Gulf War and Health Updated Literature Review of Sarin (2004) / Chapter Skim
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3 Human Health Outcome Studies
3 Human Health Outcome Studies
Pages 47-90
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From page 47... ...
Studies of Gulf War veterans include studies of veterans potentially exposed to sarin after demolition of rockets at Khamisiyah, Iraq, and a number of studies that ev aluate the relationship between symptoms md possible exposures, including to sarin or cyclosann, on the basis of a self-reporting questionnaire. Studies reviewed in GWI aoM.
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From page 48... ...
. The study examined current health status and hospital admissions to military or Veterans' Administration hospitals.
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From page 49... ...
and displayed some signs of the acute cholinergic syndrome (Baker and Sedgwick, 1996; discussed in IOM, 2000) , the authors interpreted an increased jitter 3 h after exposure and still
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From page 50... ...
= 1,324) 56 exposed rescue High- md low d nl~ 2001 workers and police exposure group from officers vs 52 nonexposed self ripens of matched controls in hospitalizations vs same departments mnptttettt ttnatmettt Knwmtn Follow-up of 582 parents Not clear from study d nl~ 2001 treated at St Luke's hospital in Toyko at 2, 3, md 5 years No control group Ahhn viadmts: IES-R-J, impact of Event Scale: PTSD, postttammadc stn ss disorder Mot ality records from VA and Social Secunty Admimsttanon, surrey of neuropsychologic impairment, illness attitudes, peripheral nerve disease.
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From page 51... ...
tecmd check conducted to verify self n ported level of exposure No control group, low response rate, methods of dose determination or subject selection not repotted
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From page 52... ...
developed the acute cholinergic syndrome; 253 sought medical assists ice 58 were admitted to hospitals, and 7 died. Several case reports, case series, md a population-based epidemiologic study conducted after that attack were described in GWI Tom.
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From page 53... ...
About 83% had intermediate exposure and 17% had high exposure, on the basis of symptom profiles and as verified by more than a 20% decrease in blood cholinesterase activity. Detailed neurophysiologic and neuropsychologic testing was conducted several months later on 18 symptom-free survivors with previous intermediate or high exposure.
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From page 54... ...
the self administered questionnaire", it is unclear from the publication whether they used medical records to verify selfreports about the site of treatment. Exposed md nonexposed groups were evaluated with five neurobehavioral tests (funser-tapping test for do~ninant and nondomm~mt hands, simple reaction time, choice reaction time, backward digit span, and Benton Visual Retention)
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From page 55... ...
GULF WAR VETERANS After the Gulf War, veterans repo ted higher rates of fatigue, headache, pam, and cognitive symptoms than did nondeployed military personnel, according to numerous populationbased studies m the United States (Iowa Persian Gulf Study Group, 1997; Kimg et al., 2000) , the United Kmgdom (Unwm et al., 1999; Cherry et al., 2001)
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From page 56... ...
; because of their mandates, past IOM committees' evaluations focused on separate exposures. Most studies of Gulf War veterans were designed to detect the nature and prevalence of veterans' symptoms and illnesses and whether they constituted a new syndromeratherthan specifically to assess the effects of exposure so particular agents of interest.
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From page 57... ...
. The remainder of this section discusses the studies of Golf War veterans that are relev rat to sarm exposure.
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From page 58... ...
McCauley et al" 2002 923 Khamisiyah-exposed US Gulf Wn veterans vs 927 Kbamisiyab nonexposed Gulf Ww veter ms vs 1,369 non-Gulf W n deployed veterms from Oregon, Washington, Califmnia, Georgia m 710nb Carolina Second exposure model by DOD of nerve agent release data, meteorological models, lad armospbenc removal meobaltirms combined wide troop positions First exposure model by DOD of nerve tqgrm release data, meteorological models combined winh troop pa visions Exposure defined by DOD as troop location winhin a 50 kilometer radius of Khamisiy th
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From page 59... ...
Hospitalization data available for only acove lard tesette Gulf Wet veterans who remained on active duty m tented widh medical benefits after She end of She war. No outpatient data available Lirdted to DOD hospitals.
