBSTASCES) or use protective gear — would you say all of the time, some of the time, or never? 1 1 1 01.. 1 I I (19H20) 1 1 1 06.. I 1 I (29)(30) 1 1 1 I I I 03.. 1 I 1 06. .1 1 1 ( 2 7 ) (28) ( 2 9 ) (30) I I I 1 i ! 03.. 1 1 1 06.. 1 1 1 ( 2 7 ) (28) (29H30) -l)(ASK Q. J. 130d) All the time. (31 ( Some of -f)(ASK Q. f 130d) All the time. (31 ( Some of the t ime -l)(ASK Q. r 130d) -2 1 Never iHAND RESPONDENT CARD "H" 1 130d. Which of the following £id you use on t h a t iob 7 IMULTIPLE REC057* IF NECESSARY) All the time(3l( Some of -3 (GO TO NEXT JOB) Never -3 ( G O T O NEXT JOB) Never -3 (GO TO NEXT JOB) Air f i l t e r (32( -?) • Goggles (33 ( -1 (GO TO Face shield (34 ( -1 NEXT JOB) Special clothing.. (35( -1 Washing f a c i l i t i e s ( ^ f t ( -1 04 Air f i l t e r (32( -l) Goggles. (33 ( -l|(GO TO Face shield (34 (' - I T NEXT Special clothing. .(35 ( -ll JOB) Washing f a c i l i t i e s U b ( -ll 05 Air f i l t e r (32 ( _-l (IF MORF Goggles (33 ( -1 THAN' ft Face shield (34 ( -1 JOBS, GO Special clothing. . (js ( _-l TO PAGE W a s h i n g f a c i l i t i e s U b ( , -1 44 IN S.R.B.) 06 �CARD 131. 131 812029 Have you ever had any other jobSj such as a temporary job or a job while you were in school, outside of the military? Yes ( 12( -1 (ASK 0.132a) No -2 (SKIP TO 0.133) lHAND RESPONDENT CARD "G"l 132a. In those jobs, did you ever come in contact with any of the substances on this card? X-Ray Or Nuclear Radiation Asbestos Q.!32a. Yes (13( -1 Industrial Chemicals -2 IRECORD AT TOP OF APPROPRIATE COLUMN: Defoliants Or Herbicides -3 Insecticides . Or Pesticides Degreasing Chemicals -f- -5 -4 i IFCF. EACH SUBSTANCE | iCODED, ASK Q.132b. 1 132b. In what years were you in contact with (SUBSTANCE) on those jobs? 1 FROM > ! ! FROM ! 1 i 1 1 1 (14) (15) TO I 1 1 1 ! (14) (15> TO 1 I I l ! l ! ! FROM 1 1 1 1 ! 1 ( 4 ' (15) 1) TO 1 1 1 1 1 ! (16) (17) 1 ( 16) ( 17) 132c. How many days altogether would you say you came in contact with (SUBSTANCE) on these jobs? I32c. On those days you came irt contact with 'SUBSTANCE) how often did /ou wash to remove the (SUBSTANCE), or use protective clothing or gear — all the time, some of the time, or never? IttAND RESPONDENT CARD "H" i T32e. Which of the following did you use? 1 MULTIPLE RECORD IF | ! NECESSARY I (16) (17) DAYS i 1 1 1 1 1 1 I <18)( 19><20) DAYS 1 1 1 1 1 1 ! ! ( 18) (19X20) All of the time.( 21( Some of the -1 All of the time.(2l( Some of the -1 FROM 1 1 FROM 1 1 i i (14) (15) TO I I I ! ! I DAYS 1 1 1 1 1 ! (18)(19)(20) -1 ! DAYS 1 1 1 1 1 1 1 1 (18)(19X20) All of the time.(2l( Some of the l 1 FROM ! I l i (14) (15) TO 1 1 i 1 1 1 (16) (17) (16) (17) 1 All of the time.(2l( Some of- the ! I -1 DAYS i I (li) (!5) TO 1 1 1 (16) (17> ! i • ! i 1 1 1 I (18X19X20) i 1 ! i l l All of the time.(2l( Some of the ' I -1 DAYS : i 1 i (l8)(l9X20) All of the time.(21( Some of the -i _*i <t. Never -3 (IF "NEVER," GO TO NEXT SUBSTANCE REPORTED) Air Filter. ( 22( -1 Goggles (~23T -1 Face Shield( 24( -I Special Clothing.. ( 5 -1 2( Washing Facilities(26( -1 (GO TO NEXT SUBSTANCE REPORTED) 01 79-80 Never -3 (IF "NEVER," GO TO NEXT SUBSTANCE REPORTED) Air Filter. (22( -1 Goggles ("231 -1 Face Shield(24( -1 Special Clothing.. ( 5 2 ( -1 Washing Facilities(26( -1 (GO TO NEXT SUBSTANCE REPORTED) 02 79-80 Never -3 (IF "NEVER," GO TO NEXT SUBSTANCE REPORTED) Air Filter. (22( -1 Goggles (23( -1 Face Shield(24( -1 Special Clothing.. ( 5 2 ( -1 Washing Facilities(26( -1 (GO TO NEXT SUBSTANCE REPORTED) 03 79-80 Never -3 (IF "NEVER," GO TO NEXT SUBSTANCE REPORTED Air Filter. (22( -1 Goggles (23( -I Face Shield(24( -1 Special Clothing.. (25( -1 Washing Facilities(26( -1 (GO TO NEXT SUBSTANCE REPORTED) 04 79-80 Never -3 (IF "NEVER," GO TO NEXT SUBSTANCE REPORTED) -3 Air Filter. (22( -1 Air Filter. (22( — 1 Goggles. . . . (23( -1 Goggles (23( -1 Face Shield(24( -1 Face ShieldC-.( -1 Specia 1 Special Clothing. .(25( -1 Clothing. .(25( -1 Washing Washing Facilities(2d( -1 Facilities(26( -1 (GO TO NEXT SUBSTANCE REPORTED) ° A 7 u~bO 05 79-80 �CARD 133 ENTER ALL COUNTRIES FROM S.R.B. - PAGE 2 AT THE TOP OF THE COUNTRY COLUMNS ON PAGES 75 AND 76. IF NO COUNTRIES ENTERED IN S.R.B. PAGE 2 , SKIP TO Q.134 IF MORE THAN SIX COUNTRIES OK S.R.B. PAGE 2, RECORD ADDITIONAL COUNTRIES AT TOP OF COLUMNS ON PAGES 46 AND 47 IN S.R.B. 133. Next, I'd like you to think again about your active duty assignments. SECOND COUNTRY FIRST COUNTRY 12-13 (14-15) [HAND RESPONDENT CARD "G"| 133a. In your job assignments while stationed in (COUNTRY), ( t h a t t i m e ) ( d o / d i d ) you come in contact with any of the following substances? lASK Q.133b FOR EACH SUBSTANCE CCOED IN Q.133a ! 133b. In general, how many days a monn ( d o / d i d ) you come in contact wit*1. (SUBSTANCE)? Ol..(16( -1 O5.(20( -1 O2..(17( -1 06. (277 -1 03..(IFT~-1 - 07.C22T -1 O4..(l9( -1 (IF "07," SKIP TO NEXT COUNTRY) 1 01.. 1 1 I ! I I 04.. | (23) (24) l ! l ! (25) (26) THIRD COUNTRY (14-15) 01..U6( 02.. (FTl -1 O5.(20( -1 -1 O6.(21( -1 O7.(22l -1 -1 (IF "07," SKIP TO NEXT COUNTRY) Ol..(16( -1 O5.(20( -1 Q2..(17( -1 06.(21 ( -L 03.. (Is!-1 07. (ill-1 (IF "07," O4..(19( -1 SKIP TO NEXT COUNTRY) 03.. (nn -i O4..(19( 1 1 1 1 1 1 1 04.. I I | 01.. 1 1 (23)(24) (25) (26) 01..I ( 3 ( 4) 2)2 (25 )(26 ) I I I 02.. 1 I | ( 2 7 ) (28) 1 1 1 I I ! 52. .1 I 1 05..! I I (27 )(28) (29) (30) I I I I I 02..I I I 05..I I (29 ) GO ) (277(28) I I I 03.. 1 I I (31) (32) i l F ANY SUBSTANCE CODED IN Q.13?r. ASK Q.133cl 133c. Did you wash to remove tr.e (SUBSTANCE) or did you use protective clothing or eear when stationed in (COUNTRY) — = i. of the time some of the time, or never? I I I 05.. 1 1 1 (29) (30) I I I 06.. 1 I 1 (33) (34) 1 1 1 I I I 03. .1 ! ! 06.. 1 i 1 (31) (32) (33) (34) 03..I I 06..I 03 (31 )(32 ) T -lT(ASK Q. f 133d) -2J All the time.( 35 ( Some of -l](ASK Q. f 133d) -2 *J All the time. (35 ( Some of the time Never iHAND RESPONDENT CARD "H" ! 133d. Which of the f o l l o w i n e c:-- vou use on t h a t iob? (MULTIPLE RECORD :• NECESSARY I All the tiroe(35( Some of the time -3 (GO TO NEXT COUNTRY ) Never -3 (GO TO NEXT COUNTRY ) Never. Air f i l t e r (36 ( Goggles (37 ( Face shield (33 ( Special clothing. .(39 ( Washing f acilit ies(40 ( -l] -1 (GO TO -1 NEXT -1 COUNTRY) -1 01 79-80 Air filter Goggles ....(36( (J?l flu ( Special clothing. .(39 ( Washing f a c i l i t iesCip ( -?) -1 (CO TO -1,'NKVT -1 C O U N T R Y ) -ll 02 79-80 T )(34 ) -ll(ASK Q. V 133d) -2j _-3 (GO TO NEXT COUNTRY Air filter 06 ( Goggles (3_7 Face shield.......(• Special clothing.. (39 ( Washing facilitiesCiO �FOURTH COUNTRY .12-13 SIXTH COUNTRY FIFTH COUNTRY (14-15) (14-15) (14-15) IHAND RESPONDENT CARD "G"| I 3 3 a . In your job assignments w h i l e s t a t i o n e d in ( C O U N T R Y ) , ( t h a t t ime) ( d o / d i d ) you come in c o n t a c t with any of the following substances? l A S K 0.133b FOR EACH SUBSTANCE CODED IN Q.133a. 1 133b. In g e n e r a l , how many days a month ( d o / d i d ) you come in contact with (SUBSTANCE)? O2..(17( 03.. (T^ O4..(19( Q5.(20( -1 O6.(21( -1 07.(~22T -1 (IF "07," SKIP TO NEXT COUNTRY) -1 -1 -1 Ol..(16( Q2..(17( -1 -1 04..(T5( -1 O5.(20( -1 O6.(21( -1 07. ("221 -1 (IF "07," SKIP TO NEXT COUNTRY) :i..(16( ^..(nC ~3..(18( :i..<19( O 5 . ( 2 0 ( -1 06. ( 2 H -1 0 7 . ( 2 2 ( -1 (IF " 0 7 , " SKIP TO NEXT COUNTRY) I I I 01..! 1 I (23)(24) 1 1 1 04.. I 1 1 ( 25) (26) 1 1 1 1 1 1 1 1 01. .1 1 1 04.. I (23) (24) (25) (26) i 01. . i 1 ! 1 02. .1 1 1 ( 2 7 ) (28) 1 1 1 05. .1 t 1 ( 29) ( 30) 1 1 1 1 1 1 02.. 1 1 1 05. .1 1 1 ( 2 7 ) (28) ( 29) ( 30) i i 1 I I I 02.. 1 i 1 05..! ! i ( 2 7 ) (28) ( 2 9 ) (30) I I I 03.. 1 ! 1 (31) ( 3 2 ) i l F ANY SUBSTANCE CODED IN Q.133b, ASK Q.133cl 133c. Did you wash to remove the (SUBSTANCE) ^•c did you use protective clothing or gear when stationed in (COUNTRY) — all of the time, some of the time, or never? 1 I I 06.. I 1 1 ( 33) ( 34) I I I 1 1 1 03..! 1 1 06. .1 I 1 (31M32) (33M34) i l l I I I 03. .1 ! ! 06.. 1 1 1 (31)(32) (33)(34) T All the tiae.(35( -1HASK Q. Some of \f 133d) the tine -2J All the time( 35( Some of -1 (ASK Q. 133d) ! Never -3 (GO TO NEXT COUNTRY ) All the time.(35( Some of -l) (ASK Q. > 133d) -2j -3 (CO TO NEXT COUNTRY) l ! -1 -I -1 -1 l 1 1 04..! <.23)(24) Never ! ! i i (25) ( 2 6 ) -3 (GO TO NEXT COUNTRY IHAND RESPONDENT CARD "H"| 133d. Which of the f o l l o w i n g did you use Air f i Iter ( 36( Face shield ( 38( Special clothing.. ( 39( Washing f a c i l i t i e s ( 40( -1 -1 (GO TO -1 NEXT -1 COUNTRY) -1 04 79-80 . . . ( 36( Face shield . ..(38( Special c l o t h i n g . .( 39( Washing facilities(~50f -l) Air f i l t e r -1 NEXT -1 COUNTRY) -1 Face shie'.d ( 38( Special cSathing. .( 39( Washing f a:ilit ies( 40( 05 79-80 ( 36( -1 (RECORD -1 T10NAL -1 COUN-1 TRIES IN S.R.B. PAGE 46) 06 79-SO �CARD 812039 lHAND RESPONDENT CARD "G" 1 134a. Have your hobbies and spores a c t i v i t i e s ever brought you in contact w i t h any of the ( a l l o w i n g s u b s t a n c e s ? X-Ray Or Nuclear Radiation Asbestos 0.134a. Yes I F O R EACH SUBSTANCE I i C O D E D , ASK Q.134b. 1 134b. I n what month a n d y e a r did y o u r hobbies and s p o r t s a c t i v i t i e s f i r s t b r i n g you in cont a c t w i t h (SUBSTANCE)? 134c. For how many years did you c o n t i n u e to come in c o n t a c t w i t h (SUBSTANCE)? !34d. In g e n e r a l , how many days per year did you come i n c o n t a c t w i t h (SUBSTANCE)? !34e. On the days you came in c o n t a c t w i t h (SUBSTANCE) how o f t e n did t h i n g or gear or wash to remove (SUBSTANCE) — all of the t i n e , some of the t i m e , or never? i H A N D RESPONDENT CARD "H" I n i f . Which of the • o l l o w i t i e did vou use? ^ i ' J . ' l IPl.r RECORD IF 1 Sr.i i-SSASV ! ( 13( -1 -2 MOSTH YEAR 1 i 1 I 1 1 1 : 1 - 1 1 1 ( 1 4 ) (15) (16) (17) YEARS ! I ! 1 I 1 (18)(,9) MONTH 1 I 1 l (14) YEAR 1 l (15) 1 - 1 I 1 l l (16) (17) -i Never -2 (!? "NEVER," GO TO NEXT SUBSTANCE REPORTED) Air F i l t e r . (24( -1 Goggles ( 25( -1 Face 3 h i e l d ( 2 6 ( -1 Scecial Clothing.. (27( -1 Washing F a c i l i t i e s ( 2 8 ( -i <V> *'.'• N E X T SUBSTASC£ REPORTED) 01 79-30 All of the time.(23( Some of the MONTH YEAR ! 1 I I 1 1 I l l I l l (14) (15) (16) (17) YEARS 1 1 1 1 1 1 U8M19) DAYS 1 1 1 1 1 1 1 1 (20)(21)(22) -i (IF "NEVER," GO TO NEXT SUBSTANCE REPORTED) Air F i l t e r . (24( -1 Goggles (25( -1 Face S h i e l d ( 2 6 ( -] Special C l o t h i n g . . ( 2 7 ( -1 Washing Facilities(28( _j (CO TO NEXT SUBSTANCE REPORTED) 02 79-80 -1 MONTH YEAR 1 1 1 1 1 1 1 1 l-l 1 I (14) (15) (16) ( 1 7 ) Degreasing C h e m i c a l s -6 MONTH YEAR 1 1 1 1 1 1 I l l I l l ( 1 4 ) . (15) (16) ( 1 7 ) YEARS 1 1 1 1 1 1 (18)(19) DAYS 1 1 1 I 1 1 1 I (20)(21)(22) All of the t i m e . ( 2 3 ( Some of the Insecticides Or Pesticides -5 YEARS ' 1 1 1 1 1 1 (18)(19) DAYS 1 1 1 1 1 1 1 1 (20H21K22) All of the time.(23( Some of the time. .. Defoliants Or Herbicides -4 -3 YEARS 1 1 1 1 1 1 (18)(19) DAYS i i I I ' I I I (20) ( 2 1 ) ( 2 2 ) All of the t i m e . ( 2 3 ( Soae of the Industrial Chemicals (RECORD AT TOP OF APPROPRIATE COLUMN] -1 DAYS i 1 1 1 1 1 I I (20)(21)(22) All of the t i m e . ( ' J ( Some of the -1 MONTH YEAR i 1 1 1 i I 1 1 i-l 1 1 (14) ( 1 5 ) (16) ( 1 7 ) YEARS 1 1 1 1 ! 1 (18)(19) DAYS I I I ! 1 i 1. i (20) ( 2 1 ) ( 2 2 ) All of the tiir.e.(- J ( Some of the -1 -2 Never -2 (IF "NEVER," GO TO NEXT SUBSTANCE REPORTED) Air F i l t e r . (24( -1 Goggles.... ( 2 5 ( '-1 Face S h i e l d ( 2 6 ( -1 Special Clothing. .(27( -1 Washing 28 F a c i l i t i e s ( ( -1 (GO TO NKXT SUBSTANCE REPORTED) 03 79-80 Never -2 (IF "NEVER," GO TO NEXT SUBSTANCE REPORTED) Air F i l t e r . ( 2 4 ( -1 Goggles ( 2 5 ( -1 Face S h i e l d ( 2 6 ( -i Special Clothing. .(27( -1 Washing F a c i l i t i e s ( 2 8 ( -1 (CO TO NEXT Sl'BSTANCE R E P O R T E D ) 04 79-80 Neve** —1 (IF "NEVER," GO TO NEXT SUBSTANCE REPORTED) Air F i l t e r . ( 2 4 ( -1 G o g g l e s . . . . ( 2 5 ( -1 Face Shieldt 2 "?! -1 i Special Clothing. .(27( -1 Washing F a c i l i t i e s ( ' a ( -1 ; (CO TO Ni£XT SUBSTANCE REPORTED) i 05 79-80 Air F i l t e r . ( 2 - » i Goggles. . . . ( - 5 ( Face S h i e l d ( - ° ( Specia 1 Clothing. .C-7l Washing Fjcilicies(~Jt -1 -I -i -1 -1 i..., "••->- �CARD 135 812039 Now I have some questions about your income. I HAND RESPONDENT CARD "l"I 1 3 5 ^ P I e a s e tell me wh ich letter on this card best represents the total household income in 1980 before taxes or other deductions for all people in your household, not including roomers. This amount should include wages, net income from business, itltSteSt, dividends, pensions, and any other money income. Tell me the letter that comes closest. A. H. t, p F.. F. r, $?0,000-$2'i 999 -1 -2 "•' 1 ~-l\ $25,000-$29,999 $30,000-$34,999 $35,000-$39,999 -6 _-^ $5,000-$9,999 (12 ( $10,000-$ 14 ,999 lit 1 *. ,110(1 $ 1 'I , ''' !)) H. T ,7. K. 1.. M. N. 0. P. 0 R. R. T. "-fi $45,000-$49,999 $50 ,000-$54 ,999 $55,000-$59,999..(13( $60,000-$64,999 $65,000-369,999 $70,000-$74,999 $75,000-$79,999 $80,000-$84,999 $85,000-189,999 $90,000-$94 ,999 $95,000-499,999 $100,000 or more..... 136a. Did you earn any income from any job during 1980? retirement plans or pensions. Yes. _-l No.. -2 "-0 -1 -? -ft -5 _1 ~-n -9 -0 Do not include income from (ASK Q.136b) (SKIP TO Q.137a) I CONTINUE WITH CARD *JI_"J 136b. In vhich of these groups did your earnings from jobs in 1980 fall that is, before taxes or other deductions? Tell me the letter that conies closest. A. B. C. D. E. F. G. H. I. J. K. L. M. N. 0. P. Q. R. S. T. j5,000-*9,999----(15 ( tlO,000-tlA,999 ...... $15,000-$19,999......" $20,000~$24,999 ...... ~ $25,000-$29,999......" $30,000-$34,999......" *35,000-*39,999......" " -1 I"6 -7 I"8 -9 $45,000-$49,999 _ $50,000-$54,999 _ $55,000-$59,999..(16 ( ' " ' -1 "" $60,000-$64,999 -2 $65,000-$69,999 ^-3 $70,000-$74 ,999 -4 $75,000-$79,999 -5 $80,000-$84 ,999 -6 $85,000-$8P,999 -7 $90,000-$94 ,999 -8 *95,000-$99,999 -9 $100,000 or more -0 �CARD 135 812039 137a. We would like your consent for the doctors and medical facilities you mentioned during this interview to provide medical records to the Air Force Health Survey. These records will help us obtain more detailed information about the health services you talked about. TURN TO S.R.B. PAGES JT-// . ENTER NAMES OF MEDICAL PROVIDERS ON APPROPRIATE PERMISSION FORMS AND ASK RESPONDENT TO SIGN EACH FORM. IFOR EACH SIGNED FORM, ASK:I 137b. What is the current address of (DOCTOR/FACILITY)? 138a. To obtain the most complete and useful information that we can, ve are asking participants to have a physical examination. The examination will be conducted by a private medical facility and will take place over a five-day period that is convenient for you. (IF DISCHARGED OR RETIRED SAY: "You will also receive a stipend of tlOO.OO a day. ) The United States Air Force will pay for all travel and per-diem expenses so that participants can go to a nationally recognized medical facility. If you were asked, would you be willing to have a physical examination at a time convenient for you? Yes. No.. 138b. (RECORD IN S.R.B. PAGE 13 AND SKIP TO Q.139) (RECORD IN S.R.B. PAGE 13 AND ASK Q.138B) What is your reason for not wanting to have the examination? 1 RECORD IN S.R.B.L PAGE 13| 138c. Under what conditions would you be willing to have an examination? [RECORD IN S.R.B., PACE 131 [CHECK S.R.B. PAGE 2. IF ANY DIVORCED OR SEPARATED WIVES, READ:I 139. It i'E very important lor the success of this survey that we also conduct a brief interview with former-wives of respondents. This will provide a more complete and accurate picture of the health of the families of Air Force personnel. We would like to send this letter signed by you Co (each of your former/your former) (wife/wives). ENTER NAME OF EACH FORMER WIFE ON A LETTER. RECORD CURRENT ADDRESS FOR EACH WIFE ON LETTER. HAVE RESPONDENT SIGN EACH LETTER. ICHECK S.R.B. PAGE 2.IF LIVING WITH WIFE, SAY:! 1AO. I would like to speak to your wife briefly. Is she available now? IF WIFE IS NOT LIVING AT SAME ADDRESS, RECORD CURRENT ADDRESS ON STUDY SUBJECT NAME ASSIGNMENT SHEET. . Thank you for participating in the Air Force Health Study. TIME INTERVIEW ENDED: (am/pro) �FOR OFFICE USE ONLY: LOUIS HARRIS AND ASSOCIATES, INC. 630 Fifth Avenue New York, New York 10111 Case No. Study No. 812039 O.M.8. NUMBER 0701-0033 Approval Expires 11/30/82 Respondent CONFIDENTIAL AIR FORCE HEALTH SURVEY SUPPLEMENTAL RECORDING BOOK �812039 Q.2. Where born: City: State: Q.8b. Employers 1st job: 2nd job: 3rd job: 4th job: 5th job: 6th job: 7th job: 8th job; 9th job: 10th job: llth job: 12th job: Q.8e Main Duties �812039 Q.Hi: Countries Served In: _______ 1. 2 .__________ _ _ 9. 10. 4. 11. 12. Q. 20-22 and J_52-JVi Marital History b. Wife's Current Full Name First/ only wife Second wife Third wife Fourth wi fe Fifth wife Sixth wife Wife's Maiden Name Living With Wife Or Divorced/ Separated/ Widowed �^.:«-T2 and 157 - 165 CHILDREN CHILD Q.29 FIRST First Last SECOND d. BIRTHDATE .-:;:•:::-: First Place C/S Last C/S MONTH 1 I I 1 l-l DAY 1 1 Place First Place I! l-l YEAR 1 i Place i ! i i C/S Last C/S MONTH DAY Place First Place C/S Last C/S i ! I I l-l 1 YEAR 1 1 i i l-l C/S Place i < i 1 C'S DAY i 1 Place 1 i :-S First Place 1 ! l-l YEAR : •' Place i MONTH ! M 1 l-l C/S Last C/S MONTH I ! ! ! !-! DAY 1 I Place : ' C S First Place II I-! YEAR ! ' Place i ! C/S Last C/S MONTH DAY Place First Place C/S Last C/S First !.a = r x- DEATH RECORDS Place First Last h. MOTHER'S FULL NAME Place i | C'S ; FT-TH CURRENT MEDICAL RECORDS YEAR 1 i First Last g. 1 1 )-! i FOL'PTH BIRTH RECORDS MONTH DAY 1 1 1 1 | |-| | First L3«=t f. i ! First Last THIRD NAME ! i I 1 l-l 1 1 YEAR 1 1 l-l • 1 Place ! ! C S �<". 2'H-32 and CHILD 157 - 165 CHILDREN q.29 NAME d. f. BIRTH RECORDS BIRTHDATE RECORDS SEVENTH First Last EIGHTH First Last NI NTH TESTH 1 1 F irst ENTH ast 1 1 'r.\~ ' F^Hr irst Last DAY I M !-l YEAR Place i l 1 1 c/s ! 1 I M l-l YEAR Place i l 1 1 C/S MONTH 1 I 1 1- -DAY i I I YEAR Place 1 . i ! l-l ! 1- DAY i 1 M l-l l 1 MONTH 1 1 1 1- DAY 1 i 1 1 l-l YEAR 1 1 MONTH 1 1 F irst Last DAY 1 1 MONTH I 1 First Last MONTH 1 1 1 1- MONTH i 1 DAY i M l 1 1- I 1 ! 1 1 1 !! 1- ! 1 1 ! c/s YEAR Place ! 1 c/s Place 1 1 YEAR l-l C/S Place NAME Place First Place C/S Last C/S Place First Place C/S Last C/S Place First Place C/S Last C/S Place First Place C/S Last C/S Place First Place C/S Last C/S Place First Place C/S Last C/S 1 1 1 c/s �CARD 136 Q.35 Medical Providers — Pneumonia jst Time a. 2nd Timr Monthe/years had that time. MONTH 812039 YEAR T a. 3rd Time Months/years had that time. MONTH a. Months/years had that time. YEAR YKAR MONTH F I (28) (29) (20) (21 ) (22) (23) TO MONTH YEAR 112') (13) (14) (15) TO MONTH YEAR MONTH h. (25) (18) (19) Doctor/facility who made diagnosis. b. (32) (33) (2h) (27) Doctor/facility who made diagnosis. YEAR i—i—ri—i r ~T (16) (17) (30) (31) TO b. (34) (35 ) Doctor/facility who made diagnosis. Name Name Name Address_ Address Address C/S C/S C/S e. Name of h o s p i t a l • e. Name of h o s p i t a l . e. Name of h o s p i t a l . Name Nnmr Naim- Address Address^ Address_ C/S C/S C/S Q.36. Medical Providers — Cancer c. Month/year first diagnosed 1 1 d. c. Month/year f i r s t diagnosed MONTH YEAR 1 I I 1 1 1 l-l 1 1 ( 36) ( 3?) &8 ) ( 39) D o c t o r / f a c i l i t y where f i r s t diagnosis made: Part 3 Part 2 Part 1 1 I d. c. Month/year first diagnosed MONTH YEAR 1 I I 1 1 l l I l l U4) ( 4 5 ) (46) ( 4 7 ) D o c t o r / f a c i l i t y where f i r s t d i a g n o s i s made; MONTH YEAR i i i r i i i (52) i (53)1-1 ( 5 4 )i ( 5 5 ) i d. D o c t o r / f a c i l i t y where f i r s t d i a g n o s i s made: Name Name Name Address Address Address C/S C/S C/S e. D o c t o r / f a c i l i t y last consulted. e. D o c t o r / f a c i l i t y last consulted. e. D o c t o r / f a c i l i t y last consulted. Name Name Nnmo Address Address Address C/S C/S C/S f. Mnnth/ypar last c o n s u 1 1 od . 1 1 MONTH YEAR 1 I I 1 1 1 l-l 1 1 ( 4 0 ) (41 ) (42 ) (43 ) f. Month/year last consu 1 t rd . 1 I MONTH 1 l l (4 a ) ftq ) I I - YEAR 1 l rI ( >() OH ) f. Mcinrh/yr.ir I n s t f O I I K I l l I I'll . F l T I MONTH l 1 YEAK T1 1 ' T l - I l l 06 ) ( 57) (58 ) ( 59) �CARD Q.3d. MONTH I 1 1 1 l-l ( 60) ( 61) d. Part 6 Part 5 Month/year first diagnosed 1 1 812039 M e d i c a l Providers --~ Cancer Part 4 c. 136-137 c. YEAR ' 1 1 1 1 ((,1) (63) Doctor/facility where first diagnosis made: c. Month/year first diagnosed MONTH T I l 1 YEAR I I 1 l - I l (68) (69) d. Month/year first diagnosed 1 l 1 I ( 70) (71) Doctor/facility where first diagnosis made: d. MONTH YEAR 1 I I 1 1 l l I l l (12) (13) (14) (15) Doctor/facility where first diagnosis made: Name Name Name Address Address Address C/S c/s e. . e. Doctor/facility last consulted. ... , C/S e. Doctor/facility last consulted. Doctor/facility last consulted. Name Name Name Address Address Address C/S C/S C/S f . Month/year last consulted . f. f. Month/year last consulted. M6NTH ! 1 MONTH I l l YEAR 1 1 1 1 l-l (64 ) US) 1 1 1 1 ( 66) ( 6>) 1 I (72 ) (7.3) Q.37 Medical Providers — Leukemia b. Month/year f ir_et diagnosed MONTH YEAR 1 ! 1 1 1 1 l-l 1 1 (20 ') ( 21)' (22 ) ( 23) 1 1 c. Doctor/facility where first diagnosis made: Name Address C/S f. Doctor/facility last consulted. Name Address C/S g. Month/year last consulted . MONTH 1 1 1 J YEAR I I ! 1 l-l 1 - . 1 1 1 - YEAR 1 I l 1 l (ft,} (75) Month/year last consulted. i 1 MONTH f 1 (16) (17) ri L-l YEAR i 1 (18) (19) i 1 �CARD 137 M f d i c . - i l P r o v i d e r s — OTHER MEDICAL CONDITIONS o.'lH. THYROID DIABETES h. b. First toldh a d : 1 I e. 812039 First told had: MONTH YEAR 1 I I 1 1 l l I l l ( 28) < 29) ( 30) ( 3l) D o c t o r / f a c i l i t y where d i a g n o s i s made: ANEMIA MONTH 1 1 1 1 b. YEAR 1 1 II H MONTH (60) ( 6 1 ) D o c t o r / f a c i l i t y where d i a g n o s i s made: YEAR ( 6 2 ) (63) i i i r i i 1 1 1 - 1 1 1 1 1 (44) (45) (46) (47) e. First t o l dh a d : e. D o c t o r / f a c i l i t y where diagnosis made: NjiriP Name Name Ad d re s s Address Address C/S C/S C/S f>. Doctor last c o n s u l t e d : 1 I h. g. Doctor last consulted: MONTH YEAR 1 I I 1 1 l l I l l <32> (J3> (j4> <3b> 1 1 h. D o c t o r / F a c i l i t y last consulted. MONTH 1 1 YEAR 1 1 1 1 l-l Us) (49) (;>o) (51) g. Doctor last c o n s u l t e d : 1 1 D o c t o r / F a c i l i t y last consulted. 1 I h. MONTH YEAR 1 1 1 1 1 l l I l l (64) (65) ( 6 b ) .(67) D o c t o r / F a c i l i t y last consulted. Name Name Name Address Address Address C/S C/S C/S ENLARGED LIVER HEART CONDITION b. b. First told had: 1 I e. First told h a d : b. First told h a d : MONTH YKAR 1. 1 1 1 1 1 1 1 l-l 1 1 (52) (53) (54) (55) MONTH YKAR 1 1 1 1 1 l l I l l (36 ) ( 37) ( 38) ( 39) e. D o c t o r / f a c i l i t y where diagnosis made: JAUNDICE D o c t o r / f a c i l i t y where diagnosis made: 1 1 e. MONTH YEAR 1 1 1 1 1 1 l-l 1 1 (68) (69) ( 7 0 ) (71) D o c t o r / f a c i l i t y where diagnosis made: Name Name Name Address Address Address C/S C/S C/S g. Doctor last c o n s u l t e d : T I MONTH l ! < 4(j» < 41> h. YEAR F 1 1 l - I l g. 1 l Doctor last consulted: I I I h. I - <56 ) (57 ) <M ) < 4 3 > D o c t o r / F a c i l i t y last consulted. MONTH I l l YEAR I I l g. I l Doctor last consulted: 1 1 ( 58) ( 59) D o c t o r / F a c i l i t y last consulted. h. MONTH YEAR 1 I I I 1 1 l - l I I ( 72) ( V3) • ( 74) ( 75) Doctor/Facility consulted . Name Name Name Address Address Address C/S C/S C/S 'J2 last �CARD 1 38 i.i. J K . M e d i c a l 1 ' r u v i d e r s -- OTHER M E D I C A L C O N D I T I O N S ( C O N T I N U E D ) C I R R H O S I S OK THE L I V E R MKI'ATITIK h. h. 1- i r s l l o l d h a d : MONTH r "i I l l " 0 ^ 5 (1 i) P. 812039 YEAH i i i - First told had: MONTH 1). First told had: YEAR T i ri r i 1 ( 2 8 1) (29 ) - (30) (31 ) 1 1 1 1 i I l l (I/, j (lrO e. H o r r o r / f a c i l i t y where d i aj'nos i fl made : INTESTINAL PARASITES D o c t o r / f a c i l i t y where diagnosis made: 1 I e. MONTH 1 I I (V, ) ( 4 5 ) I t - YEAR 1 I I (46 ) ( /|7) 1 I D o c t o r / f a c i l i t y where diagnosis made: Name Name Name Address Address Address c/s C/S C/S H. i i . i t i n r last consulted: MONTH I I I I ( l < > ) (17) li. g. Doctor last YEAR I I l-l I I ! I 1 1 ( 1 8 ) (l9l Doctor/Facility last (•(insulted. h. consulted: £. Doctor last c o n s u l t e d : MONTH YEAR 1 I I 1 1 1 l-l 1 1 ( ti ( 3 3 ) (3-4) (35) D o c t o r / F a c i l i t y last consulted. MONTH YEAR 1 I I 1 1 I I I I I ( 4 8 ) (49 ) (50) (51 > 1 I h. Doctor/Facility consulted. Name Name Name Address Address Address C/S C/S last C/S CALL BLADDER h. Fi rst told h a d : I I e. h. MONTH YEAR . I I I 1 1 l l I l l (20) (;>]} (?/>5 ( 2 3 ) D o c t o r / f a c i l i t y where diagnosis made: OTHER RESPIRATORY OTHER LIVER CONDITION First told had: MONTH b. F i r s t told h a d : YEAR in i i i . r- i i i i ii (36) (37) e. 1 1 (52) (53) (38> (39) D o c t o r / f a c i l i t y where d i a g n o s i s made: MONTH 1 1 e. II l-l YEAR 1 1 1 1 ( 5 4 ) (55) D o c t o r / f a c i l i t y where diagnosis made: Name Name Name Address Address Address C/S C/S C/S t>. Doctor l a s t c o n s u l t e d : 1 1 h. p. MONTH YF.AR 1 I I 1 1 1 l-l 1 1 <24> <25> <2b) (27> Doctor/Facility last Doctor l a s t c o n s u l t e d : MONTH 1 1 h. consulted. g. MONTH YEAR 1 1 1 1 l-l (56) ( 5 7 ) (58) ( 5 9 ) YEAR 1 1 ( ! 1 1 l - l I I (40) (/,i) ( 4 2 ) (^3) Doctor/Facility last consulted. Doctor last c o n s u l t e d : h. D o c t o r / F a c i l i t y last consulted. Name Name Name Address Address Address <:/s C/S C/S �. Q.'iH. Medical Providers — CARD 138 OTHER MEDICAL CONDITIONS (CONTINUED) OTHER MAJOR CONDITIONS b. First told had: MONTH YEAR (60) (61) (62) (63) e. Doctor/facility where diagnosis made: Name AdJress_ C/S g. Doctor last consulted: MONTH YEAR ~(6A) (65) (66) (67) h. Doctor/Facility last consulted . Name Address Q.M. Medical Providers — Acne b. Last consulted doctor TI MONTH l-l YEAR Ir T n Ii I (68) (69) fro ) (71) c. Doctor/facility last consulted: Name Address_ C/S 812039 �CARD Q.4? — McdiCii] Providers B. EASIER BRUISING OF SKIN PATCHES OF SKIN CHANCE COLOR K. 812039 Doctor/facility whore diagnosis made: e. Doctor/facility where diagnosis made: C. SKIN EXTRA SENSITIVE e. Doctor/facility where diagnosis made: Name* Name Name Address Address Address c/s C/S C/S f. f. Month/ypar diagnosis made: MONTH 1 1 1 1 K. YEAR 1 1 I I l-t Month/year diagnosis made: MONTH YEAR 1 1 1 1 1 1 l-l 1 1 (TB ) ( 2'i1 ( 30* ( 3p 1 1 g. Doctor/Facility last consulted. f. Doctor/Facility last consulted. Month/year diagnosis made: 1 I g. MONTH I II l l ^4 ) ( 4bJ YEAR 1 1 I l l ( ltd ( 4?' Doctor/Facility last consulted. Name Name Name Address Address Address C/S C/S C/S h. h. Month/year last consulted: Month/year last consulted: h. TihV'n"?)" OiO (I'J) MONTH YEAR 1 1 1 1 1 1 l-l 1 1 (32) (33) (34) (35) D. RASH ON BACK E. EXCESSIVE HAIR GROWTH 1 I e. MONTH 1 l l I I - YEAR 1 I l 1 l e. Doctor/facility where diagnosis made: Doctor/facility where diagnosis made: Name Name Address Address C/S C/S f. Month/year diagnosis made: f. MONTH YEAR '1 '1 1 '1 " 1 1 l-l 1 1 (20) (21) (22) (23) g. Doctor/Facility last consul ted . Month/year diagnosis made : 1 1 h. MONTH YEAR 1 1 1 1 1 1 l-l 1 1 (36) (37) (38) (39) Doctor/Facility last consulted. Name Name Address Address C/S C/S h. Month/year last consul red: MONTH 1 M. Month/year last consul ted : YEAR l-l J MONTH 1 I l l YEAR - I l l Month/year last consulted: 1 I MONTH YEAR 1 1 1 1 1 l l I l l (48) (49) (50) (51) �CARD 139-140 812039 Q.43 — Medical Providers A. NUMBNESS IN LIMBS h. B. C. TINGLING IN :LIMBS >•? D o c t o r / f a c i l i t y where diagnosis made: h. BURNING IN LIMBS D o c t o r / f a c i l i t y where diagnosis made: h. D o c t o r / f a c i l i t y where d i a g n o s i s made: Name Name Name Address Address Address C/S C/S C/S i. Month/year diagnosis made: MONTH I I i. l 1 Month/year diagnosis made: YEAR 1 I ! l - I l ( 52) ( 53) i. ( 54) ( 55) 1 l D o c t o r / F a c i l i t y last consulted. 1 I i. i. MONTH YEAR 1 II 1 1 l l I l l (68) (69) (70) (71) D o c t o r / F a c i l i t y last consulted. Month/year d i a g n o s i s made: 1 I j. MONTH YEAR 1 1 1 1 1 l l I l l (16) ( 1 7 ) (18) ( 1 9 ) D o c t o r / F a c i l i t y last consulted. Name Name Name Address Address Address C/S C/S C/S k. Month/year last consulted: I I k. MONTH YEAR 1 1 1 1 1 l l I l l ( 56) ( 5 7 ) 68 )( 59) 1 I D. PERSISTENT ACHES IN LIMBS h. Month/year last consulted: D o c t o r / f a c i l i t y where diagnosis made: k. MONTH YEAR 1 1 1 1 1 l l I l l (73(71) (74) (75) E. REDUCTION IN CRIP STRENGTH h. D o c t o r / f a c i l i t y where diagnosis made: Name Name Address Address C/S C/S i. Month/yeflr d i a g n o s i s made: 1 I j. i. MONTH YEAR 1 I I I I l l I l l ( 60 (61 ) (62 )( 6.3) Doctor/Facility last consulted. Month/yea! diagnosis made : 1 MONTH 1 1 1 , YEAR 1 1 i (76 ) i (77 ) i (- 7tS>i (79 ) i i j. Doctor/Facility last CO' j u l t e d . Name Name Address Address C/S C/S k. Month/year last consulted: 1 I MONTH YEAR T M 1 1 l l I l l r (64) (6 >) (66) ( 6 7 ) k. Month/year last consulted: 1 I MONTH 1 l l (12) (13) II - YEAR 1 I l (14) (15) 1 l Month/year last consulted: 1 1 MONTH YEAR 1 1 I 1 1 1 . 1-1 1 1 f20) ( 2 1 ) (22)123) �CARD 812039 Respondent answer to Q.60 was . . . Yes No „ — _ — — — — ——— . — ——• — » . . —— — — — ™ _ _ _ _ _ _ - . — • • - « — . — _—.^ ^ . . — — w —._ __ *«•,_—T . ^ — __«._«.^__ _ ^ W ^ w __ H M_ **_ M M _ K H K. , • fl(MM • ' » « . —.^ Record "Yes" or "5" 62a. Did you lose your appetite 63a. Check Box If Any Recording In Quest ion group Did you lose weight without trying to — as much as ten pounds altogether , 64a. Did your eating increase so much that you gained ten pounds altogether , fi'ja. Did you have trouble falling asleep, staying asleep, or waking up too early «. °"\ : I 66a. Were you sleeping too much? I 67a. Did you feel tired out all the time? 68a. Did you have to he moving all the time — that is, you couldn't sit still and paced up and down?..... F Did you talk or move more slowly than is usual for you? 69a. T ____ 70a. Was your interest in sex a lot less than usual? 71a. Did your thoughts come much slower than usual or seem mixed up? 73. Did you feel worthless, sinful, or guilty? 74. Did you think a lot about death — either your own, someone else's, or death in general? *j Did you have a lot more trouble concentrating than is usual for you?. 72a. r 75. Did you feel like you wanted to die? 76. Did you fee] so low you thought of committing suicide?._ 77. Did you attempt suicide? I r T : /" 97 ^ T T 1 �CARD 812030 138a. If you were asked, would you be willing to have a physical examination at a time convenient for you? Yes. No.. -<59( -1 ~-2 (ASK Q.138b) 138b. What is your reason for not wanting to have the examination? 138c. Under what conditions would you be willing to have an examination? (60 (62( (63j (641 (65( (66( (67( (8 6( (70( �CARD OOf. 141. Additional Civilian Training Programs (0-6) 4 Hi Prog rum h. 812039 5th Program For what k i n d of work was ybufr Illix'" civilian training program preparing you? f. For what kind of work was your next c i v i l i a n training program preparing you? For what kind of work was your next c i v i l i a n training program preparing you? (15 ( 05 ( 05J_ (16 ( (16 ( (10 ( (17 ( (17 ( Jill (1H( (]«( HILL CH U9(. U9( c . In what month and year did you start this training? MONTH 1 1 I 1 ! l-l 1 1 1 I h. MONTH YEAR 1 II 1 1 1 hi 1 1 C., ) (25 ) (26 ) (27 ) '' Have you participated in any other c i v i l i a n iob training program that prepared you for a major change in your occupnt ion? Yes . ( 2H No. -1 (ASK Q. l/.lf) -2 (RETURN TO Q.7) O/. MONTH 1 l l I I - (20 ) (21 ) (22 ) (23 ) In what month and year H i d you complete t h i s training? 1 1 e. 1 1 YEAR 1 I l MONTH 1 II 1 l-l (24 ) (25 ) MONTH T (20) (21 ) 1,. (22 ) (23 ) In what month and year did you complete t h i s training? 2JONTH_ YEAR 1 J ( 26) (27 ) Have you p a r t i c i p a t e d in any other c i v i l i a n job t r a i n i n g program that prepared you lor a major change in your occupa t i on? Yes.GM^ -1 (ASK Q. l./ilj) No ' ~'i (RETUKN TO 0.7) _ 79"-80" YFAK T I ( 22) (23 ) YEAR 1 In what month and year did you start this training T 1 l In what month and year did you complete this training? 1 1 i. k. In what month and year did you start, this training? YEAR I (20 ) (21 ) »l. g. I j -J I i (2/4 )" (25 ) (26 ) (27 ) Have you p a r t i c i p a t e d i n a n y other c i v i l i a n job t r a i n i n g progratn that prepared you tor a major change in your occupa t ion? Yes.CH ( -1 (RETURN TO Q.7) No -2 _ 79-80 �CARD 007 Arid i I i on,-i I M i l i t a r y Jnh T r a i n i n g Programs (<l.7) !-. 6 t h Program Mil I'l-ogi-aiii •'tflt 1'rogr.im Kui wh.it kind o( work \ j , \ ' - your no.xt m i l l t n r v I r.'i i n i nu progr.-iin pi • • • - g. Kor w h a t k i n d ot work was your n e x t m i l i t a r y t r a i n i n g program preparing you? PHI' ing y»u? 1.. For what kind ot work w.is your n e x t m i l i t a r y t r a i n i n g program preparing you? <15< <16< (16( 17< (17( (17( (18( Q8( (19( i s the AFSC job? (16< IiSL_ What that ( 15( ( c. (15( (19( (19( for h. What i s the AFSC that joh? fen ( d. T n wh.it month and year did ynu > ! t a r t t h i s training? MONTH I 1 I I l-l (21 ) (22 ) e. 1 1 i. In what month and year did you s t a r t t h i s training? MONTH 1 1 1 I (23 ) ( 24) In what month and year did you complete this j. f. MONTH YEAR 1 I I 1 1 l l I l l (25) (26) (27) ( 2 8 ) Have you p a r t i c i p a t e d in any other m i l i t a r y job training program that prepared you for a major change in your occupation? Yes.(M( -1 (ASK Q. I42j.) What i s the AFSC that joh? for (20( l l (21 ) <22 ) I I - MONTH 1 I k. 1 MONTH I l (23 ) (24 ) 1 l 1 1 l (26) I I - 1 I (27) l (28) -1 -2 o. I I l-l 1 1 ( 23) ( 24) In what month and yeardid you complete this MONTH 1 I YEAR 1 l I I - l (25 ) (26 ) p. 1 I 05 79-80 JO I) l 1 l (27 ) (28 ) Have you participated in any other military job training program that prepared you for a major change in your occupation? Yes.(29( -1 fRpTMHN TO Q . R 1 Q.8) 04 79-80 1 1 training? 1 l (ASK Q.142]) (RETURN TO Q.8) YKAR 1 1 Gl ) C2 ) Have you p a r t i c i p a t e d in any other military joh training program that prepared you for a major change in your occupation? es.<29( 0 In what month and year did you s t a r t this training? YEAR 1 l (25) n. YEAR 1 In what month and year did you complete this training? training? 1 I m. (20< YRAR 1 1 for 06 79-80 �CARD QQ8 812039 143-145 A d d i t i o n a l jobs (Q.8-13) Seventh Job Eighth Job Ninth Job 143a.In what month and year did you start your next job that lasted three months or longer? 144a.In what month and year did you start your next job that lasted three months or longer? 145a.In what month and year did you start your next job that lasted three months or longer? I 1 MONTH t 1 M l-l (i5) (16 ) YEAR i 1 i I 1 I (17 ) (18 ) MONTH YEAR 1 I I 1 1 l l I l l (15 ) (16 ) (17 > OS ) 1 I MONTH YEAR 1 1 1 1 1 l l I l l 05 ) ( 16) ( 17) ( 18) b. What (is/was) the name of your employer? 1 RECORD IN S.R.B. - PC 1 I b. What (is/was) the name of your employer? b. What (is/was) the name of your employer? c. (Is/Was) the job fulltime or part-time? c. (Is/Was) the job f u l l time or part-time? c. (Is/Was) the job fulltime or part-time? Full time.. (19 ( IRECORD IN S.R.B. - PG i i -1 Full time. . 1 ( (9 IRECORD IN S.R.B. - PG i I Full time. .(19 ( -1 -1 d. What kind of business is thaf — what (do/ did) they make or do there? d. What kind of business is that — what (do/ did) they make or do there? d. What kind of business is that — what (do/ did) they make or do there? e. What ally what your 1 RECORD e. What ally what your e. What ally what your (do/did) you actudo on the job — (are/were) some of main duties? IN S.R.B. - PC 1 I (do/did) you actudo on the job — (are/were) some of main duties? IKECORD IN S.R.B. - PG 1 | lHAND RESPONDENT CARD "B"] f. Please look at this card and tell me the number which best describes the kind of industry you (work/ worked) in. IHAND RESPONDENT CARD "B"! (WRITE IN NUMBER) (WRITE IN NUMBER) I 1 (20) ! | 1 I (21> g. In what month and year did this job end? I 1 MONTH YEAR 1 1 [ 1 1 1 .1-1 1 1 (23) (24) C5 ) (26) Current job..(27< -1 (RETURN TO Q.14a) h. What was the main reason you stopped working on your job? f. Please .look at this card and tell me the number which best describes the kind of industry you (work/ worked) in. 1 1 (20 ) ( U 2 g. In what month and year did this job end? 1 I MONTH YEAR 1 I I I I l l I l l (23) (2/0 (25) (26) Current job..(27( -1 (RETURN TO Q.lAa) h. What was the main reason you stopped working on your job? IHAND RESPONDENT CARD "B"| f. Please look at this card and tell me the number which best describes the kind of industry you (work/ worked) in. (WRITE IN NUMBER) 1 1 I | I I (20 ; (21) g. In what month and year did this job end? 1 I MONTH YEAR 1 1 1 1 .1 l l I l l (23) (24) (25) (26) Current job..(27( (RETURN TO -1 Q.14a) h. What was the main reason you stopped working on your job? (28( (29( ( 29( 07 7<j"-ft() IRECORD IN S.R.B. - PC i 1 (28( (2H( (ASK Q.144a) (do/did) you actudo on the job — (are/were) some of main duties? (ASK Q.145a) (29( (ASK __0_8 7 '"«) )"( Q. 146a) 09 T'i-'HO �CARD 008 H12039 A d d i t i o n a l Jobs (8-13) Cont'd. Trnth Job Eleventh Job 146a.ln what month and year did you start your next job that lasted three months or longer 1 1 Twelfth Job 147a.In what month and year did you start your next job that lasted three months or longer 148a.In what month and year did you start your next job that lasted three months or longer? MONTH YEAR 1 1 1 1 i 1 l-l 1 1 0'> ) 07. ) ( 17) ( IH) 1 I MONTH YEAR 1 II 1 1 l l I l l < 15) ( 16) ( 17) ( IB) MONTH ! I l I YEAR l l 45 ) (16) - l I l I I l (17) (18) h. What (in /was) the name of your employer? iHK.COHli !M S.R.R. - IT. 1 b. What (is/was) the name of your employer? b. What (is/was) the name of your employer? IRECORD IN s.u.u. - PC; i IRECORD IN S.R.R. - PG i i c. (Is/Wits) thi- job l u l l lime or part-time? c. (Ifi/Wns) the job f u l l time or part-time? c. (Is/Was) thf job l u l l time or part-limp? F u l l t i me , . ( ' '\ Full time..( l«( -1 Full time..( I9( -1 -1 d. '.'hiit k i n d of business is that -- what (do/ did) they make or do there? d. What kind of business is that — what (do/ did) they make or do there? d. What kind of business is that — what (do/ did) they make or do there? e. What ally what your ! RECORD e. What ally what your (RECORD e. What ally what your (do/did) you actudo on Che job — (are/were) some of main duties? IN S.R.B. - PG 1 1 (do/did) you actudo on the job — (are/were) some of main duties? IN S.R.B. - PG 1 1 ilUvND RESPONDENT CARD "B" f. Please look at this card and tell me the number which best describes the kind of industry you (work/ worked) in. IHAND RESPONDENT CARD "B"| (WRITE I N NUMBER) (WRITE IN NUMBER) 1 1 (20) 1 1 I | (21) g. In what month and year did this job end? 1 I MONTH YEAR 1 1 1 1 1 l l I l l (2J) <24) (25) (26) Current job..(22J -1 (RETURN TO Q.lAa) h. What was the main reason you stopped working on your job? f. Please look at this card and tell me the number which best describes the kind of industry you (work/ worked) in. I | | I | | (20) ( 21) g. In what month and year did this job end? 1 I MONTH YEAR 1 1 1 1 1 l l I l l (23) (24) (25) (26) Curre--; job..(27( -1 (RETURN TO Q.14a) h. What was the main reason you stopped working on your job? (28( (ASK Q.147n) Id <7¥< (28( (do/did) you actudo on the job — (are/were) some of main duties? IRECORD IN S.R.B. - PG i 1 IHAND RESPONDENT CARD "B"| f. Please look at this card and tell me the number which best describes the kind of industry you (work/ worked) in. (WRITE IN NUMBER) I i I I 1 1 (20 ) (21 ) g. In what month and year did this job end? 1 I MONTH 1 II l l (23 ) (24 ) Current job..(27( -1 YEAR 1 1 I l l (25 ) ( 26) (RETURN TO Q.14a) h. What was the main reason you stopped working on your jot)? (28 ( (29 ( (29 ( (ASK <).148a) 11 (RETURN TO Q.14a) 1.' �CARD 0 1 f> A d d i t i o n a l P e r i o d s ol M i l i t a r y S e r v i c i ' \ l i . l f i ) l i i w h M m o n t h ,'iiut y e a r did you next enter thr Armed f o r c e s ? MONTI! 1. MONTH YEAR i—r—r T <. In what montli ami y.';ir did you next rnt.rr tlur Armed Forces? YEAR I ! TTeTTTTf I Air Force.(j^jj Navy Army Marines Coast G u a r d . . . What branch of the m i l i tary war, that? -1 -2 -3 -4 Air Force. ( j _j Navy Army Marines Coast Guard... -5 Were you discharged or separated from the (BRANCH OF S E R V I C E ) ? "T I ' l-l h. !. . -1 -2 -3 -k -5 Were you discharged or separated from the (BRANCH OF SERVICE)? Wliat branch of the m i l . t.-iry was that? Air Force. (Ulj Navy Array.. . Marines Coast Guard... m. -1 (ASKQ.i) Discharged/ separated.( 1'X Still in (MILITARY) -2 (RETURN Still in (MILITARY) d. S t i l l in (MILITARY) TO Q.16) MONTH MONTH YEAR "(20) (21) e. (22 ) (23 ) Following your separation j. or discharge in (DATE IN "d"), did you reenter the Armed Forces? Yes..(24( -1 (ASK Q.149f) No __-2 (RETURN TO Q.16) _0_4 "79- 80 MONTH YEAR i r i i" (20 i—n—ii ) (23 ) I (20 )I (21) ) (21 ) (22 T Following your separation o. or discharge in (DATE IN "i"), did you reenter the Armed Forces? Yes..(24( -1 (ASK Q.149k) No __-2 (RETURN TO Q.16) __05_ 79-80 11)3 -/i _c -1 (ASK (J.n; _-2 V RETURN TO Q . 1 6 i In what month and year were you discharged/ separated from the (BRANCH OF MILITARY)? In w h a t m o n t h and year were yon d i s c h a r g e d / s e p a r a t e d from the (BRANCH OF M I L I T A R Y ) ? In what month and year were you discharged/ separated from the (BRANCH OF MILITARY)? -1 -2 -3 Were you discharged or separated from the (BRANCH OF SERVICE)? Discharged/ Discharged/ separated.