1 15 38 https://www.nal.usda.gov/exhibits/speccoll/files/original/b677371336f0a60017b46af9dd5a1d6f.pdf a3e56005c1947ba2597cabb4591043d8 PDF Text Text Item ID Number 01868 Author Shepard, Barclay M. Corporate Author ROpOTt/ArUdO TltlB Critique of West Virginia Mortality Study Journal/Book Title Year 1986 Month/Day February 4 Color a Number of Images 36 UOSCrtytOn NOtBS ltem inlcudes critique, as well as attached 1) M. L. Neighbors Diversified Maritime Services, Inc. advertisement and 2) Vietnam-Era Veterans Mortality Study, West Virginia Residents 1968-1983, Preliminary Report, January 1986. Wednesday, July 11, 2001 Page 1869 of 1870 �FEB 04 1986 Critique of West Virginia Mortality Study The West Virginia Department of Health has recently completed a mortality study (copy attached) of Vietnam-era veterans based on the recipients of a state bonus. The State offered a differential bonus to all West Virginia residents who served in the military during the Vietnam era with a larger amount going to those who served "incountry". 41,059 in-country (Vietnam veterans) and 41,782 non-incountry (non-Vietnam) veterans received the bonus. The list of bonus recipients was matched against state vital statistic records resulting in 1225 male Vietnam-era veterans who had died between 1968 and 1983. For each deceased male veteran a copy of the Report of Separation From Active Duty (DD 214) was reviewed to determine dates and place of service. The latter was determined by receipt of at least one of the three medals awarded for service in the Southeast Asia theater of operations. In addition, cause of death information was obtained on each deceased veteran. Of the 1225 deceased veterans, 615 were in the group of Vietnam veterans and the remaining 610 were non-Vietnam veterans, i.e., veterans who served elsewhere during the same period of time. When comparing causes of death between all veterans in the group and non-veterans of similar age only those classified as accidents, poisoning, and violence were elevated among the veteran group. Deaths due to cancer were statistically the same in both groups. Other causes of death were lower in the veteran group, a commonly observed phenomenon known as the "healthy veteran effect". A stated by the authors, the study has a number of limitations which must be kept in mind when interpreting the results: "In spite of the intense publicity given to the bonus campaign, it is likely that many veterans or their survivors never applied for the bonus. Thus, those veterans who did qualify for a bonus represent an unknown proportion of the actual number of West Virginia males'who served in the military during the Vietnam era. It cannot be assumed that the proportion was similar for both [groups]. Furthermore, because the mortality tape identified only residents of West Virginia who died during the study period, deaths in that period among veterans who no longer resided in West Virginia at the time of their demise would not have been counted among the 1,225 veterans deaths ascertained. . . With respect to a comparison between in-country and era . veterans, it cannot be assumed that similar proportions of the respective candidate population qualified for the bonus or that the death rates among in-country veterans who were no longer West Virginia residents were similar to those among era veterans who were no longer residents." �There were 145 cancer deaths of which 71 were in the group of Vietnam veterans and 74 were among the non-Vietnam veterans. In comparing specific types of cancers between these two veteran groups, only Hodgkin's disease, testicular cancer, and soft tissue sarcoma were elevated in the Vietnam veteran group. In each instance, however, the number of actual cases was small, i.e., 5 cases of Hodgkin's disease, 3 testicular cancers and 3 soft tissue sarcomas. As the authors state: "These findings must be interpreted cautiously ... since ... the site- specific cancer deaths were derived from a relatively small number . . and would . therefore be subject to ... large random fluctuations". In addition to the stated limitations of the study, as pointed out by the authors, there has been no systematic review of military personnel records, except for the DD 214 reviews as noted above, to validate the Vietnam service status of the study subjects. Because of the interest and concern over the relationship between soft tissue sarcoma and exposure to the phenoxy herbicides, the authors have now requested a review of the personnel records of the 3 veterans recorded as having this diagnosis. All.three of these were reported to have occurred in the in-country veteran group. The first of these is now known to have served in Thailand, not Vietnam, and would not have been exposed to Agent Orange. This is an example of the serious effect of misclassification especially when dealing with small numbers of subjects. In addition, there has been no systematic review of hospital or other clinical records to validate cause of death information or confirm the specific cancer diagnosis. Again, when dealing with relatively small numbers, a few errors in diagnosis can significantly alter the conclusions. In summary, this study appears to have been well designed and well conducted as far as it goes. As noted by the authors, however, it has inherent limitations and additional data are needed to validate some of the conclusions. BARCLAY M. SHEPARD, M.D. Director, Agent Orange Projects Office �«J£. tLAet&Ad&Ht- 1 January 1986 ANNOUNCEMENT M. L. NEIGHBORS, DIVERSIFIED MARITIME SERVICES, INC., announces that it is now able to offer part time consultative service or representation in the Washington, DC area to additional firms or persons that are engaged or have an interest in maritime related business ventures or business involving the disposal of chemical waste. Such work may also be arranged for in locations other than the Washington DC area as mutually agreed, and on either a prime or sub-contract basis. Among services offered are: A. Maintaining continuous contact with federal agencies having jurisdiction or control over maritime or chemical waste disposal ventures, and submittal of reports on matters of client interest. Rapid "feed-back" on specific information of more urgent interest can also be provided. B. Projection of U.S. chemical waste disposal requirements, in general or with specificity. C. Assisting in the initiation of either a maritime project or a project involving chemical waste disposal (except services involving the disposal of chemical waste by incineration at sea cannot be provided until after 30 November, 1986). CORPORATE EXPERIENCE INCLUDES: Nineteen years involvement with Department of Defense vessel charters and military cargo movement contracts. Thirteen years involvement with various offices of the Environmental Protection Agency that are responsible for regulating chemical waste disposal. This work included interaction with other federal agencies and with commercial firms offering alternative types of chemical waste disposal service. Written inquiries should be addressed to M. L. Neighbors, DMS Inc., 777 Fourteenth St., Suite 747, Washington, DC, 20005. Further information may also be obtained from Mr. Neighbors at phone number 564 1568 (area code 301 if calling from outside metro area). �WEST VIRGINIA HEALTH DEPARTMENT �VIETNAM-ERA VETERANS MORTALITY STUDY WEST VIRGINIA RESIDENTS 1968 - 1983 Preliminary Report January 1986 Arch A. Moore, Jr. Governor David K. Heydinger, M.D. Director, Department of Health �Alan P. Holmes, B.S.E.E., M.B.A. Principal Investigator WEST VIRGINIA DEPARTMENT OF HEALTH VIETNAM-ERA VETERANS MORTALITY STUDY COMMITTEE Charles Bailey Assistant Director, Health Statistics Center Roy C. Baron, M.D., M.P.H. Medical Epidemiologist Edward Bosanac, Ph.D. Research Consultant John Brough, Dr. P.H. Director, Preventive Health Services Charles Conroy, M.A. Agent Orange Program Coordinator Acting Director, Community Health Services Loretta Haddy, M.A., M.S. State Epidemiologist Alan P. Holmes, M.B.A. Director, Health Statistics Center ACKNOWLEDGEMENTS Sandra Y. Pope, Administrative Assistant, Agent Orange Program Eugenia Thoenen, Publications Coordinator, Health Statistics Center Thomas N. Leonard, Programmer/Analyst, Health Statistics Center Betty Jo Berry, Secretary, Health Statistics Center We would also like to thank Col. John W. Moon and the staff of , the West Virginia Department of Veterans' Affairs for their invaluable assistance in providing data used in this study. For further information, contact Charles Conroy, Agent Orange Program Coordinator 1800 Washington Street, East Charleston, WV 25305 Telephone: (304) 348-3210 �Vietnam-Era Veterans Mortality Study West Virginia Residents 1968-1983 The Agent Orange Assistance Program, established in 1982 by the West Virginia legislature, requested the Health Statistics Center of the Department of Health to conduct a study of the causes of death among state Vietnam veterans from 1968 through 1983.* The purpose of the study was to compare the mortality pattern among veterans with that of nonveterans in order to generate hypotheses regarding any differences in the causes of death among the former. A comparison of the causes of death among veterans who served in Vietnam with those among veterans who did not serve in Vietnam was also undertaken in order to speculate whether the Vietnam experience might be associated with a distinct mortality pattern. METHODS Identification of West Virginia Veterans West Virginia residents who served in the military during the years of the Vietnam Conflict were identified from the list *The Vietnam era is generally defined as extending from 1964 until 1973. For the purposes of this study, however, only those deaths from 1968 were considered because of the small number of deaths occurring before that year, in addition to difficulties imposed by cause-of-death coding changes over the longer interval. �of applicants for a military service bonus offered by the state Department of Veterans' Affairs in 1974. To qualify for a bonus, veterans had to meet the following criteria: 1) they must have rendered active service in the armed forces at some time between August 1, 1964, and March 28, 1973, inclusive, or have been recipients of the Vietnam armed forces expeditionary medal if they saw active service prior to August 1; 2) they must have been residents of West Virginia for at least six months prior to entry into active service; 3) they must have actively served for a period of at least ninety days unless discharged because of a servicerelated disability, and 4) they must have been honorably discharged. Efforts to notify eligible veterans or their survivors about the bonus program included one national public awareness campaign conducted in November 1975 and one conducted in July 1976. Public service announcements were issued over the television networks, and notices were posted in every major newspaper in the country and organizations on service advertised networks the bonus overseas. legislation Veterans' in their publications, and some offered assistance in filing for the bonus as a promotional device in their membership campaigns. Three different bonuses were offered. Veterans who did not serve in Vietnam ("out-of-country" or era veterans) were to receive up to $300 (Type 3 bonus); Vietnam veterans ("in-country" veterans) were to receive up to $400 (Type 4 bonus), and surviving relatives of veterans who died while in the service during the period designated by the legislature were to receive �$500 (Type 5 bonus). In West Virginia, the Department of Veterans' reported a total of 86,247 initial applicants. Affairs Of those who applied for the bonus, 83,730 veterans or survivors (97%) were eligible (Figure 1). Of these, 41,782 qualified for the Type 3 (Vietnam-era) bonus, 41,059 qualified for the Type 4 (Vietnam) bonus, and 889 qualified for the Type 5 bonus. Since this was to be a study of mortality following discharge from the service, the Type 5 bonus recipients were excluded from subsequent analyses. Names of the Type 3 and Type 4 qualifiers were, entered onto a computer tape, referred to as the "bonus tape." Identification of Veteran and Nonveteran Deaths A complete listing of West Virginia resident deaths from 1968 through 1983 was prepared from records maintained by the Health Statistics Center and entered onto a "mortality tape." The names on this list were then compared with those on the bonus tape in order to identify veterans who died during this period. For deaths from 1968 through 1978, the information had to be matched by name since social security numbers were not included on the mortality tape for these years. Any possible match generated in this manner was searched by hand and confirmed by comparing the social security number on the death certificate with that on the veteran application. From 1979 through 1983, it was possible to match by social security number. �FIGURE 1 WV VIETNAM VETERAN MORTALITY STUDY SELECTION OF STUDY POPULATION 1968-83 Bonus Tape 83,730 1 1 1 In -Country Vietnam 41,059 Not-in-Country Era 41,782 No-Match Death File 41,169 Females Era 3 Nonwhite Males Era 30 MatchedDeath File Era 613 Males Era 610 White Males Era 580 No-Match Death File 40,444 Died in Service 889 MatchedDeath File Vietnam 615 Females Vietnam 0 Males Vietnam 615 Nonwhite Males Vietnam 36 White Males Vietnam 579 �There were 1,234 initial matches between the bonus tape and the mortality tape, 614 Vietnam-era (Type 3) veterans and 620 in-country (Type 4) veterans. The veterans' discharge forms (DD-214s) were then manually checked to verify their in-country status.* This review reclassification of resulted several in records, the deletion leaving 1,228 and/or deceased veterans who qualified, 613 for the Type 3 bonus and 615 for the Type 4 bonus. Three of the deceased veterans, all Type 3 bonus recipients, were female. They were excluded from the final tape; the subsequent analyses included only deceased male veterans. Of the 1,225 male veterans who died (Table 1), 1,159 were white and 66 were nonwhite (65 black and 1 Hawaiian). nonwhite veterans were Type 3 (5%) and 36 were Type 4 Thirty (6%). Because nonwhite veterans constituted a small percentage of those who died, the study combined the mortality patterns of white and nonwhite veterans. For nonveteran males, deaths were identified from the mortality tape by deleting the records of all remaining female deaths and those of the 1,225 male veteran deaths. thus four groups defined for analysis: died; (2) male Vietnam-era-only There were (1) all male veterans who (Type 3) veterans who died; *In-country status was determined by the receipt by the veteran of one of three service medals (the Vietnam service medal, the Vietnam campaign medal, or the Vietnam expeditionary medal) as noted on the DD-214. These medals were awarded to military personnel who served in the Southeast Asia theater of operations. �TABLE 1 TYPE 3 AND TYPE 4 MATCHES BETWEEN BONUS TAPE AND MORTALITY TAPE BY YEAR 1968-83 YEAR VIETNAM-ERA (Type 3) IN-COUNTRY (Type 4) TOTAL 1968 4 13 17 1969 14 16 30 1970 17 22 39 1971 16 33 49 1972 26 31 57 1973 33 22 55 1974 25 29 54 1975 50 47 97 1976 47 46 93 1977 50 40 90 1978 54 35 89 1979 53 44 97 1980 58 51 109 1981 53 70 123 1982 55 59 114 1983 56 56 112 TOTAL 610 615 1,225 �(3) male in-country (Type 4) Vietnam veterans who died, and (4) all other West Virginia males (nonveterans) who died from 1968-83. DEMOGRAPHIC PROFILE OF DECEASED VETERANS Age Distribution The average age at death was 35.3 for all veterans, 35.1 for era veterans and 35.4 for in-country veterans. Table 2 shows that the distribution of deaths by age for Type 3 and Type 4 veterans was similar. Tables 3 and 4 present the distributions of age at death by race for Vietnam-era and Vietnam veterans, respectively. Among white Type 3 veterans, the average age at death was 35.3, among nonwhites 31.3. For Type 4 veterans, the mean age at death for whites was 35.5, with 33.5 that for nonwhites. �TABLE 2 ALL VIETNAM-ERA VETERANS Age Distribution by Type of Service VIETNAM-ERA (Type 3) TOTAL IN- COUNTRY (Type 4) AGE GROUP f % % * 4 I 15-19 4 0.7 1 0.2 5 0.4 20-24 82 13.4 92 14.9 174 14.2 25-29 139 22.8 125 20.3 264 21.5 30-34 137 22.4 143 23.2 280 22.9 35-39 83 13.6 61 9.9 144 11.7 40-44 42 6.9 53 8.6 95 7.7 45-49 36 5.9 60 9.8 96 7.8 50-54 40 6.6 33 5.4 73 6.0 55-59 24 3.9 32 5.2 56 4.6 60-64 12 2.0 12 2.0 24 2.0 65-69 9 1.5 3 0.5 12 1.0 70-74 2 0.3 0 0.0 2 0.2 TOTAL 610 100.0 615 100.0 1,225 100.0 Average Age at Death 35.4 35.1 8 35.3 �TABLE 3 VIETNAM-ERA VETERANS (TYPE 3) Age Distribution by Race WHITE TOTAL NONWHITE AGE GROUPS % # % # % 1 19 4 0.7 0 0.0 4 0.7 20-24 77 13.3 5 16.7 82 13.4 25-29 131 22.6 8 26.7 139 22.8 30-34 127 21.9 10 33.3 137 22.4 35-39 79 13.6 4 13.3 83 13.6 40-44 42 7.2 0 0.0 42 6.9 45-49 33 5.7 3 10.0 36 5.9 50-54 40 6.8 0 0.0 40 6.6 55-59 24 4.2 0 0.0 24 3.9 60-64 12 2.1 0 0.0 12 2.0 65-69 9 1.6 0 0.0 9 1.5 70-74 2 0.3 0 0.0 2 0.3 TOTAL 580 100.0 30 100.0 610 100.0 Average Age at Death 35.3 31.3 35.1 �TABLE 4 IN-COUNTRY VIETNAM VETERANS (TYPE 4) Age Distribution by Race NONWHITE WHITE TOTAL AGE GROUPS % # # % t Z 19 0 0.0 1 2.8 1 0.2 20-24 87 15.0 5 13.8 92 14.9 25-29 114 19.7 11 30.5 125 20.3 30-34 135 23.3 8 22.2 143 23.2 35-39 59 10.2 2 5.6 61 9.9 40-44 51 8.8 2 5.6 53 8.6 45-49 59 10.2 1 2.8 60 9.8 50-54 29 5.0 4 11.1 33 5.4 55-59 30 5.2 2 5.6 32 5.2 60-64 12 2.1 0 0.0 12 2.0 65-69 3 0.5 0 0.0 3 0.5 70-74 0 0.0 0 0.0 0 0.0 TOTAL 579 100.0 36 100.0 615 100.0 Average Age at Death 35.5 33.5 10 35.4 �Branch of Service Review of the DD-214 forms showed that 718 (59%) of the deceased veterans had served in the army, 210 (17%) had served in the air force, 167* (14%) had served in the navy, and 120 (10%) had served in the marines (Table 5). Seventy-five percent of the in-country veterans who died had been in either the army or the marines, in contrast to 62% of the era veterans. Twenty-five percent of in-country veterans had served in either the air force or the navy, in contrast to 37% of, the era veterans. For 10 veterans, the branch of service was not recorded on the discharge forms. *Includes 3 coast guard veterans. 