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4 Evaluation of Health Conditions
Pages 67-216

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From page 67...
... , 9th or 10th edition, is no longer used. Finally the section on chronic multisymptom illness is now called Gulf War illness in keeping with the suggestion of prior Institute of Medicine (IOM)
From page 68...
... Since the mid-1990s, numerous studies have documented that deployment to the Gulf War in 1990–1991 entailed an increased risk of developing a multitude of symptoms that veterans themselves called "Gulf War illness" or "Gulf War syndrome." Although exact numbers are not available, it has been estimated that as many as one-third of the Gulf War deployed veterans may have Gulf War illness (RAC, 2014) and in the recent survey of the National Cohort of Gulf War and Gulf Era Veterans, Dursa et al.
From page 69...
... All primary studies of Gulf War illness are summarized in Table 4-1 at the end of this section. Definitions of Gulf War Illness The proper term to use when describing the complex set of symptoms experienced by Gulf War veterans has been the subject of considerable discussion.
From page 70...
... Besides recommending that VA use both definitions, the committee also recommended that VA systematically monitor data to identify and further refine additional features of chronic multisymptom illness, such as onset, duration, severity, frequency of symptoms, and exclusionary criteria in order to produce a more robust case definition. The committee also recommended that VA use the term "Gulf War illness" rather than "chronic multisymptom illness" for symptomatic Gulf War veterans.
From page 71...
... . The large and nationally representative National Health Survey of Gulf War Era Veterans and Their Families conducted by VA in 1993–1995, found that nearly 30% of deployed veterans met the CDC case definition of "multisymptom illness" compared with 16% of nondeployed veterans.
From page 72...
... . Nondeployed veterans with multisymptom illness had more markers of obstructive liver disease than their counterparts without multisymptom illness.
From page 73...
... The prevalence in Gulf War veterans was 29% in veterans who met the criteria for multisymptom illness compared with 18% in nondeployed veterans (these percentages dropped to 26% and 16%, respectively when cases with explanatory conditions were excluded)
From page 74...
... A total of 286,995 Gulf War deployed and 296,635 era veterans received treatment at VA over the approximately 11-year period. These VA health care users represent 46% of all deployed Gulf War veterans and 36% of all nondeployed era veterans.
From page 75...
... (2012) conducted a case-control study in 2000 that compared Gulf War veterans' exposures in a population-based sample of 304 deployed veterans, 144 with Gulf War illness and 160 healthy controls.
From page 76...
... The authors also collected information on whether veterans in the validation study met the CDC's criteria for multisymptom illness, but these data were not reported. Results from the survey indicated that the overall case definition of Gulf War illness was more prevalent in the deployed than nondeployed veterans (OR = 3.87, 95% CI 2.61–5.74)
From page 77...
... Gulf War veterans from the coalition forces also reported increased symptoms indicative of Gulf War illness, but their exposures may have differed from those of U.S. service members.
From page 78...
... , thus the authors suggest an interaction between BChE genotype and PB that affects the risk of Gulf War illness such that Gulf War veterans who have BChE-LCV genotypes and took PB are at greatest risk comparatively in this study. The committee notes that the number of cases in these groups was small; there were only 28 veterans in the BChE-LCV group -- 14 with Gulf War illness (of whom 13 had PB exposure)
From page 79...
... tested the hypothesis that physiological responses to stress might differ in veterans with Gulf War illness. Nine veterans with Gulf War illness and 11 sedentary, nondeployed veterans were tested for stress-related biomarkers before, during, and after a standard bicycle ergometer exercise test.
From page 80...
... compared cytokines in peripheral blood of 20 male and 10 female Gulf War illness veterans with 12 male and 10 female CFS patients and 21 male and 9 female healthy veterans before, during, and after exercise. Analysis was performed as in the earlier studies.
From page 81...
... Peripheral blood CD4+ lymphocytes were stained using appropriate PE-conjugated anti-cytokines and were analyzed by flow cytometry for IL-2, IFN-gamma, IL-4 and IL-10 in the absence of activators. There was considerable overlap in the data but symptomatic Gulf War veterans had significantly higher mean levels of non-stimulated IL-4+ and IL-2+ cells compared to well Gulf War veterans and the control group.
