C
Epidemiologic Studies of Vietnam Veterans Health

Table C-1 provides an overview of design aspects of the epidemiologic studies related to Vietnam veterans’ health reviewed in the Institute of Medicine’s Veterans and Agent Orange report series (IOM, 1994, 1996, 1999, 2001, 2003, 2005). The summaries include the study’s design type, the numbers of subjects in the study and comparison populations, and a synopsis of how subjects were selected, how data were collected, what inclusion criteria were used, and how exposure was determined. The table was excerpted from Appendix A of the Veterans and Agent Orange: Update 2004 report. More information on these studies may be found in the reports referenced.



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Disposition of the Air Force Health Study C Epidemiologic Studies of Vietnam Veterans Health Table C-1 provides an overview of design aspects of the epidemiologic studies related to Vietnam veterans’ health reviewed in the Institute of Medicine’s Veterans and Agent Orange report series (IOM, 1994, 1996, 1999, 2001, 2003, 2005). The summaries include the study’s design type, the numbers of subjects in the study and comparison populations, and a synopsis of how subjects were selected, how data were collected, what inclusion criteria were used, and how exposure was determined. The table was excerpted from Appendix A of the Veterans and Agent Orange: Update 2004 report. More information on these studies may be found in the reports referenced.

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Disposition of the Air Force Health Study TABLE C-1 Epidemiologic Studies of Vietnam Veterans Reference Study Design Description Study Group (N) Comparison Group (N)* UNITED STATES STUDIES AFHS Studies Reviewed in Update 2004 Akhtar et al., 2004 Cohort Follow-up to Ketchum et al. (1999), comparing cancer incidence among Ranch Hands with Vietnam veterans who served in Southeast Asia but did not spray herbicides and with U.S. national cancer rates 1,189 net Ranch Hands for external analysis; 1,009 net Ranch Hands for internal analysis 1,776 net comparison subjects for external analysis; 1,429 net comparison subjects for internal analysis Barrett et al., 2003 Cohort Serum TCDD measurement and psychological functioning among Ranch Hand veterans 1,109 1,493 Michalek et al., 2003 Cohort Correlation for TCDD elimination and Ranch Hands with diabetes 343 No comparison group Pavuk et al., 2003 Cohort Study to examine the relationship between serum TCDD and thyroid function in Ranch Hand veterans 1,009 1,429 AFHS Studies Reviewed in Update 2002 Barrett et al., 2001 Cohort Based on tests of cognitive functioning in 1982 and dioxin concentrations measured in 1987 and 1992, analyzed association between serum dioxin levels and cognitive functioning 937 Ranch Hands 1,052 Ranch Hand comparisons

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Disposition of the Air Force Health Study Michalek et al., 2001a Cohort Based on physical examination through 1992 and medical records reviewed through March 1993, association between serum dioxin levels and hepatic abnormality 1,109 Ranch Hands 1,493 Ranch Hand comparisons Michalek et al., 2001b Cohort Based on physical examination in 1982, 1985, 1987, 1992, and 1997, and medical records through 1997, association between serum dioxin and peripheral neuropathy 761 Ranch Hands 1,086 Ranch Hand comparisons Michalek et al., 2001c Cohort Based on physical examination in 1982, 1985, 1987, and 1992, and medical records through 1997, association between serum dioxin and hematologic function 953 Ranch Hands 1,280 Ranch Hand comparisons Steenland et al., 2001 Cohort Reexamine and compare diabetes data from the NIOSH cohort and the United States Air Force (USAF) Ranch Hands in order to reconcile differences between the two study methods and protocols 267 NIOSH workers; 990 Ranch Hands 227 NIOSH comparisons 1,275 Ranch Hand comparisons AFHS Studies Reviewed in Update 2000 AFHS, 2000 Cohort 266 health-related endpoints, including assessments of 10 clinical areas: general health, neoplasia, neurologic, psychologic, gastrointestinal, cardiovascular, hematologic, endocrine, immunologic, pulmonary 995 1,299 Longnecker and Michalek, 2000 Cohort Based on physical examination and medical records review through 1992, association between serum dioxin and diabetes mellitus among comparison group (no Ranch Hands) — 1,197 Ketchum et al., 1999 Cohort Based on physical examination and medical records review through 1992, association between serum dioxin and cancer, skin cancer, cancer other than skin cancer 980 Ranch Hands 1,275 Ranch Hand comparisons Michalek et al., 1999a Cohort Further elucidate relationship between dioxin and diabetes mellitus, effect of dioxin body burden on sex-hormone-binding globulin and insulin and fasting glucose 871 Ranch Hands 1,121 Ranch Hand comparisons