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From page 60... ...
60 TABLE 3-2 Continued Refetence McCttuley et ttl~ 2001 GUL F WAR AND HEALTH Population 2,918 vetertms ttom Otegon, Was hington, C al i font i a, Georgia, or Notth Carolina L~posu~ ASS.~ L for Reievant Agents Exposure defined by DOD as ttoop locanon winhin a 50 kilmmeter radius of Khamisiyth Selt-Reported t xposures: Pnpulatibn-Bnstd Shidies Net~ Sh~dies IR.dd d td., 2001 Stutdientti et nl., 1999 Ishoy d td., 1999tt Subgroups of UK vetertms meeting case criteria for MCS tmd CFS (stme cohott as Unwin et al., 1999) 686 Gulf Wtt-deployed peacekeepers vs matched conttols frmm Dtmish t.rmed fmces 686 Gulf Wtt-deployed peacekeepers vs matched conttols from Dtmish tttmed forces (same cohott as Suadictmi et al., 1999)
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From page 61... ...
3A: 95% CL R6 6.0) Self-reported symptoms recalled 9 yes after exposure, DOD's models of ewe agent exposme not yet available, not leplesemtt he of entity Gulf Wtt cohort Symptom questionnaires, exposure questiommaire, hodh 6 7 years after Khamisiyah demolition Symptom questionudtes, exposure quesoomm dre up to 6 years after retune Symptom questionudles (Gl symptoms)
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From page 62... ...
nested case comtol study Ksmg et al" 2602 11,441 US veterans deployed to Gulf Wa i vs 9,476 non Gulf "nerve gas" Wa -- deployed, nested case control study Ksmg et al" 2603 GULF WAR AND lIEALTlI Laposum ... At tor Relevant Agents Three televtnt enpostnes: "chemical decontamination bottles", "inadequate ptotecoon dunug chemical/St UD alanms", "wmLed around chemical warfare at ease' 11,441 US veterans deployed to Gulf War vs 9,476 non Gulf Wa deployed, nested case control study protective gear or heard chemical alarms sounding" was one of dhtee combat gtressots: other combat gtressots: "had then involved in direct combat duty" and ``had wimessed arty deadhs"
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From page 63... ...
clinical examination to verify case of unexplained illness Potemially new neutologic syndrome via factor malysis, symptom quesoommaites, exposure quesoommaire, surreys conducted in 1995 PTSD, CFS; surveys conducted from 1995 1997 63 By simple logistic regression cases of tmexplained illness (7 = 241) mow likely th m heaRhy Gulf Wardeployed comtols (x = 113)
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From page 64... ...
64 TABLE 3-2 Continued Reference Studies Reviev cd in GWI GULF WAR AND HEALTH Inwn Persian Gulf Study Group, 1997 1,896 deployed veterans from Iowa as home of record vs 1,799 nondeployed veterans ffmm Iowa as home of record GOLD Gilroy Ine7 1998 3,113 Canadian veterans deployed to Gulf WE vs 3,439 deployed elsewhere One relevant exposure: "chemical wt.rftqe agents" Over 30 exposures divided into six categories; one category was relevant: "chemical warfare agents" (nerve gas and mustard gas or odher blistering agent) Unwin d ad., 1999 2,735 UK veterans deployed to Three relevant envirommemal Gulf War vs 2,393 deployed to exposures: "N 3C subs" "hear Bosnia vs 2,422 deployed chemical alanms", "chemical/ elsewhere nerve gas attack"
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From page 65... ...
Symptom questionnaires, hi Gulf Wtt cohort only, Self-repotted symptoms and exposute quegionnaire, dbteo exposutes associated exposutes, lack of adjustment bosh 6 7 yet ts after with chrome mulosymptom for interteltgionsbips be tweed Khamisiyah demolition illness and PTSD; for chronic multiple exposutes, use of p mukisymptom illness, ORs value of 0.05 despite mulople for dhtee eapo~n 5. 2.2 2.7, compansons Cls do not include 1; for PTSD.