From page 82...
... Other Studies of Possible Relevance In a search for persistent enteroviruses, Urnovitz and colleagues (1999) compared levels of circulating RNA in sera from 24 deployed Gulf War veterans and 50 nonmilitary controls.
From page 83...
... Studies looking for biomarkers of Gulf War illness or other health conditions face many methodological problems irrespective of the approach or technology used (neuroimaging, genetics, cytokines)
From page 84...
... OR = smoking status categories 1998 population Force, including more symptoms 4.08 (95% CI 3.39–4.93) accounted (Vol.
From page 85...
... GWVs vs 175 (1.8%) nondeployed veterans Exposures associated with four-symptom cases (n = 277)
From page 86...
... 4) in 1990–1997 including lung symptoms, and 8 out of 19 skin symptoms 57.8% vs 231 age- and function and 81% of deployed veterans vs 71% of controls nondeployed sex-matched self-report had one or more ICD-10 diagnoses at nondeployed questionnaire of examination (p = 0.002)
From page 87...
... 8) from August circulatory branch, marital outpatient data; 1991 through system disease status, rank, length restricted to September in DoD hospital of service, salary, DoD hospitals, 1993 system (ICD-9 occupation and thus classification)
From page 88...
... 8) from August selected NDVs: DoD, VA, hospitalization; 1991 through 182,164 DoD and COSHPD possible December hospitalizations; hospital systems undetected 1994 16,030 VA confounders hospitalizations; PMR has lower 5,185 COSHPD sensitivity than hospitalizations a comparison of hospitalization rates Smith Retrospective Active-duty Postdeployment Veterans of southwest Asia had slightly Sex, age, marital Lower hazard et al., cohort study personnel hospitalization higher rate of hospitalization compared to status, pay grade, ratio observed 2006 (cohort data with a single events (1991– deployed GWVs, while veterans of Bosnia race/ethnicity, in veterans of (Vol.
From page 89...
... lack of routine compared to healthy controls. physiologic Gulf War illness in GWVs not associated signs with spirometry performance, lung function, blood pressure, anemia, renal impairment, obstructive or inflammatory liver disease, or prior exposure to EBV or CMV compared to healthy controls 89 continued
From page 90...
... (2009) NDVs NOTE: CCEP = Comprehensive Clinical Evaluation Program; CDC = Centers for Disease Control and Prevention; CI = confidence interval; CIDI = Composite International Diagnostic Interview; CMI = chronic multisymptom illness; CMV = cytomegalovirus; COSHPD = California Office of Statewide Health Planning and Development; DMDC = Defense Manpower Data Center; DoD = Department of Defense; DU = depleted uranium; EBV = Epstein-Barr virus; GHQ = General Health Questionnaire; GW = Gulf War; GWV = Gulf War veteran; ICD = International Classification of Diseases; NDV = nondeployed veteran; OR = odds ratio; PB = pyridostigmine bromide; PMR = proportional morbidity ratio; PTSD = posttraumatic stress disorder; RR = risk ratio; SF-12 = 12-item short form health survey; UK = United Kingdom; U.S.
From page 91...
... Summary of Volumes 4 and 8 The Volume 4 committee reviewed four cancer studies and found no consistent evidence of a higher overall incidence of cancer in Gulf War veterans than in nondeployed veterans. However, the committee also noted that many veterans were young for a cancer diagnosis and, for most cancers, the follow-up period after the Gulf War was probably too short to expect the onset of most cancers.
From page 92...
... New Literature The Volume 10 committee identified three new studies of cancer in Gulf War veterans; two were deemed primary studies, one was considered a secondary study. Primary Studies The first primary study was the Australian Gulf War Veterans' Follow Up Health Study (Sim et al., 2015)
From page 93...
... The SIRs compared the Gulf War veterans and era veterans with the general population, adjusted for sex, race, and age. A total of 21,075 incident cancer diagnoses were identified -- 8,211 among the deployed veterans and 12,864 among the era veterans -- of these, 2,796 were identified from the VA Central Cancer Registry.
From page 94...