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Disposition of the Air Force Health Study Reference Study Design Description Study Group (N) Comparison Group (N)* Michalek et al., 1999b Cohort Based on physical examinations in 1982, 1985, 1987, and 1992, immunologic response and exposure to dioxin among Ranch Hand and comparison cohorts 914 Ranch Hands 372 (lymphocyte counts conducted) 1,186 Ranch Hand comparisons 491 (lymphocyte counts conducted) Burton et al., 1998 Cohort Based on physical examination and medical record review through 1992, association between serum dioxin and occurrence and timing (relative to Southeast Asia service) of chloracne and acne 930 Ranch Hands 1,200 Ranch Hand comparisons Michalek et al., 1998b Cohort Updates, all-cause and cause-specific post-service mortality (through 1993) among veterans of Operation Ranch Hand, using standardized mortality ratios 1,261 Ranch Hands 19,080 Ranch Hand comparisons Michalek et al., 1998c Cohort Prospective study, exposure and long-term health, survival, reproductive outcome 1,208 veterans; 903 offspring 1,549 veterans; 1,254 offspring Michalek et al., 1998d Cohort Third report in a series investigating dioxin body burden and preterm birth, intrauterine growth retardation, infant death among offspring of Ranch Hand veterans 859 1,223 AFHS Studies Reviewed in Update 1998 Michalek et al., 1998a Cohort Paternal serum dioxin levels and infant death among Ranch Hand offspring 859 children: 323 background exposure; 267 low exposure; 269 high exposure 1,223 children

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Disposition of the Air Force Health Study Henriksen et al., 1997 Cohort Relationship between serum dioxin and glucose, insulin, and diabetes mellitus in Ranch Hands through 1992 989 1,276 AFHS, 1996; Michalek et al., 1998b Cohort Mortality update, Ranch Hands through the end of 1993 in the AFHS cohort (1983, 1984b, 1985, 1986, 1989, 1991a, 1995) 1,261 19,080 Henriksen et al., 1996 Cohort Serum dioxin and reproductive hormones in Ranch Hands, 1982, 1985, 1987, and 1992 1,045 participants (1982); 474 provided semen 1,224 participants (1982); 532 provided semen AFHS Studies Reviewed in Update 1996 AFHS, 1995 Cohort Mortality updates of Ranch Hands who sprayed herbicides in Vietnam, compared with USAF C-130 air and ground crew veterans in Southeast Asia who did not spray herbicides 1,261, original cohort 19,101, original cohort Wolfe et al., 1995 Cohort Paternal serum dioxin and reproductive outcomes of Ranch Hand veterans, compared with USAF veterans from Southeast Asia who did not spray herbicides 932 1,202 AFHS Studies Reviewed in VAO AFHS, 1992 Cohort Reproductive outcomes of AFHS participants 791 942 AFHS, 1984a, 1987, 1990, 1991b Cohort Baseline morbidity, follow-up examination results 1,208 baseline 1,668 baseline

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Disposition of the Air Force Health Study Reference Study Design Description Study Group (N) Comparison Group (N)* AFHS, 1983, 1984b, 1985, 1986, 1989, 1991a Cohort Mortality updates, Ranch Hands who sprayed herbicides in Vietnam, compared with USAF C-130 air and ground crew veterans in Southeast Asia who did not spray herbicides 1,261 (original cohort) 19,101 (original cohort) Michalek et al., 1990 Cohort Mortality of Ranch Hands, compared with USAF C-130 air and ground crew veterans in Southeast Asia 1,261 19,101 Wolfe et al., 1990 Cohort Health status of Ranch Hands at second follow-up, compared with USAF C-130 air and ground crew veterans in Southeast Asia 995 1,299 Centers for Disease Control and Prevention Studies Reviewed in VAO Decoufle et al., 1992 Cohort Association between self-reported health outcomes and perception of exposure to herbicides based on Vietnam Experience Study 7,924 7,364 O’Brien et al., 1991 Cohort Interview report and mortality for NHL based on Vietnam Experience Study 8,170 7,564 CDC, 1990a Case-control Selected Cancers Study: population-based case-control study of all men born 1921–1953; cases diagnosed area covered by eight cancer registries, controls selected by random-digit dialing 1,157 NHL; 342 STS; 310 HD; 48 nasal carcinoma; 80 nasopharyngeal carcinoma; 130 primary liver cancer 1,776