(19 ( separated. <lj)_(___-l (ASKQ.d) -2 (RETURN TO 0-16 YEAR T "06)077 What branch of the m i l i tary was that? c. In what m o n t h nnd ye'.'ir did vou lU'xl rnter thu Armed Forces? YEAR Following your srparai ion or discharge in (l)ATh I N "n"), did you reentor theArmed Forces? Y e s . . ( 2 A ( -1 ( R E T U R N TO No -2 Q.16) _-. 7'J-80 �CARP OK, 150. Additional Count ri PS Stationed (Q.16/17) Srvrn t h Count ry a. 813030 Eighth Country Wli.it was the next count r t h d l you were stationed in for more than 10 days w h i l e on a c t i v e duty? f.. Ninth Country What was the next countr that you were stationed in for more than 90 days while on active duty? m. What was the next country that you were stationed in for more than 90 days while on a c t i v e duty? ( (14-15) (14-15) J4--.m (RECOUP COUNTRY HERE AN!) IN (RECORD COUNTRY HERE AND IN (RECORD COUNTRY HERE AND IN, S.H.It. I'd '} AND CONTINUE) S.R.U. PC ? AND CONTINUE) S.R.B. PC 2 AND CONTINUE) No o t h e r s . ( l f i ( -1 (RETURN TO Q.18) h. No others. (16 ( -1 (RETURN TO Q.18) In what month and vear h. did you begin and end act i v e duty in (COUNTRY)? No others. (16 ( In what month and year n. did yon hegin and end act i v e duty in (COUNTRY)? -1 ( RKTUKN TO Q.18) In what month and year did you b e g i n and end active duty in (COUNTRY)? KEG IN MONTH YEAR 1 1 M 1 1 I l l I l l < 1 7 ) (IK) (19) (20) BEGIN MONTH YEAR 1 1 1 [ 1 1 I l l I l l (17) (18) (19) (20) BEGIN MONTH YEAR 1 ! I I 1 1 I l l I l l (17 ) (.18) (19 ) (20 ) END MONTH YEAR 1 1 I I 1 1 I l l I l l (21) (22) (23) (24) END MONTH YEAR 1 1 1 1 I I I l l I l l (21 ) (22) (23) (24) END MONTH YEAR 1 1 1 1 1 1 I l l I l l (21) (22) (23) (24) Current .. .(25( Current ...(25 ( Current . . . (25 ( -1 -1 -1 c. What specific job assign- i. ments (do/did) you have in (COUNTRY)? Can you f>ivi> me the AFSC? What specific job assign- o. ments (do/did) you have in (COUNTRY)? Can you give me the AFSC? What specific job assignments (do/did) you havp in (COUNTRY)? Can you give me the AFSC? 1. (26-28) 1. (26-28) 1. (26-28) 2. (29-31) 2. (29-31) 2. 3. (32- 34) 3. (32-34) 3. (32-34) d. (Do/Did) your duties in j. (COUNTRY) include flying? (Do/Did) your duties in p. (COUNTRY) include flying? (Do/Did) your duties in (COUNTRY) include flying? Yes.(35( No p. Yes.(35( No -1 -2 How many flight hours d i d you 1 og while in (COUNTRY)? 1 I I 1 I ! Hours (36) (37) (38) I I How many flight hours did you log whi le in (COUNTRY)? 1 1 1 1 .(39( What specific letter and numerical designat ion(-s) did each aircraft have? L. q. 1 I Hours (36) (37) (38) -1 -2 How many flight hours did you log while in (COUNTRY)? 1 1 1 I 1 1 1 1 1 1 Hours (36) (37) (38) Other (SPECIFY) .(39( -1 (29-31) Yes.(35( 1o -1 -2 Other (SPECIFY) Other (SPECIFY) f. k. - .(39( -1 What specific letter and numerical designation(s) did each aircraft have? r. -1 What specific letter and numerical designat ion(s) did each a i r c r a f t have? 1. (40-43) 1. (40-43) 1. (40-43) 2. (44-47) ?. (44-47) 2. (44-47) 3. (48-51) 3. (48-51) 3. (48-51) l'i.>-y>) t>. A. ( 'i.'-V,) ,. 07 7'} -Ml . C->2-'j':) (ASK Q. 1r >l.-i) (ASK 0. 110m) (ASK <>. 1 M)r 1 08 7~')"-HU 04 79-"«0 �CARD |S|. El cvfilth Count ry S.K.B. PC 2 AND CONTINUE) Nu' oi he i :, .(lft( I n w h a t iniiiil h and y e a r li. did you begin and end act i v e d u t y in ( C O U N T R Y ) ? (RETURN TO 1,1. 18) lu u h a t m o u t l i and y e a r d i d you b e t f i n and end ac I i v c rintv i n ( C O U N T R Y ) ? J YEAIi ..-...,-. MONTH T 1 J I 1-1 I [ (1?") ( 1 8 ) (I9)~(~2<) In w h a t inontli cnul y e a r did vou he-gin and end act ive Viui y i n (COUNTRY )? ] 1 T-~] " 1 [-1 L [ I I I'.'l ) (2(1) T~~ I ( 2 3 ) (2 h ) ' (21 i -1 (2.' ) (17 ) (18 ) YEAR j [. J -1 (32-34: Current. .. (25 ( Wliat s p e i i f i c job assignmerits ( d o / d i d ) you have in (COUNTRY)? Can you K i v e me the AEKC? -1 What s p e c i f i c job assignments (do/did) you have in (COUNTRY)? Can you give me the AFSC? 1. (26-28) J^iliL 3. YEAR r ! r i—T T I (21 )I (22 )l-l (2'f )I (24 ) I 1 (2n-28) 2. (14 ) (20 ) MONTH (23 ) (24 ) Current. . . (25 ( What s p e c i f i c job a s s i g n - l i. ments ( d o / d i d ) you have ! in (COUNTRY)" Can you \ give me the AI'SC? YEAR 1' I" ' '] """T l-l I I END MONTH - T .. 1 r , L_ J_ J-1 L-J J_ J , . .Current .. .(25 ( I!_EC 1 N MONTH KN1' T (21 ) (22) c. u. YEAH (17 ) ( 1 8 ) F..N1) ___ YEAK MONTH T J -I (RETURN . I'd Q. 1H) 11 EC:: 1 N JJW: IN ] (I4-15J f RECORD COUNTRY' TiiVKiT" AND i N No , , | | , , T S . < l f ' < _ _ . - I (RETURN MONTH .. . j Wlial was (lie next country t h a t vou were stationed i n for more than 90 days w h i I e on a c t i ve duty? _ TO o . 1 8 ) 1..-..., in. (KF.COKll COUNTRY HERE AND IN S . R . I ) . PC; 2 ANII CONTINUE) S.K.l'.. PC :> AND CONTINUE) o t h l ' l :, . ( ll,( Twelft h Countiy What w a s t h e n e x t c o u n t r that you were s t a t i o n e d in for mo r i- I him 1'0 ilnys wh i 1 e on ,'ic t i ve d vit y ? What W.IK the next c o u n t r y ( Inn von were M at inned in I'M more t h a n ('U day; wh i 1 r mi .'ic t i ve d u t y ? T'KKCOKD" couN'tWiTERE'ANJ') IN' lio HI 2039 A.l'h t innvt1 I'oiiiit r i i ' S SI ,11 loiifd ( 0 . 1 ( , / i 7 ) T i ' i i t h COIIII_M-V ;i. Old d. (Do/Did) your d u t i e s in (COUNTRY) i n c l u d e t l y i n g ? (29-31) 3. 3. (32-34) j. ( D o / D i d ) your ilurips in p. (COUNTRY) include 1 l y i n R ? (Do/Did) your d u t i e s in (COUNTRY) i n c l u d e flyinfi? Yes.(35J -1 No ' 7 - ' " - ~ z e. k. Yes. (35 ( No Yos.(35( How many f l i p t i t hours d id you .1 op. wh i 1 e in (COUNTRY)? T —r I 1 how many f l i g h t liours d i d you lop w h i l e in (COUNTRY)? q. I I How many flight hours d id you log w h i l e i n ( COUNTRY ) ? 1 1 1 Hours (3d ) (37 ) (38 ) I Hours Ou") (37 roe" Other ( S P E C I F Y ) (SPECIFY) Other . (_3«,._ - 1 f . -1 ~-2 i—T —r—r J 1 Hours (3d ) (37 ) ( 3 8 ) Other -2 Ni Wh a t :; pec i I i r 1 e 11 e t and I.. numerical desi f>nar i on( s ) d i d each a i re i n 11 h.we1.' (SPECIFY) . (J9(__-1 What s p e c i f i c l e t t e r a n d nunier i ca 1 de.s i ^nat i on( s ) < l i d each a i r c r a f t have? What s p e c i f i c l e t t e r and numerical d e s i p n a l i o n ( s ) d i d each ai re r a I t have? j£°~i!L (44-47) 2. C,8-r)l) (A;;K Q.I s i p ) (4 8- 'in 3. (>2-jiii (ASK Q. I S I m ) (RETURN TO Q. 18) i_o 79-80 '79-80 �CARD 020 152-1W. A d d i t i o n a l Marriages (Q.18-22) FOURTH MARRIAGE FIFTH MARRIAGE MONTH YEAH 1 1 l l I l l (] 5 ) (] (, ) (] 7 ) ( ] fl) b. What ( i s / w a s ) her rent f u l 1 name? MONTH 1 1 1 l-l <15 ) ( 1 6 ) cur- c. What was her m a i d e n name? 154a.In what month and year did you Ret married the sixth time? YEAR 1 1 1 1 ( 1 7 ) (18) b. What ( i s / w a s ) her current f u l l name? IRECORD IN S . R . B . PC 2 1 IRECORD IN S . K . B . PC 2 I c. SIXTH MARRIAGE I S T a . I n what- m o n t h a n d y e a r d i d y o u get m a r r i e d t h e f i f t h time? 1523. In w h a t m o n t h a n d y e a r did you get married t h e f o u r t h time? I 812039 What was her maiden name? MONTH 1 YEAR 1 l-l 1 • 1 ( 15) ( 16) . ( 17) ( 1 8 ) h. What ( i s / w a s ) her current l u l l name? IRECORD IN S . R . B . .PC 2 1 c. What was her m a i d e n name? IRECOKD IN S.R..K. PC 2 1 IRECORD IN S.R.B. PG ? 1 IRECORD IN S.R^B. PC 2 1 d. What is her date oi hirth? d . W h a t i s h e r d a t e oi birth? d. What is her date of hirth? •1 I MONTH MONTH YEAR 1 1 1. 1 1 l l I l l ( 1?) ( 20) ( 21) ( 22) 1 1 ( 1 9 ) (20) f. YEAR 1 1 1 1 (21) ( 2 2 ) 1 I Yes...(23( No -1 -2 Yes...(23( No -1 -2 -l -2 f. Did your w i f e ever have any p r e g n a n c i e s hy you which ended in a miscarriage? f . D i d your w i f e ever have any p r e g n a n c i e s by you w h i c h ended in a m i s c a r riage? D i d your w i f e ever have any p r e g n a n c i e s by you w h i c h ended in a m i s c a r riage? MONTH YEAR 1 I I I 1 l l I l l (19) (20) (21) ( 2 2 ) e. Have you ever had any c h i l d r e n by ( y o u r / t h i s ) wife? e. Have you ever had any c h i l d r e n by ( y o u r / t h i s ) wife? e. Have you ever had any children by ( y o u r / t h i s ) wi fe? Yes...(23( No 1 1 l-l Yes...(24( -1 (ASK Q.g) Yes...(24( -i (ASK Q . g ) Yes...(24( -1 (ASK Q . g ) No -2\ I ( S K I P TO -3 1 Q . 1 5 2 L ) No -2") V (SKIP TO -3 1 Q.153L) No -2") L ( S K I P TO -3 f Q.154L) J D o n ' t know g. When was t h a t ? Any o t h e r s ? ) 1st " 1 I i 1 2nd " ' 3 1 d 1 4th 1 1 1 1 1 : 1 l-l 1 1 1 2nd ( 31) ( 32) YEAR 1 I I 1 1 I l l I l 3 l r (33) (34) (35) (36) MONTH YEAR 1 I I V I 1 l-l 1 1 4th ( 3 7 ) ( 38) (39) ( 40) (GO TO Q . 1 5 2 h ) J g. When was t h a t ? Any o t h e r s ? ) (PROBE: MONTH YEAR 1 1 1 1 1 l l I l l 1st ( 2 5 ) ( 26) ( 2 7 ) (28) MONTH YKAR ( 29) ( 30) MONTH r D o n ' t know MONTH "" 1 l l (25) ( 2 6 ) MONTH 1 1 1 1 (29) (30) MONTH 1 1 d I l ~ < j j ) (34) MONTH 1 1 1 1 1 I g. When was t h a t ? Any o t h e r s ? ) (PROBE: YEAR 1 1 I l l ( 2 7 ) (28) YEAK I I I 1 l-l 1 1 (31) (32) YEAR 1 1 . 1 1 l I l (35) (36) YEAR II 1 1 l-l. 1 1 1 1 - ( 3 7 ) OH) (39) ( 4 0 ) (GO TO Q. I53h) .100 D o n ' t know 1st 2 n d 3 rl d 4th (PROBE: MONTH YEAR 1 1 1 1 1 1 l-l 1 1 (25) (26) (27) (2B) MONTH YEAR 1 1 1 1 1 1 1 - 1 1 J (29) (iO) (31) (32) MONTH YEAR 1 I I 1 1 1 l - l I . I (33) ( 3 4 ) (T5) (36) MONTH YEAR 1 1 1 1 1 1 l-l ,,.[....^1 ( 3 7 ) (38) (39) (40) (GO TO Q. 1*541)) �CARD 14:1 ADDITIONAI, RECORDING SHKKT_j'OR_ N(>N-j. 1 VK-JUK'[MS_ FOURj'll MARRIAGE M 1 ST,SRta~jVC ElT:-~CJ7 ) 5 2 h F 1 FTII M A R R I A G E MLsCARRtATTES'' - Q'.* 1 53h 1 2nd l__ I_ |__ I | Months ~<1~2) (13) W a s n ' t t r y i n g (j_4( -1 D o n ' t know -2 ." (V?y (fir Wasn't trying (\l<( __ -] Don' t know ........ -3 J L ' Months (I1))' (If,)" W a s n ' t t r y i n g (J_7_J_ - I D o n ' t know ? 1 2nd j 'In) J I | Months j (]',') ( I f , ) " | W a s n ' t t r y i n g ( 17J -1 ' D o n ' t know -2 1 I T 1 T I | | Months " ( 1 2 )( 1 3 ) W a s n ' t trying (14( -1 Don 1 1 know -2 ~~T I 3rd SIXTH MARRIAGE GES - Q.~154h r~~T ?nd I Months 812039 3rd 1 I I I Months W a s 1 ' t t r y i n g (l_?i n Don I k n o w . . . . . . . . -I -2 1-------T Months "(181 ( 1 9 ) W a s n ' t I r v i n g ( 2 (K______- I D o n ' t know ........ ._.'..' 2 ' ttl ' [_ "_ "I Mo n th s 4th Wasn't trying C 2 0 ( _ _ -1 D o n ' t know ........ _ -2 (CO TO Q . l r > ? i ) 4th L I Months (18) ( 1 9 ) W a s n ' t t r y i n g (20( -1 D o n ' t know -2 (CO TO Q . I 5 4 i ) (CO Til Q. I', ii) TAFTER Q. ij> I A S K F O R KACH Were p i tlu'r (i^f you u s i n g b i r t h c o n t r o l at t h o t i m e she hecnme p r e g n a n t ? IFOR ANY "YES'r ASKlJ Please look at this card and cell mo all the numbers that apply to the types of birth control you used. 1st: _(21- • 2 2 ) 1st: _(21-22) 1st: J21-22) 2nd: _ < 2 3 - 2 4 ) 2nd : J23-24) 2nd: _(23-24) _(2 >-26) 3rd: _(25-26) (27-28) 4th : 3rd: r J25- 26) 3 r d : (27- 28) 4 t h : ftth: (GO TO 0.20L) (CO TO Q.21I.) F1FTH MAKRlAOK ST1LLIURTMS - Q. 153n KOUKTH MARRI ACK STILLBlrRTHS - Q. " 2ml (29) (30) W a s n ' t t r y i n g (31( D o n ' t know 3rd ] 3rd 4l.h -1 -2 J r [_ _ I M o n t h s ( 2 9 ) ("30)"" W a s n ' t t r y i n g ; (31( -1 D o n ' t know -2 [ Months Wasn't tryinp, (3lj_ Don't know ........ SIXTH MARRIAGE STILLBIRTHS - Q.154n i—i—r T T 2nd (27-28) (CO TO Q.22O J 2nd I r 3rd _[_ I Months I Wasn't trying (34_(_ Dor,' t know ........ I I Months (32) (33)" 1 Wasn t trying (W* _ -1 Don' t" k now -/ -1 -7 i 4th J __ I __ I M o n t h s OS) ( 6 ) 3"" Wasn't t r y i n g ( 3_7( __ -1 Don' I know ........ __ •-- I Months -1 -2 I __ I __ I Months (32F(33)~ W a s n ' t t r y i n g ( 3 4 ( -1 ^,1,'t k n o w ........ _ -2 T r—i 4th i I_ (35) I I Months HfiT" r I I Months (3ST (3(>r Wasn' t trv iny. (37( -1 Don' t kiinw -? Wasn't trying (3?( -1 D o n ' t know ........ _ -2 (U) TO (J. 1 VJo) (GO TO O..154o) (CIO TO Q.l!)2o) . - .. Were ( M t h i - r o j ym| MS i n g b i r t h c o n t r o l at t h c > r i m e she hoc nine p r c g n . m t ? |FOR"ANY""YKS""ASK : I I'leasi' look at t h i s card and t e l l nn- all thr numbers tliat a p p l y to t h e t y p e s nf b i r t h control von used. . ( 1H-.)')) I (40-41 ) 2nd: (4 .' 4 ' i ) 4th: r ( 4 4 - 4 >) 4 t h : (44-45) CO Til (;. 1 S J Ji)7 4th: (44-45) (GO TO ?)Tl54qT" �A D D I T I O N A L KKCORD1 NO SIIKK'I KOK NON-LI VK-lll KTIIS I M ..... I.:, l-.'.isn't t r y i n g DIMI' I know _.____.___ :inl 1 " I -I -? I " MOIII.IIS W . - i s n ' t t r y inc. ( S Don ' r k n o w 1 nlli Vn.l I I ' i" ' ' I I I Mnnllis T/,fiT~'a77' W . - i s n ' t I r v i n j ! (liK(_ Don 1 (• k n o w 3rd I I I I T I j' Mimllirt W a s n ' t t r y i n f ! (f>4( -I D o n ' t know . . . . . . . . _ - 2 'it. ti T I .S1XJJI M A K K I A i . K A BOUT i'ON:;"-" ~j. r>'i- (). ] 'i Is _-1 -? I I Months W a s n ' t t r y inc. 'IlU __ "1 Don't know.. ...... _~'2 T ~_ AIIOKTIONS" "T I Hr.'il.f' i - 1 ri'ii MAivi;i_A(;i; KOl'KTH MARKIAOI-: A H O K T I O N S ' " " < ; . 1 M'.-i I CARD I'i3 j I ?ml I I ' T/76T"Wi Y I I J I [ Months W a s n ' t t r y i n g (51( Don't know I I 1 I (GO TO iJ. -1 -2 -1 ~-2 I I~ Monllis ('> -1 -2 I 3rd I Mon D I N W a s n ' t I ry i nf, Don' I know I ! Miniili: W a s n ' t t r y i n f , (/i8( Don' t k n o w r~T I i I Wasn't trying ( Vi( __ -1 Don1 1 know ........ ___ -1' (GO TO Q . l W t ) (GO TO Q. [AFTER (j.l52t/l')3t/15At ASK FOB F.ACU A'SORTlpNlT Were either of you using birth control at the time she became pregnant? IFOR ANY "YES" ASK:I THANH' RESPONDENT CARD "c" I P l o a s e look a t t h i s card a n d C e l l m o a l l control you used. i t h e numbers t h a t a p p l y t o t h e t y p e s o f b i r t h 1st : _C>5-S6) 1st: 2nd: 1st : (57- r .8) 2nd : :trd: (61-62) il.li: (co TO y.iTfu Qtt 79-80 (61-62) ( G O T O O T l 53 .05 74-80 lllo 4th: (c;o To qr 06 79-80 �; . . . FIFTH MARRIAGE FOURTH MARRIAGE l ' i 2 h . H o w many m o n t h s d i d i t t n k p your w i f e t o hrcomf p r e g n a n t t h i s 1 inif? 1 1 I"" 1 1 I Months ('•1 ) ( 43 ' W a s n ' t t r y i n g (43 ( . -1 . 1 1 1 1 Months (41 ) ( 42) W a s n ' t t r y i n g (43 ( -1 1 I 1 I I 1 1 1 1 1 1 I I Weeks Yes.(52( -1 (ASK Q.k) -2 ( S K I P TO Q.152L) N o . . . . . . 1 I Weeks 1 | 1 I Weeks (50 ) (51 ) j. Did a doctor t e l l you why t h i s (1st, etc.) miscarriage might have occurred? -1 (ASK Q.k) Yes. (52 ( -2 ( S K I P TO Q.153L) No k. What did the doctor say caused the miscarriage? k . W h a t d i d t h e doctor s a y caused the miscarriage? I: I 1 I 4th j. Did a doctor t e l l you why this ( 1 s t , etc.) miscarriage might have occurred? ). Did a doctor tell you why t h i s .(1st , etc. ) m i s c a r r i a g e might have occurred? 1 I Weeks (48 ) ( 49) 1 1 1 1 1 1 Weeks 150) (51> 4th 1 | 1 3 r d| p.8 ) (4V ) I 1 Weeks I I Weeks (44 ) (iti ) 1 | 2nd 1 1 (SO) ( 5 l ) Yes.(52( No i— i—r 1st (46 ) (4? ) T 3rd (48) (49) 4th l I Weeks (46) ( 4 7 ) . 1 Weeks 1 1 •744 HAS ) (4b) (47) 3rd i . How mnny weekis had y o u r w i f e been p r e g n a n t when the ( 1 s t , e t c . ) miscarriage occurred? I Weeks 2nd i 1 1 1 1 Months ( 41) ( 42) W a s n ' t t r y i n g (43 ( -1 D o n ' t know -2 I I 1st 1 Weeks l I 1 1 Weeks I 1 T '.'ml 1 1 i . How many weeks linil your w i f e been p r e g n a n t when the ( l e t , e t c . ) miscarriage occurred? _ 1 812039 SIXTH MARRIAGE 154h.How many m o n t h s d i d i t take your w i f e t o become p r e g n a n t t h i s time? 1 1 I J_ . CARD 0 2 0 153h.How many m o n t h s did it take your wi fe to become pregnant t h i s time? i , How ninny weeks hud your w i f e been pregnant when HIP. ( 1 s t , etc. ) m i s r n r i i «K<- o c c u r red? . .— .. .. 1st . -1 (ASK Q.k) -2 (SKIP TO Q.154U k. What did the doctor say caused the miscarriage? 1st 1st 1st 2nd 2nd 2nd 3rd 3rd 3rd 4th 4th Yes...(53( -1 (ASK Q.m) -2 (SKIP TO Q. No ' " 152q) in. When was t h a t ? Any o t h e r s ? ) 1st 2nd 3id MONTH YEAR 1 1 1 1 1 1 l-l I 1 1 s ( 5 4 ) (55l (56) (57) MONTH YEAR 1 I I I I I I 1 l-l 1 1 2nd (58) (59) (60^ (61) MONTH YEAR 1 1 I I i 1 I l l I l l 3rd ( 6 2 ) (63) (64) (65) MONTH YEAR 1 1 T 1 1 1 1 1 1 l-l 1 1 (rib) ( 6 7 ) (68) ( 6 9 ) (CIO TO (}. 152n) 04 79^80" th 1 t 1 1 h. Did your w i f e have any pregnancies by ( you which ended in a s t i l l b i r t h ? -] (ASK Q.m) Y e s . . . ( 5 3 ( -2 (SKIP TO Q. No 153q) m. When was t h a t ? Any others?) (PROBE: 1 iih 4th . L. Did your w i f e have any pregnancies by you which ended in a s t i l l b i r t h ? L. D i d your w i f e have any p r e g n a n c i e s hy yon w h i c h ended in a s t i l l b i r t h ? Yes...(53( No . . m. When was t h a t ? Any others?) (PROBE: MONTH MONTH YEAR 1 I I 1 1 I l l I l 1st l (54) (55) ($6) (37 ) MONTH YEAR ! 1 I I l-l 1 I -1 (ASK Q.m) -2 (SKIP TO Q. 154q) 1 I 1 1 | I 2nd (58) (59) (60) (61) MONTH YEAR f i 1 1 1 1 I | |-| | | 3 f62) (63) (64) (65) MONTH YEAR 1 1 1 1 1 1 1 1 l-l I 1 4 (66) ( 6 7 ) (68) (69) (GO TO Q. 153n)o5 79-80 r i dI I 1 (PROBE: YEAR I (54) (b5) MONTH I l-l 1 I 1 1 (bb) (57T YEAR 1 I I 1 1 I |-| | | (58) (59) (6d) (61 J MONTH YEAR i ir i i l l I l l (62) (63) ( 6 4 ) (bi>) MONTH YEAR 1 1 1 T 1 1 t h I l l I l (66) ( 6 7 ) (68) (69^ 06 (GO TO Q.154n) 7T^8CT l �CARD 220 FIFTH MARRIAGE FOURTH MARRIAGE 812039 SIXTH MARRIAGE 152n. How many months did it take your w i f e to become pregnant this time? 1 1 1 1 I 1 Months ( 12) ( 13) Wasn 1 1 trying (14 ( -1 153n.How many months did it take your w i f e to become pregnant this time? 1 1 1 1 1 1 Months ( 12) ( 13) W a s n ' t t r y i n g ( I4( -1 154n.llow many months did it take your w i f e to become pregnant this time? 1 1 1 1 1 1 Months (12) (13) W a s n ' t t r y i n g ( l*( -1 o. Did a doctor tell you why t h i s s t i l l b i r t h might have occurred? o. Did a doctor tell you why this s t i l l b i r t h might have occurred? o. Did a doctor t e l l you why this s t i l l b i r t h might have occurred? Yes. (15 ( No -1 (ASK Q . p ) -2 (SKIP TO Q.152q Yes. (15 ( No p. What did the doctor say caused the (1st, etc.) stillbirth? -1 (ASK Q.p) -2 (SKIP TO Q.153q Yes. 05 ( No p. What did the doctor say caused the (1st, etc.) stillbirth? -1 (ASK Q . p ) -2 (SKIP TO Q.154q) p. What did the doctor say caused the (1st, etc.) stillbirth? 1st 1st 1st 2nd 2nd 2nd 3rd 3rd Ath Ath q. Did your w i f e ever have any pregnancies by you which ended in abortion' Yes...(16( No -1 (ASK Q.r) -2 (SKIP TO Q 152u) r. When was that? Any others? ) .. . Ath q. Did your w i f e ever have any pregnancies by you which ended in abortion Yes...(16( No (PROBE: -1 (ASK Q.r) -2 (SKIP TO Q 153u) r. When was that? Any others?) MONTH YEAR MONTH YEAR 1 1 1 1 1 1 1 1 1 1st 1 l-l 1 1st 1 1 l-l 1 (17) ( I B ) (19) (20) (17) (18) (19) (20) MONTH YEAR MONTH YEAR 1 1 I I 1 1 1 1 II 1 2 m lI l l I l l 2nd j 1 l-l | 1 (21) ( 2 2 ) (23) (24) (21) ( 2 2 ) (23) ( 2 4 ) MONTH YEAR MONTH YEAR 1 1 1 1 1 1 1 1 1 1 1 1 3rd I 1 I-J I I 3 r dI l l I l l (25) (26) (27) (28) (25) (26) ( 2 7 ) (28) MONTH YEAR MONTH YEAR 1 1 II 1 1 A t hI l l I l l 4 t hI l l I l l (29) (30) (31) (32) (29) (30) (31) (32) i rr i i s. How many months did it take your w i f e to become pregnant t h i s time? 1 1 1 1 -1 t. What was the main reason for the (1st, etc.) abortion? 1 1 1 1 3rd rd s. How many months did it take your w i f e to become pregnant t h i s - time? 1 I 1 I Months t. What was thp (pain reason for t h e O u t , * t p > ) abortion? Et . nd rd th (GO TO Q . 1 5 2 v ) MONTH YEAR 1 II 1 1 1st 1 l-l 1 1 (17 ) (18) (19 ) «0) MONTH YEAR 1 1 1 1 1 1 2 n dI l l I l l ( 2 1 ) (22) (23) (24) MONTH YEAR 1 1 II 1 1 3 r dI l l I l l (25) (26) ( 2 7 ) (28) MONTH YEAR 1 1 I I 1 1 4 t hI l l I l l ( 2 9 ) (30) (31) (32) (33) (34j W a s n ' t trying (ffjL_-» -1 Et nd th (CO TO Q.153v) 110 (PROBE: 1 1 1 I t. What was the main reason for the (1st, e t c . ) abortion? 2nd -1 (ASK Q.r) -2 (SKIP TO Q. 15Au) r. When was that? Any others?) 1 1 Months (33) ( 3 4 ) W a s n ' t trying (35( 1st Ath Yes...»6( No s. How many months did it take your wife to become pregnant this time? 1 1 Months (33) (34) W a s n ' t t r y i n g ( 35( q. Did your w i f e ever have any pregnancies by you which ended in abortion? (PROBE: 1 1 i 3rd (GO TO Q . l S A v ) �CARD 220 812039 SIXTH MARRIAGE FIFTH MARRIAGE FOURTH MARRIAGE V, 'liSHIf'*' Jook at this card and t e l l me a l l the numbers that apply to the types of birth control you or your wife normally used. 06.(/>2( Ol.(37( ISAii. (IF ANY CONCEPTIONS -CHILD, MISCARRIAGE, STILLBIRTH, OR ABORTION: SKIP TO Q.w ALL OTHERS: ASK Q.u) Did either you or your wife use birth control techniques regularly? Yes. . (36( -l (ASK Q.v) No -2 (ASK Q.x) THAND RESPONDENT CARP ^c VPH..( '>>( -1 (ASK O.v) Nn......._J-2 (ASK Q.x) I53u. (IF ANY CONCEPTIONS -CHILD, MISCARRIAGE, STILLBIRTH, OK ABORTION: SKIP TO Q.w ALL OTHEKS: ASK Q.u) Did either you or your wife use birth control techniques regularly? Yes..(36( -1 (ASK Q.v) No ~-2 (ASK Q.x) IM'li. ( 1 K ANY CONCEPTIONS -CHILD, MISCARRIAGE, KTII.I.III HTM, (U( AllOKII OK: SKIP TO Q.w AI.I. OTHERS: ASK l).u) l i i i l rithtr you or your w i f e u so b i r t h control techniques r e g u l a r l y ? I HAND RESPONDENT CARD "C"I v. Please look at this card and tell me all the numbers that apply to the types of birth control you or your wife normally used. v. Please look at this card and t e l l me a l l the numbers t h a t a p p l y to the types of b i r t h control you or your w i f e normally used. Ol.(37( 02.(^ -1 -1 06.(42( 07.( -J Ol.(37( -1 Q2.(38( 03.(39< -1 O6.(«f( 07.(5TT 08. ( 09.( 1Q.(46( 11. (4T( -1 -1 11.(571 -1 -1 .<48< (SKIP TO oTx) w, D i d any of .these pregn a n c i e s occur w h i l e o i t h e r you or your w i f e were p r a c t i c i n g b i r t h control? (49( Yes I I I J_ I I Times ( 50f T3TT (SKIP TO Q.aa/bh) y. How many months did you live apart the (first/ next) time? i —i 1st _. 2nd I_ r I | (50) x. During this marriage, how many times were you living apart from your wife for more^ than three months? Times Times (50) -1 (SKIP TO Q.aa/bb) I I I I Months 2nd I I I j Months ( 53) ( 54) 1 J I [_ (51) Never..(52( -1 ! let I I I (53) I J (54) 1 -1 -T — -| - I I Months I Months 3rd I I I " I" Months 3rd I I I I I I Months ( 57) ( 58) TTTTTlur [ Months 4th Ath ]_ Minirhs I I 5th [ Months 4th I Months ( 39) ( 6 0 ) i MJi | | I Months 5th I Months 6th I ( fil) 1 ~T 'T filh I I I Months (r,o TO r>. l •>?!•.') Months 1 ^ I 1 [ Months ( 55) ( 56)'" 3rd (SKIP TO Q.aa/bb) y. How many months did you live apart the ( f i r s t / n e x t ) time? y. How many months did you live apart the (first/ next) time? I J -2 No (51) Never. .(J>2(_ 1st Mont: 7 53Y TW 1 _ I hs I __ L -2 During this marriage, how mnny I imps were you living apart from your wife for more than three months? x. During (his mari iape, how nirtny 1'iim'H were you l i v i n g apart from your wife for more than three months? .-1 Did any of these pregnancies occur while either you or your wife were practicing birth control? _ No -? Never. .( 52( (SKir TO q.x) (SKIP TO Q.x) Did any of these pregnancies occur while either you or your wife were practicing birth control? -1 No -1 -1 12 (SPECIFY) 12 (SPECIFY) 12 (SPECIFY) -1 -1 i I Months ( 6 1 ) (62T 1 6tli — I I -{rrrrTwr (GO TO O.l r >3z) 111 r j [ I I ~cm TBTT \ |_ Months (GO TO Q . l S A z ) �CARD FOURTH MARRIAGE Yes No (5 ( 6 -1 153z.As a result of (this/ those) separations, did you and your wife have fewer children than you wanted to have? -1 -2 IIF ONLY MARRIAGE 1 aa.Are yon currently married an<l living with your wife, or are you divorced, widowed, or separated? living with wife... (66 ( SIXTH MARRIAGE FIFTH MARRIAGE 152z.As a result of (this/ these) separations, did you and your wife have fewer children than you wanted to have? Yes No (65 ( Divorced -2! (SKIP TO Separated. . .~-3f Q.cc) . 154z.As a result of (this/ these) separations, did you and your wife have fewer children than you wanted to have? Yes No -1 -2 IIF LAST MARRIAGE I aa.Are you currently married and living with your wife, or are you divorced, widowed, or separated? (RETURN Living with TO Q.23) wife... ( 6 ( -i 6 812039 220 (5 ( 6 -1 -2 IIF LAST MARRIAGE 1 aa.Are you currently married and living with your wife, or are you divorced, widowed, or separated? Living with (RETURN wife. . ( 6 ( .6 TO Q.23) Divorced -1 (RETURN TO Q.23) -2~)(SKIP TO Divorced -2\(SKIP TO Separated. .. . - f Q.cc) ~3 —•»• ij Separated. . . . -3V Q.cc) Widowed -4 I (RECORD IN S.R.B. PG 2 I (RECORD IN S.R.B. PG 2 1 IIF OTHER MARRIAGES! IIF OTHER MARRIAGES 1 (IF OTHER MARRIAGES! bb.How did that marriage end — were you divorced or were you widowed? bb.How did that marriage end — were you divorced or were you widowed? bb.How did that marriage end — were you divorced or were you widowed? — j (RECORD IN S.R.B. PG 2 | Divorced(67( Widowed. ... -1\(ASK -21 Q.cc) (RECORD IN S.R.B. PG 2 [ cc.In what month and year were yon (divorced/ widowed/ separated)? MONTH YEAR 1 1 I 1 1 l l I l l (68) (69) (70) ('n ) (IF A FIFTH MARRIAGE GO TO Q.153a) 1 I Divorced(67 ( -fltASK Q.cc) Widowed . . -21 •—~~ J (RECORD IN S.R.B. PG 2 MONTH I 1 —— cc.In what month and year were you (divorced/ widowed/ separated)? YEAR I I .1-1 1 1 i 1 (68) (69) (70), (71) (IF A SIXTH MARRIAGE GO TO Q.lSAa) 05 79-80 04 79-80 11 j J (RECORD IN S.R.B. PG 2 L cc.ln what month and year were you (divorced/ widowed/ separated)? I 1 Divorced(6_7j__-l\(ASK Q.cc) Widowed . . . . -2i 1 1 MONTH YEAR 1 I I I 1 1 l-.l I 1 (68) (69 ) (70) (71 ) (RETURN TO Q.23a) 06 79-80 �CARD 155. 023 812039 Additional Partners (Q PARTNER FOURTH PARTNER onth and year e g in l i v i n g r t ner time? a. In what month and ypar did you bpp, in livmj.1. wi tli a partner the lourth time? i i MONTH | YEAR MONTH T—r I -I I 1 I (in'mry' (15) (16) "(21) 1 YEAR i (22)' (23) 1 Current. .(25( -(21) (22) MONTH i YEAR i i 1 I Current. .(25 ( n) Yes.(26( No 1st 1 1 u) MONTH YEAR 1 1 1 1 (29) (30) YEAR I 1 I-I (33) 1 (34) 2nd M i 1 I-I 1 (31) (32) l 1 (33) (34) t. What was the outcome of the outcome of that pregnancy? (What nancy? (What was the outcome of the utcoroe of the second pregnancy?) egnancy? ) First 1 Second irst 1 Second 1 35 5( -l|(36( _! Live birth. ( ( -ll(36( -1 -21 -2 ."--21 -2 Miscarriage... -31 -3 • 17-31 ~-3 Stillbirth -4| -A _5| -5 nancy? No. 1 1 I-I (27) (28) r your partner control reguavoid preg- (GO -1 1 (c: , MONTH 1 1 YEAR (31) "(32) O4) TO NEXT PARTNER Q.h) 1 1 MONTH -1 (ASK Q. s) -2 (SKIP TO Q. s. When was that? M I-I r i" i i -1 r. Did this partner ever become pregnant by you? YEAR 1 1 1 1 1 (19 ) (20) MONTH YEAR 1 1 1 ! 1 l l I l l (21) (22) (23) (24) (29) (30) g. Did you or your partner use birth control regularly to avoid pregnancy? ..7773-2 V J ! 1 -1 MONTH I 1st I 2nd (33) 1 ACE) 1 . q. In what month and year did this relationship end? L. When was that? f. What was the outcome of that pregnancy? (What was the outcome of the second pregnancy?) First I Second | Live birth.(35(.__-l | (3_6(__Miscarriage... -2 I " Stillbirth Stillbirth -3| Abortion -4 I -4 Abortion. Not sure. Not sure -5 I - Yes .(37( No (23) (24) ASK Q. L) SKI P TO Q g) 2nd (31) (32) (WRITE IN partner ever egnant by you? YEAR r 1 I Current. .(25( 5( ist i (27) i ^28) iwrr^T-i-1.. i i i 1 1 YEAR 1 -1 -1 ii 1 1 MONTH i e. When was t h a t ? MONTH MONTH YEAR 1 I I 1 1 l l I l l (15) (16) (17) (18) p. How old was she at that time? >nth and year re 1st ionship d. Did this partner ever become pregnant by you? i r 1 I (19 ) (20) (24) YP«.(26( -I (ASK Q. e) No __-2 (SKIP TO Q. YEAR ! 1 1 1 (17) (18) 1 (WRITE IN AGE) 1 J [ (19) (20) c. In what month and year did this relationship end? MONTH 1 -1 o. In what month and year did you begin living wi th a partner the s i x t h rime? is she at that time ? b. How old was she at that time? (WRITE IN AGE) J SIXTH PARTNER (CO TO NEXT PARTNER Q.o) 05. 79-80 04 115 u. Did you or your partner use birth control regularly to avoid pregnancy? Yes(37( No -ll(Rt'TURN TO Q.25a) -2J 06_ �CARD 141 156. b. Additional Pregnancies (Q.25) d. When was that? FIRST MONTH ! 1 I 1 1 1 c. What was the outcome of that pregnancy? L i v e b i r t h , ( 1?( Miscarriage.... Stillbirth Were there any others? (IF YES, ASK Q.156d) -1 -2 -3 f . When was that? When was that? SECOND MONTH YEAR 1 I I 1 l l I l YEAR I (ft) l (14) - (15) (16) l l I l PROBE: 812039 1 I (13) (14) 1 l (15) (16) THIRD MONTH YEAR I I I I 1 1 I l l I l l (13) (14) ( 1 5 ) (16) e. What was the outcome of that p r e g n a n c y ? g. What was the outcome of that pregnancy? Live b i r t h . U 7 ( Miscarriage.... Stillbirth Live b i r t h . ( 1 7 ( Miscarriage. ... Stillbirth PROBE: Were there any others? (IF YES, ASK Q.156f) 114 -1 -2 -3 PROBE: -1 -2 -3 Were t h e r e any others? (RETURN TO Q . 2 6 a ) �.CARD 028 l:. V - ! r , o . Miiunii c i i i i . M FIFTH C H I L I ) SIXTH C H I L D NAME : NAME : I W a . l l o u o l d i s ( C H I L D ) now? 158a.llow old is (CHILD) now? NAME: T ~i r 812039 A d d i t i o n a l (hilclron (Q.30-32) 1 1 1 1 Ape 1 I 1 I 159a.How old is (CHILD) now? 1 1 Ape (15 ) ( 11,1 . 1, i 1 . 1 1 i . ,! . 1 1 1 h. (Is/K.-i.O ( C H I L D ) m a l e or f t'm.i 1 e? Male Femal o (|K -1 -1 Male Female POUNDS 1 I -1 -2 Male Female l l ( 19) ( 2 0 ) I I - POUNDS I I l ( 2 1 ) ( 22) D o n ' t know. ..( 23( -' 1 l 1 I -1 MONTH MONTH DAY M l-l 1 1 YEAR 1 1 1 1 1 1 l A L S O RECORD I N s'.R.B.-l'C 3 i (• . Was t h e c h i l d p r e m a t u r e , f u l l term, or overdue? P r e m a t u r e . ( '3(X FuM term Overdue (CO TO 0. 1 S7f ) l l 1 I 1 l l (21) (22) -1 d. What is ( C H I L D ) 's b i r t h date? YEAR MONTH DAY YEAR 1 1 1 1 1 1 T f 1 1 1 l-l 1 l-l 1 1 ( 2H) ( 2~9) ( 24) (25 ) ( 26) ( 27) ( 28) ( 29) ( 24) ( 2 5 ) ( 26) ( 27) (28) ( 2 9 ) 1 1 l-l ( 24)" (^5)' ( 2 6 ) "(21) DAY -1 -2 OUNCES M - D o n ' t know. ..( 23( d. What is ( C H I L D ) 's b i r t h date? 1 ! 1 ( 19) (20) d . What i s ( C H I L D ) ' s b i r t h date? 1 1 ( 18( c . H o w much d i d ( C H I L D ) weigh a t b i r t h ? OUNCES 1 1 b. ( I s / W a s ) (CHILD) male or f e m a l e ? c. How much did ( C H I L D ) wei gh at bi r t h ? POUNDS OUNCF.S 1 I I 1 1 l-l 1 ( 19) ( 20) ( 21) ( 22) A m ' t know. . . ( 23( ( 1« Age C l i i 1,1 d i r d . .( !/_(___ h. (Is/Was) (CHILD) male or f e m a l e ? ,-. How much r!id ( C H I L.D) w f i ph a t h i r t h ? 1 1 \ i In I.I .1 i i - . l . , ( | f. 1 1 1 1 1 ( 1 5) T 16) -1 -2 -3 I 1 M l-l 1 1 1 1 l-l 1 1 1 1 lALSO RECORD IN S . R . B . - P G 3| e. Was the c h i l d premature, f u l l t e r m , or overdue? P r e m a t u r e . ( 30( F u l l term (CO TO 0. I S S f ) -1 -2 lALSO RECORD I N S . R . B . - P G 3 1 e. Was the c h i l d premature, f u l l t e r m , o r overdue? P r e m a t u r e . ( 30( F u l l term (GO TO Q. 159f ) -] -2 �812039 CARD 028 FOURTH CHILD SIXTH CHILD FIFTH CHILD 157f. Where are (CHILD) 's hirth registration records located? Tn what city and state is that? IRECORD IN S.R.B. PG 3 1 158f- Where are (CHILD) 's birth registration records located? In what city and state is that? IRECORD IN S.R.B. PG 3 l g. Where are (CHILD)'s rtirront medical records located? In what city and state is that? 159* -Where are (CHILD) 's birth registration records located? In what city and state is that? IRECORD IN S.R.B. PG 3 1 g. Where are (CHILD) 's current medical records located? In what city and state is that? g. Where are (CHILD)'s current medical records located? In what city and state is that? IRECORD IN S.R.B. PG 3 I IRECORD IN S.R.B. PG 3 1 IRECORD IN S.R.B. PG 3 1 li. What was (CHILD) 's mother's full name? h. What was (CHILD) 's mother's full name? h. What was (CHII.D)'s mother's full name? IRECORD IN S.R.B. PC 3 1 IRECORD IN S.R.B. PG 3 1 IRECORD IN S.R.B. PG 3 1 i. How old was the mother when (CHILD) was born? 1 1 1 1 1 1 1 1 Age (•11) (-12) No 1 1 1 1 Age (31 ) (32 ) 1 1 Yes.(33( -l (ASK Q.k) .. -2 (SKIP TO Q.L) lHAND RESPONDENT CARD "C" I k. Please look at this card and tell me all ol the numbers that apply to the types of birth control you or your partner were practicing? Ol.(34( -1 06.(39( -1 02.(35( 03. ( 5 3( (M. ( 7 3T ()5.(38( " -1 -1 -l -1 O7.(40( -1 08. (Al(" -1 09. ( 2 71 -i I()-(5^J_... •' 1 1 , 1 /T'i'f ~ " i -1 (ASK No -2 (SKIP TO Q.L) ,U5( (CO TO Q.157L) -1 Age Yes.(33( Q.k) (HAND RESPONDENT CARD "C"l k. Please look at this card and t e l l me all oj the numbers that apply to the types of birth control you or your partner were practicing? O1.(34( -1 Oh.(39( -1 02.(35( 03. (551 o/i. (T71 05. (751 -1 -1 -] -1 O7.(40( 08.(5T( 09. (571 10. ( 7 71 i i ('I'M -1 -i -i -1 i -1 (ASK Q.k) No -2 (SKIP TO Q.L) lHAND RESPONDENT CARD "C"l k. Please look at this card and tell me a l l of the numbers that apply to the types of hirth control you or your partner were practicing? Ol.(34( 02.(35( 03. (361 04. (571 O6.(3y( O7.(40( 08. ( T "* 09. (W( -1 -1 -I -1 .<45( -1 -1 -1 -l -1 o5.(jBT ""-i lo.t/rri -ii " i i i •' '"( I'J (SI'fciMFY) [2 (SPKCIKY) K> (HI'lf-ClKY) 1 1 1 1 (31 ) ( ) M j. Were either of you using birth control at the time she became pregnant with (CHILD)? j. Were either of you usinf birth control at the time she became pregnant with (CHILD)? j. Were either of you using birth control at the time she became pregnant with (CHILD)? Yes.(33( i. How old was the mother when (CHILD) was born? i. How old was the mother when (CHILD) was born? .(45< (GO TO Q.158L) .110 -1. (CO TO Q.159O �C ARC 028 FOURTH CHILD FIFTH CHILD 15 71,. How many m o u t h s did i t t f i k o h e r Co become preg n a n t u'ith t h i s c h i l d ? 1 1 1 1 SIXTH CHILD 158L.How many m o n t h s d i d i t 159L.How many m o n t h s did it t a k e her to become pregtake her to become pregnant with this child? nant w i t h this c h i l d ? 1 I Months 1 1 1 1 1 1 Months 1 1 ( /if)) ( <W) ( 40) ( 477 1 <-nv l l u n 812039 1 i i N n l l l i • 1 /i IH 1 I.BB n m. Did ( C H I L D ) have any b i r t h defects? 1 lirtil 1 1 1 (46) In. M i l l i . ( '.III I 1 1 Months (47) l.i' M b l l u i n 1 nutn t l i . ( 48( Not t r y i n f i in. Did ( C H I L D ) have any birth defects? ~| -2 m . D i d ( C H I L D ) have a n y birth defects? Y P S . ( 4'X -1 (ASK Q . n ) Y e s . ( 49( -l (ASK Q . n ) Y e s . ( 49( -1 (ASK Q . n ) No -2 ( S K I P TO Q . o ) No -2 ( S K I P TO Q . o ) No -2 ( S K I P TO Q . o ) n. W h a t kind of b i r t h def e c t s d i d (s)he have? Any o t h e r s ? n. What k i n d of b i r t h def e c t s d i d ( s ) h e have? Any o t h e r s ? n. W h a t k i n d of b i r t h def e c t s did ( s ) h e have? Any others? o. Was ( C H I L D ) ever d i a g nosed as h a v i n g cancer? o. Was ( C H I L D ) ever diagnosed as h a v i n g cancer? o. Was ( C H I L D ) ever diagnosed as having cancer? Y e s . ( 5(X -1 ( A S K Q . p ) Y e s . ( 5<X -1 (ASK Q . p ) Y e s . ( 50( -i (ASK Q . p ) No. . -2 (SKIP TO Q . r ) N0 -? ( S K I P TO Q . r ) No -2 (SKIP TO Q . r ) p. In what month and y e a r was the d i a g n o s i s made? MONTH ! I l 1 Gl ) G2 i 63 )( 5/0 In what month and year was the d i a g n o s i s made? MONTH YEAR 1 I 1 l - I l p. 1 l q. W h a t k i n d of cancer was diagnosed? YEAR i i ii r i 1 (51 1) £521 ) - (531 ) (1 54) 1 (CO TO Q . 1 5 7 r ) -1 1 I In w h a t month and year was the diagnosis made? MONTH YEAR 1 M 1 1 l l I l l ( 5 1 ) (52) (53) (54) q. What k i n d of cancer was diagnosed? q. What kind of cancer was diagnosed? (55-56 (55-56 ( 5.'i-56 Not s u r e . . ( S 7 ( p. Not sure. .(57 ( -1 (GO TO Q.158r) 117 Not sure. .(57 ( (CO TO Q . 1 5 9 r ) -1 �CARD FOUKTII CHILD 028 FIFTH CHILD 157r.(Oopa/Did)(CHILD) have 15Sr.(Does/Did)(CHILD) have diagnosed learning, d i s diagnosed learning d i s.ihi 1 i ry? ahility? 812039 SIXTH CHILD 159r.(Does/Did)(CHILD) hov« diagnosed learning d i g ahi 1 i tv? Yps.(5H( -1 (ASK Q.s) Yes. (58 ( -1 (ASK Q.s) Yes.t 5(< -1 (ASK O.s) No -2 (SKTP TO 0. t) No.... No -2 (SKIP TO Q t) -'1 (SKI)' TO Q t) .-,. What kind of learning d i s a b i l i t y (does/did) (s)lu' have? s. What k i n d of learning d i s a b i l i t y (does/did) (s)he luive? s. What, kind of learning d i s a b i l i t y (does/did) (s)he have? t. (Does/Did) (CHILD) have any physical, mental, o motor impairments? l. (Does/Did)(CHILD) have any physical, mental, o motor impairments? t. (Does/Did)(CHILD) have any physical, mental, motor impairments? Yes.(59( -1 (ASK Q.u) Yes.(59( -1 (ASK Q.u) Yes. (59 ( -] (ASK Q.u) No -2 (SKIP TO Q.v) No -2 (SKIP TO Q.v) No u. What kind of impairment (does/did) (s)he have? CONTINUE SKIP TO NEXT CHILD u. What kind of impairment (does/did) (s)he have? -2 (SKIP TO Q.v) u. What kind of impairment (does/did) (s)he have? IF CHILD IS DEAD: IF CHILD IS DEAD: IF CHILD IS DEAD: OTHERWISE: OTHERWISE: OTHERWISE: v. On what date did (CHILD) die? MONTH . DAY YEAR 1 1 1 I I 1 1 1 1 l-l 1 l-l 1 1 [60) (61) (62) (63) 76/0 (65) CONTINUE SKIP TO NEXT CHILD v. On what date did (CHILD) die? CONTINUE SKIP TO NEXT CHILD v. On what date did (CHILD) die? MONTH DAY YEAR MONTH DAY YEAR 1 I I 1 I I 1 1 1 I I 1 I I 1 1 l-l 1 l-l 1 1 l-l 1 l-l 1 1 60) (61) (62) (637 (64) (65) 60) (61) 162) (63) (64) (65 w. What was the cause of death? w. What was the cause of death? w. What was the cause of death? x. Where is (CHILD) 's •.Ifntli r"I»i --re re '' ! " ! x. Where is (CHILD) 's x. Where is (CHILD) 's Uiat '.' RECORD IN"~S". R .'» ". "PC 3T (GO TO NEXT CHILD Q.158a) 'I^n E'h t P T1 ' •• f i- : r tJ"* T n ',--!, 1 I*• i •.'•f' '-1 '.: '•>':" * . ' '=' ' t li a t: '.' Chat? WcolD~i NT. TtTiiT "Pc~3 T RECORD ADDITIONAL CHILDREN IN S.R.B. - PC 32-35) (CO TO NEXT CHILD Q.15')a) 05 79-80 " 04 79 -HO ' lib "RECORD IN sTR'.F." pc;"3'"f 06 79-8 �CARD 160-162. 812039 Addition.il C h i l d r e n ( Q . 30-32 KCONT 1 11) SEVENTH CII1U) Klf.HTH C H I L D NINTH CHILD NAME : NAME : KiOii.How old i s ( C H I L D ) now? I f c l a . H o w o l d is ( C H I L D ) now? 1 1 r (i > ) (if. 5 1 1. i 1 .1 ,1 i i : i l ' 1 1 M Male Femal e NAME: 1 1 Ape 1 1 1 1 1 6 2 a . H o w o l d i s ( C H I L D ) now? 1 1 Ape (15 ) ( 16) i i. ; i .1 .1 ; c , i 1 h. ( I s / W a s ) (CHILD) male or f e m a l e ? (Hi ( Male Female D o n ' t know. . .(23 ( i | ;i i 1 1, 1 1 .! ,1 1 p . l ( 18( -1 d . Whnt i s ( C H I L D ) ' s b i r t h date? 1 I 1 1 Age Male Female | ( 18( -1 -2 c. H o w much d i d ( C H I L D ) weigh a t b i r t h ? POUNDS OUNCES 1 I I 1 1 l l I l l <19 ) (20 ) ( 21) ( 2 2 ) D o n ' t know. ..(23 ( 1 | ,<< b. ( I s / W a s ) (CHILD) male or f e m a l e ? -1 -2 c. How much d i d ( C H I L D ) weigh a t b i r t h ? POUNDS OUNCES I I I 1 1 l l I l l (19 ) <20 ) (21 > (22 > 1 1 0 5 ) (16) b. ( I s / W a s ) ( C H I L D ) m a l e or f e m a l e ? -1 -2 c . . H o w much d i d ( C H I L D ) weigh at b i r t h ? 1 I 028 -1 d. What is ( C H I L D ) 's b i r t h date? 1 I POUNDS OUNCES 1 I I 1 1 l l I l l ( 19) feO ) (21) (22) Don' t know. . .( 23( -1 d. What is (CHILD) 's b i r t h date? MONTH DAY YEAR MONTH DAY YEAR • MONTH DAY YEAR 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 l-l 1 l-l 1 1 1 1 l-l 1 l-l 1 1 1 1 l-l 1 l-l 1 1 (24 ) (25 ) (26 ) (27 ) (28 ) (29 ) GO (25 ) ( 26) ( 27) ( 28) ( 29) (24 ) (25 ) ( 26) ( 27) ( 28) ( 29) lALSO RECORD IN S.R.B.-PG 3l e. Was the c h i l d p r e m a t u r e , f u l 1 t e r m , or o v e r d u e ? lALSO RECORD IN S . R . B . - P G 3| o. W a s t h e c h i l d p r e m a t u r e , f u l l t e r m , o r overdue? lALSO RECORD IN S . R . B . - P G 3| e. Was the c h i l d premature, f u l l t e r m , o r overdue? l ' r e t n a t u r e . ( 3(X -1 P r e m a t u r e . ( 30( F u l l term -1 -2 P r e m a L u r e . ( 3U( -1 Not 8ure -4 Not sure -4 Not s u r e -4 (CO TO Q . 1 6 0 f ) (GO TO Q . 1 6 1 f ) 11J (GO TO Q . 1 6 2 C ) �CARD 02B SEVENTH CHILD EIGHTH CHILD 1601". Where are (CHILD) 's hirth repistration records located? In what city and state is that? 1 RECORD IN S.R.B. PC, 3 [ p. Whore arc ( CHILD) ' s current m e d i c a l records located? In what c i t y and state IE that? 1 RECORD IN S.R.B. PC 3 1 Hill'.Where nrr (CHILD) 's birth registration records located? In what city and state is that? IRECORD IN S.R.B. PG 31 h. What was (CHILD) 's mother's f u l l name? IRECORD IN S.R.B. PC 3 [ IRECORD IN S.R.B; PG 3 1 i. How old was the mother when (CHILD) was born? 1 1 Age Yes.O3( -2 (SKIP TO Q.1601^ No IHAND RESPONDENT CARD "C" | k. Please look at this card and t e l l me all of the numbers that apply to the types of birth control you or your partner were practicing? O6.(3y( 07.UO( OR. UK -1 OA.dTT '-i (iy.(T2J - Or).(j8< lf>.<43( 1 < i HIM' i: II 1 V ) " <W •</,!>< (HO TO Q.160L) 1 1 Age 1 1 1 1 Age (31) (32) (32) j. Were either of you using birth control at the time she became pregnant with (CHILD)? Yes.(33( -1 (ASK Q.k) -2 (SKIP TO Q.1611) No -1 (ASK Q.k) -2 (SKIP TO 0.162L) IHAND RESPONDENT CARD "C"l IHAND RESPONDENT CARD "cllT k. k. Please look at this card and tell me a l l of the numbers that apply to the types of .birth control you or your partner were practici ng? Ol.(3'i( 02.(:)5( 03.(36( o/i .(37T 01. ("TB? "" -1 -1 -1 -i --i 1 ' v ril'r i i f < i -1 1 1 i. How old was the mother when (CHILD) was born? j. Were either of you using birth control at the time she became pregnant with (CHILD)? No -1 1 1 (31) -1 (ASK Q.k) -1 -1 -1 g. Where are (CHILD) 's current medical records located? In what city and state is that? IRECORD IN S.R.B. PC 3 1 Yes.( 33( 01. (M 02. (3M 03.(36( IRECORD IN S.R.B. PC 3 1 IRECORD IN S.R.B. PC 3 1 j. Were either of you using hirth control at the t i m e she became pregnant with (CHILD)? . 162.* -Where are (CHILD) 's b i r t h registration records located? In what city and state is that? g. Where are (CHILD) 's current m e d i c a l records located? In what c i t y and state is that? i. How old was the mother when (CHILD) was born? 1 1 1 1 (31) (32) NINTH CHILD h. What was (CHILD) 's mother's f u l l name? h. Whnt was (CHILD) 's mother's f u l l name? IRECORD IN S.R.B. PC 3 1 1 1 81203') 06,. (39( 07.UO< OS. UK -1 -1 -1 oq.(T2T -i m.(/,3< -i i '.'II'. "•' Please look at t h i s card and tel 1 me n i l of the numbers t h a t a p p l y to tho types of b i r t h control you or your partner were p r a c t i c ing? 01.Ci4( 0?.(j5( O3.(3b( OA,(17T -1 -1 -1 -1 o5.