... In addition to the malignant neoplasms in Table 4-4, a total of 43,337 benign neoplasms were diagnosed among deployed veterans, and 43,757 benign neoplasms were diagnosed among nondeployed veterans. Conclusions Given the lack of new evidence on the effect of deployment to the Gulf War and incidence of overall or site-specific cancers from two primary studies, the committee concurs with the conclusions of the Volume 8 committee that there is insufficient/inadequate evidence to determine whether an association exists between deployment to the Gulf War and the incidence or prevalence of any cancer.
From page 95...
... (2010) found a higher proportion of lung cancer in Gulf War veterans compared with era veterans, but there was no difference when compared to the general population.
From page 96...
... due to poor health; no adjustment for other potential confounders All Cancers Macfarlane Cohort 51,721 UK GWVs, Cancers GWVs (cases = 270) vs Main analysis: sex, Follow-up period et al., (follow-up of 50,755 NDVs; random identified from NDVs (cases = 269)
From page 97...
... ; deployed cancer of the lymph nodes Canadians in (HR = 0.65, 95% CI 0.16– region during 2.62) combat Smith Hospitalizations Active-duty personnel Postdeployment Veterans of Bosnia and Sex, age, marital Active-duty personnel et al., cohort study with a single deployment hospitalization of SW Asia compared to status, pay grade, only; hospitalizations at 2006 (cohort data to: Gulf War theater (n events (1991– GWVs race/ethnicity, service DoD facilities only (Vol.
From page 98...
... to men mortality and GWVs and 2,922 NDVs incidence All malignant cancer: HR = No smoking adjustment cancer registry and mortality 1.2 (95% CI 0.83–1.73) Follow-up to Sim et al., studies (SIR, SMR, Brain cancer: SIR = 2.38 2003 and HR)
From page 99...
... cancer were not elevated PIR of a cancer site is in either GWVs or NDVs; affected by the relative SIR for testicular cancer frequencies of other in NDVs was 1.1 (95% cancer types CI 1.0–1.2) ; and SIRs for Kaposi sarcoma showed sig decreased risk in both GWVs and NDVs All other comparisons and sites were not significant NOTE: BIRLS = Beneficiary Identification Records Locator System; CCD = Canadian Cancer Database; CI = confidence interval; COSHPD = California Office of Statewide Health Planning and Development; DC = District of Columbia; DMDC = Defense Manpower Data Center; DoD = Department of Defense; GW = Gulf War; GWV = Gulf War veteran; HR = hazard ratio; ICD = International Classification of Diseases; NDI = National Death Index; NDV = nondeployed veteran; NJ = New ­ ersey; J PIR = proportional incidence ratio; PMR = proportional morbidity ratio; RR = risk ratio; SEER = Surveillance, Epidemiology, and End Results; SIR = standardized incidence ratio; SMR = standardized mortality ratio; SRR = standardized rate ratio; UK = United Kingdom; U.S.
From page 100...
... However, these studies precluded any firm conclusions being drawn because hospitalizations were mostly restricted to DoD hospitals, the studies lacked information on outpatient visits where patients with mild disorders are most likely to be seen, most studies lacked information on potential confounders, and none of them differentiated between specific hematologic disorders. Two other primary studies measured hematologic parameters in Danish and Australian Gulf War veterans compared with nondeployed veterans, but neither showed any major difference by deployment status (Ishoy et al., 1999b; Sim et al., 2003)
From page 101...
... who had also participated in the 1995 National Health Survey of Gulf War Veterans and Their Families. Compared with nondeployed veterans, deployed veterans were less likely to report having hypertension (RR = 0.85, 95% CI 0.76–0.96)
From page 102...
... found that among 6,111 Gulf War deployed and 3,859 era veterans, deployed veterans, regardless of their weight status (underweight, normal weight, overweight, or obese) , self-reported more coronary heart disease and hypertension than nondeployed veterans.
From page 103...
... deployed veterans had a significantly increased risk of having tachycardia but a second study, using the same cohort, found no significant increase in the risk of having hypertension or of having coronary heart disease, although there was a moderate increase in the risk of developing both conditions. A study of Australian Gulf War veterans found no significantly increased risk of having high cholesterol, high blood pressure, heart attacks or myocardial infarction, or angina in deployed vs nondeployed veterans.