11 �TABLE 5 ALL VIETNAM-ERA VETERANS Branch of Service by Type of Service VIETNAM-ERA (Type 3) IN-COUNTRY (Type 4) TOTAL BRANCH OF SERVICE % * t % * % Army 340 55.7 378 61.5 718 58.6 Air Force 127 20.8 83 13.5 210 17.2 16.1 69 11.2 167 13.6 Navy 98* Marines 39 6.4 81 13.2 120 9.8 Unknown 6 1.0 4 0.6 10 0.8 610 100.0 615 100.0 TOTAL *Includes 3 coast guard veterans 12 1,225 100.0 �ANALYTIC METHODS In spite of the intense publicity given to the bonus campaign, it is likely that many veterans or their never applied for the bonus. survivors Thus, those veterans who did qualify for a bonus represent an unknown proportion of the actual number of West Virginia males who served in the military during the Vietnam era. It cannot be assumed that the proportion was similar for both Type 3 (era) and Type 4 (in-country) qualifiers. Furthermore, because the mortality tape identified only residents of West Virginia who died during the study period, deaths in that period among veterans who no longer resided in West Virginia at the time of their demise would not have been counted among the 1,225 veteran deaths ascertained. Because of these limitations, the records provide neither complete information about the total candidate population nor a comprehensive estimate of the force veterans who did qualify. the veteran and the of mortality among the With respect to a comparison between nonveteran groups, the data would underestimate the relative force of mortality among the veterans, if such a comparison were made. With respect to a comparison between in-country and era veterans, it cannot be assumed that similar proportions of the respective candidate population qualified for the bonus or that the death rates among in-country veterans who were no longer West Virginia residents were similar to those among era veterans who were no longer residents. 13 �The method of choice for a study of mortality when there is incomplete data on the population at risk is a proportionate mortality analysis. In this type of study the proportion of all deaths due to the disease(s) of interest in the study population is compared with the proportion of all deaths due to the disease(s) of interest in the comparison (referent) population. Such proportional rates do not express the risk of dying from a disease since the incidence is not measured against a population base. They simply suggest that there may be a difference worth investigating further. The validity of such a study rests on the assumption that there is no association between the study factor, i.e., veteran status, and the occurrence of other diseases. Since we cannot make this assumption, such an analysis is used to generate hypotheses or to conduct preliminary tests of etiologic hypotheses without collecting much additional data. The relationship between the proportion of deaths due to a specified cause in a study population and the proportion derived from the referent population is expressed as a proportionate mortality ratio (PMR). The PMRs in this study are standardized to adjust for selected confounding variables. When the veteran group and its subgroups were compared with the nonveteran group, adjustments were made by stratifying on age at death by 5-year intervals (15-19, 20-24, . . . etc.) and on year of death by 2-year intervals stratum, (1968-69, 1970-71, expected deaths were . . . 1982-83). For each calculated by determining the percentage the cause of death of interest contributed to all 14 �causes in the referent population and multiplying this result by the total deaths from all causes in the study population. The standardized PMR statistic (sPMR) is the ratio of the number of deaths of interest observed in the study population summed over all strata, multiplied by 100, and then divided by the expected values summed over all strata. Stratification by age only and not by year of death was done when the in-country (study) group of veterans was compared to the era (referent) group. This was done in order to avoid losing data from the study group when respective strata in the referent group had no deaths. An sPMR greater than 100 indicates that the cause of interest contributes a greater percentage of all deaths in the study population than in the referent population; an sPMR less than 100 indicates that the cause contributes a smaller percentage of all deaths in the study population than in the referent population, and an sPMR of 100 indicates that the cause of interest contributes the same percentage of all deaths in both groups. expected frequencies against confidence p-value for each cause of interest were tested the null hypothesis, i.e., proportionate mortality interval expressing The observed and structure, around the each each exact sPMR by group has the same calculating a 95% and also a one-tailed probability of finding the difference between the observed and expected frequencies. RESULTS In the period 1968 through 1983, there were 1,225 deaths among males who had served in the military during the Vietnam 15 �Conflict. Six hundred fifteen of the men served at least a portion of their duty in Vietnam (in-country, Type 4 veterans) and 610 had no experience in Vietnam (era, Type 3 veterans). For both groups combined, 716 deaths (58%) were from external causes (injury from accidents, poisoning, or violence), 237 (19%) were from cardiovascular neoplasms, 48 (4%) disease, were 145 from (12%) were nonmalignant from diseases malignant of the gastrointestinal system, 24 (2%) were from nonmalignant diseases of the respiratory system, 5 (-=1%) were from allergic, metabolic, and endocrine disorders, and 50 (4%) were from all other causes. With nonveteran West Virginia male deaths from 1968 through 1983 as a reference, Table 6 demonstrates the number of observed and expected deaths in each cause-of-death category for all veterans together and for in-country and era veterans separately. For all veterans, the observed distribution of deaths over these categories was significantly different from the expected (Chi square Goodness of Fit •» 50.2 with 6 degrees of freedom, p<10~8). Accidents, significantly poisoning, greater and proportion violence of accounted all veteran for a deaths than expected (sPMR excess), while deaths from allergic, metabolic, and endocrine conditions and from all other causes accounted for significantly smaller-than-expected deaths (sPMR deficits). For 16 proportions of all veteran cardiovascular, digestive, and �TABLE 6 ALL CAUSES OF MORTALITY Vietnam Veterans vs. Nonveterans West Virginia, 1968-83 ALL VETERANS vs. NONVETERANS IN- COUNTRY VETERANS vs. NONVETERANS ALL CAUSES °/. Accidents, Poisoning, and Violence (80E9) E0-99 716, '626.74 Cardiovascular Disease (9-5) 3049 237, '251.5 Malignant Neoplasms (140-209) sPMR (95Z CI) °/ 'E sPMR ERA VETERANS vs. NONVETERANS (95Z CI) ° / sPMR (95Z CI) (106-130) 354, '318.1 111* (100-124) 'E (106-123) 362. '308.6 117** 94 (83-107) 114, '129.1 88 (73-106) 123, '122.4 100 (84-120) 145, '142.4 102 (86-120) 71, '73.6 96 (75-122) 74, '88 6. 108 (85-136) Diseases of the Digestive System (520-577) 48, '56.7 85 (62-112) 29, '29.0 100 (67-144) 19, '27.8 68 (41-107) Diseases of the Respiratory System (460-519) 24. '29 3. 73 (47-108) 12, '16.7 72 (37-125) 12, '16.2 74 (38-129) 38* (10-96) 52** (33-77) 114** y Allergic, Metabolic, and Endocrine Diseases (240-279) All Other Causes (Residual) '19 2. 50. '29 9. 23** (7-53) 'll.2 9** (-=1-47) '06 1. 54** (40-71) 26. '68 4. 56** (36-81) 24, '61 4. Goodness of Fit X2. -50.2 odt p- 1 ' 08 *polsson p value*.05 **poisson p value£.001 �respiratory diseases, the standardized proportionate mortality ratios were less than unity when all veterans were compared with nonveterans, but the observed numbers of deaths in these categories were not significantly lower than the expected. proportion of veteran The deaths due to malignant neoplasms was similar to that of nonveterans. The pattern of death for in-country and era veterans evaluated separately relative to the nonveteran population was similar in both instances to the pattern observed for the groups combined. In a separate contrast with era veteran deaths as the standard (not shown), no difference was. observed in the overall mortality pattern between in-country and era veterans (Chi square Goodness of Fit = 7.0 with 5 degrees of freedom, p - .22). In order to evaluate more specific causes of death within the leading categories, the contrasts were repeated to obtain standardized proportionate category-specific mortality ratios for external causes (injury), cardiovascular diseases, and malignant neoplasms separately. Table 7 shows the distribution of injury deaths for veterans contrasted with nonveterans over five causes: motor vehicle accidents, non-motor-vehicle accidents, suicide, homicide, and all other external causes. Homicide accounted for a significantly smaller-than-expected proportion of the injury deaths among veterans. The standardized proportionate injury mortality ratio for motor-vehicle-related deaths among veterans was greater than 100 but was not a statistically significant 18 �TABLE 7 INJURY MORTALITY Vietnam Veterans vs. Nonveterans West Virginia, 1968-83 ALL VETERANS vs. NONVETERANS ° / sPMR (95Z CD 315, '9. 206 108 (97-121) 201, '0. 293 96 (83-110) 104 (85-125) ACCIDENTS. POISONING, AND VIOLENCE (E800-999) Motor Vehicle (E810-E825) Ron-Motor Vehicle (E800-E809, E826-E949) Suicide (E9SO-E9S9) HoBiclde (E960-E969) All Other Causes (E970-E999) IN-COUNTRY VETERANS vs. NONVETERANS 'E 111 '107.2 63. '81.5 77* (59-99) 26. '74 2. 95 (62-139) Goodness of Fit X^.--6.78 P-.15 *poisson p value-=.05 sPMR 107 (115 9-2) 100, '105.1 95 (77-116) 111 (85-144) sPMR (95Z CI) 154. '4. 105 110 (318 9-2) 101, '0. 142 97 (79-118) / '54.2 96 (72-126) 35, '14 4. 85 (59-118) 87 (45-152) (95Z CI) 161, '5. 101 ERA VETERANS vs. NONVETERANS °'E / 5 9 / '53.0 28. '02 4. 1 4 / '13.6 70* 103 (46-101) (56-173) Goodness of Fit XJ^-5.43 P-.25 °'E / 5 2 12 / '38 1. Goodness of Fit X2df-2.71 p-,61 �excess. For non-motor-vehicle fatalities, suicide, and all other causes, the expected numbers were similar to the observed. The overall pattern for veterans was not significantly different from nonveterans (Chi square Goodness of Fit » 6.78 with 4 degrees of freedom, p =.15). Separate comparisons of the in-country and era veteran populations with nonveterans similarly overall difference in the distribution reflected no of injury deaths; the ratios in each of these contrasts were similar to those observed for the combined veteran group. Among the cardiovascular causes of mortality there were no veteran deaths from either (Table 8), hypertension or rheumatic heart disease (p-=.005), fewer-than-expected veteran deaths from cerebrovascular disease (difference not significant), and more-than-expected veteran deaths due to ischemic heart disease (difference standardized not significant). proportionate cardiovascular The individual disease mortality ratios for in-country and era veterans were similar to the corresponding mortality ratios derived for the combined group. Proportionate cancer mortality ratios comparing veterans to nonveterans are shown in Table 9. veterans and respiratory the system nonveteran excess contributed population, accounted proportion of veteran cancer by In the comparison between all for deaths in-country identical to that contributed by 20 a era neoplasms significantly than of greater expected. veterans veterans. was the The virtually Melanoma of �TABLE 8 CARDIOVASCULAR DISEASE MORTALITY Vietnam Veterans vs. Nonveterans West Virginia, 1968-83 ALL VETERANS vs. NONVETERANS CARDIOVASCULAR DISEASES (390-459) Ischemic Heart Disease (410-414) Cerebrovascular Disease (430-438) °/. sPMR (95Z CI) 158. '141.5 112 (95-131) 18, '50 2. 72 (43-114) Hypertension (400-405) °65 '. Rheumatic Heart Disease (390-398) °/5.4 All Other Cardiovascular Diseases (415-429, 440-459) IN-COUNTRY VETERANS vs. NONVETERANS 61 '86 5. 0** 0** 104 *poisson p valuer .05 **poisson p value «.005 °/ 'E sPMR (95Z CI) °'E / sPMR (952 CI) / '67.7 111 (87-139) 83, '40 7. 112 (89-139) 73 (32-144) 10, '40 1. 71 (34-131) 75 8 / '09 1. - °/3.4 0* - °>1.9 0 / '30.2 103 (80-134) ERA VETERANS vs. NONVETERANS 31 - °/3.0 0* - °/3.5 0* (70-146) 30 '84 2. 106 - (71-151) �TABLH. » CANCER MORTALITY Vietnam Veteran* vs. Nonveterans West Virginia. 1968-83 IN-COUNTRY VETERANS vs. NONVETERANS ALL VETERANS vs. NONVETERANS MALIGNANT NEOPLASMS (140-209) sPHR (951 CD 135* (102-174) 123 (91-162) 462* (6-9) 1897 21, '69 2. 78 (819 4-1) 12, '. 66 182* (94-318) 79 (38-145) 6 128 (46-276) 7 123 (50-254) °>E Respiratory System "4. '31 (160-163) Trachea, Bronchus, 50 and Lung '07 4. (162) Larynx (161) Digestive Organs and Peritoneum (150-159) to to Malignant Melanoma of the Skin (172) Lymphoms (200-203, 208-209) '13 '. 10 / '12.7 Hodgklns Disease (201) /4.7 Hale Genital Organs (185-187) Leukemia (204-207) >,.7 6 /13.1 3 /0.7 % sPHR (951 CD 131* (87-187) 29, '09 2. 139* (93-199) 118 (76-174) 25. '19.5 128 (83-189) 49 2* (95-1349) 49 2* (95-1349) 77 (37-142) % 7 . 4 148 (40-378) %9 . 205* (89-406) 7 >6.2 113 (45-233) % 4 . 47 (10-136) % 4 . 208 (69-497) >/2.4 42 (1-233) 4 182 (49-461) %* . 83 (18-254) (17-100) 3 48 (10-139) V. 44 (9-129) (36-334) 2 /1.4 143 (17-508) 2 118 (5-435) (11-102) '41 /. 24 (-1-137) 3 51 (10-148) 250 (52-731) % 7 . 429* (90-1271) 200 (5-1071) 46* 129 */10 Soft and Connective Tissue (171) 3 Bone (170) 2 /K4 143 (18-531) Urinary Organs (188-189) 2 /5.6 36 (4-129) /15.6 103 (59-166) 16 / '21.2 (951 CD 10, '13.0 Brain i Nervous System (191-192) All Other Halfgnancle. 25 sPNR (911 3-4) 4 /1.2 29, '22.2 NONVETERANS 79 Oral Cavity (140-149) >3.1 °>E ERA VETERANS 40* •polaaon p value*.05 11, '14.0 /2.7 /2.2 /6.3 '05 '. V, '77 '. 0* 78 /1.7 /5.9 °OS '. V . 2 - (29-170) '. 27 ' , V 0 - 125 (3-663) 74 (10-305) 127 360-231) �TABLE 10 CANCER MORTALITY FOR VIETNAM VETERANS In-Country Veterans vs. Era Veterans West Virginia, 1968-83 OBSERVED, 'EXPECTED Respiratory System (160-163) (95Z CI) 93 (63-134) NS 110 (55-197) NS 7 280 (113-577) 0.014 5 833 (271-1945) 0.0004 222 (62-579) NS 500 (103-1461) 0.023 (12-118) 0.066 - - 29, '31.0 n Digestive Organs and Peritoneum (150-159) Lymphoma (200-203. 208-209) to Hodgklns Disease (201) POISSON p VALUE (Fisher's exact) sPMR / '10.0 '2.5 '. 06 U) Male Genital Organs (185-187) *!. /. Cancer of the Testls (186) V . Malignant Melanoma of the Skin (172) VT 46 Soft and Connective Tissue (171) \ oo Leukerolas (204-207) 3 Oral Cavity (140-149) 2 / All Others /1.9 2.4 8 / '12.7 158 (33-461) NS 83 (10-301) NS 63 (27-124) NS �the skin also accounted for a significantly greater-than-expected proportion of cancer deaths among all veterans, but the contribution of in-country veterans to this excess was trivial in comparison with that of era veterans. Deaths from leukemias and malignant neoplasms of the nervous system each occurred less frequently than expected among both veteran groups. tissue tumors, For soft a significant difference between observed and expected deaths was not found for all veterans combined. These tumors occurred only among in-country veterans and not among era veterans, however. When in-country veterans alone were contrasted with nonveterans, they had a significantly elevated standardized proportionate cancer mortality .ratio for soft tissue tumors. The contrast between in-country and era veteran cancer deaths shows the difference in the observed (3) and expected (0) soft tissue tumors for in-country veterans (Table 10). In-country veterans also have significantly elevated standardized proportionate contrasted cancer with era mortality ratios veterans. The for lymphoma difference is when more specifically attributable to Hodgkin's disease, for which there were five deaths in this group, compared with an expected 0.6. Finally, there was a statistically significant excess in the sPMR from testicular cancer among the in-country veterans. Discussion The present study demonstrates that the mortality experience 24 �among persons who served in the military during the Vietnam Conflict differs substantially from that of nonveterans. It also suggests that there may be important differences between the veterans who served in Vietnam and those who did not with respect to their cancer mortality experience. Differences in the mortality experience between veteran and nonveteran groups are influenced by a selection bias initiated at the time of induction to the military service. assure that healthy individuals In order to serve in the military, the preinduction screening process excludes persons with preexisting conditions such as diabetes and allergies, asthma, hypertension, have substantially metabolic disorders, rheumatic heart disease, and clinically apparent malignancies. veterans other lower Because of this selection, mortality rates than the nonveteran population for many years following their induction. This is known as the "healthy veteran effect." In the present study, this selection bias is the most plausible hypothesis to account for the significant sPMR deficits observed among veterans for mortality from allergic, metabolic, and endocrine disorders, all other causes, rheumatic heart disease, and hypertension. Moreover, it may also have contributed to the less prominently diminished sPMRs among veterans for cardiovascular, digestive, and respiratory diseases. While real differences in the mortality rates between veteran and nonveteran groups for selected causes are reflected 25 �in the sPMRs, proportionate they also mortality complicate the for other interpretation causes. Since of the proportionate contribution from all separate causes must sum to 100, the proportionate contributions among "healthy" veterans from causes that are not screened by the induction process become artificially inflated relative to their contribution among the "unhealthy" population. Injury, the leading cause of death for both veterans and nonveterans, played a significantly greater role among veterans, accounting for 58% of their deaths as opposed to an expected 51%. Since the study did not adjust for discrepancies in the health status between veterans and nonveterans, part of the excess in injury among veterans must be due to the relative absence of deaths from conditions that would exclude persons from military service. While an excess of these deaths araong nonveterans reciprocally diminishes the proportion of their mortality attributable to injury, there may be a real difference in life style and the propensity veterans and nonveterans. for risk-taking behavior between An evaluation of injury mortality alone, performed to eliminate distortion from the healthy veteran bias, showed only that homicide was significantly less important as a cause nonveterans. of injury death among veterans than On the other hand, while not significant, among the difference between