(3aT -i Oh. O<M 07. CiO( OB.('«1( 09.1A7T -1 -1 -1 -1 io.(/TTf -i " I:,V. 1 I .' * r:l'r i l l ' , ' .(/,;>( (CO TO ( . 1611.) ) -1 . lVi( (CO TO 0. 1621.) -1 �CARD SEVENTH CHILI) EIGHTH CHILD 1601. .How many m o n t h s did it t a k e her to become preg nant with this child? 1 1 I 1 1 1 Months 1 1 NINTH CHILD I 1 1 1 Months 1 1 -1 ! I V(PI|'. •} -L Less t h a n 1 m o n t h . ( 4 8 ( Mi-, 1 i v IIIB -7 Mo, m. Did ( C H I L D ) have any birth defects? -\ (ASK Q . n ) No -? ( S K I P TO Q.o) 1 I Months I.PSS than 1 m o n t h , ( 4fl( m. Did (QIILD) have any hirth defects? Y e s . ( lA 1 1 fc6 ) ( 47) 0,6 ) (47 ) l.pss Minn 1 m o n t h . ( 4 B ( 812039 1611. .How many months did it 162L.How many months did it t a k e her to become pregtake her to become pregnant w i t h t h i s c h i l d ? nant w i t h t h i s c h i l d ? <46 ) <47 > fl'il 028 -j 1 rv ! i»ti . /' m. Did ( C H I L D ) have any birth defects? Y e s . (49 ( -1 (ASK Q.n) No -2 ( S K I P TO Q . o ) Yes.(4y( -] (ASK Q . n ) No -2 ( S K I P TO Q . o ) n. What kind of birth def e c t s did (s)he have? Any others? n. What kind of birth defects did (s)he have? Any others? n. What kind of birth defects did (s)he have? Any others? o. Was (CHILD) ever diagnosed as having cancer? o. Was (CHILD) ever diagnosed as having cancer? o. Was (CHILD) ever diagnosed as having cancer? Yes.(50( No -l (ASK Q . p ) — p. T r Yes.( -2 (SKIP TO Q.160r) : In what month and year was the d i a g n o s i s made? MONTH 1 i f 1 1-1 (51) < 5 2 > YEAR 1 i I i (53) (54) q. What k i n d of cancer was diagnosed? -1 (ASK Q.p) 50 v NO — p. Yes.(50( -2 (SKIP TO No Q.161r) In what month and year was the d i a g n o s i s made? MONTH 1 I 1 l l (51) (52) i I (GO TO Q.160r) -1 1 l l (53) (54) q. What k i n d of cancer was diagnosed? p. 1 1 -2 (SKIP TO Q.162r) In what month and year was the d i a g n o s i s made? MONTH 1 1 1 1 l-l (51 ) (52) YEAR [ 1 Not sure.. (57 ( (GO TO Q . 1 6 1 r ) -1 1 1 (53) (54 f q. What kind of cancer was diagnosed? (55-56) (55-56) (55-56) Not sure. .(57{ — YEAR M - -1 (ASK Q.p) Not sure. .(57 ( (GO TO Q . 1 6 2 r ) -1 �CARD 02« SEVENTH CHILD EIGHTH CHILD 812039 NINTH CHILD 160r.(Does/Did)(CHlLD) have a 161r.(Does/Did)(CHILD) have diagnosed learning disdiagnosed learning disabil ity? ability? 162r.(Does/Did)(CtllLD) have a diagnosed learning disabil ity? Ves.(58( -1 (ASK Yes. (58 ( -l (ASK Q.s) No -2 (SKIP TO Q.t) Q.s) Yes.(58( -1 (ASK Q.s) No -1 (SKIP TO Q.t) No -2 (SKIP TO Q.t) s. What kind of learning d i s a b i l i t y (does/did) (s)he have? s. What kind of learning disability (does/did) (s)he have? s. What kind of learning disability (does/did) (s)he have? t. (Does/DidHCMILD) have any physical, mental, or motor impairments? t. (Does/DidMCHILD) have any physical, mental, or motor impairments? t. (Does/Uid)(CHlLD) have any physical , mental , or motor impairments? Yes.(5y( -1 (ASK Q.u) Yes.(59( -1 (ASK Q.u) No -2 (SKIP TO Q.v) No -2 (SKIP TO Q.v) Yes.(59( -1 (ASK No -2 (SKIP TO Q.v) u. What kind of impairment (does/did) (s)he have? u. What kind of impairment (does/did) (s)he have? u. What kind of impairment (does/did) (s)he have? Q.u) IF CHILD IS DEAD: IF CHILD IS DEAD: IF CHILD IS DEAD: OTHERWISE: OTHERWISE: OTHERWISE: CONTINUE SKIP TO NEXT CHILD CONTINUE SKIP TO NEXT CHILD v. On what date did (CHILD) die? v. On what date did (CHILD) die? v. On what date did (CHILD) die? CONTINUE SKIP TO NEXT CHILD ) MONTH DAY YEAR 1 1 1 1 1 I I 1 l-l 1 1I I 60) (61) (62) (63) (64) (65) (60) (611 (62) (63 ) (64) (65) 60) (61) (62) (63) 6<i) (65) MONTH 1 1 1 1 l-l DAY 1 1 I I l-l YEAR 1 1 1 1 1 MONTH 1 1 1 1 l-l DAY 1 1 1 1 l-l 1 YEAR 1 1 1 1 1 w. What was the cause of death? w. What was th-e cause of death? w. What was the cause of death? X. Where is (CHILD) 's death registered? In what city and state is that? 1 l x. Whe .- is (CHILD) 's death registered? In what city and state is I ha I V x. Where is (CHILD) 's death registered? In what city and state is Mini' Rfii'Olifi THfi.R'.fl.K 1 | rKEcM1)TN"T!';v:B7 'T S'*y'T (GO TO NEXT CHILD Q.161a) jRfcofiY IN s.K.ii. f-c 3 I (GO TO NEXT CHILD Q.162a) RECORD ADDITIONAL CHILDREN IN S.R.B. - PC 36-39) 08 79-80 07 79-80 122 09 79-80 �CARD 163-165. Additional Children (Q.30-32)(CONT'D) TENTH CHILD TWELFTH CHILD ELEVENTH CHILD NAME :• NAME: 163a.How old is (CHILD) now? 164a.How old is (CHILD) now? ! I 1 1 <I5> 'IB) 1 1 Age 1 1 ( 18( Male D o n ' t know. . . ( 23( 1 I Male Female -1 YEAR POUNDS OUNCES 1 II 1 1 l l I l l (19 ) ( 20) ( 21) ( 22) MONTH 1 1 1 1 l-l DAY 1 1 1 I -1 -2 YEAR 1 1 1 1 I ALSO RECORD IN S.R.B.-PG 3 1 POUNDS OUNCES 1 I I 1 1 l l I l l 0.9 ) (20) (21) (22) D o n ' t know...(23( -1 1 i i r i i I I i i i 1-1 i 1-1 i i lALSO RECORD IN S.R.B.-PG 3| 1 1 l-l (18( c. How much did (CHILD) weigh at birth? 1 1 -1 d. What is (CHILD) 's birthdate? d. What is (CHILD) 's birthdate? d. What is (CHILD) 's birthdate? DAY ( 18( D o n ' t k n o w . . . ( 23< -1 Age b . ( I s / W a s ) ( C H I L D ) male or female? c. How much did (CHILD) weigh at birth? POUNDS OUNCES 1 I I 1 1 l l I l l (19 ) ( 20) (21 ) ( 2 2 ) 1 1 C h i l d d i e d , . <JL 7 J... ~ ' b. ( I s / W a s ) (CHILD) male or female? -1 -2 1 1 f5 ) (16) Chi I d d i e d . .( 17( -1 -1 c. How much did (CHILD) weigh at b i r t h ? MONTH 1 1 165a.How old is (CHILD) now? &5 ) ?16) b . ( I s / W a s ) (CHILD) m a l e or female? Male Female NAME : 1 1 .„ L ... 1 Age C ' h i I d d i e / I . . < |/ 1 I 812039 Q28 i i MONTH r i i i 1-1 DAY i i • M 1-1 YEAR i i i i <2O (25 ) ( 26) ( 27) ( 29 (29 ) ( 24) ( 25) ( 26) ( 27) (28 ) 09 ) ( 24) (25 ) (26 ) ( 27) ( 28) ( 29) e. Was the c h i l d premature, f u l l term, or overdue? Premature. 00 ( (GO TO Q.163f) -1 e. Was the child p r e m a t u r e , f u l l term, or overdue? Premature. ( 30( Full term (GO TO Q.164f) -1 -2 lALSO RECORD IN S.R.B.-PG 31 e. Was the child premature, f u l l term, or overdue? Premature. (30( Full term (GO TO Q.165f) -1 -2 �CARP TENTH CHILD JRECORD IN S.R.E. PG 3 I TWELFTH CHILD 164 f. Where are (CHILD) 's birth registration records located? In what city and state is that? IRECORD IN S.R.B. PG 3 g. Where are (CHILD) 's current medical records located? In what city and state is that? 1 RECORD IN S.R.B. PC 3 1 1651. Where are (CHILD) 's birth registration records located? In what city and state is that? IRECORD IN S.R.B. PG 3 | g. Where are (CHILD) 's current medical records located? In what city and state is that? IRECORD IN S.R.B. PC 3 h. What was (CHILD) 's mother's full name? IRECORD IN S.R.B. PG 3 1 g. Where are (CHILD) 's current medical records located? In what city and state is that? 1 RECORD IN E.R.R. PC 3 1 h. What was (CHILD) 's mother's full name? !>. What was (CHILD) 's mother's full name? IRECORD IN S.R.B. PG 3 1 IRECORD IN S.R.B. PG 3 i. How old was the mother when (CHILD) was born? I 1 1 1 (31) (32) 812039 ELEVENTH CHILD lf>3f. Where are (CHILD) 's birth registration records located? In what city and state is that? I 1 Q2B i. How old was the mother when (CHILD) was born? I 1 Age j. Were either of you using hirth control at the time she became pregnant with (CHILD)? l l 1 1 (31) (32) i. How old was the mother when (CHILD) was born? 1 1 Age 1 1 (31) (32)" j. Were either of you using birth control at the time she became pregnant with (CHILD)? j. Were either of you using birth control at the time she became pregnant with (CHILD)? Yes.(j3(:. -1 (ASK Q.k) Yes.(33( -1 (ASK Q.k-) Yes.(33( No No -2 (SKIP TO No ~ -2 (SKIP TO Q.163L) 01. ( j 3( 02. (3M 03.(36( (4(7 ).3( 0.(8 '.3( -1 -1 -l -l -1 Of).(39( 07. ( 6 71 08. UK 09. (42f in.(/.3( -1 -1 -1 -1 -1 1 1 . u/iT ' -i 1? (SPECIFY) lHAND RESPONDENT CARD "c" 1 k. Please look at this card and tell me a*l 1 ol the numbers thai apply to the types of hi rth control you or your partner werp practicing? Ol.(34( 02.(35( 03.(36( OA.(37( -1 -1 -1 -1 06.(39( O7.(40< 08. (41( 09.<42( -1 -1 -1 -1 OS.O«( I I0.(/i3( 1 1 .(7,'f, ( -1 ~-\ (CO TO 0.163L) -1 lHAND RESPONDENT CARD "C" 1 k. Please look at this card and t e l l me all of the numbers that apply to the types of birth control you or your partner were practicing? Ol.(34( 02. ( 3 51 03.(J6( 0/..(37( 0-).C>R( -1 -1 -1 -1 -1 Q6.O9( 07.(4<j( O8.(41< 09.(42( IO.(Vl( ll.(Vi7 17 (SI'K.CIKY) 12 (SPKC1KY) .''( (.> -1 (ASK Q.k) -2 (SKIP TO ~ Q.165L) Q.164L) (HAND RESPONDENT CARD "C" I k. Please look at this card and tell me all of the numbers that apply to the types of birth control you or your partner were practicing? 1 1 Age ,''( (.) (CO TO Q.164L) -1 .('•'>( (CO TO Q.16S1.) �CARD TENTH CHILD 028 81Z039 ELEVENTH CHILD TWELFTH CHILD 1631. .How many m o n t h s d i d i t 1 ML. How many months did it 165L.How many m o n t h s did it t a k e her to become pregtake her to become pregtake her to become pregnant w i t h this c h i l d ? nant w i t h t h i s child? n a n t with t h i s child? 1 1 1 ) 1 1 Months 1 1 Illflll | 1 I Months 1 1 U K I I l l l l . ( /|H( 1 \.pna lluui 1 lnnril h. ( AH( -I Nol trying m. Did (CHILD) have any birth defects? 1 1 1 I Months (46) (47) W !> ( 2 7 ) ?46) U7) liPBH 1 1 -2 Iri-rtn Hum | i m m f h . ( AH( Not t r y i n g m. Did (CHILD) have any birth defects? -| -2 m. Did (CHILD) have any birth defects? Yes.( 4;X -1 (ASK Q . n ) Y e s . ( 49( -1 ( A S K Q . n ) Yes.<49( -1 (ASK Q . n ) No -2 (SKIP TO Q . o ) No -2 ( S K I P TO Q . o ) No -2 ( S K I P TO Q . o ) n. What kind of b i r t h def e c t s did (s)he have? Any others? n. What kind of birth defects did (s)he have? Any others? n. What kind t>{ birth def e c t s did (s)he have? Any others? o. Was (CHILD) ever diagnosed as having cancer? o. Was (CHILD) ever diagnosed as having cancer? o. Was (CHILD) ever diagnosed as having cancer? Yes.( 50( -1 (ASK Q.p) Yes.(50( -1 (ASK Q.p) Yes.(50( -J (ASK Q . p ) No -2 (SKIP TO Q.163r) No -2 (SKIP TO Q.164r) No -2 (SKIP TO Q.165r) ... p. 1 I In what month and year was che diagnosis made? MONTH YEAR 1 1 1 I 1 l l I l l fcl ) (52 ) ( 53) ( 54) q. What kind of cancer was diagnosed? p. 1 I In what month and year was the diagnosis made? MONTH YEAR 1 1 1 1 1 l l I l l (51) ( 5 2 ) (53) (54) q. What kind of cancer was diagnosed? (GO TO Q.163r) -1 1 1 In what month and year was the diagnosis made? MONTH YEAR 1 I I 1 1 1 l-l 1 1 (51) ( 5 2 ) (53) (54!) q. What kind of cancer was diagnosed? (55-56) (55-56) ( 55-56) Not sure. .67 ( p. Not sure..(57( -1 (GO TO Q.164r) 125 Not sure..(57( (GO TO Q.165r) -1 �CARD 028 TENTH CHILD ELEVENTH CHILD 812039 TWELFTH CHILD l63r.(Uoes/Uid)(CHII.D) have a 164r. (Does/DidHCHILD) have a 165r.(Does/Did)(CHILD) have diagnosed learning disdiagnosed learning disdiagnosed learning dis ahiliry? ability? ability? Yes.(f>H( -1 (ASK Q.s) Yes.(58( -1 (ASK Q.s) No -2 (SKIP TO Q.t) No -•) fSKFP TO n.iO Yes.(58( -1 (ASK Q.s) No -2 (SKIP TO Q.t) s. What kind of learning disability (does/did) (s)ho have? s. What kind of learning disability (does/did) (s)he have? s. What kind of learning disability (does/did) (s)he have? t . (l)iies/iiLd)(Clii.l.l>) haviauv physical , m e n t a l , o mi- Lor i mpa i rim-nt ••? t. (Does:/Did)(CIIlLD) have any p h y s i c a l , mental, o motoi i mpa inm?n t s? t. (Does/rnd)(CllILD) have any physical, mental, t motor impairments? Yes.< W( -1 (ASK Q.u) Yes.CM -1 (ASK Q.u) Yes. ( 1)9 ( -1 (ASK No --2 (SKIP TO Q.v) No -2 (SKIP TO Q.v) No u. What kind of impairment (does/did) (s)he have? CONTINUE SKIP TO NEXT CHILD u. What kind of impairment (does/did) (s)he have? IF CHILD IS DEAD: IF CHILD IS DEAD: OTHERWISE: OTHERWISE: v. 0: what date did (CHILD) die? CONTINUE SKIP TO NEXT CHILD v. On what date did (CHILD) die? Q.u) -2 (SKIP TO Q.v) u. What kind of impairment (does/did) (s)he have? IF CHILD IS DEAD: CONTINUE OTHERWISE: KliTURN TO.Q.33. v. On what date did (CHILD) die? MONTH DAY YEAR MONTH DAY YEAR MONTH DAY YEAR 1 I 1 I 1 I I I 1 I I 1 1 I I 1 I I 1 1 l-l 1 11 l-l 1 l-l 1 1 l-l 1 l-l 1 60) (61) (62) (63) (64) (f-5) (60) (bl) 752) (63) M) (55) (faO) (61 ). (62) (63) (64) (65 w. What wns the cause of death? w. What was the cause of death? w. What was the cause of death? x. Where is (CHILD) 's death registered? In what r i t y and slate i ti Unit? x. Where is (CHILD) 's 'Jeath registered? In what c i t y and state is lluil ! x. Where is (CHILD)'s death registered? In what r i t y and state i i; (hut '1 IHKCOKIJ IN ti.lt. 11. i'C '! 1 RECORD IN S..R.B. i-c 3 1 (GO TO NEXT CHILD Q.lMa) IRKCORI") IN S.R.S. i'C :J 1 (CO TO NEXT CHILD Q.165n) 10 7 4- HO (RETURN TO Q.33) II /"J-HO .126 '-' y«7-~HD �CARD 03b 812039 > Part 4 Part 5 Part 6 166c In what month and year 1661 In what month and year 166o. In what month and year was cancer of the (BODY was cancer of the (BODY was cancer of the (BODY PART) first diagnosed? PART) first diagnosed? PART) first diagnosed? iRecf^ jTh fl»IUB. PG 6 1 IRECORD IN S.R.B. PG 6 1 IRECORD IN S.R.B. PG 6 1 d. What is the full name of the doctor or the fnedicfll facility where the diagnosis was made? IRECORD IN S.R.B. PG 6 1 e. j. What is the full name of the doctor or the medical facility where the diagnosis was made? IRECORD IN S.R.B. PC 6 1 What is the full name of the doctor or the medical facility you last consulted about cancer of the (BODY PART)? IRECORD IN S.RJB. PC 6 1 k. What is the full name of the doctor or the medical facility you last consulted about cancer of the (BODY PART)? IRECORD IN S.R.B. PG 6 1 p. What is the full name of the doctor or the medical facility where the diagnosis was made? IRECORD IN S.R.B. PC 6 1 q. What is the full name of the doctor or the medical facility you last consulted about cancer of the (BODY PART)? IRECORD IN S.R.B. PG 6 I f. During what month and year did you last consult (NAME FROM Q.iO L. During what month and year did you last consult (NAME FROM Q.k) IRECORD IN S.R.B. PG 6 | r. During what month and year did you last consult (NAME FROM Q.ci) g. What treatments or medicines did you take for cancer of the (BODY PART)? 1 MULTIPLE RECORD BELOW] m. What treatments or medicines did you take for cancer of the (BODY PART)? (MULTIPLE RECORD BELOW | s. What treatments or medicines did you take for cancer of the (BODY PART)? IRECORD IN S.R.B. PG 6 I Chemotherapy. '.( 16( .' -1 Other (SPECIFY) Chemotherapy... (lb( -1 Other (SPECIFY) IRECORD IN S.R.B. PC 6 I [MULTIPLE RECORD BELOW] Chemotherapy . . . (16( Surgery (TR -1 Other (SPECIFY) .(18( h. During what month and year did you first receive (EACH TREATMENT CODED IN Q.g) fur cancer of the (BODY PART)? MONTH YEAR RadiaI I I I 1 1 tion.... I I l-l 1 1 (19) (20) (21) (22) MONTH YEAR Chemo1 1 1 1 1 1 therapy. I 1 l-l 1 1 (23) (24) (25) (26) MONTH YEAR Surgery.. I i 1-1 1 1 T^7) (28) (29) (30) MONTH YEAR I t I I 1 1 Other.... I l l - I l l (31) (32) (33) (34) (GO TO NEXT BODY PART) n. During what month and year did you first receive (EACH TREATMENT CODED IN Q.m) for cancer of the (BODY PART)? t. l -1 During what month and year did you first receive (EACH TREATMENT CODED IN Q.s) for cancer of the (BODY PART)? MONTH YEAR RadiaI I I I tion.... | | I I (19) (20 (21) (22) MONTH YEAR Chemo1 1 I I therapy. I I ' I I (23) (24) (25) (26) MONTH YEAR I I 1 1 Surgery.. 1 1 1 1 Surgery.. 1 1 l-[ .1 (27) (28 J 29) UU) T27) (28) (29) (iff MONTH YEAR MONTH YEAR 1 1 I I I I I I 1 1 1 1 Other.... I I - I I I Other (3D (32T (33) (34) (3l) (32) (33) (34) (RETURN TO Q.37a) (GO TO NEXT BODY PART) MONTH YEAR Radia] 1 I I tion.... 1 1 l-l 1 1 (19) (20) <21) (22) MONTH YEAR Chemo1 T 1 1 I therapy. 1 1 ~l 1 1 (n) (24) (23) (26) MONTH YEAR i i ri i 04 /y-80 7 y-80 127 lid 79-80 �CARD 142 167. 812039 Additional Cigarette Periods (Q.45-47) 167c. After that, about how many packs per week did you smoke? i r •. I I packs per week d. Until what month and year did you continue to smoke (NUMBER) packs per week on a regular basis? MONTH YEAft 1 ~ 1 T 1 T T ( I F DATE I S T H E SAME A S Q.45c: RETURN T O Q.47a. I I j-l I I ALL OTHERS: CONTINUE) (14) (15) (16) (17) e. After that, about how many packs per week did you smoke? I J 1 \ | [_ packs per week (18) (19) f. Until what month and year did you continue to smoke (NUMBER) packs per week on a regular basis? MONTH YEAR T I T T f ~ " T (RETURN T O Q.47a) I I l-l I I . . '(20) (21) (22) (23) ' 168. 168c. Additional Pipe Periods (Q.48-50) After that, about how many pipefuls per week did you smoke? T I I I I I pipefuls per week (25) d. Until what month and year did you continue to smoke (NUMBER) pipefuls per week on a regular basis? T MONTH j.__ YEAR ' j. I -j | (ip DATE ig TIIE SAME AS Q>48c. RETURN T0 Q 5 Q_ j I |-j j | ALL OTHERS: CONTINUE) (26) (27) (28) (29) • e. After that, about how many pipefuls per week did you smoke? T J i! r . [ pipefuls per week (JO) (31) f. Until what month and year did you continue to smoke (NUMBER) pipefuls per week on a regular basis? .MONTH YEAR 1 1 Tl \ T (RETURN TO Q.SOa) I • I l-l I I (32) (33) (34) (35) 128 �CARD H2 169, 169c, 812039 Additional Cigar Periods (Q.51-53) After that, about how many cigars per week did you smoke? 1 I I J_ I I cigars per week (36) (37) d. Until what month and year did you continue to smoke (NUMBER) cigars per week on .1 regular basis? MONTH YEAR T I T T I T (IF DATE IS THE SAME AS Q.Slc: RETURN TO Q.53a. I ! I- 1 I I AU. OTHERS: CONT1NIIK) e. After that, about how many cigars per week did you smoke? I J I I I |_ cigars per U2) (A3) week f. Until what month and year did you continue to smoke (NUMBER) cigars per week on a regular basis? MONTH YEAR 1 I FT I T (RETURN TO Q.53a) I . I l-l I I (44) (45) (46) (47) 129 �CARD 142 ; 170. 170c. 812039 Additional Drinking Periods (Q.54-56) After that, about how many drinks per week did you have? I I I drinks per t* ) ( 49) week d. Until what month and year did you continue to drink (NUMBER) drinks per week on a regular basis? MONTH YEAR 1 T T1 I T ( I F DATE I S T H E SAME A S Q.54c: RETURN T O Q.56a. I I l-l I I ALL OTHERS: CONTINUE) C$0) C51 ) (52 ) ( 53 6' After that, about how many drinks per week did you have? I J I I | [_ drinks per week 64 ) ( 55) f. Until what month and regular basis? MONTH 1 I I I 66 ) 67 171, 171c. year did you continue to drink (NUMBER) drinks per week on a YEAR T 1 \ T (RETURN T O Q.56a) l-l I I ) 68 ) 69 ) Additional Marihuana Periods (Q.57-59) After that, about how many joints per week did you smoke? I J I T | [ joints per week fcO ) fcl ) d. Until what month and year did you continue to smoke (NUMBER) joints per week on a regular basis? MONTH YEAR 1 I TT I T (IF DATE IS THE SAME AS Q.57c: RETURN TO Q,59a. I I J - | j J ALL OTHERS: CONTINUE) 62 )( 63) ( 64) ( 65) e. After that, about how many joints per week did you smoke? I joints per week (66) (67) f. Until what month and year did you continue to smoke (NUMBER) joints per week on a regular basis? MONTH YEAR 1 I TT I T (RETURN TO Q.59a) I I l-l I I '«S8 ) (69) ( 70) (71 ) 130 �CARD 0.172. 812039 130 Additional Jobs and Toxic Substances (Q.13Q) NINTH JOB EIGHTH JOB SEVENTH JOB THAND RESPONDENT CARD "G"| 172a. W h i l e w o r k i n g at (EMPLOYER) as (DUTIES), d o / d i d you come in contact with any of the subs tances on t h i s c a r d ? By c o n t a c t , I mean that you inha l e d , t a s t e d , had skin contact with, or were radiated by any of these s u b s t a n c e s ? iMULTIPLE RECORD! ]ASK Q.172b FOR EACH SUBSTANCE CODED IN 0.172a. 1 172b. In g e n e r a l , how many days a month ( d o / d i d ) you come in contact with ( SUBSTANCE ) ? 01. .( 12( O2..(l3( O3..(ia( O4..(l5( 1 01. .1 1 1 -1 -1 -1 -1 ! ! ! 04. .1 (19)(20) Ol..(12( O2..(13( 03..(14( 04..(15( O5.(16< -1 06.(17( -1 O 7 . ( l 8 ( -1 < I F "07," SKIP TO NEXT JOB) I ! 1 I2l)(22) -1 -1 -1 -1 Ol..(12( O2..(13 O5.(16( -1 O6.(17( -1 O 7 . ( l 8 ( -1 (IF "07," SKIP TO NEXT JOB) -1 O5.(16( O6.(17( -1 -1 Q7.(18( -1 (IF "07," SKIP TO NEXT JOB) i l l I I ! 01.. 1 1 1 04..! 1 t (19X20> (21X22) 01..1 (19) (20) (21X22) i l l 02. .1 I 1 <23)(2A) I I I I I I 02.. | I 1 05.. 1 1 ! (23X24) (25X26) 1 1 1 1 1 1 1 ! 02. .1 1 ! 05. .1 (25) (26) (23) (24) T i l 03.. 1 I 1 (27)(28) !lF ANY SUBSTANCE CODED IN Q.172b, ASK Q.172cl 172c. W h i l e you were on that job, how o f t e n di d you wash to remove the (SUBSTANCES) or use pro- 1 1 05. .1 t 1 (25X26) 1 1 1 06.. 1 1 1 (29><30) I I I I I I 03.. | I I 06-.. 1 1 1 (27)(28) (29X30) 03..I I (27) (28) All the time(31( Some of. -l](ASK Q. | 172d) Never -3 (GO TO NEXT JOB) T (29) (30) All the time. (31 ( Some of -ll(ASK Q. V 172d) All the time. (31 ( Some of Che time -1~1(ASK Q. f 172d) -2j Never -3 (GO TO NEXT JOB) Never. -3 (GO TO NEXT JOB) J soine of the t i m e , or never? lHAND RESPONDENT CARD "H" | 172d. Which of the following did you use on t h a t iob 7 1 MULTIPLE RECORD IF NECESSARY! I Air f i l t e r (32( -?\ • Goggles (33( -i (-GO TO Face shield (34l -1 NEXT JOB) Special clothing. .(35( -1 Washing f a c i l i t i e s ( 3 6 ( ~~1 07 79-80 Air f i l t e r (32( -1} Goggles (537 -1 ( G O T O Face shield (34( -1 ' NEXT Special clothing. .(35( -1 JOB) Washing facilities(36C ~-l 08 79-80 Air filter (2 3 ( -1 Goggles (33T -1 (GO TO Face shield (34 ( -1•NEXT JOB) Special clothing..(35( -1 Washing facilities(36( -1 09 79-80 �CARD Q.172. IHAND RESPONDENT CARD "G" 1 172a. W h i l e working at (EMPLOYER) as ( D U T I E S ) , d o / d i d you come in c o n t a c t w i t h any of the subs tances or t h i s c a r d ? By c o n t a c t , I mean t h a t you inha led, t a s t e d , had s k i n c o n t a c t w i t h , or were r a d i a t e d by any of these s u b s t a n c e s ? [MULTIPLE RECORDl lASK Q.172b FOR EACH SUBSTANCE CODED IN Q.172a. 1 1 7 2 b . In g e n e r a l , how many days a month ( d o / d i d ) you come in contact with (SUBSTANCE)? Ol..(12( 02..(13< O3..(14( O4..(15( -1 -1 -1 -1 Ol..(12{ O2..(13~t 03..U4( O4..(15( 0 5 . U 6 C -1 06. (ITT -1 O 7 . ( l 8 ( -1 (IF "07," SKIP TO NEXT JOB) -1 -1 -1 -1 1 1 05.. 1 1 (25X26) I I I 06. .1 1 1 (29X30) ! ! i (21M22) All the t i m e ( 3 l ( Some of Never 1 ! 04.. 1 .. -l"\(ASK Q. f 172d) -3 (GO TO NEXT ~~ JOB) Air f i l t e r (32( Goggles (33( Face shield (34( Special clothing. .(35( Washing f a c i l i t i e s ( 3 6 ( -1 -lUGO TO -1|NEXT JOB) -1 ~lj 10 79-80 -1 I 01.. I 1 1 1 I I I 03. .1 1 ! 06. .1 1 1 ( 2 7 ) (28) (29) (30) I -1 O4..(l5l I I I 1 1 1 02. .1 1 1 05. .1 1 i (23X24) (25X26) I I I 03. .1 1 1 (27)(28) 0 2 . . (IT? I I I 1 1 1 01.. 1 1 1 04.. | I I (19X20) (21X22) t i l 02.. 1 1 1 (23X24) [HAND RESPONDENT CARD "H" ! 172d. Which of the following did you use on t h a t job? IMULTIPLE RECORD IF NECESSARY! O5.(16( O5.(16( -1 0 6 . ( 1 7 ( -1 O7.(18( -1 (IF "07," SKIP TO NEXT JOB) I I 01.. 1 (19X20) I I F ANY SUBSTANCE CODED IN Q.172b, ASK 0^172c! 172c. W h i l e you were on t h a t job, how o f t e n d' d you wash to remove the (SUBSTANCES) or use prot e c t i v e gear — w o u l d you say all of the t i m e , some of the t i m e , or never? TWELFTH JOB ELEVENTH JOB TENTH JOB Additional Jobs and Toxic Substances (Q.130) (CONT'D) 812039 130 I I I I I T T T 1 02..I T T i (23) (24) i r 03..I I I (27)(28) All the time.(31( Some of the t ime Never -3 (GO TO NEXT JOB) Never. 11 79-80 I 04..J (21 )(22 ) -l)(ASK Q. f 172d) -l\ -l}(GO TO -ITNEXT -1 JOB) -1J O7.(18( (IF "07," SKIP TO NEXT JOB) (19)UO) All the time. (31 ( Some of Air f i l t e r (32( Goggles.. (33 ( Face s h i e l d (34( Special clothing. .(35( Washing f acilities(36( - 06. (rn - (25) (26) I I T I (29) (30) -l) (ASK 0. 172d) _-3 (RETURN TO Q.131) Air filter (32 ( -1 Goggle* (33 ( -1 RETURN TO Face shield . 3 ( -1 Q.131) (4 Special clothing..(35( -1 Washing facilities(36( -1 12 79-80 �CARD 173. 133 812039 Additional Countries and Toxic Substances (Q.133) lASK Q.173b FOR EACH SUBSTANCE CODED IN Q.173a. 1 173b. In g e n e r a l , how many days a month ( d o / d i d ) you come in c o n t a c t with (SUBSTANCE)? Ol..(1h( 02. . ( ) 7 ( 03..qtT O4..(,q( 1 1 1 01. .1 1 1 (23) (24) ! 02. .i ! 1 -1 -1 -1 -1 I I ! OA..I 1 1 (25) (26) 1 I I 05. .1 ( 2 7 ) (28) i l l 03. .1 1 ! (31)(32) I ! ! 1 (29) (30) I I I 06..! I 1 (33)(34) I I F ANY SUBSTANCE CODED IN Q.173b, ASK Q.173c| 173c. Did vou wash to remove the (SUBSTANCE) or did you use protective clothing or gear when stationed in (COUNTRY) — all of the time J some of the time, or never? Never IHAND RESPONDENT CARD "H"| 173d. Which of the following did you use on that job? I MULTIPLE RECORD IF NECESSARY 1 O5.(20( -1 06. (HI -1 07.(22T -1 (IF "07," SKIP TO NEXT COUNTRY) Air f i l t e r (:te( Goggles.(-}7< Face shield (-^( Special clothing- .(:rt< Washing facilities(/|i-i( « ASK Q. 173d) -3 (GO TO NEXT COUNTRY) "U -ll(GO TO -ifNEXT -IICOUNTRY) -11 ri7 (14-15) (14-15) (14-15) IHAND RESPONDENT CARD "G" 1 173a. In your job assignments while stationed in (COUNTRY), ( t h a t t ime) ( d o / d i d ) you come in contact w i t h any of the following s u b s t a n c e s ? NINTH COUNTRY EIGHTH COUNTRY SEVENTH COUNTRY Ol..(lb( O2..(17( O3..(l8l O4..(19( 1 -1 -1 -1 -1 I -1 O2..(17( -1 Q3..(18( -1 Oi..(19j__-l 05-(20( -1 O 6 . ( 2 l ( -1 07. (22? -1 (IF "07," SKIP TO NEXT COUNTRY) I T 1 ! I 04..II 01..I 01.. 1 1 I 04.. [ 1 1 (23)(Z4) (Z5)(Zb) (25X26) 1 1 ! I I ! 02.. 1 1 ! 05.. 1 I 1 (27)(28) (29)(30) J 02 27)(28) 1 1 1 1 I I I 03.. 1 1 1 06.. 1 1 1 (31X32) (33)(34) -IHASK Q. T 173d) -2J T Never -3 (CO TO NEXT COUNTRY) (33X34) -ll(ASK Q. 173d) All the Some of the time Never. Air f i l t e r ($(,( -1 Goggles ( i y ( -1 (GO TO Face shield (^ a ( -1 NEXT Special clothing. .(-jq( -1 COUNTRY) Washing facilities(/| 0 ( ~-l [ 05.. I _ I I (29)(30) (31)(32) All the t i m e . ( 3 5 ( Same of the time 08 O5.(20( -1 O6.(21( -1 Q7.(22( -1 (IF "07," SKIP TO NEXT COUNTRY) _-3 (GO TO NEXT COUNTRY Air filter (6 3( Goggles (37 ( Face shield (8 3( Special clothing..(39( Washing facilitie?(4Q( 09 -1 -1 /GO TO -1 NEXT -1 COUNTRY) ~1 �CARD 173. 812039 133 A d d i t i o n a l C?-j-:ries and Toxic Substances (0-133) (CONT'D) ELEVENTH COUNTRY TENTH COUNTRY lASK Q.173b FOR EACH SUBSTANCE CODED IN Q.173a. ! 173b. In general, how many dayt a month (do/did) you come in contact with (SUBSTANCE)? 1 O5.(20( -1 02..(17( -1 O6.(2l( -1 03.. ( s l ^ -1 Q . ; ( -1 7(; 04. . 19( -1 ( (IF "07," SKIP TO NEXT ' COUNTRY ) 1 01. .1 i ! i 1 ! 04. .1 i 1 ! 03. .1 i 1 (31X32) IIF ANY SUBSTANCE CCi-D IN Q.173b, ASK Q.173c! 173c. Did you was'- : : remove the (SUBSTANCE) i ! < 25X26) (23) (24) ! i ! 02..! i ! (27) (28) ! 1 ! ! I 05. ( 29) ( 30) 1 i 1 06. .! 1 I (33) (34) -A (ASK 0- Never when stationed in CIVN'TRY) — some of the time, cr -ever? All the tine(35( Some o f 01..(16( -1 O2..<17( -1 03..(T8T~~-1 O5.(20( -1 O6.(2l( -1 07.C22T~-1 (IF "07," SKIP TO NEXT COUNTRY ) -,) " ' " Air filter ( 36( -1 Cosgles ( 37( -1 (GO TO ^ace shield.. , . . 3^( -1. NEXT ..( Special clothing. . 39( -1 COUNTRY) ( Washing facilit ies( 4Q( '0 *'" •• -1 -1 -1 O5.(20( -1 O6.(21< -1 07.(22( -'(IF "07," SKIP TO NEXT COUNTRY ) ! 1 1 1 I 1 1 ! 01.. 1 ! 1 04 ..! (23X24) (25X26) 1 ! I .! 1 1 02. .1 i ! 05. .1 i I (29) (30) (27) (28) i i ! 02.. 1 1 1 (27X28) 1 1 1 05 ..! i 1 (29X30) 1 I I I 1 i 03.. I I 1 06..! I 1 (33X34) (31X32) i 1 1 03..! 1 1 (31X32) 1 1 ! 1 ! 06 ..! (33X34) -fl (ASK Q. V 173d) . -2J All the tir.e.(35( Some o f the time -1)(ASK Q. V 173d) -2 -3 (GO TO NEXT COUNTRY ) All the time.( 35( Some of IHAND RESPONDENT CA=I "H"! 173d. Which of tre f:llowing did you use on that job? iMTLTiri. RECORD IF NECESSARY! O2..(r7( O3..(l8( 04..C19C 1 1 I 1 i ! I 04..! i 1 01. .1 1 (25X26) (23)(24) -3 (GO TO NEXT COUNTRY) all of the time (14-15) (14-15) (14-15) iHAND RESPONDENT CARI "G" 1 173a. In your job assignments while stationed in (COUNTRY), (that ti-« 'do/did) you come in contact with any of ~~e following substances? TWELFTH COUNTRY Never -3 (RETURN TO Q.134a) Air filter. . . . (36( (37( Goggles ( 1ST Special clotning. . ( 39i Washing faeilities( 4p( 11 79-80 Air filter ( 6 _-! (RETURN 3( -1 Goggles (37( _-1 TO Q. -1 (GO TO -1 NEXT Face shield (8 3 ( -1 1 TAa 1 -1 COUNTRY) Special clothing. .(39( Washing f acilities(40( -1 ( 12 79-80 �DEPARTMENT OF THE AIR FORCE WASHINGTON DC 20330 OFFICE OF THE SECRETARY James W. Doe 1215 Middle Grove Norfork, MD 23456 Dear i Mr Doe • ' The Air Force will soon begin conducting a very comprehensive health assessment of certain Air Force members who served our Nation in the Vietnam conflict. This health assessment is part of a medical study designed to help determine if you or your fellow Vietnam veterans may have had any compromise to your health as a result of exposure to the complex environment of Southeast Asia. Scientists at the USAF School of Aerospace Medicine have been given the responsibility for conducting this important project. The Air Force Surgeon General will contact you soon with more details and ask for your voluntary participation. . . A major focus of the President's program for veterans is the resolution of health issues raised by them. The Air Force and I are committed to doing our part in resolving these issues. I ask that you help us and all Vietnam veterans by voluntarily participating in this major study. Sincerely, Verne Orr Secretary of the Air Force 135 �DEPARTMENT OF THE AIR FORCE HEADQUARTERS UNITED STATES AIR FORCE BOLUNG AFB DC 2O332 James W. Doe 1215 Middle Grove Norfork, MD 23456 Dear Mr Doe The Air Force is conducting a very comprehensive health assessment of certain Air Force members who served our Nation in the Vietnam conflict. The USAF School of Aerospace Medicine has been given the responsibility for conducting this study. The.purpose of the study is to determine whether there may be any causal relationship between health problems and exposure to the complex and unique environment of the war in Southeast Asia. Simply stated, we do not know if such health effects exist. You are being asked to voluntarily participate in this study because of your unique Southeast Asia experience. Your participation is critical to the success of this study. However, you should not view this invitation to participate as a cause for alarm nor as an implication that you are at risk for any known disease. To insure the scientific validity of the study, both an in-depth interview and a detailed physical examination will be conducted. The administration of the interview will begin soon under the direction of a nationally recognized health survey organization. You will be contacted by phone or letter to arrange a convenient time for an in-home interview which will take from two to three hours. Shortly after the interview you will again be contacted to schedule a physical examination at a nationally recognized civilian medical facility. The physical examination will take approximately four days. Every effort will be made to minimize disruption of your normal activities and to facilitate your participation in the study. Travel and per diem will be paid by the Air Force. For those not precluded by law, a stipend of $100 per day will be paid as a partial compensation for your time. Our intent is to maintain all individual health data in strictest confidence. In case outside parties attempt to gain access to the data, the Air Force and the Department of Justice are committed to protect this individual confidentiality. Only in the event of an adverse final court decision, or in the highly unlikely instance where serious medical deficiencies must be shared with appropriate medical authorities to protect public health and safety, will any personal health data be revealed. You are referred to the Fact Sheet for further information regarding this matter. 136. �This is perhaps one of the most important health studies undertaken by the Air Force. Your voluntary participation is critical to its success. Although you may feel healthy, numerous Vietnam veterans believe that they have illnesses which may be attributable to service in Southeast Asia. The only way we can get clarification of these difficult questions is through your cooperation and participation. Sincerely PAUL W. MYERS Lieutenant General, USAF, MC Surgeon General 1 Atch Fact Sheet 137 �FACT SHEET INTRODUCTION - The USAF School of Aerospace Medicine, Brooks AFB, Texas, is conducting the study. You are being invited to participate in this study because of your specific duties and period of assignment in Southeast Asia. PURPOSE To determine whether there is a causal relationship between adverse health effects and exposure to the complex environment of Southeast Asia. METHODS - An in-depth health questionnaire will be administered to you by a member of a health evaluation team from Louis Harris and Associates, Inc. - A complete profile of your current health will be obtained by a physical examination which will be conducted by a nationally recognized outpatient clinic. - Follow-up abbreviated health questionnaires and physical examinations will be conducted at years 3, 5, 10, 15, and 20 of the study. - Travel expenses (including board and lodging) for the physical examination will be paid by the Air Force. - Stipend of $100 per day will be paid to study participants who are not on active duty, Government employed or otherwise precluded by law from receiving such a stipend. t - Confidentiality is to be maintained except in two cases: - A judicial order to release personal medical data following an Air Force and Justice Department defended lawsuit. Serious medical findings which impact public health and safety. Two examples of situations in which public health and safety would raise the questions of disclosure are: a participatnt has typhoid fever, a participant who directly impacts the safety of others either in his profession, or as a volunteer, is found to have a serious nerve, heart or mental disorder. In this instance a committee composed of a physician (whose specialty is the area of the identified problem), a physician of your choice, a flight surgeon, a judge advocate (lawyer) and a representative from your field of expertise w i l l be convened to review the medical findings. Before any disclosure is made to medical authorities, the committee must determine that the findings jeopardize the public health and safety. 138 �BENEFITS TO YOU - You will receive a complete health review and physical examination of top level executive calibre at no cost to yourself. - You will be completely informed of all examination results. The information from this study will be provided to a physician of your choice if you so request. -. Questions concerning the study may be referred to the USAF School of Aerospace Medicine, Epidemiology Division, Brooks Air Force Base, Texas 78235, or by calling collect AC 512 536-3309. - If you have recently changed your address or have an unlisted phone number, please advise the USAF School of Aerospace Medicine at the above address and phone number so that your records may be properly updated. 139. �LOUIS HARRIS AND ASSOCIATES, INC. 630 FIFTH AVENUE NEW YORK, NEW YORK 10111 Dear Mr. Doe Louis Harris and Associates has been asked by conduct interviews for a health study of Air served during the Vietnam conflict. The U.S. Medicine is undertaking this study in order to health effects of having served in Vietnam. the United States Air Force to Force pilots and servicemen who Air Force School of Aerospace answer questions about possible We need your cooperation in this study. The validity of the results of the study depends on the willingness of veterans like yourself, who have been selected for the survey, to participate. Reliable information will enable us to reach sound conclusions of vital relevance to all Vietnam veterans. One of our interviewers will be calling you in the next two weeks to arrange an appointment with you. The interview will cover many aspects of your military experience, occupational experience, family history, health history and health care utilization. Since the interview may take one or two hours to complete, we will schedule the interview at your convenience. Thank you for your cooperation. tant project. I hope that you will join us in this impor- Sincerely, LOUIS HARRIS 140 �;iS HARRIS .AND ASSOCIATES. INC. i_OdS HAPRIS INTEPNATION A _ '.. !<,. M A R » . * - rc.A-.CE - ;>PiNiOW P»ES£APCH i.'' RL £ v . ^ . ^ E N ^ ^ E 7SOCS PAP*- re TEL »6fc^ Or-260 CtNTRE -*^ *£LBEC^ 5T. »AN^£ TE..C*: » O N O O N WIM 0AB tNOlpA'Jt ffrn^r, r . "EL Oi - -66 - * > » ! TtLtJt' »- - PRIVACY ACT STATEMENT - EPIDEMIOLOGIC STUDY AUTHORITY: Section 133, 1071-87, 301.2, 5031 and 8012, Title 10, United States Code and Executive Order .9397. PRINCIPAL AND PURPOSE(S): The purpose of requesting personal information is to assist medical/technical personnel in developing records relative to your participation in an approved epidemiologic investigation. The Social Security Number (SSN) and Armed Forces Service Number (AFSN) are necessary to identify the person and records. ROUTINE USES: This information will be used to initiate, coordinate, and conduct the investigation. It will be used to compile statistical data, but information allowing identification of the individual volunteer will not be included. Data and results from this investigation may be used to supplement other approved research studies conducted at the USAF School of Aerospace Medicine or at other Federal agencies engaged in the: conduct of similar studies. WHETHER DISCLOSURE IS MANDATORY OR VOLUNTARY, AND EFFECT ON INDIVIDUAL FOR NOT PROVIDING INFORMATION: Disclosure or requested information is voluntary. If the information is not furnished, acceptance as a subject is not possible. This is an all-inclusive Privacy Act Statement which will apply to all requests for personal information made by medical/technical personnel during the time you are a volunteer subject. A copy of this form will be placed in your investigation subject folder as evidence of tnis notification. Your signature merely acknowledges that you have been advised of the foregoing. If requested, a copy of this form will be furnished to you. Signature of Volunteer SSN 141 ' Date !f �LlhEEVENTS CHART U.S. Air Force Survey YOUR AGE THEN DEATH SCHOOLS MILITARY EXPERIENCE OTHER JOBS MARRIAGE 1/19 CHILDREN FAMILY MAJOR ILLNESS OTHER SPECIAL EVENTS �SHOW CARD "A1 STUDY NO. 812039 High School Diploma High School Equivalency Diploma Associate of Arts (A.A.) Bachelor of Arts (B.A.) or Bachelor of . Science (B.S.) Masters (M.A. or M.S.) I Doctorate (Ph.D., M.D., Ed.D., Sc.D.) Others 143 �SHOW CARD "B1 STUDY NO. 512039 01 Aerospace 02 Aircraft^ 03 Agriculture 04 Automotive 05 Chemical 06 Electronic 07 Mining 08 Pest Control 09 Petroleum 10 Textile 11 None Apply 144 �SHOW CARD "C" STUDY NO. 8120: 01 Pill 02 Douche 03 Foam 04 Jelly, Cream, Suppository 05 IUD 06 Condom, Rubber 07 Diaphragm 08 Diaphragm and Jelly 09 Rhythm - Calendar 10 Rhythm - Temperature 11 Withdrawal 12 Other 145 �SHOW CARD "D( STUDY NO. 812039 a. Sterility due to surgery b. Known sterility due to injury, accident, or illness c. Sterility due to unknown causes d. Impotence e. Other known medical/physical conditions f. Some other reason 146 �SHOW •''" STUDY:^or 812039*'"' * 147 �STUDY NO. 81203C SHOW CARD "F1 Very often Fairly often Sometimes Almost never Never 148 �SHOW CARD "G1 STUDY NO. 81 01 Asbestos 02 X-ray or nuclear radiation 03 Industrial chemicals 04 Defoliants or herbicides 05 Insecticides or pesticides 06 Degreasing chemicals 07 None of these 149 �SHOW CARD "H STUDY NO. 81203- Air filter Goggles Face shield Special clothing Washing facilities 150, �SHOW CARD "I1 STUDY NO. 81 A. $5,000-$9,999 B. $10,000-$14,999 C. $15,000-$19,999 D. $20,000-$24,999 E. $25,000-$29,999 F. $30,000-$34,999 G. $35,000-$39,999 H. $40,OQO-$44,999 I'. $45,000-$49,999 J. $50,000-$54,999 K. $55,000-$59,999 L. $60,000-$64,999 H. $65,000-$69,999 N. $70,000-$74,999 0. $75,000-$79,999 P. $SO,000-$84,999 Q. $85,000-$89,999 R. $90,000-$94,999 S. $95,000-$99,999 T. $100,000 or more 151 �CARD 135 Case No._ SEI.K-ADMINtSTI-HF.I) SHKKT These next questions are about liow you have felt du_ri_nj> the last three months. for each question, please circle a number for the one answer that comes closest to the way you have been feeling during the last three months. 1. How often did you become nervous or jumpy when faced with excitement or unexpected situations during the past 3 months? Always 1 (17) Very often..... 2 Fairly often 3 Sometimes k Almost never 5 Never. 6 2. How much of the t i m e , during the past 3 months, did you feel relaxed and free of tension? All of the time 1 Most of the time 2 A good deal of the time... 3 Some of the time 4 A little of the time 5 None of the time (18) 6 3. Huring the past 3 months, how much of the time have you felt restless, fidgety, or impatient? A l l of the time Most of the i iuie 2 A good d e a l of the t i m e . . . 3 Home of tht' t i m e 'i A I iule of the time 5 None of the time l<, 1 (ly) 6 During the past 3 months, have you been anxious or worried? Yes, extremely so, to the point of being :. ick or almost sick 1 Yes, very much so 2 Yes, q u i t e a l o t . 3 Yes, some, enough to bother me 4 Yes, a l i t t l e b i t 5 No, not at a l l 6 I'l.KASE TUK.N OVKR 152 (-'") �n. .w o i i u i v , o i i r i n K tin- p a s t .) m o n t h s , have you lieen wak i'n(> up f eel id)- f resli an<j l.'Stfll? " '. ' . - ' " . " "','• • • - A l w t i V i > • evv.i y d a y ' ........ ' / ' , 1 A l m o s t e v e r y (lay . . . . . . . . . . " . ;, ' . ' ' • ••'-''•' ••'<'. '(21) 2 Mont <l;iys ....... . . . . ...... 3 Some. d a y s , ))nl u s u a l l y not 'i H a r d l y i.'Virr 5 ........ . ....... Never wake u p ( o e l i n g u - s t i ' d . . ---- ...... ........ .6 '). l u i r i i i ) ' , t h e p.'iHt '< iiiontlit. , how o l t i ' n i l l . I yoiii luiiuls shake when you t r i e d lo do . iu.)int.'Ui in^? A l w a y s , eve -y <l.iy ......... V e r y ol I #.n .......... . ..... 2 Most d a y s ........... . ..... 3 Some d a y s , hut u s u a l l y not A Hardly ever.... 7. 1 5 ........... (*-) How much of the t i m e d u r i n g the uatil 3 months have you f e l t c a l m and p e a c e f u l ? A l l of the t i m e . . . . ....... 1 (2!1) Most of the time .......... 