From page 104...
... , but analysis medical hypertension of nonparticipants and evaluation; and use of participants reveals no 1999–2001 antihypertensive differences in hypertension medications or diabetes Smith DoD 99,614 active-duty First Circulatory system Sex, age, status, Restricted to DoD hospitals; et al., hospitalization military considered hospitalization for diseases: RR = 1.07 (95% prewar restricted to hospitalizations 2003 study exposed vs 318,458 any disease of the CI 1.01–1.13) ; hospitalization, pay for only Gulf War veterans (Vol.
From page 105...
... vs age- and sex-matched 76 (sd = 10) mmHg nondeployed controls Sim Cross- 1,371 male and 30 Blood pressure High-normal blood Service type, rank, High participation in et al., sectional, female Australian measured by a pressure, males: OR = 1.1 age, education, deployed veterans (male 2003 mailed GWVs; 1,368 male physician (95% CI 0.9–1.3)
From page 106...
... undetected confounders; 1991 through hospitalizations; COSHPD hospital COSHPD PMR = 1.09 PMR has lower sensitivity December 16,030 VA systems (95% CI 0.22–1.96) than a comparison of 1994 hospitalizations; hospitalization rates 5,185 COSHPD hospitalizations Smith Retrospective Active-duty personnel Postdeployment Compared to GW veterans, Sex, age, marital Limitations: activeet al., cohort study with a single hospitalization veterans of Bosnia showed status, pay grade, duty personnel only; 2006 (cohort data deployment to: Gulf events (1991– similar risk (HR = 0.93, race/ethnicity, service hospitalizations at DoD (Vol.
From page 107...
... days deployed, marital duty after the war; no of health DoD exposure model status, occupation adjustment for confounding outcomes and exposures exposure to nerve agents (follow-up of Gray et al., 1999b) Ishoy Cross- 686 Danish Blood Hemoglobin (mmol/L)
From page 108...
... 8) questionnaire and 32 female platelet count vs 134.3 low participation in control and clinical nondeployed veterans MCV (fl)
From page 109...
... . The Volume 8 committee reported that primary studies showed no clinically relevant differences between deployed and nondeployed veterans in prevalence of different endocrine and metabolic conditions, including diabetes, thyroid disease, and obesity.
From page 110...
... In a 2003–2005 follow-up to the 1995 National Health Survey of Gulf War Veterans and Their Families, Coughlin and colleagues (2011a) investigated selfreported health outcomes among 6,111 Gulf War deployed and 3,859 era veterans stratified by weight.
From page 111...
... . These VA health care users represent 46% of all deployed Gulf War veterans and 36% of all nondeployed era veterans.
From page 112...
... than for controls nondeployed (81.9 kg, 88.3 cm) Sim Cross- 1,384 male and 30 Plasma glucose; Plasma glucose, men: 85 mg/dL Service type, rank, High participation in et al., sectional, female Australian BMI; waist in both groups; women: 90 mg/ age (< 20, 20–24, deployed veterans (male 2003 mailed GWVs; 1,379 male circumference dL vs 81 mg/dL 25 to 34, ≥ 35 81%, female 79%)
From page 113...
... undetected confounders 1991 through hospitalizations; metabolic disease COSHPD PMR = 0.81 (95% CI PMR has lower December 16,030 VA in three hospital 0.48–1.14) sensitivity than 1994 hospitalizations; systems: DoD, VA, a comparison of 5,185 COSHPD COSHPD hospitalization rates hospitalizations Smith DoD 405,142 active- Association of No significant difference Adjusted for Objective measure of et al., hospitalizations duty GWVs who exposure level with between RR for exposure at any "influential disease not subject to 2002 1991–1999; were in theater hospitalizations level vs nonexposed covariates," defined recall bias; no issues with (Vol.
From page 114...
... methods, diagnostic criteria, and procedures NOTE: BMI = body mass index; CI = confidence interval; COSHPD = California Office of Statewide Health Planning and Development; DoD = Department of Defense; GWV = Gulf War veteran; HR = hazard ratio; ICD = International Classification of Diseases; NDV = nondeployed veterans; OR = odds ratio; pmol = p ­ icomoles; PMR = proportional morbidity ratio; RR = risk ratio; VA = Department of Veterans Affairs.