the observed and expected number of veteran deaths from motor-vehicle accidents would suggest that this is at least one area where veterans may be at a substantially greater 26 �risk of death than nonveterans. This issue, however, and previous assertions that veterans are at greater risk of death from suicide cannot be adequately addressed by this analysis in the absence of more complete data on the populations at risk. While malignancies as a group accounted for similar proportions of veteran and nonveteran deaths, deaths from tumors of the respiratory system were a significantly more prominent cause of cancer death among veterans than among nonveterans. probable explanation for this finding would be A a greater prevalence of smoking among military as compared with nonmilitary personnel, but this cannot be substantiated from the limited information available on death certificates. In general, the pattern of death among in-country veterans from all causes, and within the subcategories of "accidents, poisoning, and violence" and "cardiovascular diseases," were similar to those observed for all veterans combined, and there were no substantial differences in the mortality patterns between in-country and era veterans for these categories. Among cancer deaths, however, there was strong statistical evidence to suggest that .Hodgkin's disease, cancer of the testis, and soft tissue tumors were more common among veterans who served in Vietnam than among veterans who did not. cautiously, however, These findings must be interpreted since the expected proportions of site-specific cancer deaths for in-country veterans were derived from a relatively small number (74) of cancer deaths among era 27 �veterans and would therefore be subject to considerably large random fluctuations. At the same time, the difference between the observed and expected numbers of soft tissue tumors among in-country veterans supports similar proportionate mortality findings study conducted in a previous by the Massachusetts Department of Public Health. Neither the Wisconsin study nor the New York study found significant differences between in-country and era veterans in the occurrence of soft tissue sarcomas. These studies, however, and the present one are limited by the absence of precise exposure data, unknown sizes of the candidate populations at risk, and insufficient follow-up time to account for latency from in-country veterans. exposures that might have been unique to Also, by including deaths from as early as 1968, the present study may have been biased against finding an excess occurrence of cancers with long latency periods. This study only suggests the possibility that the risk of death from soft tissue sarcomas, Hodgkin's disease, and testicular cancer are elevated among veterans who served in Vietnam. We are currently awaiting the records of the in-country veterans who died from these tumors in order to speculate about possible exposure histories and to generate hypotheses that may have some biologic plausibility. To take advantage of latency periods, cancer-specific proportionate mortality studies could be repeated in several years. Also, by excluding deaths that occurred in the late-Vietnam and early post-Vietnam period, and by improving ascertainment of exposure histories, studies can 28 �focus more sharply on etiologic hypotheses relating to possible exposures in Vietnam. On the other hand, since proportionate mortality studies are more useful to explore than to confirm hypotheses, it is recommended that more precise risk-assessment studies of Vietnam cohorts be performed using national data to further test the hypothesis that Hodgkin's disease, testicular malignancies, and soft tissue tumors may be important causes of cancer mortality among veterans who served in Vietnam. 29 �BIBLIOGRAPHY Dienstfrey, Stephen J., and James J. Bryne. Veterans in the United States; A Statistical Portrait from the 1980" Gensus. Washington, D.C.: Veterans Administration, 1985. "Final Toll for U.S. in Indb-China." (Sept. 24, 1973): 73. U.S. News £ World Report Kogan, Michael D., and Clapp, Richard W. Mortality among Vietnam Veterans in Mas sachuse t1s, 1972-1983. Boston: Massachusetts Department of Public Health, 1985. Lawrence, Charles E. et al. "Mortality Patterns of New York State Vietnam Veterans." American Journal of Public Health 75 (March 1985): 277-79. ' Shottenfeld, David, and Joseph F. Fraumeni, Jr., Cancer Epidemiology and Prevention. Philadelphia: W.B. Saunders Company, 1982. 30 � 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. 069 Folder The folder containing the original item. 1868 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 Shepard, Barclay M. Date A point or period of time associated with an event in the lifecycle of the resource February 4 1986 Title A name given to the resource Critique of West Virginia Mortality Study Subject The topic of the resource state-funded Vietnam veterans study mortality trends study criticism study protocol ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/3274dbae34e5de29e5c13b745ec55253.pdf 327ada61ba22f79e99d99f056952068b PDF Text Text Item ID Number 01353 Houk, Vernon N. Corporate Author Report/ArtidO TltlO Memorandum: to Ronald W. Hart, Chairman, Science Panel, Agent Orange Workinh Group (AOWG), from Vernon N. Houk, Assistant Surgeon General, with subject Protocol for Women's Vietnam Veterans Health Study, September 10,1987 Journal/Book Title Year 000 ° Month/Day Color D Number of Images 4 DOSCrlptOn NOtBS Memo discusses concerns that Houk has about the study protocol. He wants the concerns addressed before he will be willing to support conduct of the study. Wednesday, July 11, 2001 Page 1854 of 1870 �DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service Centers for Disease Control Memorandum Date .September 10, 1987 From Director Center for Environmental Health and Injury Control Subject Protocol for Women's Vietnam Veterans Health Study To Ronald W. Hart, Ph.D., Chairman, Science Panel Agent Orange Working Group We have reviewed the Women's Vietnam Veterans Health Study Protocol submitted by the Hew England Research Institute, Inc. We have serious concerns about this submission which we have listed below. Until these concerns are adequately addressed, I cannot support conduct of the proposed study. Detailed below are comments on the protocol for the Women's Veteran Health Study. A. Cohor^ Selection 1. Unlike the Vietnam Experience Study, there are differences between the exposed group and the comparison groups in variables other than experience in Vietnam. The presence of such differences increases potential confounding and complicates the analyses. Would it be more satisfactory to limit the scope of the study and the selection of a comparison group (e.g., Limit, the study to army cases and controls) to address the most important hypotheses rather than try to do too much? 2. It is not clear how the VA developed its list of 5000 Army Vietnam veterans—how complete is this list? How complete are the lists of Vietnam veterans in the other services? 3. The sampling frame for the non-Vietnam veterans is not clearly described. 4. How valid is their proposed capture-recapture method as a method of documenting the completeness of the cohorts. 5. What duty stations will women veterans for Cohort B come from? Will the Air Force sample of nurses be large enough for separate comparisons? 6. pages 2-3: What does matched on occupation mean and how will this be possible? 7. Consideration might be given to increasing the number of controls (per case) in the overall study, especially in some of the proposed substudies (e.g., reproductive health). �Page 2 - Ronald W. Hart, Ph.D. B. Reproductive Health 1. The expectation is to find major birth defects in 1% of offspring; a more appropriate expectation is 2-3%. It would be wise to compile a list of specific defects which are to be considered "major" before the study begins. 2. Cases are defined as women who have had a baby with a defect or "two or more spontaneous abortions not clearly attributable to an identified cause." They propose excluding those with an 1 "unequivocal karyotypic abnormality", and those with a uterine abnormality. Exclusion of women who themselves have a tcaryotypic abnormality seems reasonable, but it is unlikely that any will be found in the sample. If the reference implies that aborted fetuses that have a karyotypic abnormality will be excluded, this is not reasonable. An abortion associated with a chromosomal anomaly is a health outcome worth considering in the study. In general, more details are needed on why certain diseases/conditions are being excluded. 3. Spontaneous abortions will be difficult to validate since they are frequently not medically documented. 4. It is stated that women with diethylstilbesterol (DBS) exposure would be kept in the sample. We would suggest exclusion since they are excluding spontaneous abortions associated with uterine abnormality, and DES exposed women have a higher rate of abortion, usually from uterine abnormality. 5. We would suggest matching controls on age at the last abnormal pregnancy, rather than the first. Spontaneous abortion is strongly related to age and a woman's pregnancies may be separated by many years. 6. At the time this study will be done, most women Vietnam veterans will be 40 or more years of age. Therefore the evaluation of prolonged amenorrhea should probably be deleted from the study. 7. A definition of fertility/infertility is needed. C. PsycholoRical/KeuropsychoIoRical TestinR 1. The proposal to use the CDC Vietnam Experience Study (VES) neuropsychological battery is inappropriate. That battery was designed to assess primarily neuropsychological deficits which might be expected from exposure to a toxin (e.g. TCDD). The battery also included some assessment of psychological and neuropsychological problems that might be related to stress. �Page 3 - Ronald W. Hart, Ph.D. This latter component is not included (as far as we can tell) in the present protocol. Since TCDD exposure is unlikely to have been a major problem for most nurses in Vietnam, it would probably be better to give greater emphasis to long-term psychological stress faced by these veterans while in Vietnam. This would mean that the proposed battery should include some measures of stress which have been well validated and accepted in psychological research. ' In addition, greater emphasis should be given to depression, anxiety, and alcohol and drug use, which are possible sequelae of stress. Also, consideration should be given to including the Minnesota Multiphasic Personality Inventory (MMPI), and more of the Diagnostic Interview Schedule (DIS) than just the Post Traumatic Stress Disorder (PTSD) section. 2. Another concern in the psychological area is the testing in the home of the participant. The VES battery was designed to be administered in a standard testing environment by trained technicians under close supervision. Quality control and standardization will be difficult in the proposed setting. 3. The rationale for measurement of TCDD levels in the PTSD substudy needs further clarification/justification. 4. With respect to the psychological area in general, we suggest that advice be sought from experts in psychology/psychiatry to evaluate the proposed psychological test battery. In addition, staffing for the study should include a qualified psychologist or psychiatrist. D. Serum. Dioxin (TCDD) Measurement 1. The whole issue of Agent Orange exposure assessment/TCDD testing becomes questionable now that the results of CDC's Validation Study are known. If TCDD testing is to be done, is a whole unit of blood necessary—if willing to accept some cut-off level (e.g. 20 ppt) less blood may be required. Also, if TCDD testing is to be done, consideration should be given to using a sample of Vietnam and non-Vietnam veterans—based on the results of a sample, a decision could be made about testing other participants. 2. Serum TCDD measurements are to be used as the measure of exposure for both the Reproductive Outcomes Study and the Post Traumatic Stress Disorder Study. Apparently about 550 serum analyses will be needed for these two studies combined. The current proposal does not involve flying the participants to a centralized collection center but rather using local Red Cross Centers on contract. These approximately 550 women will be located all over �Page 4 - Ronald U. Hart, Ph.D. the United States and the Red Cross is not even present in every state, so obtaining the samples solely in this manner will not be possible. A very large number (>100) of Red Cross contracts will be involved to obtain blood on persons near a Red Cross Center under the current plan. The use of at least regional Red Cross Centers would be a marked improvement and the quality of sample acquisition would be significantly higher if only a few (even one) Red Cross Center(s) were used. 3. T|he cost of the serum 2,3,7,8-TCDD measurement should be noted to be $1000 apiece. Currently the protocol states that EHLS is the only lab in the U.S. that can perform the measurements, but clearance for such measurements at EHLS has not been obtained. Similarly, has the American Red Cross been approached as to their willingness to participate in this study? E. Operational and Other Issues 1. The protocol anticipates a fair amount of dependence on both interviews and military records. What are the limitations of these data in terms of the questions addressed (e.g., ascertainment of spontaneous abortions by history)?. 2. The authors do not provide information on how they propose to address the issue of name changes in female veterans and the difficulties this might cause in locating these veterans. 3. The operational aspects of the pediatric examination component are not clearly described. Has the Ranch Hand Study been successful in this area? What end points will be looked at and analyzed? 4. The choice of conditions to be validated might be expanded to include same conditions which have been suggested to be associated with TCDD exposure—e.g. skin conditions (chloracne, hyperpigmentation, etc.), liver disorders including prophyria, peripheral neuropathy, immunologic deficits. 5. Quality control of the physical and routine laboratory examinations must be assured. 6. Has adequate effort been made to insure that the medical records and pathology slides will be reviewed in a blinded manner? 7. What efforts are being made to insure quality assurance and quality control of hormone blood testing? Vernon H. Houk, M.D. Assistant Surgeon General � 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. 069 Folder The folder containing the original item. 1853 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 Houk, Vernon N. Title A name given to the resource Memorandum: to Ronald W. Hart, Chairman, Science Panel, Agent Orange Working Group (AOWG), from Vernon N. Houk, Assistant Surgeon General, with subject Protocol for Women's Vietnam Veterans Health Study, September 10, 1987 Subject The topic of the resource Women Vietnam Veterans Health Study study criticism study protocol dioxin ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/3dc38971d5bafbf104b4eebc59aea4d4.pdf bfe42feb88369199f8ae7bb9357e05e5 PDF Text Text ItBnUDNimbor °1852 Author McKlnlay, Sonja M. Corporate Author New ROpOrt/ArtldB TltlO Women England Research Institute, Inc., Watertown, Mass 's Vietnam Veterans Health Study Protocol Development, Summary Report of Expert Panel Review, Deliverable E Journal/Book HUB Year 000 ° Month/Day Color a Number of hnaoos 25 DBSCriptOn NOtBS Contract No. V101(93)P-1138 Wednesday, July 11, 2001 Page 1853 of 1870 �WOMEN'S VIETNAM VETERANS HEALTH STUDY PROTOCOL DEVELOPMENT CONTRACT NO. V101(93)P-1138 SUMMARY REPORT OF EXPERT PANEL REVIEW DELIVERABLE E SUBMITTED BY NEW ENGLAND RESEARCH INSTITUTE, INC. PRINCIPAL INVESTIGATOR SONJA M. MCKINLAY, Ph.D. NEW ENGLAND RESEARCH INSTITUTE, INC. 42 Pleasant Street Watertown, Massachusetts 02 i 72 (617)923-7747 �TABLE OF CONTENTS INTRODUCTION 1 SECTION 1: LITERATURE REVIEW 2 SECTION 2 : STUDY DESIGN 3 2 .1 COHORT DESIGN AND SUB-STUDIES 3 2.2 VIETNAM EXPERIENCE (VE) EXPOSURE COMPONENTS 8 2. 3 POPULATION DEFINITION AND SAMPLE SIZES 8 2. 4 GENERAL HEALTH OUTCOMES 9 2. 5 REPRODUCTIVE OUTCOMES SECTION 3 : QUESTIONNAIRE 3 .1 3. 2 TABLE 3.3 REPRODUCTIVE FUNCTION/OUTCOME MISCELLANEOUS SUGGESTIONS EXPERT PANEL COMPOSITION EXPERT PANEL AFFIDAVITS 10 11 11 12 14 16 �INTRODUCTION A key task under the current contract was the formation of an Expert Panel of Consultants who would review the following final products: • Literature Review; • Study Design; and • Questionnaire As proposed, NERI expanded this mandated function to include review of preliminary drafts and participation in a one day discussion including prepared written comments on specific assignments. Finally, the Technical Representative (Dr. H. Kang) requested written affidavits indicating acceptance, by panel members, of the final products. The following sections include a summary of input on the Literature Review (Section 1), a summary of input on the Study Design (Section 2) and on the Questionnaire (Section 3). A final section lists the panel members and their areas of expertise, includes copies of the panel assignments for the one day review and affidavits accepting the Study Design and Questionnaire submitted to the VA as final products. �1. LITERATURE REVIEW A draft of the Literature Review was sent to panel members for review and verbal or written comments in January, 1987. Apart from clarification of some ambiguous statements, the primary input was in the form of additional key references which were very recently published or in press. This input was exactly what was desired. Panel members were clearly at the forefront of important areas of research, including phenoxy herbicides, nursing exposures and reproductive toxicology in particular. Interestingly, one important occupational exposure not included in the original review and not raised by the panel was hexachlorophene - a major occupational exposure for nurses in the study period, which also has TCDD as a contaminant in its manufacture. This exposure was identified through two sources: a senior staff member at CDC (personal communication) and the updated report of the NIOSH Occupational Dioxin Registry (Fingerhut et al, 1985). A review of this potentially confounding occupational exposure is included in the final products as an Addendum to the Literature Review. �2. STUDY DESIGN Substantial input was obtained from panel members in the following forms: • written comments submitted for the one day meeting; • verbal comments at the meeting; and • verbal or written comments on a subsequently revised document. For clarity, comments and decisions will be summarized under the following sub-headings: • Basic cohort design and sub-studies; • VE exposure components; • Population definintion and sample size; • General health outcomes; and • Reproductive outcomes. 