2 A good deal of the time... 3 Some of the t ime ..... . . .. . (t A l i t t l e of the time...... 5 None of the time .......... 6 ti. During the past 3 months, how oltcjn did you put rattled, upset, or confused? Always.................... 1 Very ofti.-n ................ (24) 2 Ka i r 1 y u ( t *.' n ............. . 1 Some t ilia1 s ........... . . . A ... Almost never. ........... .. 5 Never.....................0 'i. How much have you been bothered hy nervousness, or your "nerves," during the past 3 months? Extremely so, to the point where I could not take care of things .......... 1 Very much bothered. .......... ,.....»•• Bothered ijnite a lot by nerves. ........ 2 3 Bothered some, enough to notice ........ 4 Bothered .jus I a 1 i 1 1 1 e. by nerves ...... 5 Not bothered al all hy nerves....... ... 6 you Tiavy ccimpleteTTtcma' 1 - j ' r e t u r n t f i j i h e f C 153 ( *-->) . ; �Louis HARRIS AND ASSOCIATES, INC. 63O NEW TEL FIFTH Y O R K . NEW AVENUE YORK I2iej 9 7 5 - I 6 0 O T E L E X I O I I I 148363 LOUIS H A R R I S I N T E R N A T I O N A L . INC OPINION R E S E A R C H C E N T R E LOUIS H A R R I S FRANCE 21 RUE VIV1ENNE 3 O W E L B E C K ST 7SOO2 PARIS. FRANCE LONDON WIM 6AB E N G L A N D TEL. oi-aoo -0034 TELEX: 200001 F TEL O I - i a e - 5 I S I TELEX UNITED STATES AIR FORCE HEALTH STUDY Name of Medical Provider/Medical Facility Street Address City State Zip 1 Phone Number Dear Doctor or Administrator: I am participating in a survey conducted for the United States Air Force to gather information on the health of current and former Air Force personnel. As part of this survey, medical providers who have delivered health care services to me are being asked to supplement the information that I have already provided to the study. By this statement or a pfiotocopy of it; 1 heret>y authorize and request you to furnish the United States Air Force Health Study with any medical information in your records concerning the health services received by me, These services were provided during the period to Thank you very much. Sincerely, Resp. # Signature of Patient FOR OFFICE USTOMLT: Date I I 2-a-lO3 �HARRIS AND ASSOCIATES. 'NC , £ Vv. "• C1 ° «•..' N E .'. T. Z ? $•>* •,"-'• '6CV '!.,£« 3 0 *e^8ECK ST ..CNCON W)M 6A6 TEL c .*<)£• SIB< TC. Oi- zfto -ttibJ Tluik*: zooeci Dear Louis Harris and Associates has been asked by the United States Air Force to conduct a study &f the health of Air Force pilots and servicemen who served during the Vietnam conflict. The U.S. Air Force School of Aerospace Medicine is undertaking this study in order to answer questions about possible effects of having served in Vietnam. I have just completed an interview with Louis Harris and Associates on the United States Air Force Health Study, As part of this study, they would like to interview the former wive^s of study participants. You will be asked to provide information on health and health care services. It is essential to the accuracy and completeness of the study that all selected participants and their families participate in the study. Reliable information will help produce sound conclusions of vital relevance to all Vietnam veterans and their families. I would appreciate it very much if you also would grant a representative of Louis Harris and Associates an interview. Shortly after receiving this letter, you will be called on by an interviewer from Louis Harris and Associates who, at your convenience, will either conduct the interview or set up an appointment. The interviewer will answer any questions you may have about the study. Thank you. Sincerely, (SIGNATURE OF STUDY RESPONDENT; (PRINTED NAME OF STUDY RESPONDENT) 155 �FOR OFFICE USE ONLY: LOUIS HARRIS AND ASSOCIATES, INC 630 Fi fth Avenue New York, New York 10111 Case * # 812039 Air Force Health Survey Respondent INTERVIEW EVALUATION INTERVIEWER: "COMPLETE THE FOLLOWING IN PRIVATE" IMMEDIATELY YOUR BEST JUDGMENT TO ANSWER FACH ITEM. _ AFTER THE INTERVIEW, USING] _J • lace of respondent: Black.... Nonblack. 2a. Did the respondent want to terminate the interview before it was finished? No (SKIP TO Q3a) Yes (ANSWER 2b AND ?c) 2b. At what question number or during what question series? '(. l-'hat was the reason? la i'ore there any (other) significant problems uurmg Uie interview? No. Yes (SKIP TO Q4a) (ANSWKR 3b) 3b. Describe the problems. 4a. Did respondent refer to records during the interview? No Yes (SKIP TO Q5a) (ANSWER 4b) 4b. What records did the respondent use? : 5a. Was anyone else present at any time during the interview? No Yes ^ (SKIP TO Q6) (ANSWER 5b and 5c) 5b. Who was present? | RECORD RELATIONSHIP | 5c. During which section(s)? _ 6. Length of interview: minutes 156 �l', MAR'ftl'.. '-VU) Av.''iCI.AU$",' INC, " '" Sjiydy « 812039 630. Fifth Avenue ... New. York, New York luli'J' AIR FORCE HEALTH SURVEY TO: New York Office. Louis Harris'- and Associates FROM: . . ; • ' . ' _ Int.erviewer Nairn? - PYease Print _ " „_...*_ ..... ' _____ " Ihi-, pai'kdiji.' iiontrt in , the1 Col lowing mdterial for Study*"*>uhject Respondent" Number W r i l e iii NUMW..K of'- card item being sent; on the l,ine_jit the rijjht —- "' .STUDY SUUJDCT INTERVIEW . ' Study Subject Name 'Assignment Sheet. " Study Subject Prlvvicy Act Statement (Signed), Study Subject Questionnaire Study Subject Supplemental Recording Book Study Subject Self Administered Form. Study Subject Medical Consent Form Study Subject. Former Wife Consent Letter..... Study Subject Interviewer Evaluation Form.... I PRFSF.NT Will: INTFRVII-W P'n vacy Ac t S ta"teiiK!h t. (Si gned). Spouse Questionnaire Spouse. Supplemental Recording [iook. Spouse Medical Consent Form Spouse Interviewer -L valuation form. •FfiKHl'R Win' I oniu.'r W i f e Nome As'1, iijimient Sheet.. Privricy Act St.ateim.Mit (Signed) Spouse Questionnaire. Spnir.e ',up|)lenierUal Recording Book. Spouse Medicdl Corisi.Mit Form Spouse Interviewer I'.yal'uation Form. PROXY INTERVIEW Proxy Name Assignment Sheet Privacy Act Statement (Signed) ,••..,..,..,. .m J w _ . . /•'. -._. . ' Proxy Questionnaire. •..„...;..'....'., Proxy Supplemental Recording book... ..,0.,..?.,,. Prox.y Medical Consent Proxy Interviewer; Evaluation ,-,.. ,.. •_„_„,_ Received: • ""liaTi? . ' '". ""• . I ' ,,,. ,^,_ >....( . : Ihecked in by: „ ' ' i 157 ' �CHAPTER II SPOUSE QUESTIONNAIRE The following Spouse/Partner Questionnaire was used to collect baseline data for the Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicide Orange. This data was collected during 1981-1982. All available spouse/partners, both present and former, were included in this data collection effort. The questionnaire and supplemental recording book are the actual field instruments. They have been photocopyed and reduced for the purpose of this report. Additional field documents, such as show cards, are included as attachments to the questionnaire. Additional attachments include: Introductory Letter, Privacy Act Statement, Medical Permission Form, Interview Evaluation, and Mailing Transmittal Form. The Spouse/Partner Questionnaire, as used in the field, follows. 158 �LOUIS HARRIS AND ASSOCIATES, INC. 630 Fifth Avenue O.M.B. NUMBER New York, New York 10111 0701-0033 Approval Expires 11/30/82 FOR OFFICE USE ONLY: Case No. 12-17 Study No. 812039 Respondent #: SPOUSE QUESTIONNAIRE 5-8 CONFIDENTIAL Present wife Former wife ( -1 This study is being conducted to collect information on the health of current and former Air Force personnel and their families. I will be asking background questions and questions about health. First, I have a few background questions to ask you. 1. ;Whflt is your date of birth? i (WRITE IN DATE) MONTH I DAY T 1 (19) (20) (21) (22) YEAR T I T (23) 159 I (24) �CARD 001 812039 2. How many children have you had — that is, of how many children are you the natural mother? Please include children who live w i t h you, those who live elsewhere, and those who may no longer be living. I I (WKITE IN NUMBER) I children (ASK Q.3) (25) (26) No children ....(2U -1 (SKIP TO Q.8) 3. Starting w i t h your first child, what is the first and last name of the child as it appears on the birth certificate? RECORD FIRST AND LAST NAMES OF ALL CHILDREN IN S.R.B. - PAGE 1. NAME ONLY AT THE TOP OF THE APPROPRIATE COLUMN(S). SKCOND CHILD FIRST CHILD How old is (CHILD) now? 1 1 1 1 (28) 1 1 Age Male Female (31( 1 1 5b. How much did (CHILD) weigh at birth? Male Female 5c. How old is (CHILD) now? 1 1 Age -1 (31( 6b. 6c. OUNCES I I l-l 1 1 (33) (34) (35) (32) Don' t know.. . 3 ( (6 -1 What is (CHILD) 's birth- 5d. date? -1 (Is/Was) (CHILD) male or female? (31( POUNDS OUNCES 1 1 1 1 1 1 ' l-l 1 1 (32) (33) (34) (35) Don't know. . ( 6 .3( -1 What is (CHILD) 's birth- 6d. date? -1 -2 How much did (CHILD) weigh at birth? 1 1 I Age (29) Male Female -1 -2 How much did (CHILD) weigh at birth? 1 1 1 1 Child died..(30( POUNDS POUNDS OUNCES 1 M 1 1 1 > l-l 1 1 (32) (33) (34) (35) 1 1 (28) (Is/Was) (CHILD) male or female? -1 -2 6a. (29) Child died..(30( -1 Don't know...(36( d. 1 1 (28) (Is/Was) (CHILD) male or female? 1 1 How old is (CHILD) now? (29) Jhild died..(30( 4C. 5a. NAME: ! 1 4h. THIRD CHILD NAME: MAME: ^ . WRITE IN THE FIRST -1 What is (CHILD)'s birthdate? MONTH DAY YEAR MONTH DAY YEAR MONTH DAY YEAR I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I - I l l - I l l 1 1 l-l 1 l-l 1 1 •1 l-l 1 l-l 1 1 I (42) 37) (38) (39) (40) (41) (42) (37) (38) (39) (40) (41) (42) (37) (38) (39) (40) (41) ALSO RECORD IN S.R.B. -PC l l e. (ALSO RECORD IN S.R.B.-PG ll Was the child premature, 5e. full term, or overdue? lALSO RECORD IN S.R.B.-PG ll Was the child premature, 6e. full term, or overdue? Was the child premature, full term, or overdue? remature.(43( -A(ASK Premature. (43( Overdue. .... -1\(ASK -2j Q.5f) Premature. ( 3 4( Overdue -l^ASK -2( Q.6f) ull term.... -3^ (SKIP TO Full term -3 ((SKIP TO Full term -3*1(SKIP TO ~ f. X How many weeks (overdue/ 5f. premature) was (CHILD)? 1 1 1 1 (44) . 1 1 weeks (4S) (GO TO Q.4f;) How many weeks (overdue/ 6f. premature) was (CHILD)? 1 1 1 1 (44) 1 1 weeks (45) (GO TO Q.5g) 160 How many weeks (overdue/ premature) was (CHILD)? 1 1 1 1 (44) "1 1 weeks (45) (GO TO Q.6g) �CARD 001 FIRST CHILD 812039 SECOND CHILD THIRD CHILD 4g. Where are (CHILD)'s birth registration records located? In what city and state is thqt? (RECORD IN S.R.B. PG 1 I 5g. Where are (CHILD)'s birth registration records located? In what city and state is that? 6g. Where are (CHILD)'s birth registration records located? In what city and state is that? 4h. Where are (CHILD)'s current medical records Jlocated? .In what city and state is that? 5h. Where are (CHILD)'s current medical records located? In what city and state is that? 6h. Where are (CHILD)'s current medical records located? In what city and state is that? ii. 6i. What was (CHILD)'s f a ther's f ul 1 name? I RECORD IN'S.R.B. PC i I 4i. What was (CHILD)'s father's full name? IRECORD IN S.R.B. PG 1"I IRECORD IN S.R.B. PC i I IRECORD IN S.R.B. PC i I IRECORD IN S.R.B. PG i I How old were you when (CHILD) was born? 4j. How old were you when (CHILD) was born? I I I (46) (47) What was (CHILD)'s f a t h e r ' s f u l l name? IRECORD IN S.R.B. PG i I' IRECORD IN S.R'.B. PG~ i I (RECORD IN S.R.B. PG i I How old were you when (CHILD) was born? Age I (46) (47) Age Age (46) (47) 4k' Were either of you using 5k. Were either of you using 6k, Were either of you using birth control at the birth control at the birth control at the time you became pregnant time you became pregnant time you became pregnant with (CHILD)? with (CHILD)? with (CHILD)? Ye8.(4_8(__-l (ASK Q.4L) Yes.(48( No...... -2 (SKIP TO Q.4m) No THAND RESPONDENT CARD "c'T 4L. -1 -1 -1 -1 -1 06.(54( -1 __-2 (SKIP TO Q.5m) Ol.(49( -1 06.(54( -1 Q8.(56( Q9.(J7( 1Q.(58( ll.(59( -1 -1 -1 -1 No...... -2 (SKIP TO Q.6m) .(60( .6( (0 (GO TO Q.5m) 161 Ol.(49( O2.(50( O3.(51( 04.(5_2( O5.(53(. -1 -1 -1 Q6.(54( _ -1 Q7.(55( -1 Q8.(56( -1 Q9.(57( -1 1Q.(58( -1 11.(59( -1 12 (SPECIFY) 12 (SPECIFY) (00 TO Q.4m) -1 (ASK Q.6L) I HAND RESPONDENT CARD 1rCTT Please look at this 6L. ' Please look at this card and tell me all of card and tell me all of the numbers that apply the numbers that apply to the types of birth to the types of birth control you or your control you or your partner were practicpartner were practicing? ing? Q8.(56( -1 Q9.(57( '_, -1 1Q.(58( -1 11. (59C .-1 12 (SPECIFY) Yes.(48( THAND RESPONDENT CARD "c'T Please look at this 5L. card and tell me all of the numbers that apply to the types of birth cortrol you or your partner were practicing? Ol.(49( O2.(50( O3.(51( Q4.(S2( 05.(5J( -1 (ASK Q.5L) .6( (0 (GO TO Q.6m) �812039 CARD 001 SECOND CHILD FIRST CHILD 4m. How many months did it 5m. take you to become pregnant with this child? 1 1 1 I 1 1 1 I Months Less than 1 month, (63( -1 Less than 1 month. (63( Did (CHILD) have any birth defects? 5n. How many months did it take you to become pregnant with this child? 1 I "(61) (62) (61) (62) 4n. How many months did it 6m. take you to become pregnant with this child? I 1 1 1 Months THIRD CHILD -1 Did (CHILD) have any birth defects? 1 1 I | Months (61) (62^ Less than 1 month. (63(_._ -1 6n. Did (CHILD) have any birth defects? Yes.(64( -1 (ASK Q.4o) Yes.(64( -1 (ASK Q.5o) Yes.(64( -1 (ASK Q.6o) No -2 (SKIP TO Q.4p) No -2 (SKIP TO Q.5p) No -2 (SKIP TO Q.6p) 4o. What kind of birth defects did (s)he have? Any others? 5o. What kind of birth defects did (s)he have? Any others? 60. What kind of birth defects did (s)he have? Any others? 4p. Was (CHILD) ever diagnosed as having cancer? 5p. Was (CHILD) ever diagnosed as having cancer? 6p. Was (CHILD) ever diagnosed as having cancer'- Yes.(65( -1 (ASK Q.Aq) Yes.(65( -1 (ASK Q.5q) Yes.(65( No -2 (SKIP TO Q.4s) No -2 (SKIP TO Q. 5s) No. 4q. In what month and year 5q. was the diagnosis made? 1 1 4r. MONTH YEAR 1 1 1 1 1 1 l-l 1 1 (66) (67) (68) (69) What kind of cancer was diagnosed? Not sure..(70( (GO TO Q.4s) 01 79-80 -1 5r. . . -2 (SKIP TO Q.6s) In what month and year 6q. was the diagnosis made? 1 I MONTH YEAR 1 I I 1 1 l l I l l (66) (67) (68) (69) What kind of cancer was diagnosed? Not sure..(70( -1 (CO TO Q.5s) 02 79-80 162 -1 (ASK Q.6q) In what month and year was the diagnosis made? MONTH 1 1 YEAR 1 1 1 1 (66) (67) 6r. (68) (69) What kind of cancer was diagnosed? Not sure. . 7 ( (0 (GO TO Q.fes) 03 79-fo -1 �812039 CARD 004 FIRST CHILD t;s. SECOND CHILD (Does/Did)(CIIILD) have & diagnosed learning disability? 5s. THIRD CHILD (Does/Did)(CIIILD) have a diagnosed learning disahil ity? 6s. (Does/DidMCHILD) have a diagnosed learning disability? Yes.(12( -1 (ASK Q.4t) Yes.(12( -1 (ASK Q.5t) Yes.(12( -1 (ASK No -2 (SKIP TO Q.4u) No -2 (SKIP TO No -2 (SKIP TO Q.6u) 4t. What kind of learning disability (does/did) (s,)he have? 4u. (Does/Did) (CHILD) have 5u. any physical, mental, or motor impairments? Yes.(13( -1 (ASK No -2 (SKIP TO Q.4w) 4v. Q.4v) What kind of impairment (does/did) (s)he have? 5t. What kind of learning disability (does/did) (s)he have? 6t. 6u. (Does/Did)(CHILD) have any physical, mental, 01 motor impairments? Yes.(13( -1 (ASK No -2 (SKIP TO 5v. 0.5u) Q.5v) Q.6t) What kind of learning disability (does/did) (s)he have? (Does/DidMCHILD) have any physical, mental, motor impairments? Yes.(13( -1 (ASK Q.6v) Q.5w) What kind of impairment (does/did) (s)he have? 6v. 'What kind of impairment (does/did) (s)he have? IF CHILD IS DEAD: IF CHILD IS DEAD: IF CHILD IS DEAD: OTHERWISE: OTHERWISE: OTHERWISE: iw. CONTINUE SKIP TO Q.4z On what date did (CHILD) die? MONTH DAY 5w. YEAR CONTINUE SKIP TO Q.5z On what date did (CHILD) die? 6w. CONTINUE SKIP TO Q.6z On what date did (CHILD) die? i i i i 11 r f i 1-1 i 1-1 i i 14) (155 (16) (17) (18) (19) MONTH DAY YEAR MONTH DAY YEAR 1 1 1 I I I 1 1 I I I 1 11 1 1 l-l 1 1-1 1 1 1 l-l 1 l-l 1 (14) (15) Tl6) (17) (18) (19) ( ) (15) (16) (17) (18) (19 H x. 5x. What was the cause of death? y. Where is (CHILD) 's death registered? In what city and state is that? RECORD IN S.R.B. PG 1 I (CO TO Q.4z) What was the cause of death? 5y. Where is (CHILD) 's death registered? In what city and state is that? RECORD IN S.R.B. PC 1 1 (GO TO Q.5z) 6x. What was the cause of death? "' 6y. Where is (CHILD) 's death registered? In what city and state is that? IRECORD IN S.R.B. PG 1 1 (GO TO Q.6z) �CARD 004 FIRST CHILD 4z. 812039 SECOND CHILD Did you smoke on a fairly regular basis during this pregnancy? 5z. THIRD CHILD Did you smoke on a fairly regular basis during this pregnancy? 6z. Did you smoke on a fairly regular basis during this pregnancy? Yes.(20( -1 (ASK Q.4aa) Yes.(20(_ -1 (ASK Q.5aa) Yes.(20( -1 (ASK Q.6aa) No -2 (SKIP TO NEXT CHILD) No No -2 (SKIP TO NEXT CHILD) 4aa. When you were smoking cigarettes on a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack we mean 20 cigarettes. I I I -2 (SKIP TO NEXT CHILD) 5aa. When you were smoking cigarettes on a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack we mean 20 cigarettes. T I I Packs Less than one pack.(23( 4bb. Less than one paek.(23( Did you drink alco5bb. holic beverages (beer, wine, or hard liquor) on a regular basis during this pregnancy? Yes..(24( No 4cc. (21) -1 -1 -2 (ASK Q.4cc) (GO TO NEXT CHILD) About how many drinks a week would you say that you had during this pregnancy? (25) I (26) -1 -1 -2 (ASK Q.Scc) (GO TO NEXT CHILD) About how many drinks a week would you say that you had during this pregnancy? T I drinks I Packs (21) (22) Less than one pack.(23( Did you drink alco6bb. holic beverages (beer, wine, or hard liquor) on a regular basis during this pregnancy? Yes..(2A( No 5cc. T T T I Packs (22) I (21) (22) baa. When you were smoking cigarettes on a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack we mean 20 cigarettes. Did you drink alcoholic beverages (beer, wine, or hard liquor) on a regular basis during this pregnancy? Yes..(24( No 6cc. T I drinks (25) (26) -1 -2 (ASK Q.6cc) (GO TO NEXT CHILD) About how many drinks a week would you say that you had during this pregnancy? I I drinks (25) (26) 02 03 79-80 (GO TO NEXT CHILD) 79-80 (GO TO NEXT CHILD) (RECORD ADDITIONAL CHILDREN IN S.R.B. PAGE 4) CARD 007 IF ANY CHILDREN: ASK Q . 7 . IF NO CHILDREN: SKIP TO Q.8. 7. Did you and (STUDY RESPONDENT; have the number of children you planned on? No. 8. ..... (12( (SKIP TO Q.9) Did you and (STUDY RESPONDENT) plan to have children? Yes No -1 (13( -1 "-2 104 �CARD 007 812039 9a. Did you and (STUDY RESPONDENT) ever try for a period of a year or more to conceive a child without heing able to? -1 -2 No 9b. (ASK Q.9b) (SKIP TO Q.ll) For how many periods of one year or more did this happen? \ I T I I I periods (15) (16) Not sure FIRST PERIOD lOa. i ! 1 In what month and year did the f i r s t period begin? And in what month and .year d i d it end? FROM MONTH YEAR 1 1 1 1 I I I l l I l l (18) (19) (20) (21) TO MONTH YEAR I I I 1 I I I 1 (22) (23) (24) (25) IjOb. • ' How old were you in (BEGINNING DATE OF PERIOD)? -1 ..(17( SECOND PERIOD lOd. 1 i THIRD PERIOD In what month flnd year did the second period begin? And in what month and year did it end? FROM MONTH YEAR 1 (18) 1 T ' 1 In what month and year d i d the t h i r d period begin? And in what month and year did it end? FROM MONTH YEAR 1 1 I I I 1 I l l I l l (18) (i'9) (20) (21) TO MONTH YEAR I I I I I I i 1 l-l 1 1 (22) (23) (24) (25) M i . i - i i i (19) lOg. (20) (21) i TO MONTH YEAR I I I I 1 1 I l l I l l (22) (23) (24) ( 2 5 ) lOe. How old were you in (BEGINNING DATE OF PERIOD)? lOh. How old were you in (BEGINNING DATE OF PERIOD)? • 1 1 LOc. fes (o 1 1 ! 1 AGE (26) ( 2 7 ) During t h i s period did either of you see a doctor to discuss any d i f f i c u l t i e s in conceiving children? (2R( -1 -2 1 1 lOf. , Yes I I 1 1 (26) ( 2 7 ) 1 1 AGE During t h i s period d i d e i t h e r of you see a doctor to discuss any d i f f i c u l t i e s in conceiving c h i l d r e n ? (28( -1 No Yes AGE During t h i s period did either of you see a doctor to discuss any d i f f i c u l t i e s in conceiving c h i l d r e n ? ..(28( -1 -2 02 79-80 (GO TO NEXT PERIOD) lOi. I I 1 1 (26) ( 2 7 ) 03 79-80 (GO TO NEXT PERIOD) (RECORD ADDITIONAL PERIODS IN S . R . B . PAGE 19) 11. Did you ever have difficulties in conceiving a child with any other husband or partner? Yes. No.. .(29( No other husband/ partner . 01 79-80 1.65 -1 | �.CARD 012 812039 I ASK EVERYONE I I HAND RESPONDENT CARD "D-T 12a. There are many reasons that some couples find it difficult or impossible to conceive a child. Please read this card and tell me the letter for each reason which ever applied to (STUDY RESPONDENT). Any other reason? I ASK Q.12b AND Q.12c FOR EACH REASON IN Q.I2a.I 12b. Did reason (LETTER) apply to you or your spouse? 12c. [MULTIPLE RECORD BELOW I In what year did this occur or become known to you? Q.12b Q.12a q.!2c Year A. Spouse respondent. . 18( ( 1 1 -1 1 1 1 1 (39) Study respondent. . ( 19( (31) 1 -1 ! 1 1 1 1 (3.2) Spouse respondent . . ( 0 2( B. -1 1 1 1 1 Sterility due to injury, accident, or illness (SPECIFY) .(13( (33) 1 1 (34) -1 Study respondent. .(21 ( -1 (35) ! I 1 ! (36) I 1 (37) C. Spouse respondent . . ( 2 2( Sterility due to unknown -1 1 1 1 1 (38) Study respondent.. (23( -1 Spouse respondent .. ( 4 2( -1 1 1 (39) 1 1 1 1 1 1 •(40) (4H D. Lack of interest in sex (15( -1 1 1 1 1 (42) Study ' respondent. . (25( (431 1 1 -1 1 1 1 1 (44) 1 1 (451 E. Spouse respondent. . (26( Other known medical or physical conditions (SPECIFY) I 1 -1 (46) .(16( -1 Study respondent. .(27( (47) 1 1 -1 1 1 I 1 1 1 (48) ! 1 (49) F. Spouse respondent .. (28( Some other reason (SPECIFY) .(17< -1 1" I 1 1 1 1 (50) (51) Spouse respondent . (29( . -1 1 -1 1 (52) 1 (53) �CARD 013 812039 13. Now I'd like to know about any othrr pregnancies you had that did not end in live births — that is, any pregnancies that ended in miscarriage, stillbirth, or abortion. Did you ever have a pregnancy that ended in miscarriage, stillbirth, or abortion? Yes. (ASK Q.H) No Not sure. .. -A • •' -31 (SKIP TO Q.lSa) 14. How many such pregnancies did you have? T Number (13) (14) PREGNANCY 2 PREGNANCY 1 ISa. In what month and year did the first such pregnancy end? MONTH PREGNANCY 3 16a. In what month and year did the next such pregnancy end? 17a, In what month and year did the next such pregnancy end? YEAR MONTH YEAR MONTH T (17) (18) (15) (16) (17) (18) (15) (16) tr Tr YEAR I Tl5) (16) I (17) (18) I 17b. Did this pregnancy end 16b. Did this pregnancy end 15b. Did this pregnancy end in a miscarriage, stillin a miscarriage, still' in a miscarriage, still' birth, or abortion? birth, or abortion? birth, or abortion? Miscarriage..(19( Stillbirth Abortion -1 -2 -3 15c. After how many weeks did the pregnancy end? Weeks (20) (21) Miscarriage..(19( Stillbirth Abortion 16c. I -1 -2 -3 Miscarriage..(19( Stillbirth.. Abortion After how many weeks did the pregnancy end? I (WRITE IN AGE) I I (WRITE IN AGE) I 17d. How old were you at that time? Was (STUDY RESPONDENT) 16e. your partner in this pregnancy? Were either of you using birth control at the time you became pregnant? I I (WRITE IN AGE) (22) (23) Yes.(24( -1 No. -2 15f. | Weeks (20) (21) 16d. How old were you at that time? 15e. (22) (23) Was (STUDY RESPONDENT) 17e. your partner in this pregnancy? Were either of you using birth control at the time you became pregnant? Was (STUDY RESPONDENT) your partner in this pregnancy? Yes.(24( -1 -2 No. Yes.(24( -1 No -2 16f. After how many weeks did the pregnancy end? I I I Weeks (20) (21) 15d. How old were you at that time? I I I I (22) (23) 17c. -1 -2 -3 17f. Were either of you using birth control at the time you became pregnant? Ves.(2_5 (___-! (ASK Q.15g) Yes.(_25( -1 (ASK Q.16g) Yes.(25( -1 (ASK Q.17g) No _-2 (SKIP TO Q.15h) No _-2 (SKIP TO Q.16h) No _-2 (SKIP TO Q.17h) (GO TO Q.15 g/h) (GO TO Q.16g/h) 11)7 (GO TO Q.17g/h) �CARD 013 PREGNANCY 3 PREGNANCY 2 PREGNANCY 1 812039 lHANI) RESPONDENT CARD "C" 1 (HAND RESPONDENT CARD "C" I 1 HAND RESPONDENT CARD "C" 1 15g. Please look at this card 16g. Please look at this card 17g. Please look at this card and tell me all the numand tell me all the numand tell me all the numbers that apply to the bers that apply to the bers that apply to the types of birth control types of birth control types of birth control you or your partner were you or your partner were you or your partner were using. using. using. Ol.(26( 02.(27( 03.(28( O4.(21( O5.(30( -1 -1 -1 -1 -1 06. (311 07.(32( 08.(33( ('. 34( )(( Ht.(35( ll.(3'f>( -1 -1 -1 -1 -1 -1 12 (SPECIFY) 1 I (38) O6.(31( 07.(32( 08.(33( 09.(34( 10.(35( ll.(36( -1 -1 -1 -1 -1 -1 ! 1 1 Months 1 -1 -1 -1 -1 -1 -1 O6.(31( 07.(32( 08.(33( 09.(34( 1<).'.35( ll.(36( -1 -1 -1 -1 -1 -1 .(37( -1 How many months did it take you to become pregnant this time? | (38) (39) Less than 1 month. U ( 0 16h. Ol.(26( 02.(27( 03.(28( 04.(29( O5.(30( -1 12 (SPECIFY) .(37( -1 How many months did it take you to become pregnant this time? 1 I -1 -1 -1 -1 -1 12 (SPECIFY) .(37( 15h. Ol.(26( 02.(27( 03.(28( ()4.(29< O5.(30( 1 How many months did it take you to become pregnant this time? I . I I 1 1 1 Months (38) (39) | | Months (39) Less than 1 month. ( 0 4( 17h. -1 Less than 1 month. U0( -1 17i. (IF MISCARRIAGE OR 16i. (IF MISCARRIAGE OR 15i. (IF MISCARRIAGE OR STILLBIRTH IN Q.17b, STILLBIRTH IN Q.15b, STILLBIRTH IN Q.16b, ASK Q.17i. IF ABORTION ASK Q.16i. IF ABORTION ASK Q.15i . IF ABORTION IN Q.17b, SKIP TO i). 17m) IN Q.16b, SKIP TO Q.lttm) IN Q.15b, SKIP TO Q.ISm) . Yes. UK No ... Did a doctor tell you why this (miscarriage/ stillbirth) might have occurred? Did a doctor tell you why this (miscarriage/ stillbirth) might have occurred? Did a doctor tell you why this (miscarriage/ s t i l l b i r t h ) might have occurred? Yes. UK -1 (ASK Q.15J) -2 (SKIP TO Q.15n) No.... Yes. UK -1 (ASK Q.16J) -2 (SKIP TO Q.16n) lo 7j . What did the doctor say caused the (miscarriage/stillbirth)? 15j. What did the doctor say 16j. caused the (miscarriage/stillbirth)? What did the doctor say caused the (miscarriage/stillbirth)? 15k. What is the name of the 16k. doctor or me.dical facility that you consulted about this? What is the name of the 7k. doctor or medical facili t v that you consulted about this? I RECORD IN S.R.B. - PG 3 1 15L. I RECORD IN S.R.B. - PG 3 1 In what month and year was that? .6L. In what month and year was that? (RECORD IN S.R.B. - PG 3 1 [RECORD IN S.K.B. - PG 3 1 (SKIP TO Q.5n) (SKIP TO Q.l>n) -1 (ASK Q.17J) -2 (SKIP TO Q.17n) What is the name of ths doctor or medical facil ity that you consulted about this? IRECORD IN S.R.B. - PG 3 1 7L. In what month and year was that? IRECORD IN S.R.B. - PG 3 1 (SKIP TO Q.7n) (GO TO NEXT PAGE) 168 �812039 CARD 013 PREGNANCY 1 PREGNANCY 3 PREGNANCY 2 15m. What was the main reason for the abortion? 16m. What was the main reason for the abortion? 17m. 15n. Did you smoke cigarettes on a fairly regular basis during this pregnancy? 16n. Did you smoke cigarettes on a fairly regular basis during this pregnancy? 17n. Did you smoke cigarettes on a fairly regular basis during this pregnancy? Yes.(42( -1 (ASK Q.lSo) Yes.(42( -1 (ASK Q,16o) Yes,(42( "1 (ASK Q.17o) No. -2 (SKIP TO Q.ISp) No. -2 (SKIP TO Q.l6p) No. "•2 (SKIP TO Q.l7p) 15o, When you were smoking cigarettes on a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? Dy pack we mean 20 cigarettes. 16o, When you were smoking cigarettes on a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack we menn 20 cigarettes. Packs (43) ( 4 4) Less than one pack.(45( 15p. 15q. -1 Less than one pack.(45( -1 16p. Did you drink alcoholic beverages (beer, wine, or hard liquor) on a regular basis during this pregnancy? Yes..(A6(-1 No -2 (ASK Q.15q) (GO TO NEXT PREGNANCY) About how many drinks a week would you say that you had during this pregnancy? I I I drinks (47) (48) 17o. When you were smoking cigarettes on a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack we mean 20 cigarettes. ! I I | I I Packs (43) ( 4 4) T T | I Packs (43) ( 4 4) T Less than one pack.(45( -1 17p. Did you drink alcoDid you drink alcoholic beverages (beer, holic beverages (beer, wine, or hard liquor) wine, or hard liquor) on a regular basis duron a regular basis during this pregnancy? ing this pregnancy? Yes..(A6( _-l -2 No 16q. What was the main reason for the abortion? (ASK Q.16q) (GO TO NEXT PREGNANCY) About how many drinks a week would you say that you had during this pregnancy? T \ I I | drinks (47) (48) Yes..(46( -1 No......._-2 17q. (ASK Q.17q) (GO TO NEXT PREGNANCY) About how many drinks a week would you say that you had during this pregnancy? T T I drinks 747) (48) 01 79-80 (GO TO NEXT PREGNANCY) (GO TO NEXT PREGNANCY) 109 (RECORD ADDITIONAL PREGNANCIES IN S.R.B. PAGE 20) �CARD 812039 18a. We would like your consent for the doctors and medical facilities you mentioned during this interview to provide medical records to the Air Force Health Survey. These records will help us obtain more detailed information about the health services you talked about. TURN TO S.R.B. PG 3. ENTER NAMES OF MEDICAL PROVIDERS ON APPROPRIATE PERMISSION FORMS AND ASK RESPONDENT TO SIGN EACH FORM. IFOR EACH SIGNED'FORM, ASKTT 18b. What is the current address of (DOCTOR/FACILITY)? Thank you for participating in the Air Force Health Study! TIME INTERVIEW ENDED: (am/pro) 170 �FOR OFFICE USE ONLY: LOUIS HARRIS AND ASSOCIATES, INC. 630 Fifth Avenue New York, New York 10111 Case No. Study No. H12039 O.M.B. NUMBER 0701-0033 Approval Expires 11/30/82 Respondent t: CONFIDENTIAL AIR FORCE HEALTH SURVEY SUPPLEMENTAL RECORDING BOOK SPOUSE QUESTIONNAIRE 171 �CARD Q.4a-6a and 19-21 CHILDREN CHILD Q.29 FIRST First NAME 1 1 1 1 DAY 1 1 M I-l 1 1 MONTH 1 I I 1 I-l DAY 1 1 YEAR I I ! I-l 1 ) 1 • . 1 1 MONTH 1 II 1 I-l DAY I 1 YEAR I I I I-l 1 ! 1 I 1 MONTH 1 I I 1 I-l DAY 1 1 1 1 I-l YEAR I 1 1 1 First Last SIXTH MONTH 1 1 1 1 I-l First Last FIFTH MONTH DAY 1 1 1 1 ! ! 1 1 First Last FOURTH First Last g. MONTH 1 II 1 I-l First Last THIRD BIRTHDATE 1 1 Last SECOND <J. DAY 1 1 BIRTH RECORDS i. FATHER '« FULL NAME y. DEATH RECORDS First Place C/S Last C/S Place Place First Place ffc C/S Last C/S Place First Place C/S Last C/S Place First Place C/S Last C/S Place First .Place C/S Last C/S Place First Place C/S Last C/S YEAR Place i l ! 1 C/S . 1 1 YEAR 1 I CURRENT MEDICAL RECORDS Place M I-l | | h. 1 1 YEAR Place i l I 1 C/S Place' C/S Place C/S Place C/S �CARD Q.4a-6a and 22-24 CHILDREN CHILD Q.29 NAME d. SEVENTH First BIRTHDATE g. BIRTH RECORDS h. CURRENT MEDICAL RECORDS i . FATHER ' S FULL MAffi y. DEATH RECORDS EIGHTH C/S Last C/S MONTH 1 I 1 DAY 1 YEAR i Place Place First Place 1 1 1 1 l-l C/S Last C/S DAY 1 Place First Place 1 1 ! c/s C/S Last C/S Place First Place C/S Last C/S Place First Place C/S Last C/S Place First Place C/S Last C/S 1 1 1 First l-l MONTH 1 1 1 ! l-i 1 l-l I YEAR 1 1 I c/s Place 1 1 1 MONTH DAY i 1 1 1 1 1 - 1 1 I I l-l YEAR 1 1 Place 1 1 C/S 1 1 MONTH 1 1 1 1 l-l DAY 1 ! 1 1 l-l YEAR 1 i 1 1 1 Last ELEVENTH Place First Last TENTH Place 1 1 C/S First Last NINTH YEAR 1 1 First I I 1-1 1 Last MONTH DAY 1 I I 1 1 1 - 1 1 Place ! 1 MONTH 1 1 1 DAY 1 1 1 YEAR 1 1 First Last TWELFTH First Last 1 1 1 - 1 1 l-t 1 Place C/S Place 1 c/s �CAKU Ol/i Q.l."ik-17k. Medical Providers — Miscarriages/Stillbirth Pregnancy 1 lf>k. 812039 Pregnancy 2 Doctor/facility consul ted:- 16k. Pregnancy 3 17k. Doctor/faci1ity consul tod: Doctor/facility consul ted: Name Name Name Address Address Address C/S C/S C/S 15L. 17L. 161.. MONTH YEAR 1 M "1 1 I l l I l l ( 12) ( i:i) ( 14) ( 15) ( I MONTI YEAR 1 1 I 11 I ( 16) ( 7). ( 18) ( 19) MONTH 1 I 1 l l CO ) ( 21) YEAR M - 1 I l 1 l (22) (23) Q.29k-31k. Medical Providers -- Miscarriages/Stillbirth 29k. Doctor/facility consulted: 30k. Doctor/facility consul ted: 31k. Doctor/facility consulted: Name Name Name Address Address Address C/S C/S C/S i j 31L. 301.. 29L. MONTH "T24TT255 MONTH 1 YEAH r ri i i i i - i l l (26) ( 2 7 ) I YEAR -r— f l l l ( 2 4 ) (25) (26) ( 2 7 ) 174 MONTH l I YEAR l I (24) (25) (26) ( 2 7 ) r i I �Ft] 2039 CART) 00 I Q.19-21 Additional Children FOURTH CHILD FIFTH CHILD SIXTH CHILD NAME : NAME : 19a. How old is (CHILD) now? 20a. How old is (CHILD) now? 1 1 1 1 1 Age (.28) (29) Chi Id died. ,OO( (31 ( 1 1 (2fi) (29) Male Female -1 -2 Don 1 t know. . . (36( 1 1 1 1 Age ' (28) (29) -1 Chi Id died. .(30( I 11( POUNDS 1 1 Male 1 T l-l 1 1 (32) (33) -1 POUNDS OUNCES 1 1 1 1 1 1 l-l 1 1 (32) (33) (34) (35) 1 1 1 1 -1 Don't know. , ( 6 .3( (34) (35) Don't know. . ( 6 .3( -1 (31( 21c. How much did (CHILD) weigh at birth? OUNCES 1 I -1 21b. (Is/Was) (CHILD) male or femnle? -1 -2 20c. How much did (CHILD) weigh at birth? POUNDS OUNCES 1 1 1 1 1 l l I l l (32) (33) (34) (35) 21a. How old is (CHILD) now? Age 20b. (Is/Was) (CHILD) male or t oma 1 c? 19c. How much did (CHILD) weigh at birth? 1 I 1 1 Child died. .(30( -1 191,. (Is/Was) (CHILD) male or female? Male Female NAME : -1 19d. What is (CHILD) 's birth- 20d. What: is (CHILD) 's birth- 21d. What is (CHILD) 's birthdate'? date? date? I 1 MONTH DAY YEAR I I I I I I 1 1 l-l 1 . l-l 1 1 1 1 1 MONTH 1 II 1 l-l DAY 1 1 1 1 l-l YEAR 1 1 1 1 1 1 MONTH 1 1 1 1 l-l DAY 1 1 1 1 l-l YEAR 1 1 1 1 (37) 4) (37) (38) (39) (40) (41) (42) (37) (38) (39) (40) (41) (42) (38) (39) ( 0 (41) (42) lALSO RECORD IN S.R.B.-PG l| (ALSO RECORD IN S.R.B.-PG l l lALSO RECORD IN S.R.B.-PG l| 19e. Was the child premature, 20e. Was the child premature, 2le. Was the child premature, full term, or overdue? full term, or overdue? full term, or overdue? Premature. ( 3 4( Overdue . . -lt(ASK ~2\ Q.19f) Premature. (4 3( Overdue -ll(ASK -2j Q.20f) Premature. ( 3 4( -1\(ASK Full term Not sure -3l(SKIP TO ~4J Q.19g) Full term . . .. -3)(SKIP TO Full term -3*1 (SKIP TO . 19f. How many weeks (overdue/ 20f. How many weeks (overdue/ 21 f. How many weeks (overdue/ premature) was (CHILD)? premature) was (CHILD)? premature) was (CHILD)? 1 I 1 ! 1 1 weeks 1 1 1 1 1 1 weeks (44) (45) (GO TO Q.19g) (CO TO Q.20g) 175 1 1 1 1 1 1 weeks (44) (45) (GO TO Q.21g) �CARD 001 FOURTH CHILD FIFTH CHILD 19g. Where are (CHILD) 's birth registration records located? In what city and state is that? [RECORD IN S.R.B. PG 1 1 19h. Where are (CHILD) 's current medical records located? In what city and state is that? [RECORD IN S.R.B. PG 1 1 19i. What was (CHILD) 's father's full name? (RECORD IN S.R.B. PG i 1 19 j. How old were you when (CHILD) was born? 1 1 (46) 1 1 812039 SIXTH CHILD 20g. Where are (CHILD) 's birth registration records located? In what city and state is that? TRECORD IN S.R.B. PG i 1 21g. Where are (CHILD) 's birth registration records located? In what city and state is that? 1 RECORD IN S.R.B. PG 1 20h. Where are (CHILD) 's current medical records located? In what city and state is that? 1 RECORD IN S.R.B. PG 1 1 21h. Where are (CHILD) 's current medical records located? In what city and state is that? 20i. What was (CHILD) 's father's full name? 21i. What was (CHILD) 's father's full name? (RECORD IN S.R.B. PG i 1 20j . How old were you when (CHILD) was born? 1 ! Age I 1 (46) (47) 1 1 [RECORD IN S.R.B, PG 1 IRECORD IN S.R.B. PG 1 21j. How old were you when (CHILD) was born? 1 1 Age (47) 1 1 (46) 1 1 Age (47) 19k. Were either of you using 20k. Were either of you using 21k. Were either of you using birth control at the birth control at the birth control at the time you became pregnant time you became pregnant time you became pregnant with (CHILD)? with (CHILD)? with (CHILD)? Yes.(48( Yes.(48( -1 (ASK Q.19L) No -2 (SKIP TO Q.19m) No Yes,(48( -1 (ASK Q.20L) -2 (SKIP TO Q.20m) No -1 (ASK Q.21L) -2 (SKIP TO Q.21m) IHAND RESPONDENT CARD "C"| IHAND RESPONDENT CARD "c"i IHAND RESPONDENT CARD "c"l 19L. Please look at this 20L. Please look at this 21L. Please look at this card and tell me all of card and tell me all of card and tell me all of the numbers that apply the numbers that apply the numbers that apply to the types of birth to the types of birth to the types of birth control you or your control you or your control you or your partner were practicpartner were practicpartner were practicing? ing? ing? Ol.(49( O2.(50( O3.(51( 04.C52T 05.(53( -1 -1 -) -1 -1 12 (SPECIFY) 06.(54( -1 07.<55( -1 08.(56( -1 O9.(57ij -1 I0.(?8( -1 ll.(59( -1 ' ' .6( (0 (GO TO Q.19m) Ol.(49( O2.(50( 03. (5U O4.(52l 05.(53( -1 -1 -1 -1 -1 06.(54( 07.(55( 08.(56( 09.(T77 10.(58( ll.(59( -1 -1 -1 -1 -1 -1 2 (SPECIFY) Ol.(49( O2.(50( O3.(51( O4.(52l 05-(53( -1 -1 -1 -1 -1 06.(54( -1 07.(55( ... -1 08.(56( -1 09. (TJI -1 10.(58( -1 ll.(59( -1 12 (SPECIFY) -1 .(60( (GO TO Q.20m) 17o -1 .6( (0 (GO TO Q.21m) -1 �CARD 001 FOURTH CHILD 812039 FIFTH CHILD SIXTH CHILD 19m. How many months did it 20m. How many months did it 21m. How many months did it take you to become pregtake you to become pregtake you to become pregnant with this child? nant with this child? nant with this child? 1 I ! 1 ( I Months 1 1 (615^ ( 2 6) Less than 1 month. ( 3 6( 1 1 1 I Months (1 (2 6) 6) 1 I 1 1 | | Months (1 (2 6) 6) -1 Less than 1 month. ( 3 6( "I Less than 1 month. ( 3 6( Wasn't trying , . . -2 19n. Did (CHILD) have any birth defects? 20n. Did (CHILD) have any birth defects? 21n. Did (CHILD) have any birth defects? Yes.(6A( -1 (ASK Q.19o) Yes.(64( -1 (ASK Q.20o) Yes.(64( -1 (ASK Q.21o) No -2 (SKIP TO Q.19p) No -1 .. -2 (SKIP TO Q.20p) 19o. What kind of birth defects did (s)he have? Any others? 20o. What kind of birth defects did (s)he have? Any others? 21o. What kind of birth defects did (s)he have? Any others? 19p. Was (CHILD) ever diagnosed as having cancer? 20p. Was (CHILD) ever diagnosed as having cancer? 21p. Was (CHILD) ever diagnosed as having cancer? Yes.(65( -l.(ASK Q.19q) Yes.(65(. -1 (ASK Q.20q) Yes.(65( —7 ( <1KT P TO n 1 Qs} No 19q. 1 I -2 (SKIP TO Q.20s) No No In what month and year 20q. iwas the diagnosis made? MONTH YEAR 1 M I I l l I l l ( 6 (67) ( 8 ( 9 6) 6) 6) -1 (SKIP TO Q. 21s) In what month and year 21q. In what month and year was the diagnosis made? was the diagnosis made? MONTH 1 1 -1 (ASK Q.21q) YEAR 1 1 1 1 1 1 H 1 1 ( 6 (67) (68) (69) 6) I 1 MONTH YEAR I I I 1 I 1 l-l 1 1 (66) (673 ( 8 (69) 6) 19r. What kind of cancer was diagnosed? 20r. What kind of cancer was diagnosed? 21r. What kind of cancer was diagnosed? Not sure..(70( Not sure..(70( Not sure..(70( (GO TO Q.As) 04 T^0 9$ -1 -1 (GO TO Q.5s) 05 Jtto 177 (GO TO Q.6s) 06 79^80 -1 �CARD 004 FOURTH CHILD 812039 FIFTH CHILD SIXTH CHILD 19s. (Does/Did)(CHILD) have a diagnosed Iparning disabil ity? 2()s. (Does/Did) (CHILD) have a diagnosed learning disabi 1 ity? 21s. (Does/Did)(CHILD) have a diagnosed learning disability? Yes.(12( -1 (ASK Q.19t) Yes.(l2( -1 (ASK Q,?(U) Yes.(12( -1 (ASK Q.21t) No -2 (SKIP TO () 19u) No , -2 (SKIP TO Q,20u) No -2 (SKIP TO Q.21u 19t. What kind of learning disability (does/did) Cjjhe have? 20t. What kind of learning disability (does/did) (s)he have? 2H. What kind of learning disability (does/did) (s)he have? 21u. (Does/Did)(CHILD) have 20u. (Does/Did)(CHILD) have 19u. (Does/Pid)(CHIU» have any physical, mental, any physical, mental, or any physical, mental, or motor impairments? motor impairments? motor impairments? Yes.(13( Ves.(13( -1 (ASK Q.19v) No -2 (SKIP TO Q.19w) No .. . 19v. What kind of impairment (does/did) (s)he have? -1 (ASK Q.20v) Yes.(13( -2 (SKIP TO Q.20w) No 20v. Wliat kind of impairment (does/did) (s)he have? -1 (ASK Q.21v) -2 (SKIP TO Q.21w 21v. What kind of impairmen (does/did) (s)he have? IF CHILD IS DEAD: IF CHILD IS DEAD: IF CHILD IS DEAD: OTHERWISE: OTHERWISE: OTHERWISE: CONTINUE SKIP TO Q. 19z 19w. On what date did (CHILD) die? CONTINUE SKIP TO Q.20z 20w. On what date did (CHILD) die? CONTINUE SKIP TO Q.21z 21w. On what date did (CHILD) die? MONTH DAY YEAR MONTH DAY YEAR MONTH DAY YEAR 1 I I 1 I I 1 1 1 1 1 I I 1 1 1 I I 1 II 1 1 1 1 l-l 1 l-l 1 1 i-l 1 l-l 1 1 1 1 l-l 1 l-l 1 1 14) (15) (16) (17) (18) (19) (14) (15) (16) (17) (18) (19) (14) (15) (16) (17) (18) (19 9x. What was the cause of death? 20x. What was the cause of death? 21x. Wliat was the cause of death? 9y. Where is (CHILD) 's death registered? In what city and state is that? RECORD IN S.R.B. PG 1 I 20y. Where is (CHILD) 's death registered? In what city and state is that? RECORD IN S.R.B. PG 1 I 21y. Where is (CHILD) 's death registered? In what city and state is that? RECORD IN S.R.B. PG 1 J (GO TO Q.19z) (GO TO Q.20z) 178 (GO TO Q.21z) �CARD 004 FOUKTH CHILD 812039 FIFTH CHILD SIXTH CHILD 19z. Did you smoke on a fairly regular basis during this prpgnancy? 20?,. Did you smoke on a fairly regular basis during this pregnancy? 21z. Did you smoke on a fairly regular basis during this pregnancy? Yes.(20( _ -1 (ASK Q.19aa) Yes.(20( -1 (ASK Q.20aa) Yes.(20( -1 (ASK Q.21aa) No...... No -2 (SKIP TO Q.20bb) No -2 (SKIP TO Q.21bb) "2 (SKIP TO "*" Q.l'Jbb) 19aa.Wh.en you were smoking cigarettes on a fairly regular basis during this pregnancy, on Che average, how many packs per week did you smoke? By pack we mean 20 cigarettes. I I I I Packs (21) (22) Less than one pack.(23( -1 20aa.When you were smoking cigarettes on a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack we mean 20 cigarettes. 21aa.When you were smoking cigarettes on a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack we mean 20 cigarettes. I I I ' I Packs \ I (21) (22) Less than one pack.(2_3( I I I I (21) -I Packs (22) Less than one paek.(23( -1 20bb. Did you drink alco21bb. Did you drink alco19bb. Did you drink a.lcoholic beveragfes (beer, holic beverages (beer, holic beverages (beer, wipe, or hard liquor) wine, or hard liquor) wine, or hard liquor) on a regular basis duron a regular basis duron a regular basis during this pregnancy? ing this pregnancy? ing this pregnancy? Yes..(24(T -1 No -2 ~~ (ASK Q.19cc) (GO TO NEXT CHILD) 19cc. About how many drinks a week would you say that you had during this pregnancy? I I Yes..(24( -1 No __-2 (ASK Q.20cc) (GO TO NEXT CHILD) 20cc. About how many drinks a week would you say that you had during this pregnancy? T I drinks . . .1 (2$) (26) I I drinks (25) (26) Yes..