From page 115...
... . These conditions have been an important focus of studies of military populations, and each large cohort study of Gulf War veterans has included at least some psychological assessments.
From page 116...
... Across those studies, publications from three U.S. cohorts, one Australian cohort, and one Canadian cohort reported a two- to three-fold increased prevalence of mental health conditions including generalized anxiety disorder, panic disorder, PTSD, any anxiety disorder, and substance abuse in deployed vs nondeployed veterans (Barrett et al., 2002; Black et al., 2004a,b; Brailey et al., 1998; Kang et al., 2003; Proctor et al., 1998; Wolfe et al., 1999a,b)
From page 117...
... For many of the psychiatric disorders that were measured in long-term followup studies, their prevalence even 10 years after the war was more than two-fold higher in veterans who had been deployed compared with nondeployed veterans. In particular, the Volume 8 committee found that the high prevalence of medically unexplained disability in Gulf War veterans could not be completely explained by specific psychiatric causes or disorders.
From page 118...
... . The authors report that excess PTSD in Gulf War veterans appears to persist even 20 years after the war, and it appears to be increasing with time compared with the nondeployed veterans.
From page 119...
... (2015) reviewed 14 studies that compared the presence of depression and dysthymia or chronic dysphoria in Gulf War veterans with nondeployed veterans (11 of the studies were discussed in Volumes 4 or 8)
From page 120...
... . One large study that assessed Gulf War veterans over time found that between 1995 and 2005, the number of deployed veterans with PTSD increased significantly (p < 0.05)
From page 121...
... Two secondary studies also supported the finding that even many years after the war, U.S. and Danish Gulf War veterans experience more PTSD, depression, and other mental health conditions than nondeployed veterans.
From page 122...
... allocation CAGE questionnaire (cohort from Iowa (alcohol abuse) Persian Gulf Study Group, 1997)
From page 123...
... vs 396 Depression; BSI deployed veterans from time 2 (39.8% (Vol.
From page 124...
... 4) deployed veterans PTSD: OR = 3.9 (95% CI in the Navy, 2.3–6.5)
From page 125...
... ; clinician Disability defined as administered score < 72.2 on SF-36 interview Fiedler Cross-sectional, 967 GWVs vs 784 CIDI Deployed veterans had Response et al., random sampling NDVs significantly higher 12-month rate 59% for 2006 of all U.S. prevalence of any psychiatric GWVs, 51% (Vol.
From page 126...
... onset prior symptoms to war was 10 years post-Gulf War era: significantly PTSD (1.8% vs 0.06% GWVs higher in vs NDVs, p = 0.12) ; non GWVs PTSD anxiety disorders (2.8% (12.5%)
From page 127...
... than NDVs. Both 47% in NDVs CIDI via phone 2011–2012 as group; groups reported sig worse First survey interview used to follow-up to 715 GWVs and 675 physical and mental health conducted in measure 12-month baseline 2000– NDVs participated in from baseline to follow-up 2003 PTSD, alcohol disorder, 2002 Australian follow-up study MDD, specific phobia, No significant difference in Derivative of Gulf War Veterans' social phobia, bipolar groups reporting depression, Kelsall et al., Health Study disorder, and obsessive but GWVs were more likely 2009 compulsive disorder to have mild or moderate Included Australian symptoms Department of Veterans No significant changes from Affairs health data and baseline to follow-up data from Medicare, GWVs (approx.
From page 128...
... In this section, the committee considers previous Gulf War and Health reports and new literature on neurologic conditions, specifically peripheral neuropathy, MS, ALS, and other neurodegenerative conditions in Gulf War veterans. In each section, the committee summarizes the findings and conclusions from Gulf War and Health Volume 4 and Volume 8, reviews the new literature published since Volume 8, and discusses any other studies that do not meet the criteria of a primary or secondary study but that nonetheless provide further information to assess neurological conditions in Gulf War veterans.
From page 129...