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Disposition of the Air Force Health Study CDC, 1990b Case-control Selected Cancers Study: population-based case-control study of all men born 1921–1953; cases diagnosed in area covered by eight cancer registries, controls selected by random-digit dialing for NHL 1,157 1,776 CDC, 1990c Case-control Selected Cancers Study: STS 342 1,776 CDC, 1990d Case-control Selected Cancers Study: HD, nasal cancer, nasopharyngeal cancer, primary liver cancer 310 HD; 48 nasal carcinoma; 80 nasopharyngeal carcinoma; 130 primary liver cancer 1,776 CDC, 1989b Cohort Vietnam Experience Study: random sample, U.S. Army enlisted men, 1965–1971 2,490 1,972 CDC, 1988a Cohort Vietnam Experience Study: random sample, U.S. Army enlisted men, 1965–1971, psychosocial outcomes 2,490 1,972 CDC, 1988b Cohort Vietnam Experience Study: physical health outcomes 2,490 1,972 CDC, 1988c Cohort Vietnam Experience Study: reproductive outcomes 12,788 children 11,910 children CDC, 1987; Boyle et al., 1987 Cohort Vietnam Experience Study: mortality 9,324 8,989 Erickson et al., 1984 a,b Case-control CDC birth defects study, children born in the Atlanta, Georgia, area 1968–1980, comparing paternal Vietnam experience and potential Agent Orange exposure for birth defects cases and normal controls 7,133 4,246

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Disposition of the Air Force Health Study Reference Study Design Description Study Group (N) Comparison Group (N)* Department of Veterans Affairs Studies Reviewed in Update 2002 Kang et al., 2001 Cohort Health of Army Chemical Corps Vietnam veterans, compared with Army Chemical Corps veterans who did not serve in Vietnam 2,872 2,737 Kang et al., 2000a Cohort Self-report pregnancy outcomes for female Vietnam veterans, compared with contemporary veterans not deployed to Vietnam; odds ratios calculated for reproductive history and various birth defects 3,392 women; 1,665 women with indexed pregnancy 3,038 women; 1,912 women with indexed pregnancy Kang et al., 2000b Cohort Gynecologic cancers among female Vietnam veterans, compared with veteran controls 484 5,946 Department of Veterans Affairs Studies Reviewed in Update 1998 Dalager and Kang, 1997 Cohort Morbidity and mortality experience (1968–1987), Army Chemical Corps Vietnam veterans, compared with U.S. men; extension of Thomas and Kang (1990) 2,872 2,737 Mahan et al., 1997 Case-control Lung cancer among Vietnam veterans (1983–1990) 329 269 111 McKinney et al., 1997 Cross-sectional Tobacco use in veterans and nonveterans by 1987 NMES 15,000 — Bullman and Kang, 1996 Cohort Mortality of veterans with nonlethal (combat and noncombat) wounds sustained during the Vietnam war 34,534 — Watanabe and Kang, 1996 Cohort Mortality experience (1965–1988) of Army and Marine Corps Vietnam veterans; extension of Breslin et al. (1988) and Watanabe et al. (1991) 33,833 36,797

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Disposition of the Air Force Health Study Dalager et al., 1995b Case-control HD cases diagnosed 1969–1985 among Vietnam-era veterans 283 404 Watanabe and Kang, 1995 Cohort Postservice mortality among Marine Vietnam veterans 10,716 9,346 Department of Veterans Affairs Studies Reviewed in Update 1996 Dalager et al., 1995a Cohort Update of Thomas et al. (1991) through Dec. 31, 1995 4,586 5,325 Bullman et al., 1994 Case-control Association between testicular cancer and surrogate measures of exposure to Agent Orange in male Vietnam veterans 97 311 Department of Veterans Affairs Studies Reviewed in VAO Bullman et al., 1991 Case-control PTSD cases in Vietnam veterans, compared with Vietnam veterans without PTSD, for association with traumatic combat experience 374 373 Dalager et al., 1991 Case-control NHL cases diagnosed 1969–1985 among Vietnam-era veterans, compared with cases of other malignancies among Vietnam-era veterans, for association with Vietnam service 201 358 Eisen et al., 1991 Cohort Health effects in male monozygotic twins serving in the armed forces during Vietnam era (1965–1975) 2,260 2,260 Thomas et al., 1991 Cohort Mortality experience (1973–1987) among female Vietnam veterans, compared with female non-Vietnam veterans and for each cohort compared with U.S. women 4,582 5,324