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From page 66... ...
Gray et ED 1999 527 active-duty US Seabees fonmerly deployed to Gulf War vs 969 nondeployed veterans from same Seabte commands One relevant exposure: "chemical or biological warfare (CBW) agents" Two relevant exposures: "exposme to poison gas or germ w nfate" and "placement on fonmal alert for chemical and hiologdcal watft e" One relevant exposure: "dbought biological or chemical weapons wete being used" One relevant exposure: "chemical we oft e''
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From page 67... ...
"Chemical warfare" not I of She 11 exposures studied in analyses Bell rep Ned exposures, not peppesentanve of enope Gulf War cohort Self-reported exposup.s, limbed peppesemativeness of enope Gulf War cohort Self-reported symptoms and g exposures, no repining on exact ome of exposup., exclusion of Gulf War veterans no longer in acove service, no adjustment of p value desphe multiple comparisons, limbed peppesentanveness of emipe Gulf War cohort Self-reported symptoms and exposures, potemial recall bias in symptom repmdug, moderate to low response rate, exclusion of veterans no longer in acove service, results of multivariate analysis not Reported, limbed peppesentanveness of emire Gulf War cohort continued
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From page 68... ...
"use of gas masks" Krnen}e et sol., 1998 18,495 US Gulf Wa i veterans One relevant exposute ih DOD Comprehensive Clinical "nerve gas/agents" Studies Reviewed in GWI Procter d ad., 1998 291 deployed veterans from One relevant exposure: Massachusetts (Ft. Devens)
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From page 69... ...
HUldAlV HEALTH OUTCOldE STUDIES Health hohaviors: physiciandiagnost d illnesses: selft'pott'd persistbut or t'ctanug medical mohlems: exposut' quesoommaire, at least 6 yebts aRbr Khamisiyah demolinon Physician-adminisn ted No associanon ht tween symptom checklist, exposut' individual symptoms and quesoonnait`, cmmbat md sptcinc expostaes wmk-loss quesoonnait's no mot' than 6 years aRbr Khamisiyah demolinon 22% of Gulf War vett rans met deLninon of Gulf Wbt illness: I or mot' physician diagnost d mulosymptom illnesses m at least 12 self-tt pott'd persistbut or t'ctanug medical mohlems: in mulovanatb analysis, Gulf Wbt illness associat'd with "use of gas masks" (OR, 1.40: 95% Cl, 1.07 1.84) 69 Conducn d 5 7 years after Gulf Wbt, self-tepotted symptoms md expostnes, potbnnal t'call hias in symptom repotting, limit'd tt,mesentanveness of enott Gulf Wbt cohmt Includt d only subjects who mesentbd fm evaluanon, selft'pott'd symptmms md exposutt s, lack of conttol gtoup, lack of staosocal malysis, limit'd repmsentativeness Symptom quesoonnaites; exposutn quesoommaires; clinical evaluanons for PTSD; evaluanons conduct'd in 1991, 1993 1994, md 1995 1997 In Gulf Wat cohott, Self-repotted symptoms and exposutn to C 3W agems, in exposutes, modt ran to low muh~var~att analysis, tesponseratb~limittd s~gmf~c mtly associan d with teptesentanveness of enot musculoskeletal p = 0.001)
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From page 70... ...
in relation to potential exposure to nerve agents among 349,291 active-duty military deployed to the Gulf War theater during the time of the Khamisiyah demolition. Hospitalization experience was limited to activeduty military because they seldom receive care outside of Department of
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From page 71... ...
; synergy between exposure to "chemical warta e agent and rco es on scale of advance adverse effects from pyndosogmine bromide in pwd3cting "confnsimt naxia syndrome" Abbteviahons: C 3W, chemical or biolrsic warfare; CfS, chronic faugne symtdmme: Ct confidence inretval- DOD, Department of Defense; Gl, gatutointeshnal; MCS, multiple chemical sentiovity: M3C, mtclet :, biologic, Tad chemical warfare; OR, odds rano; POMS, pmf.le of mood states; PTSD, posntattmatic smess disorder RR, relative risk; UK, United Kingdom. Defense (DOD)
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From page 72... ...