... . Objective neurologic and myopathic testing showed no significant differences between deployed and nondeployed veterans who had neuromuscular symptoms of Gulf War illness with the exception of greater effort on the bicycle exercise test.
From page 130...
... . These VA health care users represent 46% of all deployed Gulf War veterans and 36% of all nondeployed era veterans.
From page 131...
... The authors found 330 cases of MS among the 696,118 deployed veterans (250 in males and 80 in females) and 1,230 cases among the 1,780,215 nondeployed veterans (837 in males and 393 in females)
From page 132...
... (2015) Australian Gulf War Veterans' Follow Up Health Study discussed in the previous section on peripheral neurologic disorders, only 1 of the 697 deployed male Australian Gulf War veterans and 1 of the 659 nondeployed veterans reported a doctor-diagnosed case of MS.
From page 133...
... (2003) found an almost two-fold increase in the risk of ALS for the deployed Gulf War veterans compared with nondeployed (RR = 1.92, 95% CI 1.29–2.84)
From page 134...
... (2015) found that only 2 of the 697 deployed male Australian Gulf War veterans had ALS and none of the 659 nondeployed veterans reported having ALS.
From page 135...
... New Literature The committee only identified one new study that met the criteria for a secondary study of other neurodegenerative conditions in Gulf War veterans. Dursa et al.
From page 136...
... Summary of Volumes 4 and 8 In Volumes 4 and 8, the committees defined primary studies as those "studies that used neurobehavioral tests that had previously been used to detect adverse effects in population-based research on occupational groups." In Volume 4, two primary studies found significant differences in neurobehavioral performance -- specifically the Purdue Pegboard Test, the California Verbal Learning Test, and the Wisconsin Card Sorting Test -- when deployed Gulf War veterans were compared with nondeployed veterans or those deployed elsewhere (David et al., 2002; Proctor et al., 2003)
From page 137...
... (2004) examined neurobehavioral symptoms in 686 Danish Gulf War veterans and 231 nondeployed military controls that were matched to the deployed veterans on age, gender, and profession.
From page 138...
... Migraines This section contains an overview and update on migraines in Gulf War veterans compared with nondeployed veterans. Many studies have included headaches as part of multiple item, self-reported symptom checklists or clustered them with other symptoms related to a specific condition, such as CFS and Gulf War illness.
From page 139...
... nondeployed veterans received any diagnosis for ICD-9 codes 320–389. Of these 20,473 (12.3%)
From page 140...
... The Volume 8 committee concluded that there is insufficient/inadequate evidence to determine whether an association exists between deployment to the Gulf War and other neurologic outcomes. New Literature The committee did not identify any new literature that met the criteria for a primary or a secondary study of other neurological outcomes in Gulf War veterans.
From page 141...
... (2011) found no evidence of reduced NAA/Cr in Gulf War veterans with Gulf War illness compared with veterans without Gulf War illness using both the CDC and Haley syndrome 2 definitions of Gulf War illness.
From page 142...
... cingulum bundle in Gulf War veterans with PTSD (n = 12) compared to those without PTSD (n = 8)
From page 143...
... (2011) published results of cerebral perfusion measured with arterial spin labeling MRI in response to physostigmine challenge in Gulf War veterans who met Haley's criteria for Gulf War illness syndromes 1, 2, or 3 and controls.
From page 144...
... Thus, the committee does not find MRI abnormalities to be a valid biomarker of Gulf War illness. The committee emphasizes that environmental exposures at the individual veteran level cannot be determined and therefore finds that conducting studies that seek or propose a cause-and-effect relationship between environmental exposures unique to Gulf War veterans (sarin, cyclosarin)
From page 145...
... veterans, exposure- 39% in specific nondeployed component veterans Rose Case-control 49 symptomatic deployed Nerve-conduction No significant differences et al., UK veterans vs 26 healthy studies, quantitative between symptomatic deployed 2004; deployed UK veterans, sensory and autonomic and nondeployed veterans, except Sharief 13 symptomatic Bosnia testing, concentric deployed veterans had increased et al., deployed veterans, needle and single-fiber, lactate production in bicycle 2002 22 symptomatic NDVs electromyography, exercise test (Vol.
From page 146...