(24( -1 N . . . . "-2 o... (ASK Q.21cc) (GO TO NEXT CHILD) 21cc. About how many drinks a week would you say that you had during this pregnancy? I drinks I (25) (26) 05 79-80 (GO TO NEXT CHILD) (GO TO NEXT CHILD) (GO TO NEXT CHILD) �812039 CARD 001 Q. 22-24 Additional Children 1 EIGHTH CHILD SEVENTH CHILD NINTH CHILD NAME: NAMF. : NAMF: 22a. How old is (CHILD) now? 23a. How old is (CHILD) now? 1 1 1 1 I 1 (28) 1 1 Age (28) (29) C h i l d died..(30( (31( 1 I (31( -1 24b. (Is/Was) (CHILD) male or female? -1 -2 Male Female (31( -1 -2 24c. How much did (CHILD) weigh at birth? POUNDS OUNCES 1' 1 1 1 1 l l I l l (32) (33) (34) (35) Don't know. . ( 6 .3( -1 1 1 Age Child died..(30( -1 23c. How much did (CHILD) weigh at birth? POUNDS OUNCES 1 1 1 i 1 l l I l l (32) (33) (34) (35) 1 1 (28) (29) (29) Male Female -1 -2 Don' t know. . . 3 ( (6 1 1 Age 23b. (Is/Was) (CHILD) male or female? 22c. How much did (CHILD) weigh at birth? I I 1 1 Child died..(30( -1 22h. (Is/Was) (CHILD) male or female? Male. Fema le 1 1 24a. How old is (CHILD) now? 1 1 POUNDS 1 1 1 1 l-l (32) (33) OUNCES 1 1 1 1 (34) (35) Don' t know. ..(36( -1 22d. What is (CHILD) 's birth- 23d. What is (CHILD) 's birth- 24d. date? date? -1 What is (CHILD) 's birthdate? MONTH DAY YEAR 1 1 1 1 1 1 1 1 1 1 1 l-l 1 l-l 1 1 (37) (38) (39!) (405 (41) (42) (37) (38) (39) (40) (41) (42) (37) (38) (39) (40) (41) (42) I 1 MONTH 1 I I 1 l-l DAY YEAR I I I 1 1 l-l 1 1 1 1 1 MONTH 1 II 1 l-l DAY 1 1 I I l-l YEAR I 1 IALSO RECORD IN S.R.B.-PG 2| lALSO RECORD IN S.R.B.-PG 2| 1 1 lALSO RECORD IN S.R.B.-PG 2| 22e. Was the child premature, 23e. Was the child premature, 24e . Was the child premature, full term, or overdue? full term, or overdue? full term, or overdue? Premature. (43( Overdue Full term Not sure . • . Premature. (4 3( Overdue -3((SKIP TO -4 [ Q.22g) ——~~ J -l)(ASK Premature. (43( -2] Q.23f) Overdue -1\(ASK -2) Q.24f) Full term -ll(ASK -2| Q.22O -3l(';KlP TO Full term .... -3*1 (SKIP TO . 22f. How many weeks (overdue/ 23f. How many weeks (overdue/ 24f. How many weeks (overdue/ premature) was (CHILD)? premature) was (CHILD)? premature) was (CHILD)? I I 1 1 1 1 weeks (44) (45) 1 I 1 I 1 I weeks (GO TO Q.22g) (GO TO Q.23g) " 4 (45) ,) i 180 I I l I l 1 weeks (44) (45) (GO TO Q.24g) �CARP 001 EIGHTH CHILD SEVKNTH CHILD NINTH CHILD 22s. When' arc (CHILD) 's birth registration records located? In what city and state is that? 1 RECORD IN S.R.B. PG 2 1 23g. Wherp are (CHILD 's hirth registration records located? In what city and state is that? 22h. Where are (CHILD) 's current medical records located? In what city and state is that? I RECORD IN S.R.B. PC 2 \ 23h. Where are (CHILD) 's current medical records located? In what city and state is that? 22i. What was (CHILD) 's father's f u l l nnmr? IHKCORD IN S.K.It. l'<; :> F 23i. What was (CHILD) 's father" s fill 1 mum;? 22j, How old were you when (CHILD) was born? 23 j. How old were you when (CHILD) was born? T . 1 I IRECORD IN S.R.B. PC 2 i IKHCOKH IN S.R.B. ]>c. <\ I I Ag<- (46) 24j;. Where are (CHILD) 's birth registration records located? In what city an'd state is that? IRECORD IN S.R.B. PG 2 I 1 1 812039 1 1 (47) 1 1 (46) IRECORD IN S.R.B. PG 2 24h. Where are (CHILD) 's current medical records located? In what city and state is that? IRECORD IN S.R.B. PG 2 24i. What was (CHILD) 's father's f u l l name? IKKCORD IN S.R.B. PC :'. 1 24 j. How old were you when (CHILD) was born? 1 T 1 1 1 1 Age 1 .1 (47) (46) (47) 22k. Were either of you using 23k. Were either of you using birth control at the birth control at the time you became pregnant ' time you became pregnant with (CHILD)? with (CHILD)? Age 24k. Were either of you using birth control at the time you became pregnant with (CHILD)? Yes.(48( -1 (ASK Q.22L) Yes.(48( -1 (ASK Q.23L) Yes.(48( -1 (ASK Q.24L) No -2 (SKIP TO Q.22m) No -2 (SKIP TO Q.23m) No -2 (SKIP TO Q 24m) IHANU RESPONDENT CARD "C" 1 22L. Please look at this card and tell me a l l of the numbers that apply to the types of birth control you or your partner were practicing? Ol.(4i9( O2.(50( O3.(5,l( 04. ( 2 ?l 05.(53( -1 -1 -1 -1 -1 06.(54( 07.(55( 08.(S6( 09. ( 7 17 10.(58( ll.<59( -1 -1 -1 -1 -1 -1 IHAND RESPONDENT CARD "c"l 3L. l.(49( 2.(50( 3.(51( 4(2 .5l 5.(53( -1 -1 -1 -1 -1 06.(54( 07.(55( 08.(56( 09. (Til 10.(58( ll.(59( -1 -1 -1 -1 -1 -1 2 (SPECIFY) 12 (SPECIFY) .6( (0 (CO TO Q.22m) IHAND RESPONDENT CARD "c"l Pluase look at this 24L. card and tell me all of the numbers that apply to the types of birth control you or your partner were practicing? Please look at this card and tell me all of the numbers that apply to the types of birth control you or your partner were practicing? Ol.(49( O2.(50( O3.(5l( 04. ( 7 5? 05.(53( -1 -1 -1 -1 -1 06.(54( 07. ( F I? 08.(56( 09. (TR 10.(58( ll.(59( -1 -1 -1 -I -1 -1 .6( (0 -1 12 (SPECIFY) .6( (0 -1 (GO TO Q.23m) ibl -1 (GO TO Q.24m) �CARD 001 SEVENTH CHILD 1 1 24m. How many months did it 23m. How many months did it take you to become pregtake you to become pregnnnt with this child? nant with this child? 1 1 Months 1 1 (61) (62) 1 I (61) Less than 1 month. (63( NINTH CHILD EIGHTH CHILD 22m. How many monLtis did it take you to become preg riant with this child? 1 1 812039 -1 1 1 Months 1 1 1 I (61) (62) Less than 1 month. (63( -1 1 1 Months (62) Less than 1 month. (63( 22n, Did (CHILD) have any birth defects? 23n. Did (CHILD) have any birth defects? 24n. Did (CHILD) have any birth defects? Yes.(64( -1 (ASK Q.22o) Yes.(64( -1 (ASK Q.23o) Yes.(64( No -2 (SKIP TO Q.22p) No .... -2 (SKIP TO Q 23p) No -1 -1 (ASK Q.24o) -2 (SKIP TO Q.24p) 22o. What kind of birth defects did (s)he have? Any others? 23o. What kind of birth defects did (s)he have? Any others? 24o. What kind of birth defects did (s)he have? Any others? 22p. Was (CHILD) ever diagnosed as having cancer? 23p. Was (CHILD) ever diag. nosed as having cancer? 24p. Was (CHILD) ever diagnosed as having cancer? Yes.(65( -1 (ASK Q.22q) • Yes.(65( Yes.(65( No -2 (SKIP TO Q.22s) No 22q. 1 I -2 (SKIP TO Q 23s) No. In what month and year 23q. was the diagnosis made? MONTH YEAR 1 I I 1 1 l l I l l (66) (67) (68) (691) -1 (ASK Q.23q) 1 1 . -2 (SKIP TO Q.24s) In what month and year 24q. was the diagnosis made? MONTH YEAR 1 I I 1 1 1 l-l 1 1 (66) (67) (68) (69) -1 (ASK Q.24q) 1 1 In what month and year was the diagnosis made MONTH YEAR 1 II 1 1 1 l-l 1 1 (66) (67) (68) (69) 22r. What kind of cancer was diagnosed? 23r. What kind of cancer was diagnosed? 24r. What kind of cancer was diagnosed? Not sure..(70( Not sure. . 7 ( (0 Not sure..(70( (GO TO Q.4s) 07 Two -1 (GO TO Q.5s) 08 TFfo 182 -1 (GO TO Q.6s) 09 79-fiO -1 �812039 CARD 004 SEVENTH CHILD NINTH CHILD EIGHTH CHILD 22s. (Does/Did) (CHILD) have a diagnosed learning disability? 23s. (Does/Did)(CHILD) have a diagnosed learning disability? 24s. (Does/Did) (CHILI)) have a diagnosed learning disability? Vee.tlj!(....-l (ASK Q.22t) Yes.(12( -1 (ASK Q.23t) Yes.(12( No No -2 (SKIP TO Q.23u) No -2 (SKIP TO Q 22u) 22t. What kind of learning disability (does/did) (s)he have? 23t. What kind of learning disability (does/did) (s)he have? -1 (ASK Q.24t) -2 (SKIP TO Q.24u 24t. What kind of learning disability (does/did) (»)he have? 22u. (Does/Did) (CHILD) have 23u. (Does/Did)(CHILD) have 24u. (Does/Did)(CHILD) have any physical, mental, or any physical, mental, or any physical, mental, motor impairments? motor impairments? motor impairments? Yes.(13( -1 (ASK Q.22v) IF CHILD IS DEAD: OTHERWISE: CONTINUE SKIP TO Q.22z !2w. On what date did . (CHILD) die? -1 (ASK Q.23v) No 22v. What kind of impairment (does/did) (s)lie have? Yes.(13( -2 (SKIP TO Q.23w) No 23v. What kind of impairment (does/did) (s)he have? IF CHILD IS DEAD: CONTINUE OTHERWISE: SKIP TO Q.23z 23w. On what date did (CHILD) die? Yes.(13( -1 (ASK Q.24v) -2 (SKIP TO Q.24w 24v. What kind of impairment (does/did) (s)he have? IF CHILD IS DEAD: CONTINUE OTHERWISE: SKIP TO Q.24z 24w. On what date did (CHILD) die? MONTH DAY YEAR MONTH DAY YEAR MONTH DAY YEAR I I I 1 I I 1 1 1 1 1 I 1 1 1 1 1 I I I 1 I I 1 1 l-l 1 1 I - ! 1 1 - 1 1 1 1 1 l-l 1 l-l 1 l-l 1 1 (14) (15) (16) (17) (18) (19 14) (15) (16) (17) (18) (19) (14) (15) (16) (17) (IB) (19) 2x. What was the cause of death? 23x. What was the cause of death? 24x. What was the cause of death? 2y. Where is (CHILD) 's death registered? In what city and state is that? RECORD IN S.R.B. PG 2 | 23y. Where is (CHILD) 's death registered? In what city and state is that? RECORD .IN S.R.B.1 PC T[ 24y. Where is (CHILD) 's death registered? In what city and state is that? (GO TO Q.22z) (GO TO Q.23z) 183 (RECORD IN S.R.B. PC ^ i (GO TO Q.24z) �CARD 004 812039 EIGHTH CHILD SEVENTH CHILD NINTH CHILD 22z. Did you smoke on a fairly regular basis during this pregnancy? 23z. Did you smoke on a fairly regular basis during this pregnancy? 24 z. Did you smoke on a fairly regular basis during this pregnancy? Yes.(20( Yes.(20( Yes.(20( No -1 (ASK Q.22aa) __-2 (SKIP TO No. No _-2 (SKIP TO Q.23aa) Q.22aa) 22qa.When you were smoking cigarettes on a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack we mean 20 cigarettes. -1 (ASK Q.23aa) 23aa.When you were smoking cigarettes on a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack we mean 20 cigarettes. -1 (ASK'Q.24aa) _-2 (SKIP TO Q.24aa) 24aa.Wlien you were smoking cigarettes on a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack we mean 20 cigarettes. I I I Packs I Packs Packs (21) (22) ( 1 T 2 2 T 2 T Less than one pack.(23( -1 Lees than one pack.(23( (21) -1 (22) Less than one pack.(23( -1 24bb. Did you drink alco23bb. Did you drink alco22bb. Did you drink alcoholic beverages (beer, holic beverages (beer, holic beverages (beer, wine, or hard liquor) wine, or hard liquor) wine, or hard liquor) on a regular basis duron a regular basis duron a regular basis during this pregnancy? ing this pregnancy? ing this pregnancy? Yes..(2A( -1 No __-2 (ASK Q.22cc) (GO TO NEXT CHILD) 22cc. About how many drinks a week would you say that you had during this pregnancy? I I I _l (25) (26) Yes..(24( No (ASK Q.23cc) (GO TO NEXT CHILD) 23cc. About how many drinks a week would you say 'that you had during this pregnancy? I drinks -1 -2 I I I I drinks (25) (26) Yes..(24( No -1 -2 (ASK Q.24cc) (GO TO NEXT CHILD) 24cc. About how many drinks a week would you say that you had during this pregnancy? I I I I I I drinks (25) (26) 07 (GO TO NEXT CHILD) (GO TO NEXT CHILD) 184 (GO TO NEXT CHILD) �CARD 001 812039 Q.25-27 Additional Children TENTH .CHILD ELEVENTH CHILD TWELFTH CHILD NAME: NAME : 25«. How old is (CHILD) now? 26a. How old is (CHILD) now? 1 I * I 1 Age ''I t (28) 1 1 1 I ARE (28) -1 1 1 Aae (28) (29) (29) Child died..(30( 26b. (Is/Was) (CHILb) male or female? 27b. (Is/Was) (CHILD) male or female? Male -1 ..(31( -1 26c. How much did (CHILD) weigh at birth? 25c. How much did (CHILD) weigh at birth? POUNDS OUNCES 1 1 ( 1 1 1 l-l 1 1 (32) (33) (34) (35) Don't know. . .(36( 1 1 Child died..(30( -1 25b. (Is/Was) (CHILD) male or female? Male, . . . K ..O 27a. Hov old is (CHILD) now? 1 1 (29) Child djed..(30( 1 1 NAME: POUNDS 1 1 -1 Male OK Female. . . . . ... " I 1 ' 1 1 l-l 1 1 (32) (33) (34l (35) Don't know. . ( 6 .3( -1 -1 -2 27c. How much did (CHILD) weigh at birth? OUNCES I 1 -1 1 1 POUNDS OUNCES 1 1 1 1 1 1 hi 1 1 (32) (33) (34)^(35) Don't know.. . 3 ( (6 -1 25d. What is (CHILD) 's birth- 26d. What is (CHILD) 's birth- 27d. What is (CHILD) 's birthdate? date? ~ date? MONTH DAY YEAR MONTH DAY , YEAR MONTH DAV YEAR I II 1 I I 1 1 1 I I 1 I I I I I 1 1 II 1 I I 1 1 1 1 l-l 1 l-l 1 .1 1 l-l 1 .H 1 1 1 1 1 l-l 1 l-l 1 1 1 4) (37) (38) (39) (40) (41) <42) (37) (38) (39) ( 0 (41) (42) 137) (38) (39) (40) T41) (42) [ALSO RECORD IN S.R.B.-PG2 1 ALSO RECORD IN S.fe.B,-PG2 1 [ALSO RECORD IN S.R.B.-PG2 1 25e. Was the child premature, 26e. Was the child premature, 27e. Was the child premature, full term, or overdue? full term, dr overdue? full term, or overdue? Premature. (43( Overdue .. Full term Not sure i Premature. (43( -ll(ASK -2j Q.25f) Overdue -ll(ASK Premature. (43( -2j Q.26f) Overdue -3")(SKIP TO Full term ,. -3l(SKIP TO Full term .. -4i 0 25g) *—"*~~ J -l"\(ASK -2j Q.27O -3! (SKIP TO 25f . How many weeks (overdue/ 26f. How many weeks (overdue/ 27f. How many weeks (overdue/ premature) was (CHILD)? ' premature) was (CHILD)? premature) was (CHILD)? I 1 I 1 | I weeks (44) (45) (GO TO Q.25g) 1 1 1 1 (44) 1 1 weeks (45) (GO TO Q.26g) 185 I 1 l 1 (44) l 1 weeks (45) (GO TO Q.27g) �CARD 001 TENTH CHILD 812039 ELEVENTH CHILD TWELFTH CHILD 25g. Where are (CHILD)'s birth registration records located? In what c i t y nnd state is that? 26g. Where are (CHILD)'s hirth registration records located? In what c i t y nnd stnte is that? IRECORD IN S.R.B. PC TT 27g. Where are (CHILD)'s h i r t h registration records located? In what city and state in that? IRECORD IN S.R.B. 1^2~T IRECORD IN S.R.B. PG_Ji'l 25h. Where are (CHILD)'s current medical records located? In what city and state is that? IRECORD IN S.R.B. vc 2 \ 26h. Where are (CHILD)'s current medical records located? In what city and state is that? IRECORD IN S.R.B. PC 2 I 27h. Where are (CHILD)'s current medical records located? In what city and state is that? IRECORD IN S.R.B. PC 2 I 25i. What was (CHILD)'s father's full name? JRECORD IN S.R.B. PC 2 I 26i. What was ( C H I L D ) ' s f a t h e r ' s f u l l name? 27i. What was (CHILD)'s father's full name? 25j. 26j. How old were you 27j. How old were you when (CHILD) was born? i1 i1 1 IRECORD IN S.R.B. PC 2 I when (CHILD) was born? Were either of you using 26k. birth control at the time you became pregnant with (CHILD)? Were either of you using 27k. birth control at the time you became pregnant with (CHILD)? Yes.(48( -2 (SKIP TO Q.25m) Nb I HAND RESPONDENT CARD' "C" I 25L. 1 I (46) (47) (46) (47) Yes.(A8(._._-! (ASK Q.25L) No -I (ASK Q.26L) -2 (SKIP TO Q.26m) No IHAND RESPONDENT CARD "CVM Q6.(54( Q7.(5S( Q8.(56( Q9.(57( 1Q.(58( ll.(59( 12 (SPECIFY) -1 -1 -1 -1 -1 -1 Ol.(49( 02.(M>< 03 ( - JLI 0.5 4(^ 05.(52( _ 06.(54( O7.(5_l( 08. (5j> 09. (V7 10.(58 ll.(59( (GO TO Q.25m) -1 (ASK Q.27L) -2 (SKIP TO Q.27m) IHAND RESPONDENT CARD "c1 I Please look at this card and tell me all of the numbers that apply to the types of birth control you or your partner were practicing? Ol.(49( O2.(50( O3.(5l( Q4.(52( Q5.(53( -1 '-1 -1 -1 -I -1 06.(54( 0.| 7(_ 0.^ 8(6 09. (JiT. 1Q.(58( ll.(59( 12 (SPECIFY) 12 (SPECIFY) .6( (0 Age Were either of you using birth control at the time you became pregnant with (CHILD)? Yes.(48( 27L. 26L. Please look at Chis Please look at this card and tell me all of card and tell me all of the numbers that apply the numbers that apply to the types of birth to the types of birth control you or your control you or your partner were practicpartner were practicing? ing? Q2.(50T -1 O3.(51( -1 Q4.(52( ~-l Q5.(53( -1 How old were you when (CHILD) was born? Age 1 Age (46) (47) 25k. IRECORD IN S.R.B. PC.2 I .6( (0 (GO TO Q.26tn) .(60( (GO TO Q.27m) �CARD 001 TENTH CHILD 25m. ELEVENTH CHILD How many months did it take you to become preg nant with this c h i l d ? f j 1 I TWELFTH CHILD 26m. How many months did it 27m. How many months did it take you to become pregtake you to become pregnant with this child? nant with this child? 1 I Months 1 1 U t J (62) 1 1 T I Months 1 I (61) (621 Less than 1 month. (63( 25n. 812035 -1 Did (CHILD) have any birth defects? 1 I 1 | Months (61) (62) Less than 1 month. (63( -1 Less than 1 month. (63( 26n. Did (CHILD) have any b i r t h defects? 27n. Did (CHILD) have any birth defects? Yes.(64( -1 Yes.(64( -1 (ASK Q.25o) Yes.(64( -1 (ASK Q.26o) No...... -2 (SKIP TO Q.25p) No -1 (ASK Q.27o) -2 (SKIP TO Q.26p) 25o. What kind of birth defects did (s)he have? Any others? 26o. What kind of bi.rth defects did (s)he have? Any others? 27o. What kind of birth defects did (s)he have? Any others? 25p. Was (CHILD) ever diagnosed as having cancer? 26p. Was (CHILD) ever diagnosed as having cancer? 27p. Was (CHILD) ever dragnosed as having cancer? Yes.'(65( -1 (ASK Q.25q) Yes.(65( -1 (ASK Q.26q) Yes.(65( -1 (ASK Q.27q) No ..... -2 (SKIP TO Q.25s) No -2 (SKIP TO Q.26s) No -2 (SKIP TO Q.27e) 25q. 1 I In what month and year 26q. was the diagnosis made? MONTH 1 l l (66) (67) II - YEAR 1 I l (68) (69) 1 l In what month and year 27q. was the diagnosis made? 1 I MONTH YEAR 1 I I I 1 l l I l l (66) (67) (68) (69) In what month and year was the diagnosis made? 1 1 MONTH YEAR . I I I I I 1 l-l 1 1 (66) (67) (68) (69) 25r. What kind of cancer was diagnosed? 26r. What kind of cancer was diagnosed? 27r. What kind of cancer was diagnosed? Not s u r e . . ( 7 0 ( Not sure..(70( Not sure..(70( (GO TO Q.4s) 10 79-80 -1 -1 (GO TO Q.5s) 11 TF50" 1S7 (GO TO Q.6s) 12 79^50 -1 �CARD 004 TENTH CHILD 812039 ELEVENTH CHILD TWELFTH CHILD 25s. (Does/Did) (CHILD) have a diagnosed learning disability? 26s. (Does/Did)(ClllLD) have a diagnosed learning disability? 27s. (Does/Did)(CHILD) have a diagnosed learning disability? Ves.(12( -1 (ASK Q.25t) Yes.(l2( Yes.(l2( No -1 (SKIP TO Q.25u) No 25t. What kind of learning disability (does/did) (s)he have? -1 (ASK Q.26t) -2 (SKIP TO Q.26u) No 26t. What kind of learning disability (does/did) (s)he have? 26u. (Does/Did)(CHILD) have 25u. (Does/DidMCHILD) have any physical, mental, or any physical, mental, o motor impairments? motor impairments? Yes.(l3( Yes.(13( -1 (ASK Q.25v) No -2 (SKIP TO Q 25w) No 25v. What kind of impairment (does/did) (s)he have? -1 (ASK Q.26v) -2 (SKIP TO Q.27u 27t. What kind of learning disability (does/did) (s)he have? 27u. (Does/Did)(CHILD) have any physical, mental, motor impairments? Yes.(13( . . -2 (SKIP TO Q.26w) No .. 26v. What kind of impairment (does/did) (s)he have? -1 (ASK Q.27t) -1 (ASK Q.27v) -2 (SKIP TO Q.27w 27v. What kind of impairmen (does/did) (s)he have? IF CHILD IS DEAD: IF CHILD IS DEAD: IF CHILD IS DEAD: OTHERWISE: OTHERWISE: OTHERWISE: CONTINUE SKIP TO Q.25z >5w. On what date did (CHILD) die? CONTINUE SKIP TO Q.26z 26w. On what date did (CHILD) die? CONTINUE SKIP TO Q.27z 27w. On what date did (CHILD) die? MONTH DAY YEAR MONTH DAY YEAR MONTH DAY YEAR 1 I I i l l 1 1 1 1 1 1 I I 1 1 1 I I 1 I I 1 1 l-l 1 l-l 1 1 1 1 l-l 1 l-l 1 1 l-l 1 l-l 1 1 14) (15) (16) (177 U8) (19) (14) (15) (16) (17) (18) (19) (14) (15) (16) (17) (18) (19 5x. What was the cause of death? 26x. What was the cause of death? 27x. What was the cause of death? 5y. Where is (CHILD) 's death registered? In what city and state is that? RECORD IN S.R.B. PG 2 1 26y. Where is (CHILD) 's death registered? In what city and state is that? 1 RECORD IN S.R.B. PG 2 1 27y. Where is (CHILD)'s death registered? In what city and state is that? RECORD IN S.R.B. PG 2 1 (GO TO Q.25z> (GO TO Q.26z) 188 (GO TO Q.27z) �CARD 007 Q.28 Additional Periods of Infertility FIFTH PERIOD FOURTH PEKIOD 28a. In what month and year did the fourth period begin? And in what month and year did it end? FROM MONTH YEAR T 28d. In what month and y e a r d i d t h e f i f t h period h e g i n ? And in what month and y e a r did it end? FROM MONTH YEAR 1 1 i 1 1 I I l l I l l (18) ( 1 9 ) ( 2 0 ) (21) ' TO MONTH YEAR 1 1 1 1 1 1 I l l I l l (22) (23) ( 2 4 ) (25) I (187(195 (20) (21) TO MONTH YEAR I I I (22) (23) 28h. I (24) (25) How old were you in (BEGINNING DATE OF PERIOD)? 28e. (26) (27) Yes. No.. During this period did either of you see a doctor to discuss any difficulties in conceiving children? .2( (8 How old were you in (BEGINNING DATE OF PERIOD)? 1 1 AGE 28c. 812039 28f. 1 1 1 1 (26) ( 2 7 ) 2fig. 1 I 77T -2 02 79-80 (GO TO NKXT PERIOD) M - l 1 I l 1 l ( 2 0 ) (21) MONTH 1 I 1 l l YEAR M - (22) ( 2 3 ) 28h. 28i. Yes No 1 l TO 1 1 During this period did either of you see a doctor to discuss any d i f f i c u l t i e s in conceiving children? In what month and year did the sixth period h e g i n ? And in what month and year did it end? FROM MONTH YEAR fl8) (19) AGE -1 (GO TO NEXT PERIOD) SIXTH PERIOD 1 I l 1 l (24) (25) How old were you in (BEGINNING DATE OF PERIOD)? 1 1 1 1 (26) ( 2 7 ) AGE During this period did either of you see a doctor to discuss any d i f f i c u l t i e s in conceiving children? OR( No -1 -2 03 79-80 (RETUKN TO Q.].2s) �;:CARP 004. TENTH CHILD 812039 ELEVENTH CHILD TWELFTH CHILD 25z. Did ybu smoke on a fairly regular basis during this pregnancy? 26z. Did you smoke on a fairly regular basis during this pregnancy? 27z. Did you smoke on a fairly regular basis during this pregnancy? Yps.(20( Yes.(20( -1 (ASK Q.26aa) Yes.(20( -1 (ASK Q.27aa) No -2 (SKIP TO 26aa) No -2 (RETURN TO Q.7) No -1 (ASK Q.25aa) ^-2 (SKIP TO Q.25aa) 25aa.When you were smoking cigarettes on a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack wi; mean 20 c igarettes. — 26aa.When you were smoking cigarettes oh i fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack we mean 20 cigarettes. I I I 1 1 Packs I 27aa.When you were smoking cigarettes on a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack we mean 20 cigarettes. 7 1 (21) (22) <21) (22) Less than frne pack.(23( -1 I I I Packs Less than one pack. (23( Packs (21) (22) -I Less than one pack.(23( -1 25bb. Dj.d you drink alco26bb. Did you drink alco27bb. Did you drink alco-, holic beverages (beer, holic beverages (beer, holic beverages (beer, wine, Or hard liquor) wine, or hard liquor) wine, or hard liquor) on a regular basis duron a Regular basis duron a regular basis during this pregriancy? ing this pregnancy? ing ttiis pregnancy? Y..s..(24( -1 (ASK Q.25cc) Nn -2 (GO TQ NKXT ~~ CHILD) 25cc. About how many drinks a week Would you say that y6u had during this pregnancy? Yes..(24( ; -I (ASK.Q.26cc) No....... -2 (GO *0 NEXT' CHILD) Yes..(2A( -1 No _-2 26cc. About how many drinks a week would you say that you had during this pregnancy? 27cc, About how many drinks a week would you say that you had during this pregnancy? 1 (ASK Q.27cc) (GO TO NEXT CHILD) 1 drinks 1 (25) (25) 1 drinks 1 (26) to (GO tO NEXT CHILD) 1 drinks 1 (2'S) (26) 12 79-80 (GO TO NEXT CHILD) (RETURN TO Q.7) �812039 CARD 013 <>-') I Add i t ion.-i I M i ' i i - . - i r r i . T R i ' s / S r i 11 h i r r h s / A b o r t i o n s PKKCNANCV t< I'UECNANCYJH I i i wh;it t i u n i l l i a n d vi'«'ir d i d l;h*' f i r s I s u r h pregnancy end? MONTH IIOn. In w l i a t montli and y e a r did the next such pregnancy end? MONTH YKAK T YtAK MONTH Mi scar i i.i^r. . (J^(_ Si i l l b i r l l i Abortion.. _. 2''c. iI -1 -2 "3 After how mnny weeks did I (17) (is) 2'ib. Did this pregnancy end in a mi Kearriage , s t i l l b i r t h , "r abortion? (15) Misoarriage. . ( I <U SI: i I I b i rth t Abort ion 30c. r I Weeks (?0) (21) (20) d . How old were yon at that limp? -1 -2 -3 31b. Did this pregnancy end in a miscarriage, s t i l l b i r t h , or abortion? Mi scarriage. . ( 1 *)( Stillbirth Abort ion '.ilc. Was (STUDY RESPONDENT) your partner in this pregnancy? I I Weeks (20) (21) (21) 31d. How o l d were you at t h a t time? 30d. How old were you at that time? No 2c)t'. 30e. I I Were e i t h e r of you . using b i r t h control at the time you became pregnant? Y e s . ( 2 5 ( -1 ( A S K Q . 2 9 g ) No _-2 ( S K I P TO O . J O h ) (CO TO Q . 2 Q g / h ) Was (STUDY RESPONDENT) your p a r t n e r in t h i s pregnancy? Ye s. ( 2/4 ( No -1 -2 30f. -1 -2 -3 After how many weeks did the pregnancy end? ( W R I T E IN AGE) (22) (23) 2')e. ( 1 7 ) (18) I I ! Weeks (WRITE IN ACE) I (WHITK I.N ACE) I I (15) ( 1 6 ) After how many weeks did the pregnancy end? I I I I ( 1 7 ) (18) (If.) 30b. Did this pregnancy end in a miscarriage, s t i l l h i r t h , or abort ion? the prugnancy end? iI YEAR T I <n) (is) 3 1 a . In what, month and year did rhe next sucli pregnancy end? Yes.(25( -1 (ASK Q.30g) Mo _-:> (SKIP TO I (CO TO ().30g/h) 1'Jl 31e. I Was (STUDY RESPONDENT) your partner in this pregnancy? -1 -2 Were either of you using birth control at the time you became pregnant? I ( 2 2 ) (23) Ves.(2'(( No. 31f. -1 -2 Were either of you using hirth control at the time you became pregnant? Yes.(25( T-I (ASK Q.31g) No -2 (SKIP TO Q . 3 1 h ) (CO TO Q . 3 1 g . / h ) �H I2 CARD OH Q.29-31 PREGNANCY 4 PREGNANCY (> PKKGNANCY 5 lHANI) RESPONDENT CAKU "C" \ IllAND RESPONDENT CARD "C" I IllANI) RESPONDENT CARD "C" 1 29g. Please look at tliis cart 30g. Please look at this car 31g. Please look at this card and tell rap a l l the num and tell me all the numand tell me .ill the numhers that apply to the bers that apply to the bers that apply to the types of birth control types of birth control types of birth control you or your partner wen you or your partner were you or your partner were using. us inn • usiniiOl.(2(>( 0?.(27< O3.(28r~ (K..(29( O5.(30( -1 -1 -1 -1 -1 Of,. OK -1 <17.(32( -1 08. (337" "-1 09.<34( -1 10.(35( -1 ll.(30( -1 12 (SPECIFY) 1 1 (38) Ofi.OK ()7.(32( OH.(33(~ 0)U( '.4 1().(35( ll.(36( -1 How many months did it take you Co become pregnant this time? 1 -1 -1 "-1 -1 -1 -1 -1 "-1 -1 -1 -1 12 (SPECIFY) .(37( 29h. Ol.(2h< 0?.(27< 03.(2H7~ 0/..(2<M 05.(3(J( (39) Less th.in 1 month. (A0( Wasn't trying 1 I I (38) -1 -'1 T 31h. (39) 1 1 (38) LI-MS Hum ! month. UiO( -1 (IF MISCARRIAGE OR STILLBIRTH IN Q.30h, ASK Q.30i . IF ABORTION IN Q.30b, SKIP TO Q.30m) Did a doctor t e l l you why this (miscarriage/ stillbirth) might have occurred? 29j . What did the doctor say caused the (miscarringe/st i 1 Ibirth) .' ?%-. 1 1 Months (39) -1 •)i i. (IF MISCARRIAGE OR STILLBIRTH >N Q.31b, ASK Q.3H. IF ABORTION IN Q.31b, SKIP TO Q.31m) Did a doctor tell you why this (miscarriage/ stillbirth) might have occurred? -1 (ASK Q.30J) Yes.UH -i (SKIP TO Q 30n) No -1 (ASK Q.31J) -2 (SKIP TO 0 31n) Oj. What did the doctor say caused the (miscarr iaRc/st i 1 I h i rt'li)? 1 j. Wlial did the doctor say caused the (miscarriani.'/si i 1 Ibirth)? Wh.-it is NIP nniiir of 1 In' Ilk. duct 01 or mini ioi 1 1 m- i 1i t y rh.il you consul ted about this? WIl.H i K Mil- namr of I'lir tlin- 1 (>t or nusl i i- H 1 1 m- i 1 i t v t h a t yon consulted .Tlr-ut this? : Ik. Wh.il is llu> ii.-iiiu- of the doctor ttr nu'd i en 1 l a c i l i t y that you consulted about this? TRECORD IN S.K.B. - PC 3 I 29L. es.(4K (, -1 Less than 1 month. ( 0 4( Did n doctor t e l l you why t h i s (miscarriage/ s t i l l b i r t h ) might have oc c u r re d ? -1 (ASK Q.29J) -1 -1 -1 -1 -1 -1 How many months did it take you to become pregnant this time? 1 1 1 Months 29i. (IF MISCARRIAGE OK 30 i. STILLBIRTH IN Q.29b, ASK Q.29i. IF ABORTION IN Q.29h, SKIP TO Q.29m) Yes.(41( Qft.OK 07.(3?( OH.(T3l 09.(34( 1().(35( ll.(36( .(37( -1 How many months did it take you to become pregnant this time? 1 1 1 Months -1 -1 '-1 -1 -1 12 (SPECIFY) .(37( 30h. Ol.(26( 02.(27( 03.(?H( 04. (29( ()5.(30( In what month and year was that? IRECORD IN S.R.B. - pn i 1 '.)[.. In what month and year wns t h a t ? IRECORD IN S.R.B. - PC; 3 1 1L. In what month and year was that? IRECORD IN S.R.B. - PC 3 1 IRECORD IN S,R.B. - PC 3 1 (SKIP TO ij.29n) (SKIP TO Q.30n) (SKIP TO Q.31n) (CO TO NEXT PACK.) (CO TO NKXT PACK) (CO TO NEXT I'AGE) IRECORD IN S.R.B. - PC 3 1 192 �CARD 013 812039 Q.29-31 PREGNANCY 4 PREGNANCY 5 PREGNANCY 6 29m. What was the main reason for the abortion? 30m. What was the main reason for the abortion? 3)m. What was the main reason for the abortion? 29n. Did you smoke cigarettes on n fairly regular basis (lurinp this pregnancy? ')0n. Did you smoke ciparettcs on a fairly regular basis during this pregnancy? 31n. Did you smoke cigarettes on a fairly regular basis during this pregnancy? Yes.(42(. -1 (ASK Q.29o) -2 (SKIP TO Q.29p) No. 29o, When you' were smoking cigarettes qn a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack we mean 20 cigarettes. Yes.(4_2j__-l (ASK Q.30o) Yes.(42( -1 (ASK Q.31o) No. No. -2 (RETURN TO Q.lBa) 30o I I ,\ Packs (43) (44) Less than one pack.(45(__-l (ASK Q.29q) (SKIP TO About how many drinks a week would you say that you had during t h i s pregnancy? T I Packs I 30q. -1 l.ess than one pack. (45 ( -1 Tip. Did you drink alcoholic beverages (beer, wine, or hard liquor) on a regular basis during this pregnancy? Yes..(46j__-l No __'-2 T I Packs (43) (44) Less than one pack.(45( Q.30a) 29q. 31o. When you were smoking cigarettes on a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack we mean 20 cigarettes. (43) (44) 30p. Did you drink alcoholic beverages (beer, wine, or hard liquor) on a regular basis during this pregnancy? Yes..(46( -1 No __-2 When you were smoking cigarettes on a fairly regular basis during this pregnancy, on the average, how many packs per week did you smoke? By pack we mean 20 cigarettes. I T 29p. -2 (SKIP TO Q.30p) (ASK Q.30q) (SKIP TO Q.31a) About how many drinks a Wi'eVi would you say that you had during this pregnancy? Did you drink alcoholic beverages (beer, winp, or hard liquor) on a regular basis during this pregnancy? Yes. . (46( -1 (ASK Q.31q) No __-2 (GO TO NEXT PREGNANCY) 31q. About how many drinks a week would you say that you had during this pregnancy? T—r I drinks I drinks (47) (48) (47) (48) 01 70-80 I I I drinks (47) (48) 02 79-80 (ASK Q.30a) (ASK Q.31a) (RETl'KN TO Q. IPa) �Louis HARRIS AND ASSOCIATES. INC. 63O NEW TEL FIFTH AVENUE Y O R K , NEW YORK (ZI2I 9 7 5 - I 6 O C T E L E X I O I I I 146383 LOUIS H A R R I S I N T E R N A T I O N A L . INC LOUIS H A R R I S P R A N C E OPINION R E S E A R C H 21 RUE VIVI6NNE SO W E L B E C K ST. 7SOO2 PARIS, FRANCE LONDON WIM BAB ENGLAND TEL. 01- zeo -ees*! TELEX: zooeo> TEL: O I - 4 8 6 - 5 I 5 I T E L E X . 21-«O3 Dear Louis Harris and Associates has been asked by the United States Air Force to conduct a study of the health of Air Force pilots and servicemen who served during the Vietnam conflict. The U.S. Air Force School of Aerospace Medicine is undertaking this study in order to answer questions about possible effects of having served in Vietnam. I have just completed an interview with Louis Harris and Associates on the United States Air Force Health Study. As part of this study, they would like to interview the former wives of study participants. You will be asked to provide information on health and health care services. It is essential to the accuracy and completeness of the study that all selected participants .and their families participate in the study. Reliable information will help produce sound conclusions of vital relevance to all Vietnam veterans and their families. I would appreciate it very much if you also would grant a representative of Louis Harris and Associates an interview. Shortly after receiving this letter, you will be called on by an interviewer from Louis Harris and Associates who, at your convenience, will either conduct the interview or set up an appointment. The interviewer will answer any questions you may have about the study. Thank you. Sincerely, TSIGNATURE OF STUDY RESPONDENT; (PRINTED NAME OF STUDY RESPONDENT) 1Q4 CENTRE �LOUIS HARRIS AND ASSOCIATES, INC. 630 FIFTH AVENUE NEW YORK, NEW YORK 10111 Dear Louis Harris and Associates has been asked by the United States Air Force to conduct a study of the health of former .and current AirForce., servicemen who served during the Vietnam conflict. The U.S,tAir Force 5 | 1 of Aeroc^ space Medicine is undertaking this study in order to answer questions about possible effects of having served in Vietnam. In order to complete the study, we need to interview both tKe Air Force personnel selected for this study and their wives. We have alrea^ly completed an interview with your former husband and now we need your cooperation in this endeavor. The interview is quite shor*t and should take no longer than twenty minutes to complete. The questionnaire focuses on the health of you and your family. The validity of the results depends on the willingness of women like yourself to participate in the study. Reliable information will enable the Air Force to reach sound conclusions of vital relevance to all Vietnam veterans and their families. A copy of the letter from the Surgeon General of the Air Force which was sent to your former husband is attached. It will explain the purpose of the study in detail. The fact sheet, which is part of this letter, includes a telephone number which you may call if you have additional questions. One of our interviewers will be contacting you in the next two weeks to arrange an appointment. We will schedule the interview at your convenience. Thank you for your cooperation. important project. I hope that you will join us in this Sincerely, Louis Harris 195 �Louis HARRIS AND.ASSQCIATES, INC. 63O NEW TEL FIFTH AVENUE Y O R K , NEW Y O R K '2121 9 7 5 - I 6 O O T E L E X I O I I I 118383 LOUIS HARRIS INTERNATIONAL. INC. OPINION RESEARCH CENTRE LOUIS H A R R I S FRANCE 21 RUE V I V I E N N E 3O WELBECK ST. 7SOOE PARIS, FRANCE LONDON WIM BAB ENGLAND TEL. oi-zeo -9OB4 TELEX: aooeoi r TEL: oi-«iee-6i6i TELEX: 24*03 PRIVACY ACT STATEMENT - EPIDEMIOLOGIC STUDY AUTHORITY: Section 133, 1071-87, 3012, 5031 and 8012, Title 10, United States Code and Executive Order 9397. PRINCIPAL AND PURPOSEJSJ: The purpose of requesting personal information is to assis~t medipal/technical personnel in developing records relative to your participation in an approved epidemiologic investigation. The Social Security Number (SSN) and Armed Forces Service Number (AFSN) are necessary to identify the person and records. ROUTINE USES: This information will be used to initiate, coordinate, and conduct the investigation. It will be used to compile statistical data, but information allowing identification of the individual volunteer will not be included. Data and results from this investigation may be used to supplement other approved research studies conducted at the USAF School of Aerospace Medicine or at other Federal agencies engaged in the conduct of similar studies. WHETHER DISCLOSURE IS MANDATORY OR VOLUNTARY, AND EFFECT ON INDIVIDUAL FOR NOT PROVIDING INFORMATION:" Disclosure or requested information is voluntary. If the information is not furnished, acceptance as a subject is not possible. This is an all-inclusive Privacy Act Statement which will apply to all requests for personal information made by medical/technical personnel during the time you are a volunteer subject. A copy of this form will be placed in your investigation subject folder as evidence of this notification. Your signature merely acknowledges that you have been advised of the foregoing. If requested, a copy of this form will be furnished to you. Signature of Volunteer SSN 196 ' Date �SHOW CARD "C1 NO. 812039 01 Pill 02 Douche 03 Foam 04 Jelly, Cream, Suppository 05 IUD 06 Condom, Rubber 07 Diaphragm 08 Diaphragm attd Jelly 09 Rhythm *- Calendar 10 Rhythm - Temperature 11 Withdrawal 12 Other 197 �SHOW CARD "D-l? STUDY NO. 812039 a. Sterility due to surgery b. Known sterility due to injury, accident, or illness c. Sterility due to unknown causes d. Lack of interest in sex e. Other known medical/physical conditions f. Some other reason J.98 �t.S. LQUIS MARHIS AND N E W Y O R K . N E W Y O' f t' * . I O I I I TEi. 2 I Z I 9 7 5 - I 6 Q O T£i,E» ii>93e? LOVIIS HAIR'S I N T E R N A T I O N A L . ' N C . LOUIS H A R R I S FRANCE 30 21 RUE VIVI6NNE 7SOO2 PARIS, TRANCE LONDON WIM 6A6 ENGLAND TCL. oi-aoo -oestf TELEX: iooeoi TEL: Oi-«»86-6isi TELEX'. £*- UNITED STATES AIR FORCE HEALTH STUDY Name of Medical Provider/Medical Facility Name of Place Street Address "State" ( 1 Phone Number Dear Doctor or Administrator: I am participating in a survey conducted for the United States Air Force to gather information on- the health of current and former Air Force personnel and their families. As part of this survey, medical providers who have delivered health care services to 'me are being asked to supplement the information that I have already provided to the study. By this statement 0r a photocopy of it, I hereby authorize and request you to furnish the United States Health Stu^y with any medical information in your records on the health services received by me, ^ in connection with a birth on • •/_, _ , '; _,_ ,___ _ . Related health care was provided during the period to .: Thank you very much. Sincerely, Resp. ? Signature cif ;Pati;enlf FOR OFFICE USE ONLY: Date MEDICAL PROVIDER PERMISSION FORM: SPOUSE �FOR OFFICE USE ONLY: LOUIi HARRIS AND ASSOCIATES, INC 630 Fi fth Avenue New York, New York 10111 c # 812039 Air Force Health Survey Respondent # INTERVIEW EVALUATION (NI'tRVlEWER; COMPLETE THE FOLLOWING IN PRIVATE IMMEDIATELY AFTER THE INTERVIEW, USING YOUR BEST JUDGMENT TO ANSWER F.ACH ITEM. I. .lace of respondent: Black.... Nonblack. ?.a. Did the respondent want to terminate the interview before it was finished? No (SKIP TO Q3a) Yes, (ANSWER 2b AND 2c) 2b. At what question number or during what question series? >r V'hat was the reason? la viere there any (other) significant problems during f.he interview? No Yes _ (SKIP TO Q4a) _H'J (ANSWKR 3b) 3b. Describe the problems. 4a. Did respondent refer to records during the interview? No Yes (SKIP TO Q5a) (ANSWER 4b) 4b. What records did the respondent use? _____ 5a. Was anyone else present at any time during the interview? No Yes (SKIP TO Q6) (ANSWER 5b and 5c) 5b. Who was present? rRTCQROELA~TIONSHIP | 5c. During which section(s)? 6. , Length of interview: minutes 200 �LOUIS flAKKls AND ASSOCIATES, INC, 630 I i H:ji Avenue New York, New York 10.111 Study # B12039 AIR FORCE 'HEALTH SURVEY k FQRM TU: New York Office. Lbuis Harris and Associates FROM; \________.„,_..... . . . . . . . __ "" "~~* TnteTviewer'Nanie "-" "PTease" "PrTnt" • __ ...... ' fliis pat:k,tge contain:, the following material for Study Subject Respondent" Numhei- I W r i t e in NtlMnr.R of eai:h J.teni.. bgtflS. s.pn.1;. PH. .*}!§.. It.'iV. at tjl Study Subject Name Assignment Sheet Study Subject. Pri vciey Act Statement (Signed)... , __ Study Subject Questionnaire......' Study Subject Supplemental Recording Book .., Study Subject Sel f Administered Form ; Study Subject Medical Consent Form. ,, Study Subject former Wi fe Consent Letter., , Study Subject Interviewer Evaluation Form. PRESENT.WlFt INTERVir.W Privacy Act StateriuVnt (Signed) , Spouse (jui'':>t l o n r i a i i c . Spou'ii-1 '.upMliMiiontril Recording Book. SIJOUSL* Medical Consent Form Spouse .Interviewer I valuation form. Former W^Tc Name Assignment Sheet.. l'rivm.y Act. Stotemeiil. (Si(jned) Spouse (jut", t Minna i reSpouse 'iup|'li-.'iiient.<i I Kecordituj Book. Spouse M u d i c d l Coii.i'iil I orm Spoust; I n t e r v i c w e i ' I v.iluiit. ion form. PK'iXY. i f i r i k V i r w I'coxy Name Assignment. Shi-nl Privacy A c t '.taleim-nt. '.(Signed) Proxy f)ui.'Stionnaifi'.. . ......... •. .• I'roxy Supp|i'iw;nt..i I Kei.-ordin.g Book Proxy Modji'.d I LOIIMTI! ........... I'roxy I rtl.ci v ii'wci I Viiluat i on l<ci.i.'i vi/d: Date l.ln.r.|.ei! ii: by: I ! I 201 ^___ .__ , , �CHAPTER III NEXT OF KIN (PROXY) QUESTIONNAIRE The following Next of Kin (Proxy) Questionnaire was used to collect baseline data for the Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicide Orange. This data was collected during 1981-1982. All available proxies were Included in this data collection effort. The questionnaire and supplemental recording book are the actual field instruments. They have been photocopyed and reduced for the purpose of this report. One show card, anatomical representation, is included as an attachment to demonstrate to the reader complete data collection methods. Additional attachments include the Privacy Act Statement, Life Events Chart, Medical Permission Form, Introductory Letters, Interview Evaluation, and Mailing Transmittal Form. The Next of Kin (Proxy) Questionnaire, as used in the field, follows. 202 �630 Fifth Avenue New York, New York O.M.B. NUMBER 0701-0033 Approval Expires 11/30/62 10111 Case No. Study No. 812039 Respondent t: PROXY QOKST10NNAJRE CONFIDENTIAL This study is being conducted to collect information on the health of current and former Air Force personnel and their families. Since I will be asking you questions about the health, career, and personal history of (STUDY RESPONDENT), we have prepared a Life Events Chart to help you remember when various events in his life occurred. The best way to use the Life Events Chart is to first record when he was born in Column, or how old he was in 1930, if he was born before 1930. Then, record his subsoquent 5-year intervals in the Age Column. Next, note the year he graduated hiflli school and/or college in the next column. You can enter the year he joined military in the next column. There are other columns to record any marriages or children he may have had, as well as other major events in his life. the Age age at from the 1 w i l l tie asking you questions about each of these areas during the interview. If you w i l l take a few moments to fill out the Life Events Chart now, it w i l l help you to recall d,it.es and ages during Che interview. First, 1 have a feu background questions to ask you. 1. What (is/was) (STUDY RESPONDENT'S) date of birth? (WRITE IN DATE) I MONTH I DAY YEAR I I I T~7iT 1 ) ( 2. I I In what city and state was (STUDY RESPONDENT) born? T RECORD IN SUP PIGMENTARY RECORDING BOOKTON PACE l] 3. What was his religious preference — was it Protestant, Catholic, Jewish, some other, religion, or no religion? -1 Protestant Catholic Jewish Other (SPECIFY) -A "-5 None. What van the highest grade or year in high school that he completed? Less than 1 year of H.S...C (_ 1st year H.S. (9th Grade) ^ 2nd year H.S. (10th Grade)....* 3rd year H.S. (llth Grade) " Ath year H.S. (12th Grade) " Z03 -1 _ -3 �CARD 812039 I HAND RESPONDENT CARD "A"I , 5a. Please look at this card and tell roe which of these regular academic school certificates, diplomas, or degrees (STUDY RESPONDENT) had obtained? I MULTIPLE RECORD BELOWl YEAR High school diploma (__J -1 ( ) ( YEAR High school equivalency diploma ( ( -1 Associate of Arts (A.A.) ( ( -1 YEAH YEAR Bachelor of Arts (B.A.) or Bachelor of Science (B.S.)