2.1 COHORT DESIGN AND SUB-STUDIES (a) Cancer Case/Control Study The originally proposed case/control study of cancers was deleted from the study design after the following comments and issues were reviewed and discussed: �1. The inclusion of all cancers was considered insensitive to TCDD exposure. Reference was made to the SEER (NCI) data which included better incidence data with which to estimate expected numbers of relevant cancers (Soft Tissue Sarcoma, Hodgkin's Disease and Non-Hodgkin's Lymphoma). 2. Risk factors (confounders) would differ for each cancer site. 3. The inclusion of cancer cases and controls from Cohort B, which will not have been exposed to TCDD (at least to the same degree) was considered noninformational, given the aim of this substudy to investigate associations between cancer and TCDD exposure. 4. Debilitation and therapy in cancer cases will affect both immune status (one of the intervening variables to be measured) and body fat available for TCDD determinations. As suggested by panel members, the expected number of STS, HD and NHL cancer cases combined was subsequently estimated as 30 for both cohorts combined, using SEER data (NCI, 1987) . These numbers were too small for a case/control study to be feasible. Congenital Abnormality Case/Control Study The case/control study of congenital abnormalities was generally well-received as an important sub-study. The following issues were raised in its design: �1. The study should be restricted to Cohort A (VEexposed subjects). 2. The detection of abnormality in aborted fetuses was considered problematic - not all hospital records would include sufficient details. Rather, panel members recommended including only abnormalities detected in live born offspring. 3. The suggestion was made during discussion to include spontaneous abortions as the other adverse reproductive outcome for this case/control study. This last suggestion was further modified to include only multiple abortions (2+) with no clear cause, as otherwise numbers for this sub-study would have been too large. 4. The suggestion was made to use information on the half-life of TCDD in adipose tissue (if available) to estimate TCDD body burden at conception. (c) Nurses Sub-Study Because nurses are expected to comprise at least 85% of the Cohorts, this sub-study was seen by panel members as perhaps the main study. A lively discussion developed out of which a consensus was obtained that emphasis should be on as homogeneous a group as possible. The decision was therefore made to restrict this substudy to Army nurses from both cohorts. �Further discussion centered on the desirability of a civilian control group in order to unconfound, as much as possible, the basic nursing occupational exposures. This was a major concern given that nurses in Cohort B were also exposed to unique stresses of caring for wounded Vietnam veterans. Subsequent discussions with Dr. Kang on this issue of a third control group produced the alternative proposal from Dr. Kang to include Air Force nurses in Cohort B as a third, relatively unexposed group. This suggestion was also incorporated in the final design. (d) PTSD Sub-Study There was discussion at the one day meeting concerning the possibility of investigating PTSD, its relation to neuro-behavioral functioning and TCDD exposure. The final PTSD sub-study resulted from this discussion. (e) Validation Sub-Studies The following recommendations were made concerning validation of key outcomes: • It was strongly recommended that pathology slides be obtained to validate at least the following cancers - STS, HD, NHL. Early amenorrhea (< 40 years) should be verified with FSH levels. �Records should be obtained (or at least releases to obtain them) for all major diagnoses, "even if all are not verified immediately. Members of the panel also felt that pediatric examination of all congenital abnormalities may not be necessary. Rather record verification with examination of a small sub-sample may be sufficient. The operative note is the most important source for verifying endometrial pathology, rather than the pathology report and should be obtained, if possible. Results of pelvic examination were inadequate validation evidence for endometriosis. Pathology reports should be obtained for all induced abortions. (f) Mortality Study An originally proposed analytic study of deaths in both cohorts was considered not very informative as outlined and somewhat duplicative of the VA Mortality Study in progress. At the same time, it was generally considered essential to include deaths as outcomes in as many analyses as possible, to minimize bias. The final approach proposed involves analysis of primary data sets with and without deceased cohort members included. �2.2 VIETNAM EXPERIENCE (VE) EXPOSURE COMPONENTS There was protracted discussion of VE exposure components and the following points were made (and incorporated in revisions): • Exposure to TCDD and to phenoxy herbicides should be kept distinct, conceptually as there are no satisfactory direct measures of phenoxy herbicide exposure; • Emphasis should be on VE as a whole and exposure to phenoxy herbicides (TCDD); • An attempt should be made to obtain some data on use of insect repellents, even if detailed insecticide exposure is not available; and • The panel members were intrigued with the availability of workload data in the Chief Nurses' Reports and encouraged the extraction and use of such information for the final study. All of these recommendations were incorporated into the final Study Design. 2.3 POPULATION DEFINITION AND SAMPLE SIZES The panel considered that, given the difficulties in obtaining lists with current contact information, use of the VA Mortality Study lists was an acceptable compromise. At the same time the panel members urged that: �1. The sampling design used in compiling the lists be documented; 2. The adequacy (coverage) of the lists (especially for Cohort B) be verified during the Phase II study. Both of these recommendations were incorporated into the final design. With respect to sample size, there was some discussion concerning whether Cohort A constituted a sample or a population. If the emphasis is on generalization to women Vietnam veterans only, then Cohort A is a population and no sampling variation is estimable for this cohort. If the emphasis is on women Vietnam veterans as a sample of women potentially exposed to VE (or its equivalent) then Cohort A is a sample. The consensus was that Cohort A should be considered as a sample and smallest detectable relative risks calculated on this assumption. This consensus is reflected in the final study design. 2.4 GENERAL HEALTH OUTCOMES All the proposed health outcomes were reviewed by the panel and the following recommendations made: • Those cancers likely to be misclassified as organspecific when they are, in fact, STS should be included for record review; and • There should be emphasis on Post Traumatic Shock Disorder (PTSD) and selected other health outcomes. These were incorporated into the final design. �2.5 REPRODUCTIVE OUTCOMES Following panel recommendations this class of outcomes was sub-divided as follows: 1. Reproductive Function; menstrual (ovulatory) function without conception, including measures of infertility, risk factors for anovulatory or irregular cycles, presence of pelvic infection (including sexually transmitted disesases - STD's Tuberculosis of the Pelvis and other Pelvic Inflammatory Disease) and prolonged periods of amenorrhea. 2. Adverse Reproductive Outcome; this includes selected adverse outcomes of conception (major congenital abnormality, multiple spontaneous abortion). The panel also recommended that emphasis be given to adverse reproductive function and conception outcomes in the study. 10 �3. QUESTIONNAIRE The Expert Panel had several suggestions for question content and wording. Most of them were in the areas of reproductive function and outcome (Section 3.1) with some additional miscellaneous suggestions (Section 3.2). 3.1 REPRODUCTIVE FUNCTION/OUTCOME The following specific suggestions were made: (a) Emphasis was placed on obtaining menstrual histories from menarche onwards, to include an assessment of menstrual function (cycle length, regularity etc.) before the exposure period. (b) Certain menstrual symptoms/events are good predictors of ovulatory cycles. In particular, ovulating women are more likely to experience cramps or other pre-menstrual symptoms, while clotting is associated with anovulatory cycles. (c) Benign breast and uterine pathology are more likely in anovulatory women and should be recorded under diagnoses as another measure of probable reduced fertility. (d) Because this is a retrospective longitudinal study, rather than cross-sectional, the definition of infertility used on the National Center for Health Statistics National Survey of Family Growth had to be carefully adapted, using a different set of questions. It was also recommended that subjects be asked directly if they had difficulty conceiving for 11 �a period of at least twelve months of attempting to conceive. (e) Pregnancy complications (toxemia etc.) could be omitted from the pregnancy history. (f) Birth weight and length of gestation should be included as outcome variables. (g) A standard list of occupational exposures for adverse reproductive outcomes should be included. These suggestions were reviewed and revisions made to the questionnaire to accommodate them. 3.2 MISCELLANEOUS SUGGESTIONS An excellent suggestion which was incorporated into the questionnaire was the addition of questions on knowledge of and access to VA services offered to women veterans. The motivation was to help diffuse the focus of the study and was in keeping with this being a Women Veterans Health Study. A further suggestion which was considered carefully was the possibility of sending out to subjects a selfadministered questionnaire (SAQ) on some of the standard histories (pregnancy, contraceptive, military, occcupational, marital) before the telephone interview. This would prepare the subject and give her a framework within which to refresh her memory. After reviewing pre-testing experience, it was decided not to use a SAQ before the telephone interview for the following reasons: 12 �1. subjects were able to remember and complete the histories in a timely fashion; and 2. there was concern that subjects would share this information with other veterans eligible for study, before they were interviewed, increasing the potential for either non-response and/or bias in prepared answers later in the study. 13 �TABLE 3.3 EXPERT PANEL COMPOSITION Affiliation Areas of Expertlee (Reference N . \ ' o)" R. Clapp, MPH Director, Massachusetts Cancer Registry Mass. Dept. Health Boston, MA Agent Orange Exposure Vietnam Veterans (Mass.) Study Occupational/Environmental Exposure Studies T. Colton, ScD School of Public Health Boston University Boston, MA Epidemiologic Methods and Statistical Analysis Agent Orange/Vietnam Veterans Studies Dept. Reproductive Medical Management of Reproductive Health Problems Reproductive Epidemiology A. Haney, MD Medicine Duke University Durham, NC M. Hatch, PhD School of Public Health Columbia University New York, NY D. Mattison, MD Dept. of Ob/Gyn Reproductive Toxicology Div. Reproductive Pharm. and Toxicology University of Arkansas Little Rock, AK D. Ozonoff, MD, MPH School of Public Health Boston University Boston, MA Reproductive Epidemiology Occupational/Environmental Epidemiology Z. Stein, MA, MB, BCh Director, Epidemiology Psydliatric Epidemiology of Brain Disorders Rsch Agent Orange/Exposure Studies NY State Psychiatric inst Dept. Epidemiology Columbia University New York, NY 14 �WOMEN VIETNAM VETERANS HEALTH STUDY PROTOCOL DEVELOPMENT CONTRACT NO. V101(93)P-1138 EXPERT PANEL REVIEW ASSIGNMENT REVIEW Area for Review Reviewer Secondary; Reviewer 1. Phenoxy Herbicide Exposure (definition and measurement) R. Clapp D. Mattison D. Ozonoff. 2. Other VE Exposure (definition and measurement) M. Hatch A. Haney D. Ozonoff 3. General (incl. Mental) Health Outcomes (definition and measurement) Z. stein M. Hatch D. Ozonoff 4. Reproductive Health Outcomes (definition and measurement) A. Haney D. Mattison M. Hatch 5. Reproductive Outcomes D. Mattison A. Haney 6. Design Approach and Sample Size T. Colton D. Ozonoff R. Clapp 7. Population Definition R. Clapp T. Colton Z. Stein (definition and measurement) 15 �EXPERT PANEL 16 A F F I D A V I T S �NEW ENGLAND RESEARCH INSTITUTE, INC. I have reviewed the final study design and questionnaire for the proposed Women's Vietnam Veterans Health Study and my recommendation is as follows (check one option and add any comments): V I approve the design and questionnaire as presented, with no further modi jti cat ions. Any concerns have been clarified by telephone. I do not approve the design and questionnaire as presented. It will require the following revisions to meet with my approval: NAME i 42 Pleasant Street Watertown, Massadiusetts 02172 (617)923-7747 SIGNATURE 0 /L // DAfE �NEW ENGLAND RESEARCH INSTITUTE, INC. I have reviewed the final study design and questionnaire for the proposed Women's Vietnam Veterans Health Study and my recommendation is as follows (check one option and add any comments): I approve the design and questionnaire as presented, with no further modifications. Any concerns have been clarified by telephone. I do not approve the design and questionnaire as presented. It will require the following revisions to meet with my approval: It cru. V -72W NAME 42 Heasant Street Watertown, Massachusetts 02172 (617)923-7747 SMWATURE DAI �NEW ENGLAND RESEARCH INSTITUTE, INC. I have reviewed the final study design and questionnaire for the proposed Women's Vietnam Veterans Health Study and my recommendation is as follows (check one option and add any comments): I approve the design and questionnaire as presented, with no further modifications. Any concerns have been clarified by telephone. I do not approve the design and questionnaire as presented. It wall require the following revisions to meet with my approval: -5WL-V NAME SIGNATURE7T 42 Pleasant Street Watertown, Massachusetts 02172 (617)923-7747 �NEW ENGLAND RESEARCH INSTITUTE, INC. I have reviewed the final study design and questionnaire for the proposed Women's Vietnam Veterans Health Study and my recommendation is as follows (check one option and add any comments): Llit; design and questionnaire as presented, with no further modifications. Any concerns have been clarified by telephone. I do not approve the design and questionnaire as presented. It will require the following revisions to meet with my approval: NAME SIGNATURE 42 Pleasant Street Watertown, Massachusetts 02172 (617)923-7747 DATE �NEW ENGLAND RESEARCH INSTITUTE, INC. I have reviewed the final study design and questionnaire for the proposed Women's Vietnam Veterans Health Study and my recommendation is as follows (check one option and add any comments): f- . v I approve the design and questionnaire as presented, with no further modifications. Any concerns have been clarified by telephone. I do not approve the design and questionnaire as presented. It will require the following revisions to meet with my approval: Dr. Donald Mattison NAME £ t]_ _ S I G N A T U R E D A T E 42 Pleasant Street Watertown, Massachusetts 02172 (617)923-7747 �NEW ENGLAND RESEARCH INSTITUTE, INC I have reviewed the final study design and questionnaire for the proposed Women's Vietnam Veterans Health Study and my recommendation is as follows (check one option and add any comments): ^ I approve the design and questionnaire as presented, with no further modifications. Any concerns have been clarified by telephone. I do not approve the design and questionnaire as presented. It will require the following revisions to meet with my approval: SIGNATURE -' 42 Pleasant Street Watertown, Massachusetts 02172 (617)923-7747 DATE �NEW ENGLAND RESEARCH INSTITUTE, INC. I have reviewed the final study design and questionnaire for the proposed Women's Vietnam Veterans Health Study and my recommendation is as follows (check one option and add any comments): I approve the design and questionnaire as presented, with no further modifications. Any concerns have been clarified by telephone. I do not approve the design and questionnaire as presented. It w.ill require the following revisions to meet with my approval: Zena Stein. M.B.. B.Ch. NAME 42 Pleasant Street Watertown, Massachusetts 02172 (617)923-7747 II T —/ SIGNATURE /****t *1^ � 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. 