... compared with increased risk of ALS (RR = 1.92, average, annual ascertainment 2003 NDVs 95% CI –1.29–2.84) 10-year through (Vol.
From page 147...
... of the study to determine long-term trends Neurobehavioral and Neurocognitive Studies David Case-control, 200 male UK GWVs, 54 WAIS-R scaled scores: GWVs had significantly lower ANCOVA Careful et al., clinical Bosnia-deployed, 78 era Vocabulary, scores on five cognitive tests: adjusted for treatment 2002 evaluations nondeployed veterans Digit span, Digit symbol education, age, of potential (Vol.
From page 148...
... for CVLT and adjusted for age armed forces deployed and WCST, Purdue WCST nondeployed, respectively, pegboard, WAIS-R at time of Gulf War block design, CVLT, WMS visual reproductions, TOMM; individually administered tests except in computer based NES; blinded examiners Storzbach Case-control 239 randomly selected Symbol digit Cases significantly worse than ANCOVA, et al., male and female GWVs Serial digit learning controls on: adjusted for 2001 with symptoms vs ODTP Digit span backward age, sex, and (Vol.
From page 149...
... methods used All cases were male Discrepancy between DMDC recorded and self-reported deployment (43 vs 55) Multiple Sclerosis Wallin Cohort study 387 GWV cases and MS incidence rates Deployment was protective of MS Age, race, Derivative et al., 1,454 NDV cases of MS MS diagnosed using risk and all demyelinating disorders sex, or service of Wallin 2014 and clinically isolated 2005 McDonald criteria (RR = 0.7, 95% CI 0.6–0.8)
From page 150...
... ; 3 significant ones represented only small differences NOTE: AFQT = Armed Forces Qualifying Test; ALS = amyotrophic lateral sclerosis; ANCOVA = analysis of covariance; BARS = Behavioral Assessment and Research System; BDI = Beck Depression Inventory; CATSYS = Coordination Ability Test System; CI = confidence interval; CVLT = California Verbal Learning Test; DMDC = Defense Manpower Data Center; DoD = Department of Defense; GWV = Gulf War veteran; HR = hazard ratio; ICD = International Classification of Diseases; MANCOVA = multivariate analysis of variance; MS = multiple sclerosis; NART = National Adult Reading Test; NDV = nondeployed veteran; NIS = Neuropathy Impairment Score (Mayo Clinic version) ; ODTP = Oregon Dual Task Procedure; OR = odds ratio; PASAT = Paced Auditory Serial Addition Test; PB = pyridostigmine bromide; PCA = principal components analysis; RR = risk ratio; sd = standard deviation; SF-12 = 12-item Short Form Health Survey; SF-36 = 36-Item Short Form Health Survey; SIR = standardized incidence ratio; TOMM = Test of Memory Malingering; UK = United Kingdom; VA = Department of Veterans Affairs; WAIS-R = Wechsler Adult Intelligence Scale-Revised; WCST = Wisconsin Card Sorting Test; WMS = Wechsler Memory Scale.
From page 151...
... , and various symptoms consistent with respiratory disease, such as wheezing and shortness of breath, have consistently been self-reported more frequently by deployed Gulf War veterans than era veterans. Exposures of concern during deployment include smoke from oil-well fires, high levels of ambient dust, pesticide sprays, and nerve gas exposure.
From page 152...
... Gulf War deployed (n = 5,469) and nondeployed veterans (n = 3,353)
From page 153...
... . These VA health care users represent 46% of all deployed Gulf War veterans and 36% of all nondeployed era veterans.
From page 154...
... 4) evaluation reversible obstruction, with exposure to nerve confounders explanation of "matching" restrictive, small-airways agents at Khamisiyah or control of matching in obstruction based on 2002 DoD analysis exposure models Gray Cross- 527 GWVs Cough; shortness of breath; Cough: OR = 1.8 (95% Age, height, No use of modeled oil-fire et al., sectional, vs 970 NDVs FVC (L)
From page 155...
... 4) vs 231 NDVs peak flow 94.0 vs 92.8, evaluation histories similar in NS deployed and nondeployed Smith Hospitalizations Active-duty Postdeployment hospitalization Veterans of Bosnia Sex, age, Active-duty personnel et al., cohort study personnel events (1991–2000)
From page 156...