... (_J -1 I )( ) 1 YEAR Masters ( ( -1 ( ) () YEAR Doctorate ( ( -1 Others (SPECIFY) YEAR (1) -1 YEAR (2) -1 YEAR (3) -1 No certificate, diploma, or degree (/olunteered)....(( -1 IFOR EACH DEGREE. PIPLOMA. OR CERTIFICATE, ASK Q.Sbj 5b. In what year did he receive his (CERTIFICATE/DIPLOMA/DEGREE)? IRECORP ABOVET �CARD 812039 6a. 1 ai" interested in train ing programs which prepared (STUDY RESPONDENT) for a major change in his occupation. Fi rst, I will ask about civilian job training programs. Resides the formal schooling you told me about, did he participate in any civilian job training programs that prepar ed him for a major change in his occupation? Yes...( ( -1 (ASK Q.6b) No -2 1st Program b. (SKIP TO Q.7a) 2nd Program For what kind of work was his first civilian . training program preparing him? 3rd Program f. For what kind of work was his next civilian training program preparing him? (( c. d. MONTH ,1 l l 1 1 - YEAR 1 I l MONTH 1 1 T 5 '( ')' I I l-l YEAR 1 I' (")(> ( MONTH 1 1 1 1 t. I l-l I YfiAR I 1 1 1 1 1 I I 1 ( MONTH I 1 I I hi YEAR [ 1 1 1 L. In what month and year did he complete this training? 1 1 m. MONTH YEAR 1 I I I I 1 l-l 1 1 < )( ) ( J( } Did he participate in any other civilian job training program that prepared him for a major change in bis occupation? -1 (ASK Q.6j) Yes.( -2 (SKIP TO Q.7a) ( Nb....k. 205 < In what month and year did he start this training? I 1 1 1 i. Did he participate in any other civilian job training program that prepared him for a major change in his occupation? -1 (ASK Q.6f) Yes.( -2 (SKIP TO Q.7a) jjo k. YEAR I l-l ( ( 1 1 In what month and year did he complete this training? MONTH 1 1 Did he participate in any other civilian job training program that prepared him for a major change in his occupation? Yes.( No g. In what month and year did he start this training? 1 l In what month and year did he complete this training? 1 1 e. (( In what month and year did he start this training? I I < ( ( (( j. For what kind of work was his next civilian training program preparing him? -1 (RECORD ADDITIONAL TRAINING PROGRAMS . IN S.R.B. ON PG. 13) -2 (GO TO Q.7a) �CARD 812039 7a. Now, let's calk about military technical and specialized training programs that prepared (STUDY RESPONDENT) for a major change in his occupation. Besides the formal schooling (and the job training programs) you've told me about, did he participate in any military technical or specialized training programs that prepared him for a major change in his occupation? Yes...( ( No -2 1st Program b. -1 (ASK Q.7b) (SKIP TO Q.8) 2nd Program For what kind of work was his first military training program preparing him? 3rd . Program g. For what kind of work was his next military training program preparing him? L. For what kind of work was his next military training program preparing him? ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( c. What was the AFSC for that job? ( ( d. ( ( In what month and year did he start this training? i. In what month and year did he start this training? MONTH YEAR 1 1 '[ I ' " 1 ' 1 I . I H I 1 ( ) ( ) (• ) ( ) e. m. What was the AFSC for that job? h. What was the AFSC for that job? In what month and year did he complete this training? MONTH 1 1 1 1 .1-1 ( ) ( ) YEAR 1 1 1 1 ( )( ) f. Did he participate in any other military job training program that prepared him for a major change in his occupation? Yes.( ( rl (ASK Q.7g) I 1 j. MONTH YEAR I I I 1 1 1 l-l 1. 1 ( )( ) ( )( ) In what month -and year did he complete this training? MONTH 1 I ( ( n. 1 . I 1 o. 1 1 1 1 1 1 l l I l l ( )( ) ( ) ( ) k. Did he participate in any other military job training program that prepared him for a major change in his occupation? MONTH YEAR I I I 1 1 1 1 - 1 1 1 ( ) ( ). ( ) ( ) In what month and year did he complete this training? YEAR 1 es.( ( No •••• In what month and year did he start this training? MONTH YEAR 1 i 1 I I 1 l-l 1 1 ( )( ) ( )( > p. Did he participate in any other military job training program that prepared him for a major change in his occupation? -1 (ASK Q.7L) Yes.( -2 (SKIP TO Q 8 ) No ( -1 (RECORD ADDITIONAL TRAINING PROGRAMS IN S.R.B. ON PG. 14) -2 (GO TO Q.8) �612039, 8. Now I have some questions about working. please tell me about all his jobs that lasted three months or ^longer since the first elate (STUDY RESPONDENT) stopped going to school lull time. Count changes of jobs for the Same employer as separate jobs. Do npt include jobs in the military. ' First Job Ha. Second Job In what month and year 9a. In what month and year did he start his did he Start his f i r s t job that lasted next job that lasted three months or longer? three months or longer? ; YEAR •MON'fH I I 1 I -l I TTT 8b. Third Job What was the name of J|i8 employer? MONTH 10s. In what month and year did he start his next job that lasted three months or longer? VEAR 1 1 MONTH ( ) ( y (. ) < T Be. Was the job foiltime or part-time? 9b. What was the name of his emp_lojrer? 10b. What was the name of his employer? 9c, Was the job fulltime or part-time? TRECQRn i N s. R ., B . - PC i T 10c. Was the job fulltime or part-time? TRECORD IN. S.R.B, - p<j 1 " 1 -1 "-2 $d. What kind of business was that — what did they make or do there? 9d. What kind of business was that -- what did they make or do there? TRECORD TNS.R. i\ . ~-"p"(3~f T Full time. i( r ( -1 Part tin*...... ~2 Full tirae..( Part time..,? YEAR I i 1 i f i i"(•' }i I .. 5 1-1 ( )T ) i, I 1 -' I 1 l-l . . . 1 „ J Full time..( r( -1 lOd. What kind of business was that — what did they make or do there? (.( .. (( Be. Whflt did he actually dp on the job — w h a t were Some of his main ( . ( . 9e. What did he actually do on the job — what were some of his main duties? lOe. What did he actually do on the job — what were some of his main duties? 9f. 10f. Please look at this card and .tell me the number which best describes the kind of industry he worked in. IRECORD IN S.R.B. - p'd i i IRECORD IN S.IUB. - PC i I . ', . ,/ IHAND RESPONDENT CARD "Blf IHAND RESp'oNDEtif .CA'RD "ts"l Please look 4't this card and tell me the number which best describes the kind of industry he worked in. I (WRITK tH NUMBER) In whdt month find year did this job end? HdHTtl _ T r "T i Current (WRITE IN NUMBER) 9g. (SKIf TO 8h. What was the main reason he stopped working at that job? 1 I ( (WRITE I N NUMBER) | [ | I 3 ( ) In what month and year did this J6b end? YKAR T "T I (T ( ) ( ) ( ) Please look at this card and tell me the number which best describes the kind of industry he worked in. 1 1 MONTH 1 1 '11 ' l-r YEAR I' "1 1 ,_J ( ) ( ) {• ) ( ) 1 I ) 1 I . I lOg. In what month and year did this job end? r MONTH 1 i i i 1 YEAR l-l i i 1 1 Current (SKIP TO job..(_T_-l Q.l/t) Current jOb..( 9h. What was Uhe main reason he stopped working at that job? lOh. What was the main reason he stopped working . at that job? (SKIP TO ( -1 Q.14) ( ( < (ASK Q.9af (ASK Q,}6a!> 101 < ( ( (ASK Q.lla) �CARD Fifth Job Sixth Job 12a. In what month and year did he start his next job that lasted three months or longer? 13a. In what month and year did he start his next job that lasted three months or longer? Fourth Job lla. In what month and year did he start his next job that lasted three months or longer? MONTI! I I 1 I I - ( )( ) 812039 YEAR I I I I I 1 I ( )( ) lib. What was the name of his employer? 12b. What was the name of his employer? 1 RECORD IN S.R.B, - PC 1 | lie. Was the job fulltime or part-time? Full time..( MONTH YEAR 1 II 1 1 I l - l 1 1 ( )( ) ( ) ( ) ( 12c. Was the job fulltime or part-time? lid. What kind of business was that — what (do/ did) they make or do there? MONTH YEAR 1 I I 1 1 l l I l l ( )( ) ( )( ) 13b. What was the name of his employer? (RECORD IN S.R.B. - PG 1 1 Full time..( ( Part time...... -1 1 I (RECORD IN S.R.B. - PG 1 | 13c. Was the job fulltime or part-time? Full time.,( -1 -2 12d. What kind of business was that — what (do/ did) they make or do there? ( -1 13d. What kind of business was that — what (do/ did) they make or do there? ( ( ( ( ( ( ( ( ( ( ( ( 12e. What did he actually do on the job — what were some of his main duties? 13e. What did he actually do on the job — what were some of his main duties? IHAND RESPONDENT CART) "B"l IRECORD IN S.R.B. - PC i 1 IRECORD IN S.R.B. - PC i 1 IHAND RESPONDENT CARD "B"| IHAND RESPONDENT CARD "B'M llf. Please look at this card and tell me the number which best describes the kind of industry he worked in. m. Please look at this card and tell me Che number which best describes the kind of industry he worked in. 13f. Please look at this card and tell me the number which best. describes the kind of industry he worked in. (WRITE IN NUMBER) (WRITE IN NUMBER) (WRITE IN NUMBER) lie. What did he actually do on the job — what were some of his main duties? IRECORD IN S.R.B. - PG i 1 1 1 ( i 1 1 1 ) () llg. In what month and year did this job end? MONTH I 1 ( | I I 1 ).( ) 12g. In what month and year did this job end? YEAR I I I 1 1 1 l-l 1 1 ) ( .) ( ) ( ) I I ( MONTH 1 1 ( ( 1 1 I 1 ^ (1 13g. In what month and year did this job end? YEAR 1 I I 1 1 1 l-l 1 1 )( ) ( ) ( ) 1 I 1 1 MONTH YEAR 1 I I 1 1 1 l-l 1 1 ( ) ( ) ( )( ) Current (SKIP TO job..( ( -1 Q.14) Current job..( llh. What was the main reason he stopped working at that job? 12h. What was the main reason he stopped working at that job? 13h. What was the main reason he stopped working at that job? ( ( ( ( ( ( ( ( ( ( (RECORD ADDITIONAL JOBS IN S.R.B. - PG 15 AND 16) ( -1 (SKIP TO Q.14) ( ( (ASK Q.12a) (ASK Q.13a) Current job..( ( -1 (SKIP TO Q.14) �812039 .CARD 14. Now 1 am going to ask you about (STUDY RESPONDENT'S) years in the military. a. In what month and year did he first enter the Armed Forces? MONTH t. YEAR i t t i. i i i c * i ( • )1-1 (• j i r > i . h. MONTH I I I 1 l-l 1 1 YEAR 1, ,.1, -1 Coast Guard. , . _ Air Force. '( J 1 , H Discharged/ separated. ( ; ( 1 , 1 ( ) ( 1 ( •")•( )'-• Following his separation or discharge in. (DATE IN "d"), did he reciter the Armed Forces? L. 1 1 l-l )( ) YEAR 1 1 (MILITARY) ' ' ••)' T T" ( Whaf branch of the military was that? -1 -2 rS Coast Guard, . . '^ -5 { -1 (ASK m. Was he discharged or separated from the (BRANCH OF SERVICE)? Discharged/ separated. (^ -1 (ASK """ i. In what -month and year was he discharged/ separated from the (BRANCH OF MltlTARY)? T 1 MONTH 1 ' 1 1 1 Still in ••*% (SKIP TO (MILITARY).,... -2 (SKIP TO Still in YKAR i "T. ( MONTH 1 1 Air Force. ( ( Navy. . . . . . .... (BRANCH OF se^idfe)? In what month and year was he dischargee!/ separated from the (BRANCH OF MILITARY)? MONTH _ 1 1 "1 h. Was he discharged or separated from the Discharged/ separated. ( ( Jl (ASK Q.14d) S t i l l in (MILITARY)..... -? (SKIP TO ~ Q.15) r~ r™T "i ' Coast Guard... -5 c. Was he discharged or separated from the (BRANClll OF SERVICE)? d. ( k. In what month and year did he next enter the Armed Forges? 1 1 What branch of the. mili- g. What branch dj the mi}itary wa's that? tary was that? A i r Force. ( ( e. In what month and year did he next enter the Armed Forces? J 1 l-l n. YEAR 1 ' .' 1 ..1 1 j. Following his separation or discharge in (DATE IN "i"), did he teenier tlie Armed Forces? Q.15) In what month and year was he discharged/ separated from the (BRANCH OF MILITARY)? 1 1 MONTH 1 1 1 1 l-l YEAR : l 1 I ' 1 o. Following his separation or discharge in (DATE if) "n!'), did he reenter the Armed Forces? Yes..( (_ -1 (ASK q.Hif) Ye 9..^ (: _-l (ASK Q. 14k) Ves..( (^ -1 ~~'"':~1''; No. . . . . . '. -2 (SKIP TO Q.15) . .Ti . "-2 (SKIP TO Q.J5) No. . No -2 (RECORD ADDITIONAL SERVICE PERIODS IN S.R.B. PG 17) (SKIP TO Q.15) �CARD 812,039 15. I would like to ask you the names of all the countries (STUDY RESPONDENT) wag stationed in while on active duty in the Armed Forces. a. Starting with induction, in what Country was he first stationed while on active duty? Include temporary duties of greater than 90 days. g. What was the next count r> ro. What was the next count, thit he was stationed that he was stationed in for more than 90 days in for more than 90 day: while on active duty? while on active duty? ..,('(. (RECORD COUNTRY HERE AND IN S.R.B. PC 2 AND CONTINUE) . . .: ( ( (RECORD COUNTRY HERE AND IN S.R.B. PC 2 AND CONTINUE) nECORD COUNW HERE" "AND' IN" ' S.R.B. PG 2 AND CONTINUE) No others.( No others. ( ( -1 (SKIP TO Q.17) b. h. ( ( In what month and year did he begin and end active duty in (COUNTRY)? In what month and year did he begin and end active duty in (COUNTRY)? BEGIN MONTH ' YEAR 1 1 I I 1 I l l I l ( )( ) ( )( END MONTH YEAR I I I I 1 I I , l-l . 1 BEGIN MONTH I I I I 1 I l-l YEAR 1 1 1 1 ( )( ) c >< ) END MONTH YEAR 1 1 I I I I .) 1 hi 1 1 ( ) ( ) ( ) ( ( -1 (SKIP TO Q.17) Current. . ( . ( In what month and year did he begin and end active duty in (COUNTRY)? BEGIN MONTI! YEAR 1 1 1 1 1 1 1 1 l-l 1 1 ( ) ( )"' ( ) ( ) " END MONTH YEAR 1 I I I 1 1 I I l - l 1 1 ••(')<) ( )( ) 1 l ) 1 1 ( )( > ( . V ( ) J Current . . . ( ( ^ -1 n. Current. . . ( ( -1 -1 c. What specific job assign- i. What specific job assign- o. What specific job assigi ments did he have ments did he have ments did he have in (COUNTRY)? Can you in (COUNTRY)? Can you in (COUNTRY)? Can you give me the AFSC? give me the AFSC? give me the AFSC? i. < . < .:" V. ' 2. .(. < ... 2.. 3. (( 3- d. . H " (( (,( 1. ( :(.,L 2. ,( ( ( ( . 3. '_ Did his duties in j. Did his duties in p. (COUNTRY) include flying? (COUNTRY) include flying? Yes.( No ( Yes.( ( No...... -1 -2 e. How many flight hours did he log while in (COUNTRY)? 1 1 1 1 1 1 I I Hours ( )(•')( ) Other (SPECIFY) .( K. How many flight hours did he log while in (COUNTRY)? 1 1 1 1 1 1 Hours ( >(")'<'> Other (SPECIFY) f. Wliat specific letter and numerical designat ion( s) did each aircraft have? 1 I -1 -2 1 I 1 1 1 | Hours ( ) ( M .) Other (SPECIFY) .( ( -1 .( ( -1 j. d q. How many flight hours did he log while in (COUNTRY)? 1 1 ( -1 Did his duties in (COUNTRY) include flyini Yes.( ( No .. -1 -2 -,.(....( What specific letter and r. What specific letter am numerical designationCs numerical designations) did each aircraft have? did each aircraft have? 1. (( 1. (( 1. ( ( 2. (( 2. ( ( 2. ( ( 3. (( 3. ( ( 3. ( ( (( <•-. ( ( 4. 4. (ASK Q.15g) (ASK Q.lSm) 210 (( (ASK Q.lba) �ft 13.6.3 9.'. -CARP, Question id ' Country a. sixth Country Fifth Cp.Mji$.t!3! What was the nexf country g. that ho was s t a t i o n e d in far mote than 90 days w h i l e On active duty? What was the neitt q o u n f r y m. that h« was sfaliiined •' in ior more tyft .90 d«y« while on actiyl: avty? p/ What was the next country that ne w>s stationed in for more than 90 day 6 whije pn active duty? , ,.,...,;. . HERS ;: AtfO •<;..' < IN (RECORb COjMTKf ' • •-Ar - " i ' (RECORD doWfRY 'Htttp 'AND fif), ' S.R.B. PG 2 AND CONTINUE) S.R.B. PC 2 AND cBrfttNtlB) ; (RECORD COUNTRY HERE AND IN S.R.B., PC 2 AMD CONTtNUE) No other*. ( Ho others. ( No others. ( ( -1 (SKIP TO Q.17) b. In what Hionth and year did he begin and end Active d u t y in (COUNTRY)? BEQIN 4i MONtfl , , YEAR h. ( j ( 1 1 1 ( ) .J( ' H( END ' YEAR 1 .•••".'} MONTH 1 1 ( ) : MONTH i. i. *) ( ^ ..'. ' • ( n. ' PAR i I • • ' • • • ! • • . - . ?• i • Current . . .( 2. , . ..':•. ( ( • ( . ' YEAR i ; :;i r i n I1 I i hi i 1 .tv) ; ( ) ( )-<' ) END YE.AR : r .; i ' 'i 1 >" • ()V( , ^^v;**! 1 ; i • i h ) L ( Current, ..( t l 1 H ( ) ,-1 What specific )bb assign- p. What specific job as«igh; ments di4 he have Bients did he <1a^e , in (COUNTRY)? Can you in (COtJHTRY)l, iC4n you giv« Me the AFSC? give we the Ai^Sci '.• What epecifie job assign- i. ments did he have in (COUNTRY)? (Jfliv yOu give me She AFS<5? . ,: ;...>,( .:( . . ( PCIN MONTH : ,«EAR i'(•')•.(' '> ~r ( 1"",T 1 ' -1 (SKIP TO MONTH END 1 : In What month and year di,d he begin and end ait* tiv«s duty in (COUNTRY)? BEGlil MONTH i. 1*.: '..,.„., 2.."...:' . ..,.,,..,(,.. • '., i. ,.-.-• . . ; . ' . . . . < c.., ,,,.J.'.r : 2. ... .....:.•:• , (.. I' .( ( 3.-' : . . . ' ,., ''../,,,,.,...;'( i - . , 3 . ' . . .. ; ' . . . . - . ( ( , .1 Did his d u t i e s in j. Did his duties in p. Did. his duties in (COUNTRY) include flying? (COUNTRY) includij flying? (cOONTrtV) include flying? I ' ' . 3. d. Yes.( ( u < ,j-l ; No. . . . J . ' -2 Ye*.( ( No.../,. e. k. Howrosilyf l i g h t hours did he! lofc w h i l e in (COUNTRY)? 1 1 1 " 1 ' 1 i How many f l i g h t hours did he log w h i l e in (COUNTRY)? 1 ..., ."' :"(,.:.(.} q. • . . . "( (AS'K Q,ilg) ' ( -1 How many f l i g h t hours did he lot; w h i l e in (.COUNTRY)? '1 .T • • ' • ! " I l.» 1 L ,,-.!- Hours ( ) ( ) ( ) Ofh«r (SPECIFY) . .. :..• . ,. .,.--(„.. x 'TV • . ..,. . :V . . . . ....'...•(. ,( -i What spe'iifie letref arid . r. numericat de8ignatioti(s) " ' . ..did ea'ch'''fli.rc'r*ft.. (ia.v^l' ' L. : •• " . • . " • • ' • r,:;:.,, .'...-';:. .' . • • . ,' '• '.' •.• • '• ,\ .' . ''. \. :. ,' •' : '!":.• '. *} ' ' ' .. .•.;•::,;•;.:.;;:•. .-*.••:$••." ...•; ...... (.,f ... 2. .',,..:'• ••/'; :;;.' r-..( .•(• : : .. ,,',.:.'( ',(,' .': ?. ' ./... •" •:'•;., :,:.' ':^ ( 2. 3..... 'r 'i: .'.'.' ' Yes.( • • • ( ' . Other (SPECIFY) ,. ... ,., .,..(, ,(,.:.,-! "-"""• '' '"" ?' ..<'?. f. What s p e c i f i c l e t t e r and fiumcrieal designat ion(e) did each a i r c r a f t ; have!? l. -1 -2 , I 1 t . •! Hours . ,(. - y (••".y-jvy .. ;. 1 . , ,4 •>. 1 Hours ( ')(.)'( ) Other (SPtfClJ'Y) 4. ' Q.17) c > 1 { , ) M (-^-4-( .:'y j i Current * . . ( J _,via rl c. . - ''I.". ) . ( ( -i (skip TP --^Q,17j In what month «ftd year did he begin jj'jiii end a,?* tive duty in (cb'BNTRY)1 : r i ." i ' T • [ . .. i i ...1- .1 . t. ' ( : A . . .'. •(.'(' (AS'tf Q.lta) What S p e c i f i c Ht^er and nuitierical designation(s) rfid!(Bach a i r c r a f t have? i.' ;:v.;.'0 •«.'::'.: '-. •;:•."(• ( '. 2. . : ::/-' . :: • . ( ( 3;.'.:"' V.; ' • • ' • : • : ' • . . • • • . ' ,•'( ( A. .'.'.'. ( ( ( RECOR& ADDt t iONAL COU^RI ES < IN S.R.B. PC 18 ANP 19) �CARD 812039 Now I would like to ask you about about (STUDY RESPONDENT'S) marital history. 17. Was he ever legally married? (ASK Q.18) 22) ... . - . . . , . . . IB. , .* • • • . - • . . • • . . , • . •• ^ '. v . '; How many times was he legally married? : . ,: .. (WRITE IN NUMBER) 1 1 ( 1 ' 1 | I times ) ( ) FIRST/ONLY, MARRIAGE 19a. In w h a t month and year did he get m a r r i e d (the f i r s t time)? 1 MONTH 2da. tn what month and year did he get married ( t h e second tilde? YEAK " 1 ""IT" I "T 19b. What (is/was) the current f u l l name ,of that w i f e (RECORD IN S.R.B. PG. 2 1 19c. THIRD MARRIAGE What was her f u l l maiden name? ]RECORD IN S.R.B, PG 2 | 1 1 MONTH 1 .1.1 1 '. H ( ) ( ) ( 21a. In what month and y e a r did he get m a r r i e d (the t h i r d time? YEAR 1 1 1 1 ) ( ) 1 1 MONTH 1 I I 1 l-l ( ) ( ) ( YEAR 1 1 1 1 ) ( ) 20b- What (is/was) the cur21b. What (is/was) the current f u l l name of rent full name of .•V : .^vths ; t,ijife;. ••,>. •• : '-'"' .•''•'' IfcECOKD .XN S.R.B. .PG,2: 1 (RECORD IN S.R.B. P(» 2 ( 20o . Wiat w4f. hftf full . ':•"•': ^.^'waiden';n«meY '•.'•'.•• .••".". •• 21c. (RECORD m st tR.fc. . PG 2 i What was her full maiden name? 1 RECORD IN S.R.B. PG 2 | 20d. During this marriage, 19d. During this Marriage, 21d. During this marriage, how many times was he how many times was he how many times was he living apart from his living apart from his living apart from hit w i f e (you) for more than wife (you) for more than wife (you) for mote than three months? three months? three months? 1 1 1 1 ( Never.. ( • 1 J Times ) ( -I I ,1 . 1 | Times I 1 I I 1 I Times ) ( I 1 (SKIP TO Q.19f) Never. .( ( '....-1. (SKIP TO / Q.20f) ' Never.. ( ( -1 (SKIP TO . Q^if) 19e. How many months did they 20e. How many months did they 21e. How many months did they (you) live apart the (you) live apart the (you) live apart the ( f i r s t / n e x t ) time? ( f i r s t / n e x t ) time? ( f i r s t / n e x t ) time? 1st 2nd '1 I ' 1 J ( ) ( I I I 1 Ath ( I 1 Months ) ( ) I ] ( I | 1st ) I I ( 3rd Months I 1 Months ) ( i ^ i I 3rd ( Months ( 2nd | I ' . ( . ), ( ) j ) I 1 Months Ath i 2nd ) i | Months 3rd j ( Months Ath 1 1 1 | I J ( 6th — 1 I } ( I | I | Months 5th J ) I I Months TTT~T (CO TO Q , 1 9 f ) i " " • " I """"."I | I Months ( ). ( ') i .: i 6th | T Months ' . • • ( • ) ( ) (GO TO Q . 2 0 I ) 5th 6th 1 I Months ) I 1 Months 'i j j Months ) ( .) I 1 ( ( • > ( ) . 5th ) ( I I | | . ( ' • ) ( ) _ 1 1 ( ...' 1 Months I | ) ( 1 I 1st ) ( I | Months ) i 1 ) I :1 | ()•(;>• Mpnths 1 1 I I I I Months (GO TO Q . 2 1 f ) �CARD FIRST/ONLY MARRIAGE TfF ONLY MARRlAGEl 19f. At the time he (died/ became incapacitated) was he divorced , widowed, separated, or w,ls lit married and living, with his wife? Uvjiif With (SKIP TO vifp.'-'^jL--1 Divorced. ... >i °-'22) -2 (SKIP TO rM!|>nratcd....~-3 " Q.l«h) 812039 SECOND MARRIAGE THIRD MARRIAGE IIP LAST MARRIAGE! 20f. At the time he (died/ became incapacitated) was he divorced, widowed, separated, or was he married and living with his wife? llF LAST MARRIAdEl 21f. At the time he (died/ became incapacitated) was he divorced, widowed, separated, or was he married and living with his wife? Living with wife...( _j_ -1 Living with (SKIP TO wife...( ( -1 Q.22) (SKIP TO Q.22) Divorced ... -2)(SK1P TO Separated -3| Q.20h) Divorced -2/(SKlP TO Separated....~-3f Q.21h) ~— (RECORD IN S.R.B.; PG 2 1 (Kia'.Oiil) IN S.R.B. PC 2 1 IIF OTHER MARRIAGES! [IF OTHER MARRIAGES I 19g. How did that marriage end --• was he divorced or was tie widowed? 20g. How did that marriage end -- was he divorced or was he widowed? Divorced( ( -lX(ASK Q.19h) Pivorced( Widowed Widowed . . -2J J [RECORb IN S.R.B. PG 2 1 |IF OTHER MARRIAGES I 21g. How did that marriage en(J -7 w*§ he divorced or was he widowed? ( -l\(ASK Q.20h) Divorced( -2j ( -1\(ASK Q.21h) [RECORD IN S.R.B. PG 2 1 IRECORD IN S.R.B. PG 2 1 IRECORD IN S.R.B. PC 2 1 19h. In what month and year was he (divorced/ widowed /separated)? 20h. In what month and year was lie (divorced/ widowed/ separated)? 21h. In what month and year was he (divorced/ widowed/separated)? I 1 MONTH I 1 I l-l I YEAR I 1 MONTH 1 1 ( ) < ) (: ) ( ) (IK A SKCOND MARRIAGE GO TO Q.20a) YEAR I I I I l-l 1 1 ( )( ) ( )( ) (IF A THIRD MARRIAGE GO TO Q.21a) 1 1 MONTH ' YEAR 1 1 I I I I 1 1 l-l 1 1 . ' ( ) ( ) ( )( ) (RECORD OTHER MARRIAGES IN S.R.B. PG 20 AND 21) �CARD 812039 22. How many children (has/did) (STUDY RESPONDENT) (had/have) — that is, of how many children was he the natural father? Please include all children, both those who are living and those who may no longer be living. i i r I I I children (WRITE IN NUMBER) Ho children. -1 (ASK Q.23) (SKIP TO Q.27a) 23. Starting with the oldest child, what is the first and last name of the child as it appears on the birth certificate? RECORD FIRST AND LAST NAMES OF ALL CHILDREN IN S.R.B. - PAGE 3-4. WRITE IN THE FIRST NAME ONLY AT THE TOP OF THE APPROPRIATE COLUMN,(S). FIRST CHILD THIRD CHILD SECOND CHILD NAME: NAME: NAME: . How old ie (CHILD) now? 25a. How old is (CHILD) now? 1 Child died..( ( -1 ( -1 (_ 24c. How much did (CHILD) weigh at birth? OUNCES POUNDS 1 1 1 Age Child died..( 24b. (Is/Was) (CHILD) male or female? Male Female 1 ( ( -1 ( -1 24d. What is j(CHILD)'s birth- 25d. What is (CHILD) 's birth date? date? MONTH DAY YEAR i—r T r~i—ri-ir~i—n i i i i „ rT~rri-ir~rr~y r 7T~fi MONTH DAY «• 1 (_ ~-2 POUNDS OUNCES Don't know. . . ( ( 26c. How much did (CHILD) weigh at birth? 1 Don't know...( ( -1 Male Female 25c. How much did (CHILD) weigh at birth? POUNDS ! 1 AKe 26b. (Is/Was) (CHILD) male or female? -1 ~-2 (_ 1 1 Child died..( ( -1 25b. (Is/Was) (CHILD) male or female? Male Female 26a. How old is (CHILD) now? YEAR lAl.SO RECORD IN S.R.B.-PG 3| OUNCES 1 Don't know. . . ( ( -1 26d. What is (CHILD) 's birthdate? MONTH DAY YEAR I ALSO RECORD IN S.R.B.-PG'TT 24e. Was the child premature, 25e. Vi... the child premature, 26e. Was the child premature, full term, or overdue? full term, or overdue? full term, or overdue? Premature. ( Full term Overdue Not sure (_ _ (CO TO Q.24f) _ ~ Premature.( Full term Overdue Not sure ( (GO TO Q.25f) -1 -2 -3 -A Premature.( ( -1 Full term -2 Overdue ____~3 Not sure...,.. -4 (GO TO Q.26£) �.812039 F|RST CHILD SECOND CHILD 24f. Where are (CHILD) 's birth registration records located? In what city and state is that? _ ' I RECORD IN S.R.B. p'c""3"t 25f. Where are (CHILD) '« birth registration records located? In what city and state is 24g. Where are (CHILD) 's current medical records located? In whnt city and stale is .that? TRECO>D IN a.fc.b. PC 3 T ~ 25g . Where are (CHILD) 's current medical records located? In what city and state is that? TRECORD IN S.R.B; PG 3 1 26g. Where are (CHILD) 's current medical records located? In what city and state is that? [feECORD IN S.R.B. PTT '3" I 24h. What was (CHILD) 's rfiother '.s ful 1 name? I RECORD IN S . PC 3 1 25h . Wliat was (CHILD) 's mother's full name? (RECORD IN S.R.B. PC 3 1 26h. What was (CHILD) 's mother's tul 1 name? 2Ai. How old was the mother when (CHILD) was born? 25i . How old was the mother when (CHILD) was born? 26i. How old was the mother when (CHILD) was born? IRECORD IN S.R.B. PC 3 1 1 1 T"rr~r I 1 I 1 26f. Where are (CHILD) 's birth registration records located? In what city and state is .that?_ ' . IRgCORD IN S.R.B. PGTT IRECQRD IN S.R.B. PC 3 1 1 Age Age 2/ij. Did (CHILD) have any b i r t h defects? 25j . Did (CHILD) have any bin.h defects? 26j. Did (CHILD) have any birth defects? Yes.C, ( Yes _-l (ASK Q.25k) Yes.( .j -1 (ASK Q,26k) No. _-2 (SKIP TO Q.25L) No No -1 (ASK Q . 2 4 k ) __-2 (SKIP TO Q.24L) 2Ak. What kind of birth defects did (s)he have? Any others? 25k . What kind of birth defeet s did (s)he have? Any others? __-2 (SKIP TO Q.26L) 26k. What kind of birth de^ fects did (s)he have? Any others? ( ( ( "( 24L, Was (CHILD) ever diagnosed as having cancer? 25L . Was (CHILD) ever diagnosed as having cancer? 26L. Was (CHILD) ever diagnosed as having cancer? Yes.( Yes ( Yes.( No 26m. ( -1 (ASK Q.24m) ( -1 (ASK Q.25m) -2 (SKIP TO Q.24o) No. _-2 (SKIP TO Q.25o) No ( -1 (ASK Q.26m) _-2 (SKIP TO Q.26o) In wlmt month and year 25m was the diagnosis made? In what month and year 26m. was the diagnosis made? In what month and year was the diagnosis made? MONTH MON Til MONTH YEAR 1 T I I YEAR 1 1 1 24n. W)iat k i n d of cancer was diagnosed? 25n. What kind of cancer was diagnosed? 1 1 (GO TO Q.24o) -1 Not sure. .( ( (CO TO Q.25o) -1 II l-l YEAR 1 1 26n. What kind of cancer was diagnosed? . .. Not stire..( ( 1 1 ''-r";''.. /...If; < Not sure.,( J (GO TO Q.Z6o) -I �CARD FIRST CHI 1.1) SECOND CHILD 2Ao. (DofS/Did)(CHII.n) have a diagnosed learning disability? Yes.( 812039 THIRD CHILD s/Did)(CinLD) have nosed learning disity? ( -1 (ASK Q.24p) -1 (ASK Q.2Sp) No...... -2 (SKIP TO Q.24q) No. 26o. (Does/DidXCHILD) have diagnosed learning disability? Yes.( _-2 (SKIP TO Q.25q) No kind of learning b i l i t y (does/did) «• have? ( ( Uliat k i n d o f l e a r n i n g d i s a b i l i t y (does/did) (s)h<> have? ( -1 (ASK Q.26p) -2 (SKIP TO Q.26q 26p. What kind of learning disability (docs/did) (s)he have? ( ( ( ( 24q. (Do<.'s/Did)(CHJU>) have any physical, mental, or motor impairments? Yes.( s/nid)(CHILD) have physical, mental, o r impairments? (__-! (ASK Q.2Ar) No ( ( 26q. (Does/DidHCHILD) have any physical, mental, motor impairments? Yee.C -1 (ASK Q.25r) _-2 (SKIP TO Q.25s) No __-2 (SKIP TO Q.24s) No. 2Ar. What kind of impairment (does/did) (s)he have? kind of impairment s/did) (s)he have? ( -1 (ASK Q.26r) ' -2 (SKIP TO Q.26s 26r. What kind of impairment (does/did) (s)he have? ( ( ( ( OTHERWISE: 24s. E: DAY CONTINUE SKIP TO NEXT CHILD IF CHILD IS DEAD:. OTHERWISE: tat date did LD) die? On what date did (CHILD) die? MONTH ( ( IS MAD: ONTINUE SKIP TO NI'.XT CHILD i—r~T r~~i ( ( YEAR 1 DAY 1 1 1 -1 ! 26s. l-l MONTH YEAR 1 I 1 I ( ) ( )( ) ( ) ( ) ( ) ( 24t. What was the cause at death? was the cause of i? death? CONTINUE SKIP TO NEXT CHILD On what date did (CHILD) die? MONTH 1 I I 1 l-l DAY 1 1 I I l-l YEAR 1 1 )( ) ( ) ( )( ) ( 26t. What was the cause of death? ( ( ( ( Where is (CHILD)'s death registered? In what city and state IE that? _ JJL S. R. B PC 3 J v (GO TO NEXT CHILD Q.25a) ( ( ( ( is (CHILD) 'B registered? In city and state is 26u. Where is (CHILD) 's death registered? In what city and state is that? that? S.R.B. PG 3 1 NEXT CHILD 26a) [RECORD IN S.R.B. PC 3 1 (RECORD ADDITIONAL CHILDREN IN S.R.B. - PG 22-30) �CARD 27a. 812039 Now let's talk about (STUDY SUBJECT'S) health. Did (STUDY SUBJECT) ever have pneumonia? Yes.( No 27b. ( , -1 _-2 (ASK Q.27b) (SKIP TO Q.29a) How many times did he have pneumonia? (WRITE IN NUMBER) times I ( )< T First Time 28a. Second Time- During what months and years did he have pneumonia (the first time)? 28f. During what months and years did he have pneumonia (the second 28k. 1 RECORD IN S.R.B. PC 5 1 IF IlliKORE 1961, SKIP TO Q.28f , RECORD IN S.R.B. PG 5 1 IF 'BEFORE 1961, SKIP TO Q.28k. 28g. What is the full name of the doctor who mode the diagnosis or the medical facility where the diagnosis was made? RECORD IN S.R.B. PG 5 1 IF BEFORE 1961, SKIP TO Q.29a. What is the full name 28L. of the doctor who made the diagnosis or the medical facility where the diagnosis was made? 28h. What is the full name of the doctor who made the diagnosis or the medical facility where the diagnosis was made? I RECORD IN S.R.B. PG S 1 (RECORD IN S.R.B. PC 5 1 8c. What prescribed medicine did he take for the pneumonia he had that time? During what months and years did he have pneumonia (the third time)? r i rue ) ? RECORD IN S.R.B. PC 5 1 !8b. Third Time 28m. What prescribed medicine did he take for . the pneumonia he had that time? What prescribed medicine did he Cake for the pneumonia he had that time? 1. t / ( ( 8d. t?s.( c, Be, Was he hospitalized for the pneumonia he had that time? ( -1 (ASK Q.28«) -2 (SKIP TO Q 28f) What was the full name of that hospital? RECORD IN S.R.B. pcf'5 ] ( ( 1. (. ( 2. ( ( 2. (( 3. (( 3. (( 28i. 28n. Was he hospitalized for the pneumonia he had that time? Yes.( ( -1 (ASK Q.28i) Yes.( No ... -2 (SKIP TO Q.28k) No, Was he hospitalized for the pneumonia he had that time? ( -1 (ASK Q.28o) -2 (SKIP TO Q.77a IN S.R.B. PG 31) 28 j . What was the full name 2 80. What was the full name of that hospital? of that hospital? 1 RECORD IN SiR.B^lp 5"! 1 RECORD IN S.R.B. PG 5 1 (RECORD, ADJD.ITION.AI. PERIODS IN S.R,B. PAGE 31) 1 -' 217 �CARD 29a. 812039 Did (STUDY RESPONDENT) ever have cancer? Yes..(_J (ASK Q.29b) No 29b. -1 -2 (SKIP TO Q. 30) In which parts of his body was cancer located? LIST EACH BODY PART BELOW. FOR ADDITIONAL PARTS. IF MORE THAN THREE BODY PARTS, USE S.R.B. - PAGE 32 Part 1 Part 3 Part 2 29c. In what month and year was cancer of the (BOD PART) first djagnoBed? I RECORD IN j R. B. P(T .6, I . 29i. In what month and year 29o. In what month and year was cancer of the (BODY was cancer of the (BODY PART) first diagnosed? PART) first diagnosed? I RECORD IN S.R.B. PC 6 I IRKCORD~TN S.R.B. PC 6 I 29d. What is the full name 29j. Wliat is the full name 29p. What is the full name of the doctor or the of the doctor or the of the doctor or the medical facility where medical facility where medical facility where the diagnosis was made7 the diagnosis was made? the diagnosis was made? I RECORD IN S.R.B., PC' f>_"\_ |RECORD~~IN S.R.B. PC 6 I I RECORD IN S._R.B. PC 6 I 29e. What is the full name of the doctor or the medical facility he last consulted about cancer of the (BODY PART)? {RECORD IN Sr.R.B.L PC 6 j 29k. Wliat is the full name of the doctor or the medical facility he last consulted about cancer of the (BODY PART)? 'IRECORD IN S.R.B. PG~ 6 j 29f. 29q. What is the full name of the doctor or the medical facility he last consulted about cancer of the (BODY PART)? I RECORD IN S.R.B. 'PC 6 I 29L. D u r i n g what month and year did he last cons u l t (NAffljJtOM Q.29e)? During what month and 29r. During what month and year did he last conyear did he last consult (NAME FROM Q.29q)? suit (NAME FROM Q.29k)? [RECORD IN S.R.B. PC 6 1 jRECORD IN S.R.B. PC 6 I TRECORD IN'S.R.B. PC (TT PART)? "IMULTIPLE RECORD BELOW I ' What treatments or 29e. What treatments or medicines did he take , medicines did he take for cancer of the (BODY for cancer of the (BODY PART)? FART)? IMUI.TI PLE RECpRD"BEi.OWI TMU'LTI PLE 'RECORD TF.IXJW I Radiation (_ ( -1 Chemotherapy...(~ ( -1 Surgery (_ ( -1 Other (SPECIFY) Radiation......( ( -1 Chemotherapy...( ( -1 Surgery ( ( -1 Other (SPECIFY) 29g. 29m. What treatments or medicines did he take for cancer of the (BODY ( .( 29h. DurinK what month and year did he first receive (EACH TREATMENT CODF.O IN Q.29g) for cancer of the (BODY PART)? MONTH Radiation... .( ( -1 9n. MONTH I I 29t. MONTH YEAR hemoT I T 1 I I j-| \ l-l I I therapy. I ( M ) ( M ) ( )( ) 7~7T~ I MONTH YEAR MONTH YEAR Surgery. . J \ I MONTH _ ~~TT I urgery. 1 I I I YEAR YEAR hemotherapy 1 MONTH I T [_ _H urgery. J ther... i i M I I l-l YEAR ther... (GO TO NEXT BODY PART) 1 YEAR ( )( T r MONTH r~T Other.... I !_ I-J J J < ) ( ) < ) ( )" (CO TO NEXT BODY PART) MONTH | j MONTH *adiaI tion.... I T) < ) ( ) ( ) MONTH YEAR Chemotherapy. -1 During what month and year did he first receive (EACH TREATMENT CODED IN Q.29s) for cancer of the (BODY PART)? YEAR i n r adiation .( ( -1 During what month and year did he first receive (EACH TREATMENT CODED IN Q.29m) for cancer of the (BODY FART)? YEAR Radiation (_ ( -1 Chemotherapy... ( ( -1 ~ Surgery ( ( -1 Other (SPECIFY) YEAR i r I I (GO TO NEXT BODY PART IN S.R.B. PAGE 32) �61203$ (JOT PREVIOUSLY MENTIQNte.P, ASKVj loinDid (STUDY RESPONDENT) ever have leukemia? Yes..( •..(.t . -1 No 30b. (ASK Q.30b) (SKIP TO Q.31a) -2 In what month and year Was his leukemia first diagnosed? I RECORD IN S . R | •, -, PC ?,.]. .., 30c. What is the. full name of the doctor or the medical facility where the diagnosis was made? J RECORD IN.; S,-K».B.-.- -v '$.. 7,. I 30d. b. What treatments or medicines did he take for leukemia? |REC_Q^D JBELpjIj hCPIClNE/TREATMEj4T |..yiRST..RECEIVED MONTH. .,..YEAR T I " ' I l'"\"-' | I I l-l I. I I. ) ( ) I ) ( ) 2. _ 3. ' , ,_ :i ( ..( ( 1 11 { iI.....H......L T i y ( <•>(j MONTH .YEAR. . \T Tl T T I ... I .... ...... . . T J{ ) ( )( ) 30e. During what month and year did he first receive (EACH TREATMEHT OR MtDICINE IN Q.30d>? J.RECORD. ABOVE |. 30f. What is the full name of the doctor or medical facility he last consulted about his leukemia? .1 RECORD IN .S..R..B. - PC .?.. |. 30g. During what month and year did he last consult (NAME IN Q.30O? FREGORD IN S.R.B. - PG 7 �CARD 812039 31a. I would like to ask you some questions about other medical conditions (STUDY RESPONDENT) may have had. 1. Did he ever have diabetes? Yes........( (_ No............._ 2. -1 -2 ("X" BOX ON PAGE 18) Did he ever have thyroid problems? Yes (SPECIFY) ____ . ( _ ( ___ -1 ("X" BOX ON PAGE 18) _ No.....". ~................._ -2 3- Hid he ever have anemia? Yes........( (_ No............._ A. -1 -2 ("X" BOX ON PAGE 18) Did he ever have a heart condition? Yes (SPECIFY) ______ . ( _ ( ___ -1 ("X" BOX ON PAGE 18) No----. 7 ................._ "7 _-2 5. Did he ever have an enlarged liver? Yes........( (_ No............._ 6. Yes........( j_ No......... . . _ .. ("X" BOX ON PAGE 19) -1 -2 ("X" BOX ON PAGE 19) -1 ("X" BOX ON PAGE 19) -2 Did he ever have gall bladder problems? Yes........( (_ No............._ 11. -1 -2 Did he ever have intestinal parasites? N 10. ("X" BOX ON PAGE 19) Did he ever have cirrhosis of the liver? Yes........(__<_ No............._ 9. -1 -2 Did he ever have hepatitis? Yes........( (_ No............._ 8. ("X" BOX ON PAGE 18) Did he ever have jaundice? Yes........( (_ No............._ 1. -1 -2 -1 -2 ("X" BOX ON PAGE 19) Did he ever have any other liver condition? Yes (SPECIFY) ._. _____ . ( (_ -1 ("X" BOX ON PAGE 20) No....... ................._ ' _-2 12. Did he ever have a respiratory condition other than pneumonia? Yes (SPECIFY) ___ . ( (_ No........................_ 13. -1 ("X" j-2 BOX ON PAGE 20) Did he ever have any other major condition? Yea (SPECIFY ALL OTHER CONDITIONS) <"X" BOX ON PAGE 20) No "-2 �CARD DIABETES 1/tSK (J.jl'b THROUGH Q.31e ifos E/ICW BOX "X"ED ON ipp. J£-20 1 ! 1 1 ! 1 I ! 1 I 1 THYROID PROBLEMS 1 ! 1 ! i t 1 ! 31-t?., Wfftm <Jid a doctor first e«lt him than he had eeeiJDITION)? 3i-c. ANEMIA I 1 SI2039 I 1 ! 1 ! 1 A HEART CONDITION 1 1 i 1 1 1 1 1 Whwt is- th« f u l l name of the doctor who made the rfi^gnosis or the medical facility where the diag- a doctor for (CONDITION)?. Jle. 1 1 1 1 [RECORD -IN S . R . B . 1 IPAGE 8 1 IRECORD IN S. R . B . I t IRECORD is S.R.B.I IPAGE 8 ! IRECORD is S.R.B.I . (RECORD IN S.R.B.] IPAGE 8 ! , IRECORD is S.R.B. ! IPAGE 8 1 iRECORD IK S.R.B. ! (PAGE 8 1 iRECORD IK S . R . B . I JRECORD IN S.R.B. I IPAGE 8 ! (RECORD IN S.R.B. I IPAGE 8 ' 1 IRECORD IN S.R.B. i IPAGE 8 1 IRECORD IN S.R.B.I IPAGE s 1 (PAGE 8 I RECORD IN S.R.B.! IPAGE 8 1 IRECORD IN S.R.B.! IPAGE s i [RECORD IN S.R.B. 1 IRECORD IN S.R.B.I IPAGE 8 i IRECORD iw S.R.B. 1 IPAGE 8 I (GO TO NEXT CONDITION "X"ED) (GO TO SEXT CONDITION 'X"ED) (GO TO NEXT COSDITIOW "X"ED) TO NEXT COROTTION "X"ED) ) IPAGE 8 (PAGE 8 IPAGE 8 I j 31 d. Vffifeti1 did he l»»t consult •~j •^i AK ENLARGED LIVER Wha-t is the full name of tlte doer tor o^r ined-ica.!; facility he last eonsfttlted about hi s> teOSDITIOU)? ....«.„. -.,...„ TO NEXT CONDITION "X"ED) IPAGE s 1 IRECORD IN S.R.B. 1 i IPAGE 8 IRECORB IN S.R.B. 1 IPAGE 8 1 IRECORD IN S.R.B. 1 1 �CARD JAUNDICE !ASK Q.31b THROUGH Q.3.1e [FOR EACH BOX "X"ED ON [PP. 18-20 31b. 31c. 1 1 1 1 1 i 1 1 1 I 1 812039 HEPATITIS i CIRRHOSIS OF THE LIVER ! I 1 1 1 1 1 1 1 ! 1 i 1 1 1 1 1 1 1 1 1 1 1 GALL BLADDER PROBLEMS i 1 ! ! When did a doctor first tell him that he had (CONDITION)? (RECORD IN S. R.B.I IPAGE 8 I [RECORD IN S.R.B. 1 IPAGE 9 1 IRECORD IN S.R.B.I i [RECORD IN S.R.B.I IPAGE 9 • 1 IRECORD IN S.R.B.I IPAGE 9 I What is the full name of the doctor who made the diagnosis or the medical facility where the diag- [RECORD IN S.R.B. I I [RECORD IN S. R.B.I IPAGE 9 1 [RECORD IN S.R.B. 1 JPAGE 9 1 IRECORD IN S.R.B.I IPAGE 9 1 IRECORD IN S.R.B. 1 iFAGE 9 1 .RECORD IN S.R.B. I IPAGE 8 1 [RECORD IN S.R.B. 1 IPAGE 9 1 [RECORD IN S.R.B. I IPAGE 9 1 IRECORD IN S.R.B. I IPAGE 9 ! i RECORD IN S.R.B. 1 IPAGE 9 1 [RECORD IN S.R.B. | JPAGE 8 1 (GO TO NEXT CONDITION "X"ED) [RECORD IN S.R.B.i IRECORD IN S.R.B. 1 IPAGE 9 .1 i RECORD IN S.R.B. I [RECORD IN S.R.B.I IPAGE 9 1 (GO TO NEXT CONDITION "X"ED) (GO TO NEXT CONDITION "X"ED) IPAGE e IPAGE 9 31d. When did he last consult a doctor for (CONDITION)?. 31e. INTESTINAL PARASITES What is the full name of the doctor or medical facility he last consulted about his (CONDITION)? IPAGE 9 1 (GO TO NEXT CONDITION "X"ED) IPAGE 9 1 (GO TO NEXT CONDITION "X"ED) ) �CARD [ASK Q.31b THROUGH Q.31e (FOR EACH BOX "X"ED ON IFF, 16-20 31b. 31c, 31d. I I I When did a doctor f i r s t tell him that he had (CONDITION ) ? What is the f u l l name of the doctor who made the diagnosis or the medical f a c i l i t y where the diag- Wben did he last consult a doctor for (CONDITION)?. What is the f u l l name of the doctor or medical facility he last consulted about his (CONDITION)? , 1 (RECORD IN S. R . B . I IPAGE 9 1 ! 1 1 (RECORD IN S. R.B.I IPAGE 9 1 ANY OTHER MAJOR CONDITION 1 1 i i 1 1 1 1 SECOND OTHER MAJOR CONDITION i ! 1 ! I 1 i 1 THIRD OTHER MAJOR CONDITION 1 [ 1 1 IRECORD IN S.R.B.I IPAGE 10 1 IRECORD IN S.R.B.I IPAGE 10 1 IRECORD IN S.R.B. 1 1 IPAGE 10 « IRECORD IN S.R.B. | IPAGE 9 ! IRECORD IN S.R.B. I IRECORB IN S.R.B. [ IPAGE 10 1 iRECORD IN S . R . B . 1 | 1 IRECORD IN S.R.B. 1 IPAGE 10 1 IRECORD IN s. R . B . I 1 IRECORD IN s. R . B . I IPAGE 9 1 [RECORD IN S . R . B . | 1 PAGE 10 1 IRECORD IN S . R . B . 1 IPAGE 10 1 IRECORD IN S.R.B. 1 IPAGE ib 1 (RECORD IN S.R.B. I IPAGE 9 1 IRECORD IK S.R.B. 1 IPAGE 9.. 1 (RECORD IN S . R . B . I (RECORD IN S.R.B. 1 IPAGE 10 1 iPAGE 9 31e. |A RESPIRATORY CONDITION I ! OTHER THAN PNEUMONIA 1 ! I I 1 ANY OTHER LIVER CONDITION 1 1 1 1 812039 (GO TO NEXT CONDITION "X"ED) I PAGE 9 (GO TO NEXT CONDITION "X"ED) IRECORD IN S.R.B.I iPAGE 10 I (GO TO NEXT CONDITION "X"ED) IPAGE 10 IPAGE 10 I (GO TO NEXT CONDITION "X"ED) �CARD 812039 32. Did (STUDY RESPONDENT) ever have acne on hie face? Yes..( ( -1 (ASK Q.33a) No.. 33a. -2 (SKIP TO Q.35a) As far as you know, during what year did he last have acne on his face? I Year J. (ASK Q.33b) T (WRITE IN YEAR) First Period YKAK MONTH r I 33c. Until when did that last? 33j. Think about the third time he had acne on his face — when did it start? MONTH YEAR I I MONTH YEAR —i—n—i— i r 33g. Until when did that last? MONTH YEAR I T T 1 T I H I I (SKIP TO Q.35a) Third Period 33f. Think about the second time he had acne on his 'face -- when did it start? L 1( 1 I -l (_ Second Period 33b. Think about the first time he had acne on his face -- when did it start? MONTH Before 1961.. ( l-l I 33k. Until when did that last? YEAR 1 I MONTH YEAR i i rr i r I I j I I 7 n l-li n r 7 n nnr 33d. Please show me on this diagram where the acne was located (the first time). 33h. Please show me on this diagram where the acne was located. 33L. Please show me on this diagram where the acne was located. THAND RESPONDENT CARD "E"| I MULTIPLE RECORD BELOW I I HAND RESPONDENT CARD "E"T IllAND RESPONDENT CARD "E" | I MULTIPLE RECORD BELOW| [MULTIPLE RECORD BELOW I Temples ."(_ Eyes or eyelids.( ( Ears ( Cheeks ( Nose ( Forehead ( Jaw, Chin, Other( -1 -1 Eyes or eye] ids. ( ( _-l Ears ( T~ -1 Cheeks ( ( Nose ( ( -1 ~-l Jaw, Chin, Other( ( -1 33e. Did he ever have another period of acne on his face? 33i. Did he ever have another period of acne on his face? Yes.( Yes.( No <__-l (ASK Q.33f) N . . 7 " -2 (SKIP TO Q.41a) o.7. Temples .( Eyes or eyelids.( Ears ( Cheeks ( Nose ( Forehead ( Jaw, Chin, Othert ( -1 ( -1 (""" -1 ( -1 ( -1 ( -1 ( -1 33m. Did he ever have another period of acne on his face? ( -1 (ASK Q.33J) Yes.