069 Folder The folder containing the original item. 1852 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 McKinlay, Sonja M. Description An account of the resource <strong>Corporate Author: </strong>New England Research Institute, Inc., Watertown, Massachusetts Title A name given to the resource Women's Vietnam Veterans Health Study Protocol Development, Summary Report of Expert Panel Review, Deliverable E Subject The topic of the resource Women Vietnam Veterans Health Study study criticism VA ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/35c777d716742ce9f3614ec6762cd87b.pdf 3bed5479e628b180f4e47d63e20b991e PDF Text Text Item ID Number °1829 Author Corporate Author Report/Article Title Materia|s from the VETS II Review, including agenda, participant list, and summary, August 30,1984. Journal/Book Title Year 000 ° Month/Day Color n Number of hnaues 25 UOSCrtatOn NotBS ^'v'n ^- Young filed this item under "Vietnam Veterans Twin Study." Duplicate is of summary only. Wednesday, July 11, 2001 Page 1830 of 1870 �AGENDA TO REVIEW VETS II August 30, 1984 TIME SUBJECT SPEAKER OR PARTICIPANTS 8:00 a.m. - 8:30 a.m. Welcome and Charge to Committee Dr. Greene 8:30 a.m. - 9:15 a.m. Ranch Hand Study (U.S. Air Force) Dr. Wolfe a) Epidemiological Study of the Health of Vietnam Veterans Dr. Erickson 9:15 a.m. - 10:00 a.m. b) Agent Orange Birth Defects Study (Centers for Disease Control) 10:00 a.m. - 10:15 a.m. Questions Concerning Studies of Exposure to Agent Orange 10:15 a.m. - 10:45 a.m. Vietnam Twin Register Study, Protocol I (Medical Follow-up Agency National Academy of Sciences) Dr. Robinette 10:45 a.m. - 11:00 a.m. National Needs Assessment of Vietnam Era Veterans Dr. Greene (Veterans Administration's RFP 101-9-84) 11:00 a.m. - 3:00 p.m. Review of VETS II and Working Lunch Review Committee 3:00 p.m. - 5:00 p.m. Meeting with Principal Investigator and Staff of VETS II Review Committee Discussion, Recommendations, and Preparation of Summary Statement Review Committee 5:00 p.m. - 8:00 p.m. Attachment A �Participants "Vietnam Experience Twin Study" August 30, 1984 Review Committee Theodore Colton, Sc.D. (Chairman) Professor of Public Health Boston University School of Public Health 80 East Concord Street Boston, MA ^02118 Arthur B. Bloom, M.D. ^ Professor Department of Pediatrics Columbia Medical School Babies Hospital - Room 115 3959 Broadway .New York, NY 10032 Patricia A. luffler, Ph.D. Associate Dean for Research Professor of Epidemiology University of Texas P. 0. Box 20186 Houston, TX 7702] s^~~ W. Day, M.D., Ph.D. Robert Director Fred Hutchinson Cancer Research Center, 1124 Columbia Street Seattle, WA 98104 Thomas Associate Senior Vice Chancellor, Health/Sciences "University of Pittsburgh 3811 O'Hara Street Pittsburgh, PA 15213 Larry Ewing, Ph.D. Director of Reproductive Biology Department of Population Dynamics Johns Hopkins School of Hygiene and Public Health 615 North Wolfe Street Baltimore, MD 21205 Dhodanand Kowlessar,- M.D. Professor of Medicine Director of Gastroenterology Thomas Jefferson University 1025 Walnut Street Philadelphia, PA 19107 Lewis Kuller, M.D., D.P.H. Chairman, Department of Epidemiology University of Pittsburgh Pittsburgh, PA 15261 or MAIL TO: House Aging Committee 715 House Annex 1 Washington, D. C. 20515 Robert W. Miller, M.D. Chief, Clinical Epidemiology Branch National Cancer Institute - NIH Landow Bldg. Room 8C41 Bethesda, MD 20205 Walter E. Nance, M.D., Ph.D. Professor and Chairman Department of Human Genetics Box 33 MCV Station Virginia Commonwealth Univ. College of Medicine Richmond, VA 23298 Andre Ognibene, M.D. Hospital Director San Antonio State Chest Hospital P. 0. Box 23340 San Antonio, TX 78223 Morris Parloff, Ph.D. Consultant 5010 Wickett Terrace Bethesda, MD 20814 �Review Committee, (Cont.) Ming Tso Tsuang, M.D., Ph.D. > Professor and Vice Chairman ' Department of Psychiatry and Human Behavior Brown University MAIL TO: Director, Psychiatric Epidemiology Research Unit Butler Hospital 345 Blackstone Blvd. Providence, Rhode Island 02906 John Wilson, Ph.D. Professor Department of Psychology Cleveland State University Cleveland, Ohio 44115 Alastair J.J. Wood, M.D. Associate Professor of Medicine and Pharmacology Department of Clinical Pharmacology Vanderbilt University Medical School Medical Center North Nashville, TN 37232 �Related Studies Personnel J. David Erickson, D.D.S., Ph.D. Birth Defects Branch Centers for Disease Control 1600 Clifton Rd., Chamblee Bldg. 5 Atlanta, GA 30333 William H. Wolfe, M.D. Colonel, USAF, MC, FS Chief. Epidemiology Services Branch USAF, SAM/EKE Brooks AFB, TX 78235 C. Dennis Robinette, Ph.D. Director of Twin Registries National Research Council National Academy of Sciences 2101 Constitution Avenue Washington, D.C. 20418 St. Louis Investigators and Hines VAMC Cooperative Studies Center Personnel Seth Eisen, M.D. - Principal Investigator VA Medical Center (151A-JB) Research and Development Service St Louis, MO 63125 Dan Blazer, M.D., Ph.D. Associate Professor Department of Psychiatry Head Division of Social and Community Psychiatry Duke Medical Center Box 3173 Durham, NC 27710 Jack Goldberg, Ph.D. Staff Epidemiologist (151K) Cooperative Studies Program Coordinating Center VA Medical Center Hines, IL 60141 William G. Henderson, Ph.D. Chief, Cooperative Studies Program Coordinating Center (15IK) VA Medical Center Hines, IL 60141 John Leavitt, Jr., Ph.D. (151A-JB) Psychology Service VA Medical Center St Louis, MO 63125 William True, Ph.D., M.P.H. (151A-JB) Staff Anthropologist Psychiatry Service VA Medical Center St Louis, MO 63125 �William H. Wolfe, M.D. Colonel, USAF, MC, FS Chief, Epidemiology Services Branch USAF, SAM/EKE Brooks AFB, TX 78235 is VAMC Cooperative Studies Center Personnel /estigator munity Psychiatry xrdinating Center gram Coordinating Center (15IK) i-JB) 151A-JB) �VA Central Office Richard J. Greene, M.D. Director Medical Research Service VA Central Office 810 Vermont Avenue N.W. Washington, D. C. 20420 Ralph E. Peterson, M.D. Deputy Director Medical Research Service VA Central Office 810 Vermont Avenue, N.W. Washington, D. C. 20420 Robert E. Allen, Ph.D. Special Assistant Medical Research Service VA Central Office 810 Vermont Avenue N.W. Washington, D. C. 20420 James A, Hagans, M.Di, Ph.D. Chief, Cooperative Studies Program VA Central Office 810 Vermont Avenue N.W. Washington, D. C. 20420 Ping C. Huang, Ph.D. Staff Assistant, Cooperative Studies Progr, VA Central Office 810 Vermont Avenue N.W. Washington, D. C. 20420 �PARTICIPANTS "Vietnam Experience Twin Study' August 30, 1984 Review Committee Theodore Col ton, Sc.D. (Chairman) Lewis Roller, M.D., D.P.H. Professor of Public Health • Chairman, Department of Epidemiology Boston University School of Public Health University of Pittsburgh 80 East Concord Street Pittsburgh, PA 15261 Boston, MA 02118 Arthur B. Bloon, M.D. Professor Department of Pediatrics Columbia Medical School Babies Hospital - "Room 115 3959 Broadway New York, NY 10032 Robert W. Day, M.D., Ph.D. Director Fred Hutch inson Cancer Research Center 1124 Columbia Street Seattle, WA 98104 Detre, M.D. Associate Senior Vice Chancellor, Health Sciences University of Pittsburgh 3811 O'Hara Street Pittsburgh, PA 15213 Larry Ewing, Ph.D. Director of Reproductive Biology Department of Population Dynamics Johns Hopkins School of Hygiene and Public Health 615 North Wolfe Street Baltimore, MD 21205 MAIL TO: House Aging Committee 715 House Annex 1 Washington, DC 20515 Robert W. Miller, M.D. Chief, Clinical Epidemiology Branch National Cancer Institute - NTH Landow Bldg. Room 8C41 Bethesda, MD 20205 Walter B. Nance, M.D., Ph.D. Professor and Chairman Department of Human Genetics Box 33 MCV Station Virginia Commonwealth Univ. College of Medicine Richmond, VA 23298 Andre Ognibene, M.D. Hospital Director San Antonio State Chest Hospital P.O. Box 23340 San Antonio, TX 78223 Moris Parloff, Ph.D. Consultant 5010 Wickett Terrace Bethesda, MD 20814 ; Dhodanand Kowlessar, M.D. Professor of Medicine Director of Gastroenterology Thomas Jefferson University 1025 Walnut Street Philadelphia, PA 19107 Attachment A �eviewCommittee/ (Cont.) Ming Tso Tsuang, M.D., Ph.D. Professor and Vice Chairman Departnvant of Psychiatry and Hunan Behavior Brown University * : MAIL TO: Director, Psychiatric Epidemiology Research Unit Butler Hospital, 345 Blacks tone Blvdi" ' ' Providence, *hode Island 02906 John Wilson, Ph.D. Professor Department of Psychology Cleveland State University Cleveland, Ohio 44115 Alastair J.J. Wood, M.D. Associate Professor of Medicine and Pharmacology Department of Clinical Pharmacology Vanderbilt University Medical School Medical•Center >torth Nashville, TO 37232 �Related Studies Personnel J. David Erickson, D.D.S., Ph.D. Birth Defects Branch Centers for Disease Control 1600 Clifton Rd., Chamblee Bldg. 5 Atlanta, GA 30333 ^ William H. Wolfe, M.D. Colonel, USAF, MC, FS Chief, Epidemiology Services Branch OSAF, SAM/FXE Brooks, AFB, TX 78235 C. Dennis Robinette, Ph.D. Director of Twin Registries Kat-ional Research Council National Academy of Sciences • 2101 Constitution Avenue Washington, DC 20418 St. Louis Investigators and Hines VAMC Cooperative Studies Center Personnel Seth "Eisen, M.D. - Principal Investigator VA Medical Center (151A-JB) Research and'Development Service St. Louis, MO 63125 Dan Blazer, M.D., Ph.D. Associate Professor Department of Psychiatry Head Division of School and Community Psychiatry Duke Medical Center Box 3173 Durham, KC 27710 Jack Goldberg, Ph.D. Staff Epidemiologist (151K) Cooperative Studies Program Coordinating Center VA Medical Center Hines, IL 60141 William G. Henderson, Ph.D. Chief, Cooperative Studies Program Coordinating Center (151K) VA Medical Center Hines, IL 60141 John Leavitt, Jr., Ph.D. (151A-JB) Psychology Service VA Medical Center St. Louis, MD 63125 William True, Ph.D., M.P.H. (15lA-xTB) Staff Anthropologist Psychiatry Service VA Medical Center St. Louis, MO 63125 �VA Centred Office Richard J. Greene, M.D. Director Medical Research Service VA Central Office 810 Vermont Avenue N.W. Washington, DC 20420 ' Ralph T=\ Peterson, M.D. Deputy Director • Medical Research Service VA Central Office 810 Vermont Avenue N.W. Washington, DC 20420 Robert E. Allen, Ph.D. Special Assistant Medical Research Service VA Central Office 810 Vermont Avenue N.W. Washington, DC 20420 James A. Hagans, M.D., Ph.D. Chief, Cooperative Studies Program VA Central Office 810 Vermont Avenue N.W. Washington, DC 20420 Ping C. Huang, Ph.D. Staff Assistant, Cooperative Studies Program VA Central Office 810 Vermont Avenue N.W. Washington, DC 20420 �AGENDA TO REVIEW VETS II August 30, 1984 TIME . jt . ,- SUBJECT SPEAKER - -OR PARTICIPANT! -- ._ ! •*• l 8:00 a.m. - 8:30 a.m. Welcome and Charge to Committee Dr. Greene 8:30 a.m. - 9:15 a.m. Ranch Hand Study (U.S. Air Force) Dr. Wolfe a) Epidemiological Study of the Health of Vietnam Veterans Dr. Erickson 9:15 a.m. -'10:00 a.m. b) Agent Orange Birth Defects Study (Centers for Disease Control) 10:00 a.m. - 10:15 a.m. Questions Concerning Studies of Exposure to Agent Orange 10:15 a.m. - 10:45 a.m. Vietnam Twin Register Study, Protocol I (Medical Follow-up Agency National Academy of Sciences) Dr. Robinette 10:45 National Needs Assessment of Vietnam Era Veterans i a.m. - 11:00 a.m. (Veterans Administration's RFP 101-9-84) 11:00 a.m. - 3:00 p.m. Dr. Blank Dr. Denny - Review of VETS II and Working Lunch Review Committe j 3:00 p.m. - 5:00 p.m. Meeting with Principal Investigator Review Committe and Staff of VETS II 5:00 p.m. - 8:00 p.m. Discussion, Recommendations, and Preparation of Summary Statement Review Committe Attachment �VIETNAM EXPERIENCE TWIN STUDY PROTOCOL NO. 2 CSP #256 RESUME The Cooperative Study Protocol (CSP) under review is designed to investigate the impact of military service on the Vietnam veterans' medical, psychological and overall social adjustment. This study has one primary purpose/and two ancillary purposes: the primary purpose is to further examine the nature and degree of relationship between characteristics of Vietnam service and a range of medical, psychiatric, psychological, and psychosocial aspects of the veteran's health. Secondary purposes include the investigation of possible relationships between exposure to Agent Orange and the health of the veteran and his offspring, and efforts to define and measure Post Traumatic Stress Disorder. One of the unique features of this approximately 10 million dollar investigation is the inclusion of monozygotic co-twin pairs. It is proposed to locate and intensively study 600 male monozygotic twin pairs born during 1939-1953 who served in the military between 1965-1971. It is anticipated that of this sample about 360 will be discordant for service in Vietnam and 240 will be concordant, i.e., 120 co-twin pairs in which neither member had any Vietnam service and 120 co-twin pairs in which each member had some period of Vietnam service. The investigation will test whether there is reliable evidence of differential post-service medical, psychological or social well-being changes associated with different service experiences. The plan is to bring subjects to St. Louis for a week of extensive examinations. The feasibility of the proposed study is, of course, contingent on the prior successful completion of the Vietnam era Twin Registry. The preparation of such a registry was approved (Protocol fl) and is being undertaken by the National Research Council Commission on Life Sciences—Medical Follow-up Agency of the National Academy of Sciences. The application for review (Protocol 12) does not, however, include a report indicating the successful completion of this Registry or its readiness for use in Protocol 12. Also to be completed prior to initiating the study are such instruments as the DIS III, Current Behavioral Indices, the Life History and Medical History Questionnaires. CRITIQUE - General criticisms of project design and concepts. The overall impression of the proposed study is that it is fundamentally overambitious, with not enough serious, scientific rationale provided for the work described. The hypotheses for performing »the numerous laboratory procedures outlined in the proposal are not based on solid scientific data. This is basically ATTACHMEMT C �2. a "fishing expedition" among cohorts of twins, in which the focus will be on clinical, laboratory, and behavioral parameters of disease, or of disease indicators. The General Medical Assessment, as outlined in this protocol, represents a cosmic approach to clinical assessment, which may also be said for the extensive battery of laboratory tests proposed. Instead of a proposal consisting of a series 6f well-defined questions for which research studies are to be done, the veterans will be subjected to all manner of tests, clinical and other, on basically flimsy scientific evidence, to see what emerges. Even the more specialized tests have insufficient justification and weak scientific rationale. The only independent variable in this proposed study is service in Vietnam. A reasonable hypothesis might be generated that links Vietnam service to psychiatric sequelae, however, other studies directed to this goal are already being undertaken. Because the nn" (sample size) is small the study has only a low statistical power to detect modestly increased risks for medical or psychiatric illnesses. The small "n" may also invalidate the meaning of a negative result. While it may be true, as the investigators argue, that the "n" is large enough to detect subclinical differences in continuous variables such as laboratory values, such differences would have no clinical significance and are of insufficient importance to argue for implementing such a massive study. What are the implications of finding small deviations from normality in the co-twin pairs? Two problems with the data analysis presentation deserve some comment. First, information on data analysis is scattered throughout the proposal. Although each of these subsections is clearly presented, the relationships between the various types of analyses is not fully discussed. The second problem is relevant to the issue of multiple comparisons and spurious effects. This would be less of a problem if the data anaylses were divided into confirmatory and exploratory analyses. The confirmatory analyses should test a prior hypotheses which are explicitly specified by the investigators. These hypotheses could be based on either past empirical findings or theoretical developments. Since this group of tests will be less than the number pf tests discussed in the proposal, it would be reasonable to apply a higher alpha level to them than to the exploratory analyses. The medical illnesses of Vietnam servicemen, were for the self-limiting and will likely have long ago disappeared. acute and/or chronic exposure to drugs or chemicals might some abnormal test results initially, 14 or 20 years have elapsed since active Vietnam service and any -relationship and effect will be compromised. most part Although yield now of cause �3. A basic problem is that health differences between twins may be unrelated to Vietnam service, and may have developed in the 14 to 20 years post-Vietnam. Since it will not be possible to obtain accurate data on which servicemen were exposed to Agent Orange this study has essentially no relevance to the problem of Agent Orange effects on health. Thus, the hypothesis that the numerous psychological and biochemical tests are for purposes of evaluation of Agent Orange effects are invalid because, 1) of uncertainty of Agent Orange exposure, 2) the long period of time that has elapsed after a possible exposure to this herbicide and 3) the small number (65) of twins to be studied, who might have been exposed to Agent Orange. i A basic concern is possible sample bias. The twins to be studied appear to be coming from only 4 or 5 states, however, this is a problem that is disregarded by the investigators. The individuals picked at random, who are invited to participate in the study cannot be assumed to be neutral with regard to the outcome of this study. Some may be recipients of medical care for service connected or service aggravated disabilities or may be receiving pensions. As a consequence there may be a problem in gaining full and objective cooperation from those veterans who fear that they may be jeopardizing their future or present VA claims. Some subjects may be selected out because of illness or their job commitment, and are unable to travel to St. Louis. Others, because of an affluent life-style or professional commitments may not wish to volunteer for the extensive studies and trip to St. Louis. This may then result in the study assembling a group of volunteers who are unrepresentative of the population of Vietnam veterans. Another general problem of concern to the reviewers was the feasibility of assuring quality of medical, psychological and laboratory examinations via competitively bid contracts. What input will the investigators have on the letting of the contract and sub- contracts, and how will they monitor the competence of these contractors. SPECIFIC CRI'TICIMS OF EXAMINATION ELEMENTS Mental Health Examinations: (1 Psychiatric assessment is to be made using the Diagnostic Interview Schedule (DIS), medical records, and interview with spouse or equivalent. The preferred diagnostic instrument is to be the. DIS III. This may strike the psychiatric community as an odd choice. The major value of the DIS, to date, is as an epidemiological- survey instrument �4. that can be administered by non-clinicians; however,in the contemplated study expert clinicians could more appropriately be used. The poteatial contribution of this instrument for clarifying PTSD is not self-evident. It is ironic that the protocol involves transporting 1,200 person to St. Louis, but ignores the opportunity for expert clinical examination in favor of a survey instrument.' ^ ^. •r A more serious and certainly more