The authors identified study limitations as restriction to DOD hospitals (because of the availability of computerized records) , restriction to hospitalizations of active-duty Gulf War veterans who remained on active duty after the war, and restriction to hospitalization because outpatient data were unavailable.
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From page 73... ...
The sample was divided mm Gulf War veterans potentially exposed to saTm and cyclosarin on the basis of their units bemg located withm 50 km (according to DOD information) of the demolition at Khamisiyah (Khamisiyah-exposed veterans; n = 653)
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From page 74... ...
As m the earlier study, exposure was designated as being within 50 km of Kharnisiyah. Khamisiyah-exposed Gulf War veterans wete compared with Khamisiyah-nonexposed Gulf War veter Ins md nondeployed veterans.
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From page 75... ...
That study, however, is not yet published. Self-Reported Exposures This section summarizes studies of Gulf War veterans m which possible indications of potential exposure to SaTm or cyclosarin are self-reported.
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From page 76... ...
(1998; IOM, 2000) mailed a questionnaire to the entire cohort of almost 10,000 Canadian Gulf War veterans and Canadian forces deployed elsewhere during the same period.
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From page 77... ...
It was significantly associated with self-report of PTSD diagmosed by a health-care provider through a question on the symptom questionnaire rather than a structured clinical interview (OR, 5.25; 95% Cl, 1.36 20.30) or by symptom reporting (OR, 10.79; Cl, 3.11-37.49)
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From page 78... ...
Gulf War veterans reported having the symptombased criteria for chrome fatigue, posttraumauc stress reaction, and "chronic multisymptom illness" more often than comparison subjects. The fact that the Bosria cohort, which also was deployed to a combat setting, reported fewer symptoms than the Gulf War cohort, suggests that combat deployment itself does not account for higher symptom reporting.
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From page 79... ...
. in Gulf War veterans, MCS was associated with self-reports of hearing chemic al alarms (OR, 2.5; 95% Cl, 1.0 5.9)
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From page 80... ...
(2001) conducted a nested case conhol study of the exposuresymptom relationships in Gulf War veterans with unexplained illness (n = 241)
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From page 81... ...
. Cases reported exposure to nine potential exposures on the questionnaire at a rate three or more times higher than Gulf War veterans who did not exhibit all four symptoms (controls)
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From page 82... ...
The study concluded that there was subjective and objective evidence of injury to the vestibular system in this group of Gulf War veterans with newly defined syndromes. Haley and Kurt (1997)
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From page 83... ...
Adjusted step-wise logistic regressions were then performed with each syndrome to adjust for correlations between exposures. The p criterion was set at 0.005 because of the multiple comparisons performed.
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From page 84... ...
Of the Gulf War veterans, 22% met the case defmition. The authors report that "no Seabees had been located under the atmospheric plume subsequent to the March 1991 dest uction of munitions at the Khamisiyah site", a statement for which they cited another of their studies (Gray et al., 1999)
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From page 85... ...
(2001) also studied the cohort of Gulf War veterans from Massachusetts (Ft.
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From page 86... ...
agents", was relevant to the present report. In regression analyses, Gulf War veterans exposed to CBW agents were more likely than nonexposed Gulf War veterans to have mood, memory, and cogmitive deficits.
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From page 87... ...
2001. Heakh and exposmes of United Kingdom Gttf War veterans.
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From page 88... ...
2002.1Rness experience of Gttif Wtt vetet ns possibly exposed to chemical warfare agents. Amtritun Joutnal af Preventive Medicimt 23(3)
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From page 89... ...
1999. Ocnlar mmifestanons in the follow-np of vichms afer sarin poisoning in Mat3nmoto tqea Rinaho Gmia (Japsmexe Jaurnal Clini al Ophthahmak gy)
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From page 90... ...
1998c. Chtonic neutobehavioml effects of Tobo subway sntin poisomug in telabon to postmAttmaue stress disorder.
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