( -2 (SKIP TO Q.34a) No ( -1 -2 IF ANY~nY"ES1' TO TEMPLE ,~fY*ES",EYELlUS7"OR1 IN Q.33d, ABOVE: ASK Q.34a. ALL OTHERS: SKIP TO Q.35a. 3Aa. Did he ever consult a doctor or medical facility about the acne on his (temples/eyes or eyelids/ears)? Yes. No Don't know.. -1 (ASK Q.34b) ~2 KSKIP TO Q.35a) -3J 34b. When did he last consult a doctor about the acne on his (temples/eyes or eyelids/ears)? [RECORD IN _S^R.j^._- PC 34c. What w.-is the name of the doctor or medical J_ facility he consulted at the time? �812039 Did (STUDY RESPONDENT) ever have (READ EACH COLUMN HEADING)? I IF "YES" TO AUY COLUMN HEADING,'ASK Q>35^-hFORTHAT COLUMNt A. ( p£ B,._'_ Patches hie. .stein change color? Easier bruising of the akin than usual? Yes..( No DK Yea..( ( -1 No. .. -2 DK. . . . -!i Yes..( ( -1 No -2 DK ...~3 ( -1 -2 ~~-3 b. On what part of his body did he have (CONDITION)? Any other part? b. On what part of his body did he have (CONDITION)? Any other part? b. On what part of his body d i d he have (CONDITION)? Any other part? •' C. Skin that was extra sensitive or seemed to hurt for no reason? ( ( < ( ( ( < ( ( ( ( ( c. Did he discuss (CONDITION) with a doctor? c. Did he discuss (CONDITION) with a doctor? c. Did he discuss (CONDITION) with a doctor? Yes.( Yes.( Yes.( No. DK ( -1 (ASK Q.35d) .. -2\(CO TO NEXT -3| CONDITION) *" — No DK ( -1 (ASK Q.35d) -2\(GO TO NEXT -3J CONDI TION) No DK ( -1 (ASK Q.35d) -2") (SKIP TO -3J Q.36a) iJ Wliat was the diagnosis? d. -What was the diagnosis? d. What was the diagnosis? ( ( ( ( ( ( ( ( d. ( ( ( ( e. What is the name of the e. What is the name of the e. What is the name of the doctor who made the diagdoctor who made the diag. doctor who ma do the diagnosis or the medical nosis or the medical nosis or the medical facility where the diagfacility where the diagfacility where the diagnosis was made? nosis was made? nosis was made? (RECORD.- IN S.R.B. - PG ill f. During what month and year was the diagnosis made? 1 RECORD IN S.K.B. - PO 111 f. During what month and year was the diagnosis made? IRECORD IN S.R.B. - PG ill f. During what month and year was the diagnosis, made? IRKCORD IN S.R.B. - PG li 1 I RECORD IN S.R.B. - PG 1 1 1 [RECORD IN S..R.B. - PC ill g. What is the name of the doctor or medical facility he last consulted about (CONDITION)? g. What is the name of the doctor or medical facility he last consulted about (CONDITION)? g. What is the name of the doctor or medical facility he last consulted about (CONDITION)? FRE'CORD IN S.R.B. - PC nl h. During what month and year did he last consult (NAME IN Q.35g)? 1-HECOUI) IN S.R.B. - PG 111 ] RECORD IN S.R.B. - PG 111 h. During what month and year did. he last consult (NAME IN Q.35g>? (RECORD IN S.R.B. - PG 111 -"•••: .:••••./• -.•:.; ,•'• 225 [RECORD IN S.R.B, - PG III h. During what month and year did he last consuit (NAME IN Q.35g)? IRECORD IN s j | , - ?& nl ..l �812039 CARD 36a. Aside from injury, (was there ever/has there ever been) a period of time when (STUDY RESPONDENT) had (READ EACH COLUMN HEADING)? IIF "YES" TO ANY COLUMN, HEADING, ASK Q.36b-j FOR THAT COLUMN! B. Persistent tingling sensations in any of his limbs? A. Persistent numbness in any of his limbs? Ycs..( No DK b. ( -1 -2 ' -3 When did he first notice (CONDITION)? MONTH C. Persistent deep burning sensations in any of his limbs? Ye s.. (__(__- 1 No. . . . . . . -2 DK -3 Yes..(. 4 -1 No -2 DK -3 b. YEAR b. When did he first notice (CONDITION)? ii ii • - r i i i i (>()()() c. . MONTH YEAR 1 1 1 1 1 1 I l l - I l l ( ) ( ) ( ) ( ) Which limbs or muscles were affected? (CONDITION)? Any other part? c. Which limbs or muscles were affected? (CONDITION)? Any other part? When did he first notice (CONDITION)? MONTH YEAR 1 1 I I 1 I I I I I ( ) ( ) ( ) ( ) c. Which limbs or muscles were affected? (CONDITION)? Any other part? ( ( e. ( ( ( ( d. ( ( ( ( ( ( d. During what period was the (CONDITION) most intense? FROM MONTH YEAR I I I I 1 1 r H 1 ( )( ) ( ) ( ) TO MONTH YEAR 1 1 1 1 1 1 1 1 l-j 1 1 ( ) ( ) ( ) () Did he see a doctor for (CONDITION)? Yes.( No DK ( -1 ((IF NO OR DK, -2< GO TO NFXT -3 (^CONDITION) During what period was the (CONDITION) most intense? FKOM MONTH YEAR 1 1 1 1( )( )( )( ) TO MONTH YEAR d. During what period was the (CONDITION) most intense? FROM MONTH YEAR 1 1 1 1( )( )( )( ) TO MONTH YEAR 1 1 1 1 1 1 1 1 l-l 1 1 ( } ( )( )( 1 e. Did he see a doctor for (CONDITION)? e. Did he see a doctor for (CONDITION)? Yes.( ( -1 (?IF NO OR DK. No ... -2J GO TO NEXT Yes.( ( -1 | F NO OR DK, U No . . . -2J CO TO NEXT . DK -3\ CONDITION) DK 1 1 I 1 What was the diagnosis? :. 1 1 1 1 ( V( ) ( ) ( ) -3 1 CONDITION) __«- f. M hi ^ What was the diagnosis? :. What was the diagnosis? ( ( ( ( ( ( ( ( ( ( ( ( g. What is the name of the doctor who made the diagnosis or the medical facility where the diagnosis was made? JRECPRD IN S.R.B. - PC 12j [RECORD IN S.R.B. - PC 12] [RECORD IN S.R.B. - PC 12| h. During what month and year wae the diagnosis made? |RECORD IN_ S.R.B. - PC 12J IRECORD IN S.R.B. - PC 12| IRECORD IN S.ft.B. - pc 121 i. What is the name of the doctor or medical facility he last consulted about (CONDITION)? TRECORD IN S.R.B. -~PG 12! IRECORD IN S.R.B. - PG 121 IRECORD IN; S.R.B: - 3' Pur ing what month and_year did he last consult (NAME IN Q.36g)? TRECORD IN S.R.B'. '-'PC 12]' JRECORD i N "s". R^ sT_ - PG^ 1 2! 220 I2 ___ IRECORD IN S.R.B. - PC 121 �36a. Aside Irom injury, (was there ever/has there ever been) a period of time when (STUDY RESPONDENT) had (READ EACH COLUMN HEADING)? TlF "YES" TO ANY COLUMN HEADING, ASK Q^3b-j FOR THAT COl.UMJj1 D. E. P e r s i s t e n t aches and paint in any of his l i m b s ? A reduction in grip strength? YL-S..< ( Yes..( -1 No DK b. • ' -3 [)(: b. When did he f i r s t nulice (CONDITION)? MONTH 1 1 -1 ! ~~~-3 When did he f i r s t notice- (CONDITION)? YEAR M ( No. . . . . . . -2 ....-? 1 I I I l l I l l. 7— TIT- r~rr~7 MONTH YEAR 1 M i l l l - I l l Which limbs or muscles were affected? (CONDITION)? Any other part? Which limbs or muscles were aftncted? (CONDITION)? Any olher part? ( ( During what period was the (CONDITION) most intense? FROM MONTH YEAR 1 1 1 1 I V ! l-l 1 d. During what period was the (CONDITION) most intense? FROM MONTH YEAR 1 1 I 1 T C ") ( 7 ( ) ( 5 I 1 I l-l ) ( TO ) ( TO MONTH 1 1 fJ YEAR 1 IH ) ( 1 ) ( 1 ) 1 ( e. ( I - 1 K 1 F NO ..OR DK , 1 ) ( YEAR 1- , 1 ( ) ( ) ( ) ( ) e. Did lie sec- a doctor for (CONDITION)? Yes . ( Mn MONTH T 1 ) ( 1 1 1 ) Did he see a doctor for (CONDITION)? Yes.( ( -1 No -2 IH' -2 J GO TO NKXT . . . . -3J CONDITION) DK -3 f. What was the d i a g n o s i s ? f. What was the diagnosis? ( ( ( ( g. ( ( ( ( What is the name of the doctor who made the diagnosis or the medical facility where the diagnosis was made? TRECORD IN s.R.B.^- PC nl [RECORD IN S.R.B. - PC 12! h._ During "hat month ami year wa» the dia^nosie madgl I RECORD IN S.R.B. - P C 12 1 I RECORD 1 N S, R ~,"i"f'-* W " '' ' ' " " • -- i. What is the name of the doctor or medical facility he last consulted about (CONDITION)? "> ! j. During what month and year did he lust consult (NAME IN Q.36g)? ___ „ __ -.-._..., __ ,..-.-_____K .r, TRKCORD IN S . K . B . - J7: ijT "i RECORD TN S . R . B . - pc_tiT 227 �CARD 812039 37a. Did (STUDY RESPONDENT) ever smoke cigarettes regularly for a period of ac least onemonth? \ Yes ..( ( -1 (ASK Q.37b) No 37b. -2 (SKIP TO Q.39a) In what month and year did he start smoking cigarettes on a fairly regular basis? MONTH _JEM_. I I ( n r ( ) () 37c. In what month and year did he jast smoke cigarettes on a fairly regular basis? MONTH YEAR T I I l-l I I 37d. Between (START DATE) and (END DATE), for about how many years altogether did (STUDY RESPONDENT) smoke cigarettes, not counting times when he stopped smoking? I ( I I Years )( ) 38. When (STUDY RESPONDENT) was smoking cigarettes on a fairly regular basis, about how many packs per week did he smoke? By "pack" we mean 20 cigarettes. I J I j I |_ packs per ~i n r week 39a. Did (STUDY RESPONDENT) ewer smoke a pipe regularly for a period of at least one month? Yes 39b. ( ( -1 (ASK Q.39b) No -2 (SKIP TO Q.Ala) * In what month and year did he start smoking a pipe on a fairly regular basis? MONTH YEAR i i n i r I I I"!.. I T~rr~r '"i > I(• r 39c. In what month and year did he last smoke a pipe on a fairly regular basis? MONTH YEAR <:n. r (i ( ) 3<ld. Between (START DATE) and (END DATE), for about how many years altogether did (STUDY RESPONDENT) smoke a pipe, not counting times when he stopped smoking? T—i—r Years I I I ( )( ) 40. When (STUDY RESPONDENT) was smoking a pipe on a fairly regular basis in (START DATE), about how many pipefuls per week did he smoke? I I I pipefuls per TTT T week �Ala. Did (STUDY RESPONDENT) ever smoke cigars regularly for a period of at least one month? Yes ( ( -1 (ASK Q.Alb) No Alb. ,,-2 (SKIP TO Q,A3a) In what month and year did he start smoking cigars on a fairly regular basis? MONTH YEAR 1 1 1 1 _ Ale. In what month and year did he last smoke cigars on a fairly regular basis? MONTH YEAR 1 1 11 1- 1 1 1 Aid. Between (START DATE) and (END DATE), for about how many years altogether did (STUDY RESPONDENT) smoke cigars, not counting times when he stopped smoking? 1—T—T I J , J Years ( V (' ) 42. When (STUDY RESPONDENT) was smoking cigars on a fairly regular basis in (START DATE), about how many cigars per week did he smoke? 1 I I I \ 1 cigars per week v ) (r 'IJt^STUDV.'R^spONbfeMf SMOKED' tiftXKgTt^. A' pip|^b£fcjeA|s7Tgg;T A3. In general, when he was smoking did he inhale the smoke? ( ( ,r -1 -2 Yes No AAa. Now let's talk about drinking alcoholic beverages, that is, beer, wine, or hard liquor. Did he ever drink alcoholic beverages on a fairly regular basis? Yes ( ( No ,:..-! .....2 .'.,- (ASK Q.AAb) (SKIP TO Q.46) AAb. When did he start drinking alcoholic beverages on a fairly regular basis? MONTH YEAR 1 T ' ~ I I ... AAc. When did he lajj drink on a fairly regular basis? MONTH YEAR I i T I" I I ( ) ( ) ( M ) A5. When (STUDY RESPONDENT) drank alcoholic beverages on a fairly regular basis in (START DATE), about how many drinks per week did he Usually have?. I ( I I drinks per ) ( T week �_____ CARD 812039 Now I'm going to ask you a feu questions about his recreation and leisure activities. 46. What are some of the hobbies and sports he participated in on a regular basis? Any others? (( 1. . 2,. . 3. „ (. ( ; (( (_ ( ____. ' 5. (( 6. 47. Did he p a r t i c i p a t e three or more times in (READ EACH 1TKM)? ITEM MKNT10NEU IN Q.46 AND DO NOT READ THAT ITEM) (CODE "YES" FOR ANY Yes 1. ( ( . ~1 2. Auto, boat, or motorcycle racing ( ( -1 3. Skydiving ( ( -1 -2 4. Mountain climbing ( ( -1 -2 5. Hang gliding ( ( -•! -2 ( ( ~1 ~2 6. Scuba diving Plane racing or plane acrobatics, not including flight training or any assignments for the Armed Forces.. �CAkD J 812039 TlK STUDY KKSl'QNDENT IS DECEASED, ASKQ.48-52; OTHERWISE CO TO (J.53.J Now T would like to know more about the circumstances surrounding (STUDV RESPONDENT'S) death. 48. What was the official cause of Ins death? H9. In what c i t y and state was (STUDY RESPONDENT) living at the time of his death? £i_,j! __________ , _____________________ , ____ ; ______ : - J -. Kcnte ( ( (IF OUTS IDK U. S . )_CounMrg , r (rj(. 50u. Wns lie in a hospital at the t imo of his death? Yes No.. 50b. (......(-...,,--1 -2 < ASK Q-50b) (SKIP TO Q.51) What was the name of the hospital? iRKCORj).' IN S.R.B. PAGE 33 i 51. What is the name of the primary physician who was responsible for his care at the timi1 of death? SK.B..PAGE S2. Was an autopsy performed? Yes ......... (_J ___ -1 No.............._ -2 S"i. Wu would like your const-lit for the doctors and medical facilities you mentioned .luring this interview lo p r o v i d e (STUDY UliSPONDIvNT'S) medical records to the Air Force H e a l t h Smvuy. This w i l l h e l p us to obi. lin uituu complete and detailed information about rhe h e a l t h services you talked about, Thank you loi participating in the Air Force Health Study! TIMI-: ItriKHVII-.W KIIOEI): ______________ ...... __ __ (um/|.i.,) �LOUIS HARRIS AND ASSOCIATES, INC. 630 Fifth Avenue New York, New York 10111 FOR OFFICE USE ONLY: Case No. Study No. 812039 O.M.B. NUMBER 0701-0033 Approval Expires 11/30/82 Respondent #: CONFIDENTIAL AIR FORCE HEALTH SURVEY SUPPLEMENTAL RECORDING BOOK PROXY 232 �812039 Q.2. Where born: City: State: ; Q.8b-13b, ! 1st job: 2nd job: 3rd job: 4th job: 5th job: 6th job: 7th job: 8th job: 9th job: 10th job: llth job: 12th job: Employers Q.8e -13e Main Puties �812039 Q.16: Countries Served In: 1. 7. 2. 8. 3. 9. A. 10. 5. 11. 6. 12. Q. 19-21 and (.';-(>? Marital History f/K b. Wife's Current Full Name First/ only wife Second wife Third wife Fourth wife Fifth wife Sixth wife Wife's Maiden Name Living W i t h W i f e Or Divorced/ Separated/ Widowed �i and 68- 7 b CHILDREN CHILD Q.29 FIRST NAME i . BI RTHDATE First . First ; : Last THIRD First ' Last FOURTH First First ; Last First La s t . MONTH C/S Place First Place C/S Last C/S YEAR Place i l 1 1 C/S Place First Place C/S Last C/S YEAR 1 ! Place First Place 1 1 l-l C/S Last C/S YEAR Place i l 1 1 C/S Place First Place M l-l C/S Last C/S YEAR I 1 Place First Place I I l-l C/S Last C/S DAY i I M l-l YEAR Place i l I 1 C/S MONTH 1 1 1 1 l-l DAY 1 1 M l-l DAY 1 i i l-l I-! . 1 1 I DAY II I-! 1 1 MONTH DAY 1 1 1 1 1 l-l 1 u.- DEATH RECORDS Last Place 1 1 C/S Place 1 1 C/S Place I 1 C/S Place h. MOTHER'S FULL NAME Place YEAR 1 1 i I g. . CURRENT MEDICAL RECORDS First II l-l MONTH ! SI XTH. DAY 1 1 1 Last FIFTH MONTH 1 1 1 1 l-l BIRTH RECORDS MONTH 1 1 1 Last SECOND f. ' C/S �Q.2A-26 and 63-76 CHILDREN CHILD Q.29 NAME d. MONTH SEVENTH First Last EIGHTH NI NTH ELEVENTH DAY 1 1 !-| MONTH DAY 1 1 1 1 I-l 1 ! YEAR 1 i YEAR 1 1 1 I I-l I I I-l 1 1 T 1 MONTH \ 1 1 1 I-l DAY i 1 YEAR 1 1 T 1 MONTH 1 I I 1 l-t DAY YEAR 1 I I i I I I 1 g. CURRENT MEDICAL RECORDS h. MOTHER'S FULL NAME u. DEATH RECORDS First Place C/S Last C/S Place First Place C/S Last C/S Place First Place C/S Last C/S Place First Place C/S Last C/S Place 1 1 C/S • Place First Place C/S Last C/S Place 1 1 r/s Place First Place C/S Last c/s • Place ' 1 1 c/s YEAR DAY 1 1 ! I I 1 BIRTH RECORDS Place YEAR I 1 1-1 MONTH 1 1 1 1 I-l 1 I TWELFTH First Last 1 1 1 ! i-l First Last DAY I ! I-! MONTH First Last 1 1 f. T 1 1 ! 1 I I I - ! ! First Last TENTH ! 1 First Last BIRTHDATE Place 1 1 c/s Place ! 1 C/S Place I I c/s �136 CARD Q.28 Medical Providers — Pneumonia 1st Tint' a. 1'nd Time M o n t h s / y e a r ; ; lint) th.it t i me . 1 L MONTH f YEAR 1 1 1 L . l-l (1.3 0 1 ) 1 n. MONTH 1 1 1 1 1 I 1 1 l - l YEAR ' 1 I t:1 •) CM ) CM > ) C'i ) <!•'. ) (TO a. M o n t h s / y e a r s had t h a t time. MONTH T I 1 I i I D o c t o r / f a c i l i r y who murie dingnosis. 1 I hi YEAR 1 l l (!•', ) I'O I I - 1 1 1 1 (10 ) (U ) TO MONTH YKAR YEAR M l-l C'H ) C.") ) TO i "' V ' i i i i i (| h 5 i ( 1.7 ) 1-1 d (j ) i <| o } i b. 3rd Time M o n t h r . / y o i i r s h.ld t h a t t imo , TO MONTH. 812039 1 I l (;>{, ) C-'?1) 1 I 1 l D o c t o r / f a c i l i t y who made diagnosis. b. MONTH YEAR 1 1 1 1 -I l l I l l ( 3 2 ) (3'3) (.14) ( i S ) D o c t o r / f a c i l i t y who made d i a g n o s i s. Name Name Name Address Address Address C/S C/S C/S e. Name of h o s p i t a l . e. Name of h o s p i t a l . e. Name of h o s p i t a l . Name Name Name Address Address Address C/S C/S C/S a. Months/years had that time. a. MONTH YEAR 1 I I 1 1 l l I l l 1 ) '( } ( ) ( ) TO MONTH YKAR I I I I I I I I I I ( ) ( ) ( ) ( ) D o c t o r / f a c i l i t y w h o made diagnosis. M o n t h s / y e a r s had that t ime. 1 I 1 I b. 6th Time 5th Time 4111 Time I I MONTH YEAR 1 1 1 1 1 l l I l l ( ) ( ) ( ) ( ) TO MONTH YEAR I i ( ) ( ) h. a. M l-l MONTH YEAR T 1 I I 1 ' i I l l - I l l ( ) ( ) ( ) ( ) TO MONTH 1 1 I I 1 1 l-l ( ) ( ) ( I I I .1 ( ) ( ) Doctor/ f a c i l i t y who made diagnosis. Months/years had that time. b. YEAR 1 1 1 .1 ) '( ) Doc tor/ f a c i l i l y who made diagnosis. Name Name Name Address Address Address C/S C/S C/S e. Name of h o s p i t a l . e. Name of h o s p i t a l . e. Name of hospital. Name Ma me Name Address Address Address C/S C/S •.""/• •'.' .' . ••'/:'. C/S . . �CARD Q.29. Part 2 Month/year f i r s t diagnosed 1 I d. 812039 Medical Providers -- Cancer Part 1 c. 1 (6-H7 c. Month/year f i r s t diagnosed MONTH YEAR 1 1 1 1 1 l l I l l ( ) ( > ) ('17") (J8> (•]«> Doctor/ f a c il i t y where f i r s t d i a g n o s i s made: Part 3 c. Month/year first diagnosed MONTH YEAR 1 1 I I 1 1 I l l I l l (/,.', ) (45 ) ( 4 ( > ) (47 ) <1. D o c t o r / f a c i l i t y where f i r s t d i a g n o s i s made: 1 1. d. MONTH YEAR 1 1 1 1 1 1 l-l 1 1 ( W ) (VJ) (54) (55) D o c t o r / f a c i l i t y where f i r s t diagnosis made: Name Name Name Address Address Address C/S C/S C/S e. D o c t o r / f a c i l i t y last consulted. e. D o c t o r / f a c i l i t y last consulted. e. Doctor/facility consulted. Name Name Name Address Address Address C/S C/S last C/S f. Month/year last consulted • MONTH 1 l l 1 I YEAR I I l 1 1 - (40) ( 4 1 ) f. f. M o n t h / y e a r last consulted . 1 I 1 l 0,2> 0 , j ) M o n t h / y e a r last consulted. MONTH YEAR 1 1 1 I 1 l l I l l ( 4 8 > O.y) ( 5 0 ) (51 ) Part it 1 I MONTH YEAR 1 I I 1 1 l l I l l ('>6> (57) (58 > < 5 9 > Part 5 Part 6 * c. * Month/year f i r s t diagnosed 1 1 MONTH 1 1 (do) <6i ) d. YEAR 1 1 I I l-l c. Month/year f i r s t diagnosed 1 I 1 I (6:') ( b j ) D o c t o r / f a c i l i t y where f i r s t d i a g n o s i s made: d. c. Month/year f i r s t diagnosed MONTH YEAR 1 I I 1 1 l l I l l (68) ( 6 4 ) (?()) ( ? l ) D o c t o r / f a c i l i t y where f i r s t d i a g n o s i s made: 1 I d. MONTH YEAR 1 I I 1 1 l l I l l (12) (13> <14> <15> D o c t o r / f a c i l i t y where f i r s t diagnosis made: Name Name Name Address Address Address C/S C/S e. D o c t o r / f a c i l i t y last consul ted . C/S 1 e. Doctor/ " .icil itv l a s t consu 1 ted . e. D o c t o r / f a c i l i t y last consul ted. Name Name Name Address Address Add res s C/S C/S C/S f. Mnnth/vfliir last r o i i K u l I .••!. MONTH I l (64) f. Munrh/yoai- lasl m i i K t i i t ctl . YKAR l I l l (63) (6(1) ( ( > ? ) 1 J MONTI! 1 .1 1 I i-l f. M o n t h / y e a r last I . . I I H I l l 1 ,-.!. YKAR 1 1 1 1 1 I MONTH 1 l l ( I I . ) (17 ) II fl.H YEAR 1 I l ) 0') ) 1 l �137 Q.30 Medical Providers — Leukemia b. Month/year first diagnosis! MONTH YKAR —i—n—r~ 1-1 c. Doctor/facility where first diagnosis made: Name Add ress_ c./s f. Doctor/facility last consulted. Name Address_ C/S g. Month/year last consulted. I I MONTH I I YEAR 8)2039 �CARD Q.31. Medical Providers — THYROID b. First Cold h a d : MONTI! 1 I l First told h a d : YEAR I I 1 l 1 - (28) (29) 812039 OTHER MEDICAL CONDITIONS DIABETES b. 137 I ! l 1 I l (IJO) (31) c. D o c t o r / f a c i l i t y where diagnosis made; c. ANEMIA b. First told h a d : MONTH YEAR 1 I I 1 1 l l I l l (44) (45) <4(>) (-'•?) Doctor/ f a c i l i t y where diagnosi s made: 1 1 MONTH YEAR 1 I I 1 1 1 l-l 1 1 (6()) (<>] ) (62) (63) D o c t o r / f a c i l i t y where d i a g n o s i s made: c< Name Name Name Address Address Address C/S C/S C/S d. Doctor last consulted: 1 I ,| Doctor last c o n s u l t e d : MONTH YEAR 1 1 1 1 1 l l I l l (32) ( 3 3 ) (34) (15) e. Doctor/Facility consulted. last 1 I e. Doctor last consulted: d MONTH YEAR 1 1 1 1 1 l l I l l (48) ( 4 9 ) ( 5 0 ) (51 ) Doctor/Facility last consulted. 1 1 e. MONTH YEAR 1 I I 1 1 1 l-l 1 1 (64) (65) (66) (67) Doctor/Facility last consulted. Name Name Name Address Address Address C/S C/S C/S ENLARGED LIVER HEART CONDITION b. First told had: 1 1 b. First t o l d h a d : MONTH YEAR 1 I I 1 1 1 ' l-l 1 1 (36) (37) (38) (39) c. Doctor/ f a c i l i t y where diagnosis made: 1 I c. JAUNDICE b. First told had: MONTH YEAR 1 . 1 1 1 1 l l I l l (52) (53) ( 5 4 ) (55^> D o c t o r / f a c i l i t y where diagnosis made: 1 I MONTH l (68) c. 1 YEAR I I I l - I l (69) T l (70) (71) D o c t o r / f a c i l i t y where diagnosis made: Name Name Name Address Address Address C/S C/S C/S d. Doctor last consulted: MONTH 1 I l (40) e. l (41) 1 1 - d. YKAR 1 1 I l l ( 4 2 ) (43) Doctor/Facility last consulted. Doctor j as t c o n s u l t e d : 1 I e. d. MONTH YKAR 1 1 1 1 1 l l I l l (56) ( 5 7 ) (58) (59) u o c t o r / F a c i l i t y last consulted. Doctor last consulted: 1 I e. MONTH YEAR 1 I I 1 1 l l I l l (72) ( 7 3 ) (74) (75) Doctor/Facility last consulted. Name Name Name Address Address Address C/S C/S C/S Mi) _ _ �CAKD Q.31. CIRRHOSIS OF THE L1VEK First told had: MONTH i l 1 b. YEAR 1 (12) (13) 1 b. MONTH YEAR 1 I I I 1 1 l-l 1 1 (28) (29) (.30) (31) 1 1 (14) (15) Doctor/facility where diagnosis made: INTESTINAL PARASITES First told had: 1 1 l I,.. .1 . .!-.!.. c. §12039 Medical Providers -- OTHEK MEDICAL CONDITIONS (CONTINUED) HEPATITIS b. I.JH c. Doctor/facility where diagnosis made: First told had; MONTH YEAR 1 I I 1 1 1 l-l 1 1 (44) (45) (46) (47) I '1 c. Doctor/facility where diagnosis made: Name Name Name Address Address Address C/S C/S C/S ^ Doctor last consulted: MONTH I 1 ' I 1 (1_ Doctor last consulted: MONTH 1 1 r <16) (17) (18) 1 1 I 1 1 l I! l - (32) (33) (19) Doctor last consulted: YEAR 1 YEAR I I . l-l. d. I 1 l l MONTH YEAR 1 I I 1 1 .1 l-l 1 | (48) (49) (50) (51) 1 1 (34) (35) c. Doctor/Facility Vast consulted. c. Name Name Name Address Address Address C/S C/S C/S Doctor/Facility last consulted. GALL BLADDER b. MONTH - l 1 1 h. i ( 20)r ( 21) i-i YEAR 1 i Doctor/Facility last consulted. OTHKR I.1VKK CONDITION First told had: l c. First told had: 1 1 1 i ( 22) ( 23) c. Doctor/facility where diagnosis made: c. OTHEft RESPIRATORY h. First told had: MONTH YEAR MONTH YEAR 1 .1 1 . 1 1 1 1 I I I I 1 l-l 1' 1 I l l I l l ( 36) ( 37) ( 3H> ( 39) 62 ) 63 ) ^54) (55) Doctor/facility where diagnosis made: c. Doctor/facility where diagnosis made: Address Name i 'Address Address C/S C/S C/S Name d- Doctor last consulted: MONTH 1 1 e. 1 1 („>/,) (Zljj d. Doctor last consulted: YEAK i 1 l-l 1 1 (26) (27) Doctor/Facility last consulted. Name MONTH 1 1 i ! : 1 1 i'. j ! 1 d< Doctor last consulted: YEAR 1 ! l-l ( 40) ( 41) 1 1 1 1 1 I (42) Uj> Doctor/Facility last consulted. e. MONTH YEAR 1 M 1 1 l l I l l < 56) ( 5?) < 58' '( 59' Doctor/Facility last consulted. Name Name Name Address l\d dress Address C/S :/s :/s J4J .. �138 CARD Q.31. Medical Providers -- OTHER MEDICAL CONDITIONS (CONTINUED) OTHER MAJOR CONDITIONS b. F i r s t told h a d : c. SECOND MAJOR CONDITIONS b. MONTH YEAR 1 1 ! I I l l I l l (60) (61) ( 6 2 ) (63) I I 812039 THIRD MAJOR CONDITIONS F i r s t told h a d : MONTH 1 l l 1 I I I - YEAR 1 I l b. 1 l F i r s t told h a d : : 1 I MONTH 1 l l i I l ^ Doctor/ f a c i l i t y where d i a g n o s i s made: D o c t o r / f a c i l i t y where diagnosis m a d e : YEAR I I l II - D o c t o r / f a c i l i t y where diagnosis made: Name Name Name Address Address Address C/S C/K C/S d. Doctor l a s t c o n s u l t e d : Doctor l a s t c o n s u l t e d : MONTH YEAR 1 I I I I l l I l l (64) (65) ?66) ( 6 7 ) 1 I e. Doctor/Facility consulted. 1 I ( MONTH 1 l l i ( !) I I - YEAR 1 I l ( ) ( ) 1 l Doctor l a s t c o n s u l t e d : 1 - D o c t o r / F a c i l i t y last consulted. last MONTH 1 1 1 I l l - ( ) ( ) Namp Name Address Address Address C/S C/S C/S Q. 34 Medical P r o v i d e r s — Ac First b. Last consulted doctor 1 I c. MONTH YEAR 1 1 1 1 1 l l I l l ( 6H> (6<l ) C 7 ( i » ( 7!) D o c t o r / f a c i l i t y last consulted: Name Address C/S 242 ( ) ( ) Doctor/Facility consulted. Name YEAR 1 I l last 1 l �CARD A. PATCHES OF S K I N CHANCE COLOR c. D o c t o r / f a c i l i t y where diagnosis made: 812039 C. SKIN EXTRA SENSITIVE B. EASIER BRUISING OF SKIN e. D o c t o r / f a c i l i t y where diagnosis made: e. D o c t o r / f a c i l i t y where diagnosis made: Name Name Name Address Address Address c/s C/S C/S f. Month/year diagnosis made: f I g. f. MONTH . YEAR "i I 1 1 1 l l I l l (11!) ( 1 ! ) ( I t , ) (!')) D o c t o r / F a c i l i t y last consulted. f. Month/year diagnosis made: 1 I MONTH 1 l l I I - (28) (L'y) g. YEAR 1 I l Month/year" diagnosis made: MONTH 1 1 l I (ill) ( i l ) l •! l ( 4 4 ) (45) g. D o c t o r / F a c i l i t y last consulted. YEAR II - I 1 l l 1 (46) (47) D o c t o r / F a c i l i t y last consulted. Name Name Name Address Address Address C/S C/S C/S h. Month/year last consulted: I 1 MONTH YEAR 1 1 1 1 1 1 1-1 1 1 ( ] f , ) ( 1 7 ) (18) ( 1 9 ) h. h. Month/year last consulted: ' MONTH 1 I 1 l (32) l (33) Month/year last consulted: YEAR I I - 1 I l ( 3 4 > (15) 1 l 1 1 MONTH YEAR I I I 1 i 1 l-l 1 I (48) (49) . (50) (51) �CARD 1'30-UO 812039 Q.36 -- M e d i c a l P r o v i d e r s >;. C. B U R N I N G I N LIMBS B. T I N K L I N G I N 1. 1 MBS A. NUMBNKSS I N I.IMBS g. K . Doctor/ f a c i l i t y where d i a g n o s i s made: D o c t o r / f a c i l i t y where d i a g n o s i s made: Doctor/ f a c i 1 i t y where d i a g n o s i s made: Name Name Name Address Address Address C./S C/S C/S li. 1 I i. h. h. M o n t h / y e a r d i a g n o s i s made: M o n t h / y e a r diagnosis made: MONTH MONTH YEAR 1 1 1 1 1 l l I l l <:>2> < 5 J > ( 5 4 ) tyj ! I ! Doctor/Facility last consulted. YEAR ! l ! l (68) Month/year diagnosis made: ! - (69) I ! l l 1 I : ( 7 0 ) (71.) i. i. D o c t o r / F a c i l i t y last consulted. MONTH YEAR 1 I I 1 1 l l I l l (16 ) ( 1 7 ) (18) (19) D o c t o r / F a c i l i t y last consulted. Name Name Name Address Address Address C/S C/S C/S j_ M o n t h / y e a r last consul t e d : 1 I MONTH YEAK 1 I I 1 1 l l I l l <56> (57) ^58) «59'" MONTH 1 I 1 l l 1 I l ( //.) ( 7 r >) 1 l E. REDUCTION IN C R I P STRENGTH g. D o c t o r / f a c i l i t y where d i a g n o s i s made: D o c t o r / f a c i l i t y where d i a g n o s i s made: Name Name Address Address C/S . h, C/S M o n t h / y e a r diagnosis made : MONTH YEAR r i i i i r I l l - I l l h. Month/year diagnosis made : = i 1 MONTH i 1 D o c t o r / F a c i l i t y las I consulted. Name Address C/S YEAR i i l-l ( 7<>) (/ / ) i. i 1 1 1 ' 7.s' ( ?')) i. Doctor/Facilitv last . c o n s u l ' . d. i i Namp 1 Address C/S i. Month/year last consulted: 1 I MONTH YEAR 1 I I "1 1 l l I l l (04) ((>'>) (6f>) ( ( > 7 ) i . Month/year last consul ted: 1 1 M o n t h / y e a r last consulted: YEAR M - ( 7 2 ) ( 7l) D. PERSISTENT ACHF.S IN L I M B S g. j. j . Month/year last consul ted : MONTH 1 II 1 l-l ( 12) ( J .1) YEAR 1 1 ( 1 ',) ( 1 5) 244 r. 1 I MONTH YEAR 1 1 1 1 1 l l I l l (20 ) ( 21) ( 22) ( 23) �CARD °06 Q.5A 812039 Additional Civilian Training Programs (Q.6) b. For what kind of work was his next civilian training program preparing him? ... , , 6th Program 5th Program 4th Program f. For what kind of work was his next civilian training program preparing him? ar>( j. For what kind of work was his next civilian training program preparing him? < \ h< nsc nisr C\f,t (\7( (17( . .. (17 C [l8-19[ |l8-19| ...... c. In what month and year did he start this training? 1 1 MONTH I I I 1 l-l (2<>) (:>i> YEAR 1 1 1 1 g. In what month and year did he start this training? 1 1 (22) (•>•}) d. In what month and year did he complete this training? MONTH YEAR 1 1 II 1 1 I . I l-l 1 1 (24) (25) (26) (27) n ^t MONTH YEAR 1 I I 1 1 1 l-l 1 ] (20) <!l ) ( ) (2:i) « h. In what month and year did he complete this training? MONTH 1 1 18-19 k. In what month and year did he start this training? MONTH 1 1 1 1 l-l (24) (25) 1 1 (26) (27) 1 1 1 1 (22) ( ' ) 2) L. In what month and year did he complete this training? MONTH 1 1 YEAR 1 1 l-l (20) (>l ) YEAR 1 1 1 1 1 1 YEAR 1 1 1 1 1 l-l 1 C24 > < 25) ( 26) ( 27) e. Did he participate in any other civilian job training program that prepared him for a major change in his occupation? i. Did he participate in any other civilian job training program that prepared him for a major change in his occupation? m. Did he participate in any other civilian job training program that prepared him for a major change in his occupation? Yes.(jp( Yes.(?8( No. • Yes.(28( -1 (ASK Q.f) " Q.7a) 04 79-80 -1 (ASK Q.j) -2 (RETURN TO Q.7a) 05 79-8"0 245 -1 (RETURN TO 0.6 75^80 �007 CARD Q.55. A d d i t i o n a l M i l i t a r y T r a i n i n g Progr.-ims ( Q . 7 ) 4th P r o g r a m b. 812039 6th Program 5t.li Program For w h a t k i n d of work was h i s next m i l i t a r y t r a i n i n g program prep a r i n g him? g. L, Kor what k i n d of work was h i s next m i l i t a r y t r a i n i n g program preparing him? For what k i n d of work was h i s next m i l i t a r y t r a i n i n g program prep a r i n g him? d')( (!')( (!'->( • (lb( (16( (16( (U ( (17( ' c. W h a t was the AFSC for t h a t job? < d. \ I MONTH l \ (21) e. l l - (22) \ \ ( I i. \ l l MONTH \ 1 l (21) ( 2 2 ) In what month and year did he complete t h i s training? j. m. l-l \ YKAR 1 \ What was the AFSC for t h a t job? ( ( In what month and year did lie s t a r t t h i s training? \ 1 (23) (24) ^B.2()| What was the AFSC for t h a t job? ( YEAR d7( [IH-2()|- h. 7n what month and year did he s t a r t t h i s training? ' \ 1 n. . In what month and year did he start this training? ! 1 : MONTH ! 1 (21) (23) (24) In what month and year did he c o m p l e t e t h i s training? ( o. YEAR 1 1 H (22) 1 1 1 1 (23) (24) In what month and year did he complete this training? • MONTH •1 I f. 1 YEAR II 1 1 MONTH YEAR 1 1 1 i 1 1 1 1 1 1 1 1 (2rO (2(0 (27)(2H) 1 l l I l l ( L ' r > ) (2(0 ( 2 7 ) (28) Did he participate in any other m i l i t a r y job t r a i n i n g program that prepared him for a major change in his occupation? Yes.Q'it No -1 (ASK Q.g) "-2 ( R K T U K N TO Q.8) k. Did he p a r t i c i p a t e i n a n y other m i l i t a r y job t r a i n i n g program that prepared him for a major change in his occupation? Yus. (;>•)< No -1 (ASK Q . L ) -2 ( R K T U K N TO Q.S) 1).'. ()'> 7<f-HO 7y"-'m> 240 1 1 : MONTH 1 1 1 r 1 1 - (J O (26) p. YEAR 1 1 1 1 1 ( 2 7 ) (28) D i d he p a r t i c i p a t e i n a n y other m i l i t a r y job t r a i n i n g program t h a t prepared him for a m a j o r change in his occupation? Yes.(:")( No -1 (RETURN TO -2 Q.8) 06 79-80" �CARD Q. iio-bl. , , MO.OTH ... 1 . I I 1 . (l'j) (id) I .1 (17) I 1 1 1 (18) b. b, Wh*f was th* name of his employer? IRECORD IN S.R.B. - PC I I MONTH YEAR 1 I I 1 1 1 l-l I I (15) (10) (17) (18) 1 1 What was the name of his employer? b. c. Was the job fulltime or part-time? c. Fu 1 1 t ime . . ( I <)( -1 MONTH YEAR 1 I I 1 1 1 l-l 1 1 (15) (16) (17) (18) What was the name of his employer? IRECORD IN S.R.B. - PC 1 i TRECORD IN S.R.B. - PG i \ Was the job fulltime or part-time? Full tim«. . I9( ( 58a. In what month and year did he start his next job that lasted three months or longer? 57a. In what month and year did he start his next job that lasted three months or longer? YEAR ! l-l Ninth Job Eighth Job 56a. In what month and year did he start his next job that lasted three months or longer? c. 812039 Additional Jobs (C .8-13) Seventh Job I 1 008 -1 Was the job fulltime or part-time? Full time..(!9( d. What kind of business was that — what did they make or do there? d. What kind of business was that — what did they make or do there? d. e. What did he actually do on the job -- what were some of his main duties? e. What did he actually do on the job — what were some of his main duties? -1 e. What kind of business was that — what did they make or do there? What did he actually do on the job — what were some of his main duties? IRECORD IN S.R.B. - PC 1 1 TRECORD IN S.R.B. - PC i I IRECORD IN S.R.B. - PG I 1 IHAND RESPONDENT CARD "B"| IHAND RESPONDENT CARD "j»"| IHAND RESPONDENT CARD "B"| n,, i f. Please look at this card and tell me the number which best describes the kind of industry he worked in. (WRITE IN NUMBER) g. 1 1 1 I I 1 (20) (2l) In what month .and year did this job end? I I f. -1 (RETURN TO Q.14) What was the main reason he stopped working .il that job? - " ' !, ' „ f. Please look at this card and tell me the number which best describes the kind of industry he worked in.' Please look at this card and tell me the number which best describes the kind of industry he worked in. (WRITE IN NUMBER) 1 I 1 1 (WRITE IN NUMBER) 1 1 | I I I .1 1 (20) (21) r-, Ell In what month and year did this job end? (20) (21) g. MONTH YEAR I I I 1 1 l l I l l (2H) (24) (25) (2ft) Current job..(27( h. r r.lr In what month and year did this job end? 1 1 MONTH 1 1 Current job..(27( h. I I l-l -1 YEAR 1 I . g. 1 1 1 I (RETURN TO Q.14) MONTH 1 II 1 l-l (2;)) (24) Current job,.(27( -1 YEAR 1 (25) 1 1 (26) (RETURN TO Q.14) What was the main rea- i h.. What was the main reason he stopped working son he stopped working at that job? at that job? (28 (28 i (28 (20 (29 i (29 (ASK Q.57a) no-Try (ASK Q.58a) 07 79-80 "Oo-'l /) OH 70-80 247 I (ASK Q.59a) Vi'o-fi') _o.9. 79-80 �CARP 59a. In what month and year did he start his next job that lasted three months or longer? 60a. In w h a t month and year MONTH 1 I (15) ( i n ) 61 a. did he s t a r t his next job t h a t lasted three months or longer? YEAR UTTOH) YEAR 1 M 812039 T w e l f t h Job Eleventh Job Tenth Job MONTH OQH In w h a t month and year did he s t a r t his next job t h a t l a s t e d three months or .longer? MONTH I I I l l I l l <15 > (16 ) (17 ) (18 ) I YEAR 1 II l l 1 - 1 I (15 ) (16 ) l l C17 ) U8 ) b. What was the name of his employer? [RECORD, IN S.R.B,. - PC f I b. What was the nnme of h i s employer? I RECORD IN S.R.B. - PG 1 I ! b. What was the name of his e m p l o y e r ? (RECORD IN S.R.B. - PC 1 c. Was the job fulltime or part-time? c. Was the job fulltime or part-time? c. Was the job fulltime or part-time? Fu 11 t ime..( Part Lime... Full time..(l9( Part time -1 -2 Full time..(l9(_ Part time -1 -2 d. What kind of business was that — what (do/ did) they make or do there? d. What kind of business was that — what (do/ did) they make or do there? d. What kind of business was that — what (do/ did) they make or do there? e. What did he actually do on the job — what were some of his main duties? e. What did he actually do' on the job — what were some of his main duties? e. What did he actually do on the job — what were some of his main duties? IRECORD IN S.R.B. - PG i 1 IHAND RESPONDENT CARD "B"| f. Please look at this card and tell me the number which best describes the kind- of industry he worked in. (WRITE IN NUMBER) g. 1 | (20) 1 1 1 1 H In what month and year MONTH YEAR I I I 1 1 l l I l l (23) ( 2 4 ) (25) ( 2 6 ) Current j o b . . ( 27( -1 (RETURN TO Q.14) h. What was the m a i n reason he stopped working at that job? IRECORD IN S.R.B. - PG j 1 i IHAND RESPONDENT CARD "Bir| f. Please look at this card and t e l l me the [ number which best describes the kind *of industry he worked in. • (WRITE IN NUMBER) 1 I 1 | 1 I IHAND RESPONDENT CARD "B"| f. Please look at t h i s card and tell me the number which best describes the kind of ind u s t r y he worked in. ; (WRITE IN i NUMBER) 1 I (20) ( 2 1 ) (21) did this job end? 1 I IRECORD IN S.R.B. - PG i 1 I (20) g. In what month and year did t h i s job end? 1 I I I MONTH YEAR 1 1 1 1 1 l l I l l r (23) (24) (2 >) (26) Current (RETURN TO job..(_27(__-l Q . 1 4 ) h. What was the m a i n reason he stopped working at t' ...t job? (21) HI ; g. In what month and year did t h i s job end? MONTH 1 I YEAR 1 l I I l - (23) (24) Current job..(27( -1 1 I (25) 1 l (26) (RETURN TO Q-14) h. What was the m a i n reason he stopped working at that job? (28( (28( (2B( (29( (29( (29 ( (ASK Q.60a) (ASK Q.61a) TJo"-7jy (RETURN TO Q.14) ~(To-T7j" 11 10 '7 9- HO O't-36) l TiTT-TJ")" 12 "79-80 7<J-~80 Cl/,-36) (34-36) 248 �015 CARD 812039^ Q.62. Additional Periods in Military (Q.U) a. In what month and year did he next enter the Armed Forces? 1 1 MONTH ' YEAR 1 I I 1 1 1 l-l 1 1 (14) (15) (16) (17) f. In what month and year did he next enter the Armed Forces? MONTH 1 1 k. In what month and year did he next enter the Armed Forces? YEAR 1 1 1 1 I I l-l (14) (15) 1 1 (16) (17) 1 1 MONTH YEAR 1 1 1 I I 1 l - l I I (14) (15) (16) (175 b. What branch of the mili- g. What branch of the mili- L. What branch of the military was that? tary was that? tary was that? Air Force. ( 8 1( -1 Army -3 Coast Guard... -5 c. Was he discharged or separated from the (BRANCH OF SERVICE)? Air Force. ( 8 1( -1 Air Force. (IB( Coast Guard... -5 Coast Guard. . . 'r h. Was he discharged or separated from the (BRANCH OF SERVICE)? -1 -5 m. Was he discharged or separated from the (BRANCH OF SERVICE)? Discharged/ Discharged/ Discharged/ separated. (ig( -1 (ASK separated. (19( -1 (ASK separated. ( ig( -1 (ASK Q.62d) Q.62n) Q.62i) Still in Still in Still in (MILITARY) -2 (RETURN (MILITARY) -2 (RETURN (MILITARY) -2 (RETURN TO Q.15 ~" TO Q.15 1 TO Q.15) d. In what month and year was he discharged/ separated from the (BRANCH OF MILITARY)? 1 I MONTH YEAR 1 I I 1 1 l l - I l l (20) (21) (22) (23) i. In what month and year was he discharged/ separated from the (BRANCH OF MILITARY)? 1 1 MONTH YEAR 1 1 I 1 1 1 l-l 1 1 (20) (21) (22) (23) n. In what month and year was he discharged/ separated from the (BRANCH OF MILITARY)? I I MONTH YEAR I I 1 I -1 1 (20) (2l) (22) (23) e. Following his separation j. Following his separation o. Following his separation or discharge in (DATE IN or discharge in (DATE IN or discharge in (DATE IN "i"), did he reenter the "n"), did he reenter the "d"), did he reenter the Armed Forces? Armed Forces? Armed Forces? Yes..(24( -1 (ASK Q.62f) Yes..(24.( -1 No -2 No....77T -2 (RETURN TO " Q.15) 04 79-80 249 Yes..(24( -I\;(ReTURN TO (ASK Q.62k) (RETURN TO No.... 771 -2 ( (JilS) Q.15) Q5 06 79-80 79-80 �CARD Q.63. 812039 016 Additional Countries (Q.15-16) Seventh Country Ninth Country Eighth Country What was the next country that he was stationed in for more than 90 days while on active duty? What was the next countr that he was stationed in for more than 90 days while on active duty? a. What was the next country that he was stationed in for more than 90 days while on active duty? (14 -15 (lit -15 (14 -15 (RECORD COUNTRY HERE AND IN (RECORD COUNTRY HERE AND IN (RECORD COUNTRY HERE AND IN S.R.B. PG 2 AND CONTINUE) S.R.B. PG 2 AND CONTINUE) (S.R.B. PG 2 AND CONTINUE) ! (No others.(l(,( -1 (RETURN No others.(j,6< -1 (RETURN No others.(lb( -1 (RETURN TO Q.17) TO Q.17) j TO Q.17) b. n. In what month and year did he begin and end active duty in (COUNTRY)? In what month and year |h. did he begin and end ac- | tive duty in (COUNTRY)? j In what month and year did he begin and end active duty in (COUNTRY)? BEGIN BEGIN MONTH YEAR 1 1 I I 1 1 I l l I l l (17) (18) (19) (20) BEGIN MONTH YEAR 1 1 1 1 1 1 I l l I l l (17) (18) (19) (20) END MONTH YEAR 1 1 II I 1 I l l I l l (21) (22) (23) (24) END MONTH YEAR 1 1 I I 1 1 I l l I l l (21) (22) (23) (24) END MONTH YEAR 1 1 I I 1 1 I l l I l l (21) (22) (23) (24) Current . . . (25( Current... (25( Current . . . (25( -1 1 I •-! MONTH 1 l l I I - (17) (18) YEAR I I l Tl9) (20) 1 l -1 c. What specific job assign- i. ments did he have in (COUNTRY)? Can you give me the AFSC? What specific job assign- o. ments did he have in (COUNTRY)? Can you give me the AFSC? What specific job assignments did he have in (COUNTRY)? Can you give me the AFSC? 1. (26 -28 1. (2f> -28 1. (?6-28 2. (29 -31 2. (29 -31 2. (29'-31 3. (32 -34 3. (32 -34 3. (3,2 -34, d. Did his duties in j. (COUNTRY) include flying? Did his duties in p. (COUNTRY) include f l y i n g ? Did his duties in (COUNTRY) include flying? Yes.<35( No e. -1 -2 Yes.(35( No How many flight hours did he log while in (COUNTRY)? 1 1 1 1 1 1 k. 1 1 Hours 1 1 -1 -2 How many f l i g h t hours did he log while in (COUNTRY)? 1 1 (38) -1 What specific letter and numerical deeignation(s) did each a i r c r a f t have? q. 1 1 Hours 1 1 1 1 (36) (37) 1 1 Hours (38) Other (SPECIFY) Other (SPECIFY) .(39( f. 1 1 (36) (37) Other (SPECIFY) Yes.(35< No How many f l i g h t hours did he log while in (COUNTRY)? 1 1 (36) (37) (38} -1 -2 .(IQ( •<32< -l L. What specific l e t t e r and numerical designation(s) did each aircraft have? r. -1 What specific letter and numerical designation(s) did each aircraft have? 1. (<W><-43 1- (4n(_4f 1. 2. (44 (-47 2. ( 4 4 ( - 4 7 2. j44(-47 3. (48(-'>l 3. (48(-. r >L 3. (48(-51 4. (56-59) (60-63) ((..'.- h 7) (56-59) (ISO- ft 3) (i.-'i • ( . / ) J il_M( 1 ?r, (40{-43 (52(-55 (ASK Q.64a) (ASK Q.m) (68-71) "(72-75) 07 . (52(-55 4. (52(-55 4. (ASK Q.g") „ (68-71) " (7?-7r>) on /'/-HO (56-59) "(60-r.-)) (d.'i- I./) (68-71) (72-75) D'J 79-80 �CARD 01b 812039 Q.64. Additional Countries (Q. 15-16) Tenth Country Eleventh Country a. What was the next country g. that he was stationed in for more than 90 days while on active duty? Twelfth Country What was the next country m. that he was stationed in for more than 90 days while on active duty? (i4(-u (14(-15 (RECORD COUNTRY HERE AND IN (RECORD COUNTRY HERE AND IN S.R.B. PG 2 AND CONTINUE) S.R.B. PG 2 AND CONTINUE) No others. (lb( b. -1 (RETURN No others. (]f>( TO Q.17) In what month and year did he begin and end active duty in (COUNTRY)? h. What was the next country that he was stationed in for more than 90 days while on active duty? (14(-15 (RECORD, COUNTRY HERE AND IN S.R.B. PG 2 AND CONTINUE) No other s ( 6 .!( -1 (RETURN TO Q.17) In what month and year did he begin find end active duty in (COUNTRY)? n. tn what month and year did he begin and end active duty in (COUNTRY)? BEGIN BEGIN MONTH YEAR 1 1 I I I I 1 1 .. l-l . 1 1 (17) (18) (19)"(20) MONTH 1 1 1 1 BEGIN YEAR 1 I I I l-l -1 (RETURN TO Q.17) MONTH 1 I 1 1 1. l YEAR 1 T 1 l - I l 1 l END MONTH YEAR 1 1 1 1 1 1 1 1 l-l 1 1 ( 2l5 ( 22V ( 23) ( 24) END MONTH YEAR 1 1 I I I 1 1 1 l-l 1 1 ( 21) ( 22) ( 23)" I 2&) ' END MONTH YEAR I I I I I 1 I l l I l l (21 ) ( 22) ( 23) ( 24) Current ... ( 25( . .. - 1 Current . . . ( 25( Current . . . C5 ( c. -1 -1 What specific job assign- i. ments did he have . in (COUNTRY)? Can you give me the AFSC? What specific job assign- o. ments did he have in (COUNTRY)? Ca.n you give me the AFSC? What specific job assignments did he have in (COUNTRY)? Can you give me the AFSC? 1. (26 (-28 1. ( 2d -28 1. (26 (-28 2. ( 2<X -31 2. ( 2 * -31 2. C29 (-31 3. ( 3 2 ( - 3 4 3. ( 3 * -34 3. (3X-34 d. Did his duties in j. (COUNTRY) include f l y i n g ? Did his duties in p. (COUNTRY) include flying? Did his duties in (COUNTRY) include flying? Yes.