pragmatic concern is that at the time this protocol was prepared the DIS III had not yet become available for inclusion in this study. The Psychological assessment is to use a wide array of psychological instruments: 1) four self report measures of psychological distress, 2) three measures of cognitive deficit, 3) one measure of psychological constriction, 4) three coping measures, 5) two measures of cognitive measures, 6) life events, and 7) a measure yet to be developed (Current Behavioral Indices). In general, the theoretical and conceptual specification of the diagnostic outcomes of primary interest is adequate; however, there are several points of concern. First, regarding diagnostic outcome of primary interest, there is no DIS algorithm for the schizotypal ' borderline or narcissistic personality disorders which current research suggests overlaps with PTSD. Secondly, the specification of four distinct groups of veterans is not well conceputalized, either theoretically or operationally. The delineation of construct areas is a useful procedure, however, the proposed scales to measure the construct area do not always represent the best possible measures, i.e., CPT to assess psychological constriction, or the resurrection of the out-moded California P scale as an index of cognition. A more detailed operational definition of hypotheses is necessary. What is it about war stress that contributes differentially to PTSD, primary diagnostic outcomes and psychosocial measures? What independent validations are being employed to cross-check preservice risk factor variables? There is a need to interview significant others and obtain documentation for the occurrence of a self-reported risk factor. ., Of great concern is the need to establish the feasibility of subjecting individuals to the onerous chore of completing the timeconsuming battery of tests. Could there be a serious sample biasing effect toward compliance and perhaps "health" for those subjects who fully cooperate in this heavy assessment program? What will b,e the rate of subject attrition? Consider the likelihood of a movie-version PTSD patient holding still for these evaluations. �5. Overall, th,e measures will generate a plethora of data which ultimately may have to be factored into empirically derived rather than rationally predetermined dimensions suggested. The limits of the study, include 'such factors as: 1) inability to match within twin pairs for post military experience, 2) possible relevant aspects of military service, e.g., duration of service, rank, time of service, branch, etc,,, and 3) the limits of the cross-sectional design involving measurement of "effects" taken 15-20 years after the putatively critical service experiences. It is difficult to be reassured by the argument that a "longitudinal" view will be constructed. Medical and Laboratory Examinations. < It is proposed to perform a multitude of liver function tests. This combination of tests, if abnormal, may indicate that the subject has hepatic dysfunction, however, it will not define the type liver disease. The primary usefulness of assays of gammaglutamyl transpeptidase (GGT) as a diagnostic test is limited to confirmation of elevated alkaline phosphatase of bony origin, since GGT is not found in bone and should be low in isolated disease of the bone. ^ finding of elevated GGT has limited usefulness, because the enzyme is ubiquitous and elevation of GGT in no way specifies hepatic disease. Of concern in this study is the fact that this is an inducible enzyme. Numerous enzyme-inducing drugs, most notably alcohol, elevate the serum level of the enzyme in the absence of other evidence of hepatic disorder. In reading their protocol it would appear that the Pi's will depend solely on the subject's concepts of his drinking habits. On the other hand if all of the other liver associated tests are within normal limits, an elevated GGT may be an indication of recent and/or continous alcohol intake. In summary, results will be obtained from the performance of a battery of liver associated tests. The interpretation of these results will be difficult unless those with abnormalities undergo liver biopsy to determine the morphologic changes associated with liver diseases. It will be difficult to interpret whether Agent Orange is responsible for any of the biochemical changes that may be found. The section on porphyria is weak. The'authors have failed to delineate the modern day concepts of hepatic porphyrias. The latent and manifest forms of acute intermittent porphyria and porphyria cutanea tarda (PCT) differ in the excretion of porphobilinogen, delta-aminolevulinic acid, uroporphyrin and coproporphynn. They do not specify which of these intermediates of heme synthesis they will measure. Most cases of PCT are sporadic, although there is a inherited enzymatic defect (deficient �6. activity o'f uroporphyrinogen decarboxylase) that predisposes to development of PCT4 The "andrology" studies, as proposed, have little intellectual basis, with the literature briefly summarized instead of critically reviewed. The studies of spontaneous abortion are seriously undersold in their complexity;" The cytogenetic testing for sister chromatid exchanges and chromosomal aberrations has several specific flaws, but the allusion that somatic cell chromosome alterations may reflect alterations in haploid cells which, in turn, bear on sterility, fetal wastage, teratogenesis, etc., is especially troublesome in its conceptualization, even more so than in its implementation. The mechanism of communication of cytogenetic test results is left, pretty much as it was at the Love Canel, unexplained. The semen analysis is unfortunately open to serious question for several reasons. It is stated that only a single semen sample will be collected. This is inadequate because of the variability in ejaculate volume, sperm numbers and sperm motility in human semen samples. A minimum of two and optimally three semen samples collected at 1-2 month intervals should be obtained. The qualitative assessment of sperm motility is inaccurate and unacceptable. A quantitative estimate of sperm motility is essential. There is a question about the wisdom of freezing semen for assessment of sperm numbers and morphology since there is no description of the method of freezing semen and no assurance that it will be done properly. Recent large, independent investigations of Australian Vietnam veterans (NEJM 308:719, 1983) and American Vietnam veterans (JAMA 252s903, 1984) concluded that there was no evidence that service in Vietnam was related to the risk of fathering a child with a birth defect, and thus there is little reason for further evaluation of this topic with such a small number of subjects. A wide range of immunological assays, particularly of T cell function are proposed, again with little evidence of a rationale for the studies. No review of Agent Orange effects on this immune system is provided, in humans or in experimental systems, and there is no specific reason to believe that being in Vietnam per se alters immune function. Tmmunotoxicolpgy is a developing science,, and is not yet applicable for definitive studies of humans exposed to toxins. What are normative Values in the population? What would small alterations of suppressor T cells mean for these subjects? In summary, it is felt that the many specific laboratory tests proposed would be of little value. More troublesome is the weak or absent rationale for including many of the laboratory procedures. �7. BUDGET Since the prospects^ of generating objective, scientifically sound data from this project are slim, the total costs of approximately 10 million dollars is highly cost ineffective. The request for 100 percent support for so many principal investigators is surprising. The budget justificatiop .indicates that the staff members are to work on other projects and conduct clinical duties in addition to work, on this proposal. INVESTIGATORS The reviewers expressed considerable concern about the competence of most of the investigators, who have never before directed a project of this magnitude. The physician PI, Dr. Eisen has no significant research experience and no scientific publication for the past 8 years, except for a case report in 1982. He has one active VA supported research project through HSR&D, but has demonstrated no expertise in any of the areas of this proposal. Dr. Levitt, Ph.D., psychologist has no publication as a primary author and no research support. Dr. True, Ph.D., anthrophology and MPH in epidemiology has no publications in refereed journals and no research support. Dr. Goldberg, Ph.D. in epidemiology has 12 refereed publications in health service research and is senior author of five of these. He lists no research funding. Susan Fisher has a BS in Nursing and an MS in Biostatistics. She is the primary or coauthor of eight publications in the field of nursing. Dr. Henderson, Ph.D. in biostatistics is Associate Professor, Department of Pharmacology, Loyola University and Chief, Hines VA Cooperative Prograrm, Hines, Illinois. He has an impressive list of publications, mostly in field of Clinical Trials and is considered to be a global authority in this area. RECOMMENDATIONS Disapproval of Twin Protocol #2, CSP #256 (by a vote of 13 to 1). Protocol #1 should continue to develop the registry of Vietnam, twins and increase the scope of the mortality and morbidity questionnaire for all of the approximately 10,000 male twin pairs born between 1939-1953 with military service from 1965-1975. If necessary additional funds should be provided to expand the questionnaire and/or sample size in order to provide an improved data base for a possible future implementation of a clinical study on a subset of twins. The questionnaire for the morbidity study might be expanded to include selected behavioral questions, family and social history and other confounding variables such as drug and alcohol abuse. �VIETNAM EXPERIENCE TWIN STUDY PROTOCOL NO. 2 CSP 1256 RESUME The Cooperative Study Protocol (CSP) under review is designed to investigate the impact of military service on the Vietnam veterans' medical, psychological and overall social adjustment. This study has one primary purpose/and two ancillary purposes: the primary purpose is to further examine the nature and degree of relationship between characteristics of Vietnam service and a range of medical, psychiatric, psychological, and psychosocial aspects of the veteran's health. Secondary purposes include the investigation of possible relationships between exposure to Agent Orange and the health of the veteran and his offspring, and efforts to define and measure Post Traumatic Stress Disorder. One of the unique features of this approximately 10 million dollar investigation is the inclusion of monozygotic co-twin pairs. It is proposed to locate and intensively study 600 male monozygotic twin pairs born during 1939-1953 who served in the military between 1965-1971. It is anticipated that of this sample about 360 will be discordant for service in Vietnam and 240 will be concordant, i.e., 120 co-twin pairs in which neither member had any Vietnam service and 120 co-twin pairs in which each member had some period of Vietnam service. The investigation will test whether there is reliable evidence of differential post-service medical, psychological or social well-being changes associated with different service experiences. The plan is to bring subjects to St. Louis for a week of extensive examinations. The feasibility of the proposed study is, of course, contingent on the prior successful completion of the Vietnam era Twin Registry. The preparation of such a registry was approved (Protocol 11) and is being undertaken by the National Research Council Commission on Life Sciences—Medical Follow-up Agency of the National Academy of Sciences. The application for review (Protocol 12) does not, however, include a report indicating the successful completion of this Registry or its readiness for use in Protocol 12. Also to be completed prior to initiating the ;study are such instruments as the DIS III, Current Behavioral Indices, the Life History and Medical History Questionnaires. CRITIQUE - General criticisms of project design and concepts. The overall impression of the proposed study is that it is fundamentally overambitious, with not enough serious, scientific rationale provided for the work described. The hypotheses for performing -the numerous laboratory procedures outlined in the proposal are not based on solid scientific data. This is basically ATTACHMENT C �2. t a "fishing expedition" among cohorts of twins, in which the focus will be on clinical, laboratory, and behavioral parameters of disease, or of disease indicators. The General Medical Assessment, as outlined in this protocol, represents a cosmic approach to clinical assessment, which may also be said for the extensive battery of laboratory tests proposed. Instead of a proposal consisting of a series of well-defined questions for which research studies are to be done, the veterans will be subjected to all manner of tests, clinical and other, on basically flimsy scientific evidence, to see what emerges. Even the more specialized tests have insufficient justification and weak scientific rationale. The only independent variable in this proposed study is service in Vietnam. A reasonable hypothesis might be generated that links Vietnam service to psychiatric sequelae, however, other studies directed to this goal are already being undertaken. Because the "n" (sample size) is small the study has only a low statistical power to detect modestly increased risks for medical or psychiatric illnesses. The small "n" may also invalidate the meaning of a negative result. While it may b« true, as the investigators argue, that the "n" is large enough to detect subclinical differences in continuous variables such as laboratory values, such differences would have no clinical significance and are of insufficient importance to argue for implementing such a massive study. What are the implications of finding small deviations from normality in the co-twin pairs? Two problems with the data analysis presentation deserve some comment. First, information on data analysis is scattered throughout the proposal. Although each of these subsections is clearly presented, the relationships between the various types of analyses is not fully discussed. The second problem is relevant to the issue of multiple comparisons and spurious effects. This would be less of a problem if the data anaylses were divided into confirmatory and exploratory analyses. The confirmatory analyses should test a prior hypotheses which are explicitly specified by the investigators. These hypotheses could be based on either past empirical findings or theoretical developments. Since this group of tests will be less than the number pf tests discussed in the proposal, it would be reasonable to apply a higher alpha level to them than to the exploratory analyses. The medical illnesses of Vietnam servicemen, were for the self-limiting and will likely have long ago disappeared. acute and/or chronic exposure to drugs or chemicals might some abnormal test results initially, 14 or 20 years have elapsed since active Vietnam service and any -relationship and effect will be compromised. most part Although yield now of cause �3. A basic problem is that health differences between twins may be unrelated to Vietnam service, and may have developed in the 14 to 20 years post-Vietnam. Since it will not be possible to obtain accurate data on which servicemen were exposed to Age'nt Orange this study has essentially no relevance to the problem of Agent Orange effects on health. Thus, the hypothesis that the numerous psychological and biochemical tests are for purposes of evaluation of Agent Orange effects are invalid because, 1) of uncertainty of Agent Orange exposure, 2) the long period of time that has elapsed after a possible exposure to this herbicide and 3) the small number (65) of twins to be studied, who might have been exposed to Agent Orange. A basic concern is possible sample bias. The twins to be studied appear to be coming from only 4 or 5 states, however, this is a problem that is disregarded by the investigators. The individuals picked at random, who are invited to participate in the study cannot be assumed to be neutral with regard to the outcome of this study. Some may be recipients of medical care for service connected or service aggravated disabilities or may be receiving pensions. As a consequence there may be a problem in gaining full and objective cooperation from those veterans who fear that they may be jeopardizing their future or present VA claims. Some subjects may be selected out because of illness or their job commitment, and are unable to travel to St. Louis. Others, because of an affluent life-style or professional commitments may not wish to volunteer for the extensive studies and trip to St. Louis. This may then result in the study assembling a group of volunteers who are unrepresentative of the population of Vietnam veterans. Another general problem of concern to the reviewers was the feasibility of assuring quality of medical, psychological and laboratory examinations via competitively bid contracts. What input will the investigators have on the letting of the contract and sub- contracts, and how will they monitor the competence of these contractors. SPECIFIC CRI'TICIMS OF EXAMINATION ELEMENTS -- Mental Health Examinations: . T ^ Psychiatric assessment is to be made using the Diagnostic Interview Schedule (DIS), medical records, and interview with spouse or equivalent. The preferred diagnostic instrument is to be the DIS III. This may strike the psychiatric community as an odd choice. The major value of the DIS, to date, is as an epidemiological- survey instrument �4. that can be administered by non-clinicians; however,in the contemplated study expert clinicians could more appropriately be used. The potential contribution of this instrument for clarifying PTSD is not self-evident. Tt is ironic that the protocol involves transporting 1,200 person to St. Louis, but ignores the opportunity for expert clinical examination in favor of a survey instrument.' ^ ,. •v A more serious and certainly more pragmatic concern is that at the time this protocol was prepared the DIS III had not yet become available for inclusion in this study. The Psychological assessment is to use a wide array of psychological