... only DoD hospitals, only oil-well fire Respiratory conditions due to OR = 0.78 (95% CI active duty, no information smoke chemical fumes and vapors 0.38–1.57) on smoking or other Other respiratory diseases OR = 1.36 (95% CI confounders related to 0.62–2.98)
From page 157...
... occupation nervous system conditions models NOTE: CI = confidence interval; DMDC = Defense Manpower Data Center; DoD = Department of Defense; FEV1 = forced expiratory volume in 1 second; FVC = forced vital capacity; GWV = Gulf War veteran; HR = hazard ratio; ICD = International Classification of Diseases; MRR = mortality rate ratio; NS = not significant; OR = odds ratio; PFT = pulmonary function test; UK = United Kingdom; U.S. = United States.
From page 158...
... The Volume 8 committee found in numerous studies that Gulf War veterans self-reported more GI symptoms than nondeployed veterans (Kang et al., 2000; Kelsall et al., 2004a; Proctor et al., 1998; S ­ immons et al., 2004; Sostek et al., 1996; Unwin et al., 1999)
From page 159...
... . There were statistically significantly more deployed veterans who met the Rome III criteria for IBS based on self-reported symptoms than nondeployed veterans (13% vs 8%; RR = 1.64, 95% CI 1.18–2.27)
From page 160...
... In another analysis of the second wave of VA's National Health Survey of Gulf War Veterans, Coughlin and colleagues (2011a) found that among 6,111 Gulf War deployed and 3,859 era veterans, deployed veterans, regardless of their weight status (underweight, normal weight, overweight, or obese)
From page 161...
... The committee finds that given the aging of the population of Gulf War veterans and the unlikelihood that new gastrointestinal conditions will develop 25 years after the Gulf war that are attributable to their Gulf War service, it is doubtful that further assessments will show increased risk of these conditions. T  herefore, the Volume 10 committee concludes that there is sufficient evidence for an association between deployment to the Gulf War and gastrointestinal symptoms consistent with functional gastrointestinal disorders such as IBS and functional dyspepsia.
From page 162...
... 4) symptoms and years of education time since war; medical conditions weak diagnostic reported from earlier criteria survey Gray Retrospective DoD hospitals: Digestive system All ORs < 1.0 Hospitalization Data et al., cohort study 547,076 GWVs, diseases rates and rate ratios reflect only 1996 (hospitalization 618,335 NDVs adjusted for age, sex; hospitalization (Vol.
From page 163...
... ; new GI disease diagnosed alcohol drinking exclusively, since September 1990 (OR = 2.10, response rate 95% CI 1.39–3.17) ; clustering of 70%, large CFS, PTSD, MCS, IBS: Seabees sample who had one averaged 13–18 other symptoms; Seabees without one averaged only 6 other symptoms NOTE: CFS = chronic fatigue syndrome; CI = confidence interval, COSHPD = California Office of Statewide Health Planning and Development; DoD = Department of Defense; GI = gastrointestinal; GWV = Gulf War veteran; IBS = irritable bowel syndrome; MCS = multiple chemical sensitivity; NDV = nondeployed veteran; OR = odds ratio; PMR = proportional morbidity ratio; PTSD = posttraumatic stress disorder; U.S.
From page 164...
... . Additional secondary studies that relied on long lists of self-reported symptoms indicated that the prevalence of generally nonspecified skin conditions or conditions in deployed Gulf War veterans was greater than in nondeployed veterans including skin allergies or other skin conditions, sweating, itching skin, hair loss, boils, or abscesses; physician-diagnosed or treated skin conditions other than skin cancer; moderate or multiple skin symptoms; eczema; skin allergies; and dermatitis (Cherry et al., 2001a; Goss Gilroy Inc., 1998; Gray et al., 1999a; Kang et al., 2000; Proctor et al., 2001a; Simmons et al., 2004; Steele, 2000; Wolfe et al., 1998)
From page 165...
... Results were adjusted for age, rank category, and service branch, but not for smoking. Of the 1,456 eligible deployed