( 3* e. -1 Yes. 05 ( No . . How many f l i g h t hours did he log while in (COUNTRY)? I 1 l 1 l 1 1 1 Hours (36) ( 3 7 ) (38) Yes.(35( | Hr, How many f l i g h t hours did he log while in (COUNTRY)? 1 1 1 1 1 1 q. .<3?( L. 1 1 1 1 Hours Other (SPECIFY) -1 What specific l e t t e r and numerical designation(s) did each aircraft have? 1 1 (36) ( 3 7 ) (38) Other (SPECIFY) • <39< -1 -i "• How many f l i g h t hours did he log while in (COUNTRY)? 1 1 1 1 Hours ( 36) ( 37) ( 38) Other (SPECIFY) f. k. -1 -2 .<V* -1 What s p e c i f i c letter and numerical designat ion(s) did each a i r c r a f t have? r. -1 What specific letter, and numerical des,igna,<i:Q,0.(s): did each a i r c r a f t have.? 1. ( 4 0 ( - 4 3 1. ( i p ( - 4 ' l 1. (40(-43 2. ( 4 4 ( - 4 7 2. < 4 4 ( - 4 7 2. (44(-47 3. (48(-51 _3. Ufi(-5l 3. (48(-51 1 (52(-55 r 4, ( ) 2 ( - V j 4, (56-59.) (60-63) "(64-07). (6K-7I ), "(72-7'j) 10 T 7 .. . (5.6-59) "(60-63) ••"(64-67) (^(-S -, 4 . (68-71) ~ (72-7'i) I1 77-TTO 251 (56-5.9.) (60-63) '(64-,67.) (68-71.) "(72-75) 12 Tf-'fffl �CARD Q. 65-67. 020 A d d i t i o n a l Marriagiis FOURTH MARRIAGF. FIFTH MARRtACK b ^ f l . I n w h a t month am! yt*«r did he get married the fourth time? h f m . I n w h n i month nm1 year did hp get married the f i f t h time? 1 I MONTH YEAR 1 1 1 1 1 l l I l l <15) <16> ( l 7 > d « ) I I c. What was her f u l l maiden name? I RECORD IN S . R . B . PG 2 I What was her f u l l maiden name? 1 1 T I l l 1 1 I Times 1 1 Never.. (52( (SKIP TO Q.f) Never. .(52( e. ; What was her f u l l maiden name? (RECORD IN S.R.B. PG 2 I BeRin card 220 19-49 d. During this marriage, how many times was he living apart from his wife (you) for more than three months? 1 1 1 I 1 1 1 1 Months 1st 1 I 1 I 1 I 1 1 Months 2nd 1 1 1 I 1 I Months 3rd 1 I 1 1 1 Months -1 (SKIP TO Never. .(52( 1 Months t 61) ( 6T" 1 Months (63) (64) (GO TO Q.65f ) -i 1 I 1 I Months 1 1 1 I 4th 1 I 1 1 5th 1 I 1 1 e. How many months did they (you) live apart the ( f i r s t / n e x t ) time? 1st I I iI i1 I I 1 I Months (53) < 5 4 ) 1 I Months 2nd 1 1 I I . I I Months (55) (56> 1 I Months 3rd 1 I 1 I 1 I Months (57) (58) 1 1 Months 4th 1 1 1 I 1 I Months (59) (60^ 1 I Months 5th 1 1 1 1 1 1 Months (&l) (62) (61 > ( 6 2 ) 6th (SKIP TO Q.f) <59~5 ( 6()> 1 1 | Times (50) (51) ( 5 7 ) (58) ( 59> ( 6(i 1 I | (55 ) (56 ) ( 57) ( 5® 1 1 I 1 (53) (54) (55) (56) , I e. How many months did they] (you) live apart the ; ( f i r s t / n e x t ) time? ( 53) ( 54) 1 1 i Q.f) e. How many months did they (you) live apart the ( f i r s t / n e x t ) time? 6th < : (50) (51) -1 cur- IRECORD IN S.R.B. PC 2 I 1 Times (50) (51) 5th MONTH YEAR 1 1 1 1 1 l l I l l (15) (16) (17) (18) b. What ( i s / w a s ) the rent f u l l name of that w i f e Bet-in curd 220 19-49 : d. During this marriage, i how many times was he ! l i v i n g apart from his j w i f e (you) for more than three months? d. During this marriage, how many times was he living apart from his w i f e (you) for more than three months? 4th 1 I cur- IRECORD IN S.R.B. PG 2 1 19-49 3rd bla. In what month mij y e a r did he get married the sixth time? IRECORD IN S.R.B. PG 2 I c. 2nd STXTH MARR1AGK MONTH YEAR I I I I I l l I l l (15> dh> d?) < 1 8 > b. What ( i s / w a s ) the rent f u l l name of that wife b. What ( i s / w a s ) the current f u l l name of that w i f e 1 RECORD IN S.¥.B. PG 2 1 1st 812039 r1 Months (63) (64) (GO TO Q . 6 6 f ) 6th 1 1 1 1 1 1 Months (63) < 6 4 ) (GO TO Q . 6 7 f ) �020 CARD Q,65-67. 812039 Additional Marriages (CONTINUED) FOURTH MARRIAGE FIFTH MARRIAGE IIF ONLY MARRIAGE! SIXTH MARRIAGE 65f. At the time he (died/ became incapacitated) was he divorced , widowed, separated, or was he married and living with his wife? llF LAST MARRIAGEl 66f. At the time he (died/ became incapacitated) was he divorced, widowed, separated, or was he married and living with his wife? JIF LAST MARRIAGEl 67f. At the time he (died/ became incapacitated) was he divorced, widowed, separated, or was he married and living with his wife? Living with wife...((j6( Living with wife...((,6( Living with wife...(66( Divorced Separated Widowed (RETURN TO Q.22) -1 -?](SKM' TO .Z-^IQ.h) ~4j -1 (RETURN TO Q.22) nivorrprf -?1(SKIP TO S<"p/ir«l«-<1....~-3( Q.h) -1 (RETURN TO Q.22) i Separated Widowed J ~-3f Q- h ) -4 1 ""*"* J IRECORD IN S.R.B. PG 2 1 IRECORD IN S.R.B. PC 2 ,1 JRECORD iii S.R.B. PG 2 I |lF OTHER MARRlAGESl ll F OTHER MARRlAGESl IIF OTHER MARRlAGESl g. How did that marriage end —- was he divorced or was he widowed? Pivoreed(67( -1\(ASK Q.h) Widowed..T T - J .22 g. How did that marriage end — was he divorced or was he widowed? Divorced(67( Widowed -UUSK Q.h) -2\ IRECORD IN S.R.B. PG 2 ) IRECORD IN S.R.B. PG 2 I h. In what month and year was he (divorced/ widowed'/separated)? h. In what month and year was he (divorced/ widowed/separated)? MONTH 1 I i l YEAR l l (68) (69) 1 l - I l MONTH 1 l (70) (71) (IF A FIFTH MARRIAGE GO TO Q.66a) 1 I Divorced(67( -ll(ASK Q.h) Widowed -2) IRECORD. IN S.R.B. PG 2 I h. In what month and year was he (divorced/ widowed/separated)? MONTH YEAR 1 l g. How did that marriage end — was he divorced or was he widowed? 1 1 1 - I l l (68) ( , ) (9 1 l Oo) (71) (IF A SIXTH MARRIAGE GO TO Q.67a) 1 1 YEAR 1 1 1 1 l-l (68) (69) 1 I 1 I (70> (71-) (RETURN TO Q.22) (72-73) (72-73) (72-73) (74-75) (74-75) (74-75) (76-77) (76-77) (76-77) 79-80 �CARD 68-70. 02H 812039 Additional Children (Q.22-2 FOURTH CHILU FIFTH CHILD SIXTH CHILD NAME: NAME: 68a. How old is (CHILD) now? 69a. How old is (CHILD) now? I I I I I I I I I I I I .(l'5) (10) Age (15) (16) Child died..(U( Child died..( 17( -1 b. (Is/Was) (CHILD) male or female? Male Female. I OUNCES T b. (Is/Was) (CHILD) male or female? I (19) (') .() (21) (22) Don't know. , ,(_23( d. What is (CHILD)'s birthdate? ! POUNDS I (21) (22) I I OUNCES I (19) (2"0)(21) (22) Don't know...( 23( d. What is (CHILD)'s birthdate? -1 d. What is (CHILD)'s birthdate? YEAR MONTH DAY MONTH DAY YEAR 1 1 I I 1 I I 1 1 1 1 I I 1 1 1 1 1 1 1 l-l 1 l-l 1 1 1 1 l-l 1 l-l 1 1 28) ( 29) (24) (25) (26) (27) (28) (29) ( 24) ( 25) ( 26) ( 27) ( (2/0 (25) (26) (27) (28) (29) MONTH I I 1 1 II l-l DAY 1 1 1 1 l-l YEAR T I IT l-l Don't know.. .(23( -1 c. How much did (CHILD) weigh at birth? OUNCES POUNDS I I -1 Male. Female. c. How much did (CHILD) weigh at birth? T I I I Age (15) (16) Child died..(17( -1 Male. Female. c. How much did (CHILD) weigh at birth? (19) (20) 70a. How old is (CHILD) now? ! | Age b. (Is/Was) (CHILD) male or female? <18( POUNDS NAME: 1 1 1 1 [ALSO RECORD IN S.R.B.-PG 3| e. Was the child premature, full term, or overdue? Premature. ( jg( (CO TO Q.f) -1 lALSO RECORD IN S.R.B.-PG 3| e. Was the child premature, full term, or overdue? Premature. ( ^o( Full term..... Overdue (GO TO Q.f) 254 -1 -2 -3 lALSO RECORD IN S.R.B.-PG 31 e. Was the child premature, full term, or overdue? Premature. ( ,J(/( Full term. • • . . (GO TO Q.f) -1 -2 �CARD FOURTH CHILD 68f. Where arc (CHILD) 's birth registration records located? In what city and state is that? IRECORD IN S.R.B. PC 3 | 028 FIFTH CHILD SIXTH CHILD 69f. Where are (CHILD) 's birth registration records located? In what city and state is that? IRECORD IN S.R.B. PC 3 I g. Where are (CHILD) 's current medical records located? In what city and state is that? .812039 g. Where are (CHILD) 's current medical records located? In what city and state is that? 70f. Where are (CHILD) 's birth registration records located? In what city and state is that? 1 iREcdRD IN"SVR:B. PC'S' r g. Where are (CHILD) 's current medical records located? In what city and state is that? IRECORb ih S..R.B. PC 3 1 IRECORD IN S.R.B. PC 3 1 IRECORD IN S.R.B. PG 3 1 h. What was (CHILD) 's mother's full name? h. What was (CHILD) 's mother's full paiiie? h. What was (CHILD) 's mother's full name? (RECORD IN S.R.B. PC 3 1 IRECORD IN S.R.B. PG 3 1 1 1 i. How old was the mother when (CHILD) was born? i. How old was the mother when (CHILD) was born? i. How old was the mother when (CHILD) was born? 1 1 IRECORD IN S.R.B. PC 3 1 1 1 1 I . I 1 Age < 3 I > <32> 1 1 Age (J].i <32) 1 1 1 1 Age <31> <32> [33-48] . . |33-48| j. Did (CHILD) have any birth defects? j. Did (CHILD) have any birth defects? j. Did (CHILD) have any birth defects? 1 1 Yes.Uq( Yes.(49( -1 (ASK Q.k) Ye8.(49( -1 (ASK Q.k) No. No No -1 (ASK Q.k) . . -2 (SKIP TO Q.L) k. What kind of birth defects did (s)he have? Any others? -2 (SKIP fO Q.L) , -2 (SKIP TO Q.L) k. What kind of birth defects did (s)he have? Any others? k. What kind of birth defects did (s)he have? Any others? L. Was (CHILD) ever diagnosed as having cancer? L. Was (CHILD) ever diagnosed As having cancer? ' t. Was (CHILD) ever diagnosed as having cancer? Yes.(50( No.. lit. 1 1 -1 <ASK Q.m) . -2 (SKIP TO Q.o) In what month and year was the diagnosis made? MONTH YEAR i l l 1 1 1 l-l 1 1 (SI) ( 52) (5)) (V.) n. What kind of cancer was diagnosed? m. In what month arid year was the diagnosis made? 1 I MONTH VfiAR 1 } i \ 1 l l I l l (SI) (Sl>) (S3) (Vi) n. What kind of cancer was diagnosed? <5.5-5h) Not sure..( 57( (GO TO Q.o) -1 . (5.5-5.6) . Not sure. . ">l( ( -1 (GO TO Q.o) 255 Yes.(3Q( -1 (ASK Q.m) No Yes. (JQ(_ . -1 (ASK Q.m) -2 (SKIP TO Q.o) m. In what month and year was the diagnosis made? MOUTH 1 ' 1 1 1 YEAR 1 1 I I l-l (50 (52) ! L (S3) (54) n. What kind, of cancer Was diagnosed? . Not sure..(^7< (CO TO Q.o) (35-56). -1 �CARD FOURTH, CHILD 680. 812039 028 FIFTH CHILD (Does/Did)(CHILD) have diagnosed learning disability? Yes.(5H( -l (ASK No SIXTH CHILD 69o. (Does/l)id)(CHlLD) have a 70o. (Does/Did)(CHILD) have a diagnosed learning disdiagnosed learning disability? ability? Q.p) -2 (SKIP TO Q.q) -1 (ASK |No Q.p) Yes.(58( -2 (SKIP TO Q.q) No -1 (ASK Q.p) __-2 (SKIP TO Q.q) I p. What kind of learning d i s a b i l i t y (does/did) (s)he hnve? p. What kind of learning d i s a b i l i t y (does/did) (s)he hnve? p. What kind of learning disability (does/did) (s)he have? q. (Does/nidMCHILD) have any physical, mental, or motor impairments? q. (Uoes/nid) (CHILD) have any physical, mental, or motor impairments? q. ( Does/Did) (CHILD) have any physical, mental, or motor impairments? Yes.(59( -1 (ASK Q.r) Yes. (39 ( -1 (ASK Q.r) No -2 (SKIP TO Q.s) No -2 (SKIP TO Q.s) r. What kind of impairment (does/did) (s)he have? ,Yes.(3^( i 'No r. What kind of impairment j (does/did) (s)he have? ; -1 (ASK Q.r) -2 (SKIP TO Q.s) r. What kind of impairment (does/did) (s)he have? j IF CHILD IS DEAD: OTHERWISE: CONTI NUE. SKIP TO NEXT CHILD DAY 1 1 OTHERWISE: ', s. On what date did (CHILD) die? MONTH 1 II 1 l-l IF CHILD IS DEAD: OTHERWISE: IF CHILD IS DEAD: CONTINUE SKIP TO NEXT CHILD s. On what date did (CHILD) die? YEAR 1 1 CONTINUE SKIP TO' NEXT CHILD s. On what date did (CHILD) die? MONTH DAY YEAR MONTH DAY YEAR 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 l-l 1 l-l 1 1 1 l-l 1 l-l 1 (60) (61 ) (62) (63) (64) (6r>) : (60) (61 ) (62) (6J) (64) (65) (60) (61) (62) (63) (64) (65 I I l-l t. What was the cause of death? ! 1 1 t. What was the cau?,: of death? u. Where is (CHILD) 's death registered? In what city and state is that? RECORD IN S.R.B. PG 3 I u. Wh^.e is (CHILD) 's death registered? In what city and state is that? 1 RECORD IN S.R.B. PC 3 I (GO TO NEXT CHILD Q.69a) (GO TO NEXT CHILD Q.70a) t. What was the cause of death? u. Where is (CHILD) 's death registered? In what city and state is that? [RECORD IN S.R.I. .f<5.^ (GO TO NEXT CHILD Q.71a) 6Hn. (66-67) 68u. (66-67) 6MI . (!-)) («(') I,H, . (h«-M) f.Hf. (6K-69) drin. (./0-7J) (iHn. (711-71) i.Hn. (70-71) .a,,. </.',-7/) 6Hp. (7.'i-7'7) OHp. (7/,-77) 06 /M-Hil �CARD . 028 71-73. 812039 Additional Children F.ICillTII CM (I,I) SEVENTH CHILD NINTH CHILD i NAME: NAMK; 71a. How old is (CHILD) now?j 72a. I.. .. .1. - J Age (16) Child died..(l?( Male Female. c. How much did (CHILD) weigh at birth? I T POUNDS "(21) (22) (20) I I Don't know...(j>j( i -1 : b. (Is/Was) (CHILD) male or female? ( | c. How much did (CHILD) weigh at birth? OUNCES T -I b. (Is/Was) (CHILD) male or female? .(JH( 73a. How old is (CHILD) now? I I I Age (15) (16) I l Child died..(17( -1 • I I Age (13V (16) Child died,.(l7( -1 Female. POUNDS How old is (CHILD) now? I b. (Is/Was) (CHILD) male or female? Male NAME: I OUNCES r (19) ( 20) ( 21) (22) Don't know. ..(2J< -1 c. How much did (CHILD) weigh at birth? T i POUNDS i i ri i-i ( 19) ( 20) OUNCES r i r i (21) (22) Don't know...( 23( -1 j d. What is (CHILD)'s birthdate? d. What is (CHILD)'s birthdate? d. What is (CHILD)'s birthdate? YEAR MONTH DAY YEAR MONTH DAY I I 1 I I 1 I I 1 1 1 1 I I 1 1 I I 1 1 1 1 l-l 1 l-l 1 1 1:1 1 l-l I ' l -1 (24) (25) (26) (27) (28) C29) (24) (25) (26) (27) (28) (29) (24) (25) (26) (2?) (28) (2?) 1 1 MONTH 1 1 1 1 l-l. DAY 1 1 1 1 1 -1 YEAR 1 1 IALSO RECORD IN S.R.B.-PG 4| lALSO RECORD IN S.R.B.-PG 4| IALSO RECORD IN S.R.B.-PG 4 | i e. Was the child premature, full term, or overdue? ; e. Was the child premature, full term, or overdue? -1 Premature. (jp( -1 Full terra.. . . ._ -2 -7 -4 e. Was the child premature, full term, or overdue? -4 _ (GO TO Q.f) ' Premature. ([( j) (GO TO Q.f) 257 Premature. ( -jf)( Full term (GO TO Q.f) -1 -2 �CARD SEVENTH CHILD EIGHTH C1UI.1) 71 f. Where are (CHILD)'s birth registration records located? In what city and state is that? ; [RECORD IN S.R.B. PC~VT TRECQRD IN S.R.B. pgjtj i g. Where are ( C H I L D ) ' s current medical records located? In what c i t y and state is t h a t ? IRF.IIORO I N S . R . B . I'C I, [ TKECOHD IN S.R.'B. re '< I h, What was (CHILD)'s mother's lull name? I RECORD IN S.B.B. PC It \ h. What was (CHILD)'s mother's full name? I RECORD IN S.R.B. PC k \ i. How old was the mother when (CHILD) was horn? 73f. Where are (CHILD)'s birth registration records located? In ' what city and state is that? IRECORD IN S.R.B. PC V | g. Where are (CHILD)'s current medical records located? In what city and state is that? TRECORD IN S.R.B. roT | h. What was (CHILD)'s m o t h e r ' s f u l l name? IRRCORD IN S.R.B. PC a I i. How old was the mother when (CHILD) was born? . Age I I I i. How old was the mother when (CHILD) was born? Age Age ( 31) ( 32) j. Did (CHILD) have any birth defects? No (3.1) (32) j. Did (CHILD) have any birth defects? j. Did (CHILD) have any birth defects? Yes.(A9( (SKIP TO Q.L) -I (ASK Q.k) Yes.(49( -1 (ASK Q.k) No -1 (ASK Q.k) _-2 812039 NINTH CHI 1.11 T2{. Where are (CHILD)'s birth registration records located? In what city and state is j that? g. Where are (CHILD)'s . current medical records: located? In what city and state in that? Yes.(49( (K'H -2 (SKIP TO Q.L) No -2 (SKIP TO Q.L) k. What kind of birth defects did (s)he have? Any others? k. What kind of birth defects did (s)he have? Any others? k. What kind of birth defects did (s)he have? Any others? L. Was (CHILD) ever diag- j nosed as having cancer? i L. Was (CHILD) ever diag- : nosed as having cancer? | L. Was (CHILD) ever diagnosed as having cancer? Yes. (''"(-] (ASK Q.m) No iYes.(r''K -1 (ASK Q.m) -2 (SKIP TO Q.o) I No m. In what month and year ^ was the diagnosis made?) MONTH YKAK T—i—ri—i—r i (51.) i (52) i-i (53) i TV.)i _ n. What kind of cancer was diagnosed? Not sure..O7( (GO TO Q.o) m. . Yes.(r)()( -2 (SKIP TO O.o) In what month and year was the diagnosis made? MONTH YKAR -1 (ASK Q.m) No m. -2 (SKIP TO Q.o) In what month and year was the diagnosis made? MONTH YKAR T (.',]) f : >0 (53) (54) n. What kind of cancer was diagnosed? Not sure..('>/( (GO TO Q.o) (51) (52) . n. What kind of cancer was diagnosed? Not sure. .(r17 (GO TO Q.o) -1 �CARD SEVENTH CHILD 812039 ()2« EIGHTH CHILD NINTH CHILD 71o. (Does/Did)(CHILD) have diagnosed learning disability? 72o. <Does/Did)(CHILD) have a 73o. (Does/Did)(CHILD) have S diagnosed learning disdiagnosed learning disability? ability? Yes.(j«( -1 (ASK Q.p) Yes.<58( -1 (ASK Q.p) Yes.(58( No...,.i -2 (SKIP TO Q.q) No -2 (SKIT TO Q.q) No -1 (ASK Q.p) _-2 (SKIP TO Q.q) i p. What kind of learning disability (does/did) (s)he have? p- What kind of learning disability (does/did; (s)he have? p. What kind of learning disability (does/did) (s)he have? ' q. (Does/Did)(CHILD) have any physical, mental, or motor impairments? Yes.(39( -1 (ASK q. (Does/Did)(CHlLD) have I q. (Does/Did)(CHILD) have any physical, mental, or j any physical, mental, or motor impairments? j motor impairments? Yes.(59( Q.r) No r. What kind of impairment (does/did) (s)he have? CONTINUE SKIP TO NBXT CHILD -1 (ASK Q.r) |Yes.(59< -2 (SKIP TO Q.s) r. What kind of impairment (does/did) (s)he have? N" -1 (ASK Q.r) —— -- - (SKIP Th n.oi ' r. What kind of impairment (does/did) (s)he have? IF CHILD IS DEAD: IF CHILD IS DEAD: IF CHILD IS DEAD: OTHERWISE: OTHERWISE: OTHERWISE: s. On what date did (CHILD) die? CONTINUE SKIP TO NEXT CHILD 1 s. On what date did (CHILD) die? CONTINUE SKIP TO NEXT CHILD s. On what date did (CHILD) die? MONTH DAY YEAR MONTH DAY YEAR MONTH DAY YEAR 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 I I 1 1 l-l 1 l-l 1 I I 1 l-l 1 1 1 l-l 1 l-l 1 1 1 (id) <6|) <62) ( 63) ( 64> (6r>)(ftO) <oO (62) (63) (64) (65) (60) (6l) <62> (63> (64> <6i t. What was the cause of death? t. What was the cause of death? t. What was the cause of death? u. Where is (CHILD) 's death registered? In what city and state is that? RECORD IN S.R.B. fG 4. 1 u. Where is (CHILD) 's death registered? In what city and state is that? IRECORD IN S.R.B. PG A i u. Where is (CHILD) 's death registered? In what city and state is that?. . (GO TO NEXT CHILD Q.72a) (GO TO NEXT CHILD Q.73a) IRECORD IN S.R.B. PG.A T (GO TO NEXT CHILD Q.74a) dftu. 6Hu. (>Hf. (66-67) fi8f . llK "'. (>»p. O'f '70-80 _08 /74-77J . , 79-80 �CARD 74-76. <>2« 812039 Additional Children ELEVENTH CHILD TENTH CHILD NAME: NAME: 74a. How old is (CHILD) now? TWELFTH CHILD 75a. How old is (CHILD) now? 1 r I I .._ I (l >) (Tf>) i Child died..(I;( I I Age r I I I I Age r h i l d died..(I/( -1 POUNDS I L ! (21) ( 22) D o n ' t know...(_,M( Male... Female. c. How much did (CHILD) weigh at hirth? OUNCES I I I I I i_ J_ _l-l _ I -1 -I b. (Is/Was) (CHILD) male or female? Male (J Female... c. How much did (CHILD) weigh at birth? f I I I A g e (I >) ( I ft) r Child died..(I/( -1 b. (Is/Was) (CHILD) male or female? -1 Male... Female. POUNDS I I 76a. How old is (CHILD) now? (I'i) (I <S) b. (Is/Was) (CHILD) male or female? (20) NAME: OUNCES I I T l \ I I I l-l I I Tn) ( • > ( { ) (717 (22r -2 c. How much did (CHILD) weigh at birth? : i , POUNDS 1 J OUNCES I I I 1_ 1-J (19) (20) I I ( 2'l) ( 22) Don't know...( :'X D o n ' I know. . .(JJ(_ -1 I d. What is (CHILD)'s birth-; date? MONTH DAY YEAR d. What is (CHILD)'s birth-' date? MONTH DAY YEAR d. What is (CHILD)'s birthdate? j ' MONTH 1 DAY I T YEAR I I T I r (24) (25) ( 2(J ( 27) ( 28) ( 29) j ( 2-'.) ( 2 >) ( .If.) ( 27) C!H ) (29 ) (24) (21) (26) ( 27) (28) ( 29) RECORD IN S.R.B.-PG A I I j"Al.SQ^R'ECORb_IN" S.R.R.-PC 4| jlALSQ RECORD IN S.R.B.-PG A l e. Was the child premature, full term, or overdue? Premature. (_ilK Full term Overdue Not sure (GO TO Q.f) -1 -2 -3 -A e. Was the child premature,' e. Was the child premature, full term, or overdue? ! full term, or overdue? Premature. (___»<_ Full term _ Overdue _ Not surr (GO TO Q.f) 260 Premature. (_UX Full term Overdue Not sure (GO TO Q.f) -1 -2 -3 -A �812039 (I2R TENTH CHILD TWELFTH. CHILD ELKVKNTH CIULD 7/.f. Win-re a r c ( C H I L D ) 's 7 5 f . Where are ( C l J I L D ) ' s hi r t l i r o g i i i t rat i o n i h i r t l i ri'Ri ^ t r i l l i o n ri'ctmls l o c a t e d ? In j records located? In w h a t c i t y and s t a t e i s ! w h n t c i t y a n d s t a t e Is t h a t ?_ ! that? |RECO;Rp.lH..S.>ft.B. PC k \ '; IRECORD IN S.R.B. P G 4 f g. Where are ( C H I L D ) ' s c u r r e n t medical records located? In what c i t y artd s t a t e is that? I RECORD,IN S.T.B. PC: 4 f g. Where are (CHILD) 's current medical records! located? In what city I ---RECORD 11 _ S . R . B . PG It T • ".................• '- 76f. Wliere are (CHILD) 's birth registration records located? In what city and state is that? _ 1 RECORD I N S_. R . B . PC It I g. Where are (CHILD) 's current medical records located? In what city and state io that? h. What was (CHILD)'s m o t h e r ' s f u l l name? h. What was (CHILD) 's mother's . f u l l _ name? IRECORD IN S.R.B. PG 4 I h . What was (CHILD) 's m o t h e r ' s f u l l name? [RECORD I N S.R.B. PC |_ &_ I IRECORD IN S-R-B/PG u \ i. How old was the mother whnn (CHILD) was born? i. How old was the mother when (CHILD) was born? i . How old was the m o t h e r when ( C H I L D ) was h o r n ? J L.._ I Age ~(t'i) TuV No j. Did (CHILD) have any birth defects? Yes.(4g( (SKIP TO Q.L) -1 (ASK Q.k) Yes.(4?( -1 (ASK Q.k) No -1 (ASK Q.k) _-2 (32> j. Did (CHILD) have any birth defects? j. Did (CHILD) have any birth defects? Yes.(/it)( G It \ IJJECQfrP IN f -2 (SKIP TO Q.L) No -2 (SKIP TO Q.L) k. What kind of birth defects did (s)he have? Any others? k. What kind of birth defects did (s)he have? Any others? k. What kind of birth defects did (s)he have? Any others? L. Was (CHILD) ever diag- | nosed as having cancer? > L. Was (CHILD) ever diagnosed as having cancer? L. Was (CHILD) ever diagnosed as having cancer.? Ves.(^( -1 (ASK Q.m) ' Yes.(^p(._-l (ASK Q.m) No No -2 (SKIP TO Q.o) m. In what month and year was the diagnosis made?: 1 1 MONTH 1 1 I I l-l (51) (!>::) ( YEAR 1 1 1 1 53) ( 54) n. What kind of cancer was diagnosed? (55-56) Not sure. . '>?( ( (GO TO Q . o ) -1. Yes.(5Q( -? (SKIP TO Q.o) m. 1 .1 In what month and year was the diagnosis made?' YEAR MONTH 1 I I 1 l-l ( r il ) ( 51') ( 53) ( 54) I 1 ! I n. What kind of cancer was diagnosed? .• (55-56) Not sure. . ( ,';( (GO TO Q . o ) 201 -1 No -1 (ASK Q.m) -2 (SKIP TO Q.o) in. 1 1 In what month and year was the diagnosis made? MONTH YEAR 1 1 1 1 1 1 l-l 1 1 (51) ( 52) (53) (54• n. What kind of cancer wa-s diagnosed? (55- 56) Not sure. . ( ^?( (GO TO Q . o ) -1 �OJH CARD EI.KVKNTH C H I L D TENTH CHILI) 812039 TWELFTH CHILD 74o. (Does/Did)(CHILD) have a 75o. (Does/Did)(CHILD) have £ 76o. (Does/DidMCHILD) have a diagnosed learning disdiagnosed le.irning dindiagnosed learning disability? I ' abiIity? ability? Yes.(58( -1 (ASK Q . p ) Yes.(r,n( -1 (ASK Q.p) No. ._-2 (SKIP TO Q.q) No. ! Yes.(38( -2 (SKIP TO Q.q) No. -1 (ASK Q.p) . - (SKIP TO Q.q) _ 2 p. Whnt kind of learning disability (does/did) (s)he have? p. What kind of learning disability (does/did) (s)hc have? p. What kind of learning disability (does/did) (s)he have? q. (Does/Did)(CHILD) have any physical, mental, or motor impairments? q. (Does/Did)(CI!ILD) have any physical, mental, or motor impairments? q. (Does/Did)(CHILD) have any physical, mental, or motor impairments? Yes.(59 ( -1 (ASK Q.r) | Yes. (Jig Yes.(^q( -1 (ASK Q.r) -1 (ASK Q.r) i No -2 (SKIP TO Q.s) ~ No I r. What kind of impairment > (does/did) (s)he have? IF CHILD IS DEAD: CONTINUE OTHERWISE: SKIP TO NEXT CHILD s. On what date did (CHILD) die? MONTH DAY i i i: i 1 l-l -2 (SKIP TO Q.s) No ...... -2 (SKIP TO Q.s) i ; IF CHILD IS DEAD: OTHERWISE: : YEAR M i j r. What kind of impairment i (does/did) (s)he have? ! CONTINUE SKIP TO NEXT CHILD s. On what date did (CHILD) die? MONTH i 1 1 - 1 1 i i 1 l-l DAY i 1 i i IF CHILD IS DEAD: CONTINUE OTHERWISE: SKIP TO NEXT CHILD s. On what d a t e did (CHILD) die? . YEAR l-l r. What kind of impairment (does/did) (s)he have? MONTH i 1 1 1! i 1 i i l-l DAY i 1 i i YEAR l-l i 1 (ilj ( 61) ( 62) ( 63) ( 64) ( f>5) ; ( 60) ( 61) ( 63 ( 6'D ( 64) ( 6 ? j ( 60) ( 61) ( 6 2 ) ( 6 3 ) ( 64) ( 6 t. What was the cause of death? t. What was the cause of death? t. What was the cause of death? u . Wh.M-r i » ( c i l l l . D ) 's d e a t h registered? I n what c i t y and state is that? u . Wlu-n> i s ( C H I L D ) '« d.-..tli r i ! n i n t e r e d ? I n what c i t y and s t a t e is that? n . Win-re I H (.CHILD) 'f d e a t h registered? In what c i t y and s t a t e is that? RECORD IN S.R.B. PG 4 I IRECORD IN S.R.B. PG 4 [ IRECORD IN S.R.B. PG A I (GO TO NEXT CHILD Q . 7 5 a ) (GO TO NEXT CHILD Q . 7 6 a ) (RETURN TO Q . 2 7 a ) 68u. (66-67) 68u. (66-67) 68u. (66- 6 '71 "Hi- (68-M) hHf. (hH-6<J) (,«f (f)H-<,<)) 681,. (7u- / 0 (1811. _ ( 7 0 - 7 t) 6811. ( 7 0 - ; 1) 68p. (74-77) _ (//-//J ')-»(! J02 �CAJD._ .-~*-~"''l.?>' •..'.". «, ,_ 812039 ! « T ~ — 77. Additional pneumonia (Q. l») Fourth Time 77a. Fifth Tiiw During what months and yi'«r t. d id hi* have pneumonia (the fourth r i me ) ? 77f. .RECORD IN. S.R.B. PG 5 1 During what months, and . 77k. yearn <1 i<l In hafiv pneumonia dhe fifth time)? IRECORI) IN S.R.H. PG 5 1 IF BEFORE 1961 , SKIP TO Q.f. h. lylxch Time IRECORD IN S.R.B. PG 5 1 IF BKFORE 1961, SKII* TO IF BEFORE 1961, RETURN TO Q.29a. Q.k. What i s th<; f u l l name, of t h e d n c t o r who made ' t h f d i a g n o s i s or I IIP ', meilii'al f a c i l i t y whi-rc I h e d i a >MIO s i ,s Wcis nuidt- ? '• g. Wliat is th« full name of rhc doctor who made the diagnosis or thf ' medical . f a c i l i t y when! tin' diagnosis was made? ^ ^^ / ^ t IHE(X)KI) IN S.K.H. PU 3 f Wliat prescribed medicim> did he take for the pniMimonia he had that lime? I.. h. iRKCORI) IN S.K.B. PO 5.-1 m. ( ( ,2. ( .< 3. ( ( J3. ( ( Was ht> hospitalized . for clip pneumonia he _ had thai time? Yes.( _ (__-! (ASK Q.u) No ...... _^-'2 (SKIP TO Q.f) e. What w.is the f u l l nan of that hospital? Tm-xcfRD 'IN sTk.¥. pcTTl ( ( 13. ( ( Was he hospitalized for the pneumonia he had that time? ' Yes . ( No \>/hal was the f u l l name of t h a t h o s p i t a l ? i I N S . R . B . ,PG 5J J65 What prescribed medicine did he take for the pneumonia he had t h a t time? 2. Was lie hospitalized for the pneumonia he had that t ime? JYes.( ( -1 (ASKQ.J) JNo ...... __-2 (SKIPTOQ.k) What is the full name of the doctor who made thp diagnosis or the medical facility where thf diagnosis was made? S.R.B. PC TT What prescribed medicine did he take for the pneumonia he had that t in.e? 2. d. During what months and yearn ct id ho hnye pneumonia (the sixth t imp)? o. .- 1 (ASKfl.o) -2 I RETURN TO Q.29a) What was th'e f u l l name of t h a t h o s p i t a l ? 1RKCOBD IN S . R . B . PG �CARD 78. 817030 Additional Cancer (Q.29) Part t, Part Part 6 7tic. . I n what, month and year S i . In what m o n t h a n d year 78o. In what month and year was cancer of the ( B O D Y J was c a n c e r of the (BODY was cancer of the (BODY f.jxst. diajjjnos e d ? PART) f i r s t diagnosed? PART) first diagnosed? RECORD S . R . B . PC 6 I TRECORrijN _S.R.E.^ PC: 6J i I RECORD IN S.R.R. PC 6 I What i s tin 1 f u l l min»> of the d o c t o r or tinm e d i c a l f a c i l i t y where _ the d i a g n o s i s was ma d e ? I RECORD IN S .R_. B . PC I (1 . e. What is the f u l l name | of the doctor or f l i p mo d i c a 1 f a c i l i t y he '. l a s t c o n s u l t e d about i cancer of the (BODY | _ PART)? __ ! I RECORD IN S . R . H . PG ft I | f. D u r i n g what month and ! year di<3 he last con- ; suit (NAME FKOM Q. e ) ? ! [RECORD IN S . R . R . PC.; h \ g. j. Wlint is tlu> f u l l rinmp l of tin- doctor or the ! m e d i c . i l f a c i l i t y where I t h e d i a g n o s i s waa m a d e ? ; iRECORirTN s-R-B r ., Pf:.. 'Q' k. _.. PART)?_ IRECORD I N S . R . B . PC ft r I Other (SPECIFY) _ I RECORD L. During what month and year did he last consult (NAHK FRO_M Q.kj? j RECORD lj) S.R.B. PC b'T Radiation. (l5.( Chemotherapy.. .(|(,( Surgery (y (_ Other ( S P E C I F Y ) What is t lit1 t u l I nnmt' of the doctor or HIP medical L a c i l i t y where the diagnosis was made? RECORD IN S.K.b. "I'l; t, T Wliat i s t h e f u l l name of the d o c t o r or the m e d i c a l f n r i l i t y he l a s t c o n s u l t f d ,iho>it cancer of the (BODY Wliat is the full name of thr doctor or tinmpdic.'il facility hr last consulted about cancer of the (BODY PART_)_? 1 r. S .K._B_._. PC fr I DurinR what month and year did he last connult'._(HAME FROM Q.9>? I RECORD/IN' s.j^.BT^ PC & F What t r e a t m e n t s or , in. What treatments or medicines did he take medicines did he take ! for cancer of the (BODY for cancer of the (BODYPART)? ; PART)?_ . I [MULTIPLE RECORD BELOWf MULTIPLE RECORD BELOW I | Radiation......(15 ( Chemotherapy . . . (jj ]j Surgery ........ (17 ' P i. What treatments or medicines did he take for cancer ot the (BODY PART)? _ I MULTIPLE RRCORI) BKLOWl Radiation (L;.I.( Chemotherapy. .. (|ii ( -1 -1 -1 : Surgery i -1 ~1 Other (SPECIFY) (L/ ( -1 MONTH Radia1 tion. .. . 1 1 1 YEAR 1 1 1 l-l I J I ! I-J (21) C!H) ( MONTH Other I 1 I I 1 ! l-l l r i i 2<O (.»<() YEAR r 1 1 YEAR MONTH 1 Radia1 t i on .... I 1 I I 1 MONTH MONTH YEAR Chemo1 1 1 1 1 Chemo1 therapy . 1 1 l-l 1 1 t horapv . 1 (:• i) (;'/.) ( .",) (.'») YEAR MONTH MONTH I Surgery. . 1 During what month and year did he first receive (EACH TREATMENT CODED IN Q.s) for cancer of the (BODY PART)? Durinfi what month and year did he first receive (KACII TREATMENT CODED IN Q.m) for cancer of the (BODY PART)? During what month and year did he first receive (EACH TRF.ATMKNT CODED IN Q.g) for cancer of the (BODY PART)? l-l 1 1 1 1 YEAR" 1 l-l C ! 7 ) (I'M) ( ."*) ( 1 0 ) MONTH YEAR I I l-l 1 1 YEAR MONTH 1 M l 1 1 l-l Ml 1 1 1 Surgery.. 1 i 1 ( I I ) ( ( . ' ) < M) ( l / , ) (GO TO NEXT BODY PART) MONTH 1 I I 1 l-l YEAR MONTH Chnmo1 thi-rapv. 1 YEAR ! 1 i 1 1 Radia1 tion —r~T l-l i i SurgTy . . 1 1 1 1 Other. . . . 1 ( t i ) (•!;') ( n) (t.',) (GO TO NEXT BODY HART) ! YEAR 1 1 (<'l] (.' MONTH ! 1 l-l. 1 1 1 I O (:"i) (in) YEAR 1 (RETURN TO Q.lOa) 04 7'1-HO JO-J 1 1 M i l 1 1 I-! 1 1 ( II ) ( 1 •) (u) (i/,) 1 Other 1 1 �, "L " ——— II .....:• I I CARD "I I»H 'I »• " . ' . ..III 812039 ' Q.50b-51 Medical Providers — DEATH 50b. Name of Hospital Address City ^^ _____^___,________,,_____rt_____.________ ' . State 51. ^ • .^ • ^ , ., ., Address State _ -... ^ Zip Primary/Physician Name City ..-...,,- ._ t _ _ „ _• _ _.__., .• . L1.... . .L ._ r i .--. • - - -••- -• .... 205 ' .. „„,.....-. .; . ••_,.._.. • • .. ^ ' �DEPARTMENT OF THE AIR FORCE USAF SCHOOL OF AEROSPACE MEDICINE (AFSC! BROCKS AIR FORCE BASE. TEXAS 78235 The Air Force is conducting a very comprehensive health study of certain Air Force members who served our nation in the Vietnam conflict. The purpose of the study is to determine the potential adverse health effects resulting from the complex environment of Southeast Asia. Federal record systems identified your late as having been assigned in Southeast Asia. The collection of information concerning his health prior to his death is essential to the Air Force study. You are the best individual to give us the information we need. We ask that you help us and all Vietnam veterans by voluntarily participating in this major health study. Your participation will consist of an in-depth interview-in your home. The administration of the interview will begin in a few weeks under the direction of a nationally recognized health survey organization, Louis Harris and Associates, Inc. You will be contacted by phone or letter by them to arrange a convenient time for your interview which will take about two hours to complete. Our intent is to maintain all individual health data in the strictest confidence. In case outside parties attempt to gain access to the data, the Air Force and the Department of Justice are committed to protect this individual .confidentiality. This is one of the most important health studies undertaken by the Air Force, Your voluntary participation is critical to its success. The only way we can get clarification of the difficult questions being asked by the Vietnam veterans is through your cooperation and participation. Any questions that you may have concerning this effort can be answered by letter from the United States Air Force School of Aerospace Medicine, Epidemiology Division, Brooks AFB, Texas 78235, or a collect call to Area Code 512-536-3309. .Thank you. Sincerely GEORGE D. LATHROP, M.D., Ph.n, Colonel, USAF, MC Chief, Epidemiology Division 266 �Louis HARRIS AN.O ASSOCIATES, INC. >' • ,• Vf-.". ti ' "•• - 63O FIFTH .AVEN'l/e' NEW Y O R K , NEW Y O R K I Q I M TEL (2121 975-I6OO TELEX 148383 UOUtS HARRIS INTERNATIONAL. INC. OPINION fcESEAPCH CENTRE LOUIS HARRIS FRANCE 3O weUfSCCK ST. 21 OUt VIVIENNt LONDdN WIM 8* 76OO2 PARIS, rflANCE TEU1 OI-*8«-SI TEL. O I - 2 O O - » « S 1 TttEX! PRIVACY ACT STATEMENT - EPJDEMIOIOSIC STUDY AUTHORITY: Section 133, 1071-87, 3012, 5031 and 8012, Title 10, United States Code and Executive Order 9397. PRINCIPAL AND PURPQSEJS): The purpose of requesting personal information is to assist medical/technical personnel in developing records relative to your participation in an approved epidemiologic investigation. The Soda] Security Number (SSN) and Armed Forces Service Number (AFSN) §re necessary to Identify the person and records. ROUTINE USES: This information will be used to initiate, coordinate, and conduct the Investigation. It will be used to compile statistical data, but information allowing identification of the individual volunteer will not be included. Data and results from this investigation may be used to supplement other approved research studies coHduct^d at the USAF School of Aerospace Medicine or at other Federal agencies engaged in the conduct of similar studies. WHETHER DISCLOSURE IS MANDATORY OR VOLUNTARY, AND EFFECT ON INDIVIDUAL FOR NOT PROVIDING INFORMATION: Disclosure or requested information is voluntary. If the information is not furnished, acceptance as a subject ^s not possible. This is an all-inclusive Privacy Act Statement which will apply to all requests for personal information made by medical/technical personnel during the time you are a volunteer subject. A copy of this form will be placed in your investigation subject folder as evidence of this ratification. Your signature merely acknowledges that you have been advised of the foregoing. If requested, a copy of this form will be furnished to you. Signature of Volunteer SSN 267 Date �LIFE EVENTS CHART U.S. Air Force Survey YOUR AGE THEN SCHOOLS MILITARY EXPERIENCE OTHER JOBS MARRIAGE CHILDREN DEATH IN FAMILY MAJOR ILLNESS OTHER SPECIAL EVENTS 1930 31 . , 32 33 34 - „ 1935 36 37 38 _ 39 1940 41 . 42 '„ 43 44 1945 46 47 48 49 1950 51 52 ^j 54 195556 _ 57 _ 58 59 1960 61 62 63 „, . 64 1965 66 67 . 68 69 1970 t 7i 72 _ _ 73 74 1975 - 76 77 78 79 1980 81 » ~\ ^ rt r * v -----. ' ' ? " �SHOW CARD "B1 01 Aerospace 02 Aircraft 03 Agriculture 04 Automotive 05 Chemical 06 Electronic 07 Mining 08 Pest Control 09 Petroleum 10 Textile 11 None Apply 269 �SHOW CARD "E" STUDY NO. S120'59 \ 270 �LOUIS HARRIS AND ASSOCIATES. INC N £vV Y C P K . N £w Vffip* iO I II • NTCPNATiONAL , > ^ C -30IS T' -ABDIS FRANCE 3O w(CL8eCl\ ST »U£ V I V I E N N E -aooz P»(?IS. FBAMCE -EI. 01- zeo •«««•» TELEX: iooso1 r .ONOON W I M 8 A 8 ChfOLANC TCL. o : - < « o - 6 i S i TELEX zi UNITED STATES AIR FORCE H|ALTH STUDY Name of Medical Provider/Medical Facility ? '" Name of Place ' " •' Street Address State City Zip ) ( hone Number Dear Doctor or Administrator: As an authorized representative for .,,..... .1...: ....;-:,. I ani participating in a survey conducted for the lihited States Air Force to gather information on the health of current and fofffie> A'ir Force personnel. As part of this survey, medical providers who have delivered health care services to .^ . ^ are being asked to supplement information that I have already provided about him. ay this statement or a photocopy of it» I, .. hereby authorize and request you furnish to the United States Air Force Health Study any medical information in your records concerning health services received by: These services were provided during the'1 p'ertocT' tO .; . Thank you very much. Sincerely, Resp. Signature ;of Autnorized Representative FOR OFFICE USE ONLY: Full Name of Authorized Representative 271 Date M£OICAL PROVIDER POpM -- pRQYV �FOR OFFICE USE ONLY: LOUIS HARRIS AND ASSOCIATES, INC 630 Fi fth Avenue New York, New York 10111 Case # Hf 812039 Air Force Health Survey Respondent INTERVIEW,EVALUATION (NlERVIEWER: I WMP'fFJE THE FOLLOWfNGTN~PRTvATE IMMEDIA~TELY~AFTER THE"fNTERVIEW, UsTNG~| I YOURfiEST_JUpGMENT_TOANSWER F.ACH ITEM. _ J i .:acfi of respondent: Black.... Nonblar.k. 2a. Did the respondent want to terminate the interview before it was finished? No (SKIP TO Q3a) Yes _.HZ (ANSWER 2b AND 2c) 2b. -At what question number or during what question series? 'c l-'hat was the reason? la -*i?re there any (other) significant problems during '".he interview? No Yes (SKIP TO Q4a) ." (ANSWKR 3b) 3b. Describe the problems. 4a. Did respondent refer to records during the interview? No Yes _ (SKIP TO Q5a) (ANSWER 4b) 4b. What records did the respondent use? 5a. Was anyone else present at any time during the interview? No Yes (SKIP TO Q6) (ANSWER 5b and 5c) 5b. Who was present? | RECORD RELATIONSHIP | 5c. During which section(s)? 6. Length of interview: minutes 272 �lOiils H/vHKI'. AN!) A:r.ni:iAll : ->; iw:, t i . f i i I i i I li Avenue . Hew 'M,rl , ()i. w \'ork [ H i 1 1 ' ' ;.o . ; ; , • • ; • . S t u d y 1812039. . . . . . . . A I R K)k(.l III AI.III SIMVIY HAD.INO II<AM',,MI I fAl. IORM 111, Ui-,v fnrt 01 I i. >• ';- .'••- - I Dili" liitnis ((nil A s s o c i a t e s i KliM. . ... ' Interviewer U<i.ine; -. !'l,r'<lsc Print. . ' " 1 111! , (iji tii«|i.' (;nnlaii;. (lie I n] lowinij nidtorinl for Study "Sulj.joc't Respbndent NumtKjr W r i l i ' iii'N'DMIir.K of iMi:h ituni hoiiig sent o'n thi- line at the ricjht :.riiL'Y M!ii,ilCi l N J L k ¥ i ! W litiitJy I'uli.jt'ct Namo .A:'.:, ignnifn't- Sheet . Study ji(li.i'.'(M. Privitcy Act Statement (Signed) , . : ,.. •; ^ _ ..;... Study Sub.locf Questionnaire. Study Suliject Supplemental Recording Book. Study Subject Self Administered form w Study Subject. Medic<il Consent Form Study Subject Former W i te Consent Letter , Study Suliject: Interviewer Evaluation I'onn PRISfNT W I T K Privacy Act Statement. (Signed). Spouse line', t ionnairr Spouse 'iu|j|)K:meiitfil Uncording lioot-. Spouse MediiMl r.ori'.n'nt form Spousi; Interviewer [valuation Form. Former W i f e Name Assignment Sheet.. Privacy Art Statement (Signed) Spouse (Jues tionnai re Spouse Supplemental Recording Book. Spouse MediC'il Consent form Spouse Interviewer (.valuation Form. PROXY 1.NTI K V l l W Proxy Name Assignment. Sheet Privacy Act Statement ( S i g n e d ) . . . . Proxy Questionnaire'. Proxy Supplemental Recording Book. Proxy Medical Consent! Proxy Interviewer fvflluation Received: Jlate i het ki^cl id hv: 273 _^ �CHAPTER IV NON-COMPLIANT (MINI) QUESTIONNAIRE The following Non-compliant Questionnaire was used to collect baseline data for the Epidemiologtc Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicide Orange. This data was collected during 1981-1982. The Mini-questionnaire was used for individuals who refused the Study Subject Questionnaire (in person and telephonically). This instrument was administered in person, via telephone, and independently (mailed to study subject). The Non-compliant Questionnaire, as used in the field, fol1 ows. 274 �CONFIDENTAL O.M.B. NQ: 0701-003; APPROVAL EXPIRES: 11/30/82 UNITED STATES AIR FORCE STUDY NON-INTERVIEW HEALTH QUESTIONS CASE NUMBER 01Q2/45992A INTERVIEWER NAME: DATE OF NON-INTERVIEW HEALTH QUESTIONNAIRE: ' . «*' MONTH DAY YEAR 1. Compared to other people youh age would you say that your health is... Excellent,...........01 good, 02 fair, or . . . ; . , 0 ......3 poor? . . . . . . . . 4 .......0 2. Are you currently taking prescribed medicines for any Illness? Yes...... No .,.01 .....2 ....0 3. For what condition are you taking prescribed medicines? Any other conditions? 275 �4. Within the past three months, did illness or injury keep you from work, not counting work around the house? Yes.. ...01(A&B) No doesn't work..02 A. How many days did you miss from work within the past three months? Days B. What illness or conditions caused you to miss work? 5. Did you earn any income from any job during 1980? 01(A) Yes No.. . . 02 A. Was your income less than $20,000, $20,000 to $40,000 or more than $40,000? ' less than $20,000 $20,000 to $40,000 02 More than $40,000 6. .01 03 In order to obtain the most complete and useful information that we can, we are asking some participants to have a physical examination. The USAF will pay for all travel and per diem expenses sd that participants may go to a nationally recognized medical facility. (IF SEPARATED OR RETIRED FROM USAF, SAY: In addition, you will receive a $100.00 per day stipend.) The examination will take place over a five day period that you find convenient. If you are asked would you be willing to have a physical exam at a time most convenient for you? ..01 Yes 02(A) No A. What is your reason for not wanting to have the examination? 5 days too long from family...01 5 days too long from work 02 Don't want to travel 03 Other reason (SPECIFY) Thank you very much. ' 276 . � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 058 Folder The folder containing the original item. 1567 Series The series number of the original item. Series III Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Lathrop, George D. Patricia M. Moynahan Richard A. Albanese William H. Wolfe Description An account of the resource <strong>Corporate Author: </strong>United States Air Force School of Aerospace Medicine, Aerospace Medical Division (AFSC), Brooks AFB, Texas Date A point or period of time associated with an event in the lifecycle of the resource 1982-11-01 Title A name given to the resource Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides: Baseline Questionnaires Subject The topic of the resource Air Force Health Study ao_seriesIII