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Disposition of the Air Force Health Study Reference Study Design Description Study Group (N) Comparison Group (N)* Watanabe et al., 1991 Cohort Mortality experience (1965–1984) in Army and Marine Corps Vietnam veterans, compared with: (1) branch-specific (Army and Marine) Vietnam-era veterans, (2) all Vietnam-era veterans combined, (3) the U.S. male population 24,145 Army 5,501 Marines (1) 27,145 Army 4,505 Marines (2) 32,422 combined Vietnam era (3) U.S. male population Bullman et al., 1990 Cohort Mortality experience in Army I Corps Vietnam veterans, compared with Army Vietnam-era veterans 6,668 deaths 27,917 deaths Farberow et al., 1990 Case-control Psychological profiles, military factors associated with suicide and MVA fatalities in Los Angeles County Vietnam-era veterans (1977–1982) 22 Vietnam suicides; 19 Vietnam-era suicides 21 Vietnam MVA; 20 Vietnam-era MVA Thomas and Kang, 1990 Cohort Morbidity and mortality experience (1968–1987) in Army Chemical Corps Vietnam veterans compared with U.S. men 894 — True et al., 1988 Cross-sectional PTSD and Vietnam combat experience among Vietnam-era veterans 775 1,012 Breslin et al., 1988; Burt et al., 1987 Cohort Mortality experience (1965–1982) in Army and Marine Corps Vietnam veterans, compared with Vietnam-era veterans who did not serve in Southeast Asia, standardized by age and race; nested NHL case-control study 24,235 26,685

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Disposition of the Air Force Health Study Kang et al., 1987 Case-control STS cases (1975–1980) diagnosed at the Armed Forces Institute of Pathology (AFIP), compared with controls identified from patient logs of referring pathologists or their departments, for association with Vietnam service and likelihood of Agent Orange exposure 217 599 Kang et al., 1986 Case-control STS (1969–1983) in Vietnam-era veterans, for association with branch of Vietnam service as a surrogate for Agent Orange exposure 234 13,496 American Legion Studies Reviewed in VAO Snow et al., 1988 Cohort PTSD in association with traumatic combat experience among American Legion members serving in Southeast Asia (1961–1975) 2,858 Study group subdivided for internal comparison Stellman et al., 1988a Cohort Physical health, reproductive outcomes among American Legion members who served in Southeast Asia (1961–1975), for association with combat and herbicide exposure 2,858 3,933 Stellman et al., 1988b Cohort Social, behavioral outcomes among American Legion members who served in Southeast Asia (1961–1975), association with combat and herbicide exposure 2,858 3,933 State Studies Reviewed in Update 1998 Clapp, 1997 Case-control Selected cancers identified (1988–1993) among Massachusetts Vietnam veterans, compared with Massachusetts Vietnam-era veterans with cancers of other sites; update of Clapp et al., 1991 245 999 State Studies Reviewed in Update 1996 Visintainer et al., 1995 Cohort Mortality experience (1965–1971) in male Michigan Vietnam veterans, compared with non-Vietnam veterans from Michigan 3,364 deaths 5,229 deaths

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Disposition of the Air Force Health Study Reference Study Design Description Study Group (N) Comparison Group (N)* Greenwald et al., 1984 Case-control New York: STS cases, compared with controls without cancer for Vietnam service and herbicide exposure including Agent Orange, dioxin, or 2,4,5-T 281 281 live controls; 130 deceased controls Newell, 1984 Cross-sectional Texas: preliminary (1) cytogenetic, (2) sperm, (3) immune response tests in Vietnam veterans, compared with controls (1) 30; (2) 32; (3) 66 (1) 30; (2) 32; (3) 66 Other U.S. Veterans Studies Reviewed in VAO Tarone et al., 1991 Case-control Testicular cancer (18–42 years old) cases, January 1976–June 1981, compared with hospital controls, for association with Vietnam service 137 130 Aschengrau and Monson, 1990 Case-control Cases with late adverse pregnancy outcomes compared with normal control births, for association with paternal Vietnam service (1977–1980) 857 congenital anomalies 61 stillbirths; 48 neonatal deaths 998 Goldberg et al., 1990 Cohort Male twin pairs who served in Vietnam era (1965–1975), for association between Vietnam service and PTSD 2,092 2,092 Aschengrau and Monson, 1989 Case-control Association between husband’s military service and spontaneous abortion at or by 27 weeks, compared with women delivering at 37 weeks 201 1,119