instruments: 1) four self report measures of psychological distress, 2) three measures of cognitive deficit, 3) one measure of psychological constriction, 4) three coping measures, 5) two measures of cognitive measures, 6) life events, and 7) a measure yet to be developed (Current Behavioral Indices). In general, the theoretical and conceptual specification of the diagnostic outcomes of primary interest is adequate; however, there are several points of concern. First, regarding diagnostic outcome of primary interest, there is no DIS algorithm for the schizotypal borderline or narcissistic personality disorders which current research suggests overlaps with PTSD. Secondly, the specification of four distinct groups of veterans is not well conceputalized, either theoretically or operationally. The delineation of construct areas is a useful procedure, however, the proposed scales to measure the construct area do not always represent the best possible measures, i.e., CPT to assess psychological constriction, or the resurrection of the out-moded California F scale as an index of cognition. A more detailed operational definition of hypotheses is necessary. What is it about war stress that contributes differentially to PTSD, primary diagnostic outcomes and psychosocial measures? What independent validations are being employed to cross-check preservice risk factor variables? There is a need to interview significant others and obtain documentation "for the occurrence of a self-reported risk factor. ^ Of great concern is the need to establish the feasibility of subjecting individuals to the onerous chore of completing the timeconsuming battery of tests. Could there be a serious sample biasing effect toward compliance and perhaps "health" for those subjects who fully cooperate in this heavy assessment program? What will be the rate of subject attrition? Consider the likelihood of a movie-version PTSD patient holding still for these evaluations. �5. i Overall, the measures will generate a plethora of data which ultimately may have to be factored into empirically derived rather than rationally predetermined dimensions suggested. The limits of the study, include 'such factors as: 1) inability to match within twin pairs for post military experience, 2) possible relevant aspects of military service, e.g., duration of service, rank, time of service, branch, etc,,.and 3) the limits of the cross-sectional design involving measurement of "effects" taken 15-20 years after the putatively critical service experiences. It is difficult to be reassured by the argument that a "longitudinal" view will be constructed. Medical and Laboratory Examinations. It is proposed to perform a multitude of liver function tests. This combination of tests, if abnormal, may indicate that the subject has hepatic dysfunction, however, it will not define the type liver disease. The primary usefulness of assays of gammaglutamyl transpeptidase (GGT) as a diagnostic test is limited to confirmation of elevated alkaline phosphatase of bony origin, since GGT is not found in bone and should be low in isolated disease of the bone. * finding of elevated GGT has limited usefulness, because the enzyme is ubiquitous and elevation of GGT in no way specifies hepatic disease. Of concern in this study is the fact that this is an inducible enzyme. Numerous enzyme-inducing drugs, most notably alcohol, elevate the serum level of the enzyme in the absence of other evidence of hepatic disorder. In reading their protocol it would appear that the Pi's will depend solely on the subject's concepts of his drinking habits. On the other hand if all of the other liver associated tests are within normal limits, an elevated GGT may be an indication of recent and/or continous alcohol intake. In summary, results will be obtained from the performance of a battery of liver associated tests. The interpretation of these results will be difficult unless those with abnormalities undergo liver biopsy to determine the morphologic changes associated with liver diseases. It will be difficult to interpret whether Agent Orange is responsible for any of the biochemical changes that may be found. * f • The section on porphyria is weak. The authors have failed to delineate the modern day concepts of hepatic porphyrias.. The latent and manifest forms of acute intermittent porphyria and porphyria cutanea tarda (PCT) differ in the excretion of porphobilinogen, delta-aminolevulinic acid, uroporphyrin and coproporphyrin. They do not specify which of these intermediates of heme synthesis they will measure. Most cases of PCT are sporadic, although there is a inherited enzymatic defect (deficient �• *•. 6. activity of uroporphyrinogen decarboxylase) that predisposes to development of PCTt The "andrology" stu'dies, as proposed, have little intellectual basis, with the literature briefly summarized instead of critically reviewed. The studies of spontaneous abortion are seriously undersold in their complexity.' The cytogenetic testing for sister chromatid exchanges and chromosomal aberrations has several specific flaws, but the allusion that somatic cell chromosome alterations may reflect alterations in haploid cells which, in turn, bear on sterility, fetal wastage, teratogenesis, etc., is especially troublesome in its conceptualization, even more so than in its implementation. The mechanism of communication of cytogenetic test results is left, pretty much as it was at the Love Canel, unexplained. The semen analysis is unfortunately open to serious question for several reasons. It is stated that only a single semen sample will be collected. This is inadequate because of the variability in ejaculate volume, sperm numbers and sperm motility in human semen samples. A minimum of two and optimally three semen samples collected at 1-2 month intervals should be obtained. The qualitative assessment of sperjii motility is inaccurate and unacceptable. A quantitative estimate of sperm motility is essential. There is a question about the wisdom of freezing semen for assessment of sperm numbers and morphology since there is no description of the method of freezing semen and no assurance that it will be done properly. Recent large, independent investigations of Australian Vietnam veterans (NEJM 308:719, 1983) and American Vietnam veterans (JAMA 252:903, 1984) concluded that there was no evidence that service in Vietnam was related to the risk of fathering a child with a birth defect, and thus there is little reason for further evaluation of this topic with such a small number of subjects. A wide range of immunological assays, particularly of T cell function are proposed, again with little evidence of a rationale for the studies. No review of Agent Orange effects on this immvane system is provided, in humans or in experimental systems, and there is no specific reason to believe that being In Vietnam per se alters immune function. Tmmunotoxicology is a developing science,, and is not yet applicable for definitive studies of humans exposed to toxins. What are normative values in the population? What would small alterations of suppressor T cells mean for these subjects? In summary, it is felt that the many specific laboratory tests proposed would be of little value. More troublesome is the weak or absent rationale for including many of the laboratory procedures. �7. •, BUDGET Since the prospects, of generating objective, scientifically sound data from this project are slim, the total costs of approximately 10 million dollars is highly cost ineffective. The request for 100 percent support for so many principal investigators is surprising. The budget justification indicates that the staff members are to work on other projects and conduct clinical duties in addition to work on this proposal. INVESTIGATORS The reviewers expressed considerable concern about the competence of most of the investigators, who have never before directed a project of this magnitude. The physician PI, Dr. Eisen has no significant research experience and no scientific publication for the past 8 years, except for a case report in 1982. He has one active VA supported research project through HSR&D, but has demonstrated no expertise in any of the areas of this proposal. Dr. Levitt, Ph.D., psychologist has no publication as a primary author and no research support. Dr. True, Ph.D., anthrophology and MPH in epidemiology has no publications in reiereed journals and no research support. Dr. Goldberg, Ph.D. in epidemiology has 12 refereed publications in health service research and is senior author of five of these. He lists no research funding. Susan Fisher has a BS in Nursing and an MS in Biostatistics. She is the primary or coauthor of eight publications in the field of nursing. Dr. Henderson, Ph.D. in biostatistics is Associate Professor, Department of Pharmacology, Loyola University and Chief, Hines VA Cooperative Prograrm, Hines, Illinois. Re has an impressive list of publications, mostly in field of Clinical Trials and is considered to be a global authority in this area. RECOMMENDATIONS Disapproval of Twin Protocol 12, CSP 1256 (by a vote of 13 to 1). Protocol II should continue to develop the registry of Vietnam, twins and increase the scope of the mortality and morbidity questionnaire for all of the approximately 10,000 male twin pairs born between 1939-1953 with military service'from 1965-1975. If necessary additional funds should be provided to expand the questionnaire and/or sample size in order to provide an improved data base for a possible future implementation of a clinical study on a subset of twins. The questionnaire for the morbidity study might be expanded to include selected behavioral questions, family and social history and other confounding variables such as drug and alcohol abuse. � 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. 067 Folder The folder containing the original item. 1829 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/. Title A name given to the resource Materials from the VETS II Review, including agenda, participant list, and summary, August 30, 1984. Subject The topic of the resource Vietnam Experience Twin Study study criticism ao_seriesIII 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. 067 Folder The folder containing the original item. 1827 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 Klerman, Gerald L. Title A name given to the resource Memorandum with cover letter: to James Hagans, Jr. from Gerald Klerman, with subject Evaluation of Psychiatric Section of Revised VETS Project, August 22, 1984. Subject The topic of the resource Vietnam Experience Twin Study study criticism ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/dd4660bd93dd8719bc9ccf39f7287fef.pdf 446ae0e63f8c12420e0ee569b4e02833 PDF Text Text Item ID Number °1812 AllthOT Eisner, Seth Corporate Author RBDOrt/APtldB Tltte Typescript: Report of Contact - contacted by Larry Hobson, February 27, 1984 Journal/Book Title Year Month/Day Color Number of forages DBSCrlptOn NOtOS Alvin L Youn 9filed tnis item under "Vietnam Veterans Twin Study." Discusses Hobson's Option and Decision Paper regarding continuation of the study. Wednesday, July 11, 2001 Page 1813 of 1870 ��REPORT OF CONTACT Contacted by: Larry Hobson Date of Contact: February 27, 1984 Hobson has been asked to prepare an Option and Decision Paper for review by the CMD. He was calling to read his current draft to me for my comments. The various options that Hobson will present are: 1. Discontinue the VETS, including withdrawing from Twinfind Pro - money will be saved Con - the VA will be subject to adverse criticism 2. Direct that a non-VA contractor perform the entire study Pro - claims of possible VA bias in the data collection and analysis will be eliminated Con - bias does not appear to be a major issue (note the Ranch Hand study's relative freedom from the bias criticism), the cost of the project under contract will markedly increase, there will be a demoralizing effect on the project's principal investigators, and the VA will appear to lack confidence in the quality of its own research 3. Continue the NAS Twinfind and questionnaire survey but abandon the St. Louis intensive health assessment portion Pro - money will be saved and the twin register concept and its future scientific value will be retained Con - the NAS questionnaire is so limited in scope that its value to the VA will be m i n i m a l , and the VA will be subject to the criticism of refusing to support quality research because of what might be revealed 4. Support only the NAS Twinfind but expand the detail in the mailed questionnaire, perhaps including a telephone survey Pro - the cost of the project will be reduced and the expanded questionnaire will increase the usefulness of the data Con - the data will be of questionable reliability, its usefulness will be quite limited, and the cost savings will be reduced because of the increased cost of the expanded questionnaire survey 5. Retain the VETS in its c u r r e n t f o r m a t , w i t h or w i t h o u t modification. The following are possible modifications: a. P e r f o r m the psychological assessment under contract Pro - the c r i t i c i s m of b i a s in the d a t a c o l l e c t i o n w i l l be reduced �Con - the cost will be increased b. E l i m i n a t e some of the proposed e x p e n s i v e m e d i c a l tests but r e t a i n the p e r f o r m a n c e of the psychological assessment by the VA Pro - the cost of the project will be reduced Con - t h e V A m a y s t i l l b e c r i t i c i z e d f o r p e r f o r m i n g an incomplete research p r o j e c t purposely c. C o n t i n u e the present VETS plan in an u n m o d i f i e d form Pro - an excellent s t u d y , a p p r o v e d by the CSP, will thereby result and be subject to the least c r i t i c i s m from the s c i e n t i f i c c o m m u n i t y and the general public Con - the s t u d y w i l l be s u b j e c t to the c r i t i c i s m of b i a s and high cost Hobson said that his own position is option 5b. He will r e c o m m e n d e l i m i n a t i n g tests such as the e n d o c r i n e and i m m u n o l o g i c studies, and t h e c y t o g e n e t i c a n a l y s e s . H e p e r s o n a l l y i s i n f a v o r o f r e t a i n i n g the sleep study. I m e n t i o n e d to him that this would r e d u c e t h e o v e r a l l cost o f t h e p r o j e c t b y o n l y s e v e r a l h u n d r e d thousand dollars. He agreed and pointed out that he purposely p r o j e c t e d n o cost s a v i n g f i g u r e s i n t h e O p t i o n a n d D e c i s i o n Paper. He hoped that a n t a g o n i s t s w i t h i n the VA w i l l be s a t i s f i e d w i t h a n a p p a r e n t cost r e d u c t i o n v i c t o r y w h i l e t h e s t u d y w i l l a c t u a l l y r e m a i n essentially intact. He agreed that he had little idea of how well this strategy might work. "I d o n ' t know the best way to play this," he said. Hobson said there is supposed to be a m e e t i n g with Custis later this week to discuss the VETS. SOME PERSONAL COMMENTS In response to one of my questions, Hobson noted that Greene i s t h e m a i n a n t a g o n i s t t o t h e VETS. " G r e e n e h a s b e e n t a l k i n g quite loudly." Hobson noted, however, that Boren had not yet taken any public stand. Greene is a r g u i n g that the study does not have s u f f i c i e n t statistical power. H o w e v e r , our sample size a n a l y s i s ( w h i c h no one has c r i t i c i z e d ) d e m o n s t r a t e s that this is not v a l i d . Greene is also a r g u i n g that the t w i n concept is not appropriate to the questions being addressed. But our review groups, who include some of the most p r e s t i g i o u s m e m b e r s of the s c i e n t i f i c c o m m u n i t y , do not agree. It seems to me that Greene's o b j e c t i o n s may be based, in p a r t , on a " h i d d e n a g e n d a " . Hobson noted t h a t in a r e c e n t m e e t i n g , G r e e n e b e c a m e v e r y angry a n d a c c u s e d t h e A g e n t O r a n g e P r o j e c t s O f f i c e (AOPO) of not i n f o r m i n g him about every aspect of the progress of the p r o j e c t . Perhaps this r e p r e s e n t s one aspect of t h e t r u e p r o b l e m . T h a t i s , G r e e n e f e e l s t h a t t h e AOPO i s e x e r c i s i n g t o o m u c h p o w e r i n G r e e n e ' s d o m a i n . P e r h a p s t h e real conflict is a "turf battle". � 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. 067 Folder The folder containing the original item. 1812 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 Eisen, Seth Title A name given to the resource Typescript: Report of Contact - contacted by Larry Hobson, February 27, 1984 Subject The topic of the resource Vietnam Experience Twin Study AOPO study criticism VA policy ao_seriesIII 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. 067 Folder The folder containing the original item. 1811 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 Eisen, Seth Title A name given to the resource Letter: from Seth Eisen to Alvin L. Young, February 24, 1984 Subject The topic of the resource Vietnam Experience Twin Study VA policy study criticism PTSD ao_seriesIII 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. 067 Folder The folder containing the original item. 1808 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 Walters, Harry N. Title A name given to the resource Memorandum: Vietnam Experience Twin Study (VETS), from Harry N. Walters to Chief Medical Director, February 8, 1984 Subject The topic of the resource VA policy PTSD study criticism ao_seriesIII 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. 