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Disposition of the Air Force Health Study AUSTRALIAN VETERANS STUDIES Australian Studies Reviewed in Update 2000 AIHW, 1999 Cohort Validation of the male veterans study (CDVA, 1998a) by medical documents, doctors’ certification, records on a disease or death registry 6,842 — CDVA, 1998a Cohort Self-reported data on male members of the Australian Defence Force and the Citizen Military Force who landed in Vietnam or entered Vietnamese water. Questions on physical (including reproductive history) and mental health, and that of their partner(s) and children 49,944 mailed; 39,955 responded — CDVA, 1998b Cohort Self-reported data on female members of the Australian Defence Force and the Citizen Military Force who landed in Vietnam or entered Vietnamese water. Questions on physical (including reproductive history) and mental health, and that of their partner(s) and children 278 mailed 225 responded — Australian Studies Reviewed in Update 1998 Crane et al., 1997a Cohort Mortality experience (through 1994) of Australian veterans who served in Vietnam 59,036 men 484 women — Crane et al., 1997b Cohort Mortality experience (through 1994) of Australian national servicemen who served in Vietnam 18,949 24,646 O’Toole et al., 1996a,b,c Cross-sectional Survey of self-reported health status (1989–1990) of Australian Army Vietnam veterans 641 — Australian Studies Reviewed in VAO Field and Kerr, 1988 Cohort Tasmanian Vietnam veterans, compared with neighborhood controls for adverse reproductive and childhood health outcomes 357 281

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Disposition of the Air Force Health Study Reference Study Design Description Study Group (N) Comparison Group (N)* Fett et al., 1987a Cohort Mortality experience in Vietnam veterans, compared with Vietnam-era veterans through 1981 19,205 25,677 Fett et al., 1987b Cohort Cause-specific mortality experience in Vietnam veterans, compared with Vietnam veterans through 1981 19,205 25,677 Forcier et al., 1987 Cohort Mortality in Vietnam veterans by job classification, location, time of service 19,205 Internal comparison Donovan et al., 1983, 1984 Case-control Congenital anomalies in children (1969–1979), compared with infants born without anomalies, for association with paternal Vietnam service 8,517 8,517 OTHER VIETNAM VETERANS’ STUDIES Other New Vietnam Veterans’ Studies Reviewed in Update 2004 Kim H-A et al., 2003 Cohort Immunotoxicologic effects of Agent Orange exposure on Korean Vietnam veterans 51 (24 veterans– patient; 27 veterans– normal) 36 Kim J-S et al., 2003 Cross-sectional Agent Orange exposure and Korean Vietnam veterans 1,224 154 Mo et al., 2002 Cohort Skin and general disease patterns among Korean Vietnam veterans 332 None

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Disposition of the Air Force Health Study Other Vietnam Veterans Studies Reviewed in Update 1998 Chinh et al., 1996 Cohort Antinuclear antibodies and sperm autoantibodies among Vietnamese veterans who served 5–10 years in a “dioxin-sprayed zone” 25 63; 36 NOTE: Abbreviations: 2,4,5-T, 2,4,5-trichlorophenoxyacetic acid; AFHS, Air Force Health Study; CDC, Centers for Disease Control and Prevention; CDVA, Commonwealth Department of Veterans’ Affairs (Australia); HD, Hodgkin’s disease; MVA, motor vehicle accidents; NIOSH, National Institute for Occupational Safety and Health; NHL, non-Hodgkin’s lymphoma; NMES, National Medical Expenditure Survey; PTSD, post-traumatic stress disorder; SMR, standardized mortality ratio; STS, soft-tissue sarcoma; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; Update 2004, Veterans and Agent Orange: Update 2004 (IOM, 2005); Update 2000, Veterans and Agent Orange: Update 2000 (IOM, 2001); Update 1998, Veterans and Agent Orange: Update 1998 (IOM, 1999); Update 1996, Veterans and Agent Orange: Update 1996 (IOM, 1996); USAF, United States Air Force; and VAO, Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam (IOM, 1994). *Comparison group based on a population (e.g., U.S. white males, country rates); details are given in the text for population sp ecifics.

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