067 Folder The folder containing the original item. 1806 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 Eisen, Seth Title A name given to the resource Letter: from Seth Eisen to Alvin L. Young, January 23, 1984 Subject The topic of the resource Vietnam Experience Twin Study CSP VA policy study criticism ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/df8d66e51c40779e9d002e14c30e9caf.pdf a7bbaebbe750a995b0af55bc3d939eb6 PDF Text Text Item ID Number 01735 Author Keller, Carl A. Corporate Author RODOrt/ArtlOlO TitlO Typescript: Review of Vietnam Veterans Mortality Study, September 14,1987 Journal/Book Title oooo Month/Day Color Number of Images n 1 Doscripton Notes Monday, June 11, 2001 Page 1786 of 1793 �REVIEW OF VIETNAM VETERANS MORTALITY STUDY A study of proportionate mortality among U.S. Army and Marine veterans who served between July 4, 1965 and March 1, 1973 and died before March 1, 1982 was reported by the Veterans Administration. The study included 19708 Army and 4527 Marine veterans who had served in Vietnam and 22904 Army and 3781 Marine veterans who had not served in Southeast Asia during tis period. The study included a random sample of about one-third of the potentially elligible veterans who had died during this period. The selection of study subjects and recovery of information on them appears to have been unbiased and appropriate. The major findings from this study included a statistically significant excess of accidental and drug related deaths and paucity of suicides among Army veterans who had served in Vietnam compared to those who had not served in Southeast Asia. In addition, there was a statistically significant excess of lung cancer and non-Hodgkins lymphoma among Marine veterans who had served in Vietnam compared to those who had not. Several other findings were not mentioned in either the conclusions nor in the narrative, but are evident in the tables. These include a statisically significant decrease in mortality due to genitourinary diseases and cancer of the extra-cranial nervous system among Army Vietnam veterans. In addition, there appears to have been a signifcant decrease in cancer deaths among enlisted Army veterans with only one tour of duty in Vietnam, and among similar Marine veterans before 1975. There was also a significant increase in accidental poisonings among enlisted Marine Vietnam veterans dying before 1975. The authors computed Standardized Proportionate Mortality Ratios (SPMR) and tested with the Chi-Square statistic (not presented in the tables). According to the reference used to justify this procedure (ref # 13), Professor Monson suggests using the Poisson approximation of the variance of the expected deaths, i.e., that the expected number of deaths approximates the variance. If this procedure is applied to the information which can be deduced from the observed number of deaths and the SPMR as given in the tables, several additional SPMRs appear to be statistically significant. These include an excess of all cancer deaths among Marine veterans who served in Vietnam, particularly single tour enlisted Marines after 1975. Other possibly significant findings would include a decrease in deaths due to infectious diseases and diseases of the blood, an increase in deaths due to musculoskeletal and connective tissue diseases, and a decrease in deaths from thyroid cancer and non-Hodgkins lymphoma among Army Vietnam veterans. While there is no way to determine which statistical procedures are "correct", these results indicate that more significant findings are available in these data than have been dicussed in the manuscript. While this does not make it any easier to interpret the results, it does serve to point out the selective nature of the findings which have been emphasized in the manuscript. In particular, the inclusion of one-seventh of the abstract and considerable dicussion in the narrative to Agent Orange is misleading. Other possible explanations for the findings should receive relatively more emphasis. Carl A. Keller, Ph.D. Epidemiologist, NIEHS � 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. 066 Folder The folder containing the original item. 1785 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 Keller, Carl A. Title A name given to the resource Typescript: Review of Vietnam Veterans Mortality Study, September 14, 1987 Subject The topic of the resource VA Mortality Study mortality trends study criticism cancer risk assessment ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/0397ef45f6a5749c72a829b6264147b2.pdf e95d695e5c8772b844e37ed1186077ad PDF Text Text Item ID Number 01734 Author Houk, Vernon N. Corporate Author RepOrt/ArtiClB TltlO Memorandum: Review of VA Mortality Study, from Vernon N. Houk to Ronald W. Hart, September 11, 1987 Journal/Book Title Year 000 ° Month/Day Color D Number of unaoos 2 Desorlpton Notes Monday, June 11, 2001 Page 1785 of 1793 �DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service Centers for Disease Control Memorandum Date From .September 11, 1987 Director Center for Environmental Health and Injury Control Review of VA Mortality Study Subject To Ronald W. Hart, Ph.D. Director National Center for Toxicological Research i The Veterans Administration (VA) has conducted a proportionate mortality study (PMR) of 24,235 deaths among U.S. Army and U.S. Marine male veterans who served in Vietnam and 26,685 deaths among male veterans of the same two services who did not serve anywhere in Southeast Asia. All deaths were identified from the VA BIRLS file and occurred between July 4, 1965, and March 1, 1982. These deceased veterans had to have served in the military sometime between July 4, 1965, and March 1, 1973. Career and non-career, officers, and enlisted men, as well as reservists, were included. In-service deaths occurring before 1974 and men dying from war-related injuries were excluded. In service deaths after 1973 were included. Within the group of Vietnam veterans, the fraction of all deaths attributable to a particular cause was computed and compared to the corresponding proportion for non-Vietnam veterans. The comparison was done using the proportionate mortality ratio (PMR) technique in which age at death, race, and branch of service were taken into account. There was no adjustment for calendar year of death or rank. Altogether, PMRs were computed for 18 major cause of death groupings and for 23 specific cancer sites. We will address our concerns in data collection, data analysis, and interpretation. Data Collection. Are the BIRLS tapes truly at least 94 percent complete? From the CDC Mortality Study which used multiple sources of mortality we found that BIRLS was less complete. Data Analysis. Why do the authors emphasize only the statistically significant positive findings? Why were not the significant decreases in deaths from genitourinary diseases (Table 3) and the decrease in deaths *. from all cancers for one-tour of duty veterans (Table 5) not discussed? The lack of association between service in be reevaluated in light of the CDC finding in the first 5 years after discharge. CDC discharge rather than year of death. This Vietnam and suicide needs to that they were increased only used the time period since subject was repeatedly brought �Page 2 - Ronald W. Hart, Ph.D. up with the VA prior to completion of their analysis. The CDC study would indicate that grouping by 10 year periods would minimize the effect. The findings for lung cancer and NHL in Marine Vietnam veterans are provocative, although similar observations were not made in other studies of Vietnam veterans. The absence of unusual mortality from soft-tissue cancers is consistent with some previous studies but at variance with others. Because so many statistical tests were done on the data set, these ^apparent findings could be due to chance. It would be helpful to see a more detailed analysis in which mortality from these cancer sites is examined by calendar year in Vietnam, rank, MOS, and principal duty. These additional analyses would help in deciding whether some factor related to the Vietnam experience is responsible for the apparent association. Interpretation. The authors suggest that these were major differences in the findings of previous studies cited, but there are in fact few major differences in the findings. Referenced studies were not critically discussed. There has never been, for example, an association demonstrated between lung cancer and phenoxy herbicides except in the Zack Study (Ref. 29) where 3.6 cases were expected and 6 were found in those exposed to 2,4,5-T. Those authors state that they cannot evaluate trends in lung cancer deaths as they relate to occupation because of "limitation in the data." As noted above, it is not surprising to encounter the small number of statistical departures from expected mortality seen in this study. These could easily have arisen by chance alone. This study, as originally designed, cannot conclusively clarify mortality risks for Vietnam veterans, let alone elucidate possible causative factors within, or outside of, the Vietnam experience. Reasons include lack of a defined population-at-risk, incomplete ascertainment of deaths, and absence of "exposure" data on individual veterans. This PMR study appears to be well executed in mechanics. However, the presentation and discussion of the results do not provide the necessary caution in interpretation and allow the uninitiated to make causal inferences where they do not exist. Vernon N. Houk, M.D. Assistant Surgeon General � 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. 066 Folder The folder containing the original item. 1784 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 Houk, Vernon N. Title A name given to the resource Memorandum: Review of VA Mortality Study, from Vernon N. Houk to Ronald W. Hart, September 11, 1987 Subject The topic of the resource VA Mortality Study BIRLS study criticism cancer risk assessment ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/303056d230e58afc50f49f117e65dcf4.pdf 74d93fdd921ad400779edc1c34632f44 PDF Text Text Item ID Number 01733 Author Barnes, Donald G. Corporate Author Roport/Artido TitlO Typescript: Comments on "Proportionate Mortally Study of Army and Marine Corps Veterans of the Vietnam War," Septembers, 1987 Journal/Book Titlo Year oooo Month/Day Color n Number of Images 1 Doscrlpton Notes Monday, June 11, 2001 Page 1784 of 1793 �9/8/87 COMMENTS ON "PROPORTIONATE MORTALITY STUDY OF ARMY AND MARINE CORPS VETERANS OF THE VIETNAM WAR" Donald G. Barnes U.S. Environmental Protection Agency 1. Proportionate mortality studies have inherent limitations which restrict their interpretation and conclusions; e.g., reduced PMR in one area necessitates increased PMR in another area. This particular study is a generally welldesigned example of this type of investigation. The report clearly discusses the procedures, methods of analysis, and the conclusions, including caveats. The results should not be cited without an thorough appreciation of these caveats. 2. The study is a descriptive study which essentially suggests hypotheses for further investigation. As such, the study does not test any particular association, let alone prove any cause-effect relationship. 3. It should be noted that of all the PMRs the two identified as being of concern, while statistically significant, are modest (roughly 2) — a tribute to the scale of the study. 4. Among the areas of concern is the question of whether there is an inherent difference between Marines in Vietnam, compared to non-Vietnam Marines and all Army troops. It has been suggested that the Marines in Vietnam had attitudes and behaviors (e.g., risk takers) which were distinguishable from other troops. 5. The diagnosis of Non-Hogkins lymphoma is not easy. There might be a bias in the recording of this diagnosis in cases in which it was known that the patient had served in Vietnam. 6. If one is concerned about the etiology of cancer vis a vis Vietnam, it would be preferable to exclude any cancers that' appear prior to some minimal latency period; e.g., 10 years. 7. It would be enlightening to look at the proportionate cancer mortality ratios (PMCRs), which would examine the relative cancer experience in greater detail. 8. Possible followups include: a. An I Corps study of the Army veterans — planned b. A periodic updating of the current study to take into account latency, etc. — planned? c. A cohort study of the Marines d. A case-control study of the NHL and lung cancers in the Marines. The question of exposure still remains. Given the recent results of the CDC exposure validation study, it is not clear that options c and d are tenable. � 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. 066 Folder The folder containing the original item. 1783 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 Barnes, Donald G. Title A name given to the resource Typescript: Comments on "Proportionate Mortality Study of Army and Marine Corps Veterans of the Vietnam War," September 8, 1987 Subject The topic of the resource VA Mortality Study lymphomas study criticism ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/93a1d4b92c903d16c2fd8681bac5be25.pdf c48fbd9edfd45b05704367bfe00b1744 PDF Text Text Item ID Number Author 01732 Youn 9-J F Corporate Author Report/Article TltlB Typescript: Summary of Review of VA Submission to JAMA, "Proportional Mortality Study of Army and Marine Corps Veterans of the Vietnam War" by P. Breslin, et al., September 8, 1987 Journal/Book Title Year 000 ° Month/Day Color Number of Images L 1 Descrlpton Notes Monday, June 11, 2001 Page 1783 of 1793 �Summary of Review of VA submission to JAMA "Proportional Mortality Study of Army and Marine Corps Veterans of the Vietnam War" by P. Breslin, H.K. Kang, Y. Lee, V. Burt, and B.M. Shepard Summary prepared by J.F. Youngj D.W. Gaylor, R.L. Kodell, and J. Chen National Center for Toxicological Research Jefferson, Arkansas 7E079 September 8? 1987 Regardless of any possible methodological flaws, this study can not be used to infer anything about Agent Orange or any other specific cause of effect other than being a Vietnam veteran. From the write up, one can not check the statistical procedures and therefore must assume that it was done correctly using acceptable methods; however, a more detailed description of the methods with references would be helpful. From this study Non-Hodgkins expected but risk is less the Marines have an increased risk due to Lymphomas? however, the Army risk is lower than not significantly. When combined, the overall than expected with a PMR *" 0.95. The manuscript is for the most part written clearly; however, there are still obvious errors and statements made that are not well documented. Positive findings are pointed out but corresponding negative findings are not discussed. Statements are made on page I ft that PMR values may be inflated or deflated. Life-table analyses could be conducted to overcome these limitations. It is not clear how age and race adjustments were made in the analyses. Were the average age of the Vietnam and non-Vietnam groups the same? � 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. 066 Folder The folder containing the original item. 1782 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 Young, J.F. D.W. Gaylor R.L. Kodell J. Chen Title A name given to the resource Typescript: Summary of Review of VA Submission to JAMA, "Proportional Mortality Study of Army and Marine Corps Veterans of the Vietnam War" by P. Breslin, et al., September 8, 1987 Subject The topic of the resource VA Mortality Study lymphomas study criticism ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/063bb16d96e7401f4e4643efa67413a3.pdf 91410704d340733b48e2ed1c52d0fb24 PDF Text Text Item ID Number 01731 Author Fingerhut, Marilyn Corporate Author RdpOrt/ArtiClO TltlB Typescript: Comments on "Proportionate Mortality Study of Army and Marine Corp Veterans of the Vietnam War" by P. Breslin et al., Septembers, 1987 Journal/Book Title Year 000 ° Month/Day Color Number of Images D 1 Descrlpton Notes Monday, June 11, 2001 Page 1782 of 1793 �Comments on "Proportionate Mortality Study of Army and Marine Corp Veterans of the Vietnam War" by P. Breslin et_ al. Marilyn Fingerhut September 6, 1987 Use of BIRLS for a PMR study is reasonable. Structure of PMR study is reasonable: Random sample of complete file of BIRLS, with Vietnam exposure confirmed; death certificates obtained (96.9% followup), adequate size (at least for Army). PMR studies are usually used to generate, not test hypotheses. The article appropriately recommends further work to evaluate etiological factors. The media reports have not conveyed this information. The problem at hand results from the timing of the release of the article, and the inclusion of a sentence in the Abstract (inappropriately) referring to Agent Orange exposure. The structure of the study is appropriate; the scientific weakness of the article lies in the analysis and interpretation of the results. The authors can revise the article for submission to a journal. The weakness of the article results from 1) the absence of data evaluating elevations in other smoking related diseases in the Marines, 2) absence of latency evaluations for the malignancy outcomes, 3) lack of data evaluating the adequacy of the marine comparison group, and 4) inadequate evaluation of the limitations of the PMR study design. No evaluation of latency is presented for lymphoma or lung outcomes. Service was '64-'73, deaths were '65-'82. The article does not evaluate the relationship of time of exposure to time of death. No data are provided to show whether other circulatory or respiratory deaths were elevated in army and marines for conditions associated with smoking. It is unclear whether the cancer outcomes were obtained in the overall PMR, or in a separate Proportionate Cancer Mortality Ratio (PCMR). The results for deaths from external causes and accidental poisonings are consistent with other studies of veterans and point out problems for veterans following this war. The nonVietnam comparison group for the Army is large, so the numbers can be expected to be stable; the same may not be true for the marines. It would have been helpful if, 1) the authors had carefully presented data to show that the marine Vietnam vs. nonVietnam populations were truly comparable, and 2) the authors had provided a table showing the expected numbers for each cause of death if the national population had been used as the comparison. � 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. 066 Folder The folder containing the original item. 1781 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 Fingerhut, Marilyn Title A name given to the resource Typescript: Comments on "Proportionate Mortality Study of Army and Marine Corp Veterans of the Vietnam War" by P. Breslin et al., September 6, 1987 Subject The topic of the resource VA Mortality Study BIRLS study criticism cancer risk assessment ao_seriesIII 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. 066 Folder The folder containing the original item. 1780 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 Dan, Bruce B. Title A name given to the resource Letter: from Bruce B. Dan to Han K. Kang, July 14, 1987 Subject The topic of the resource VA Mortality Study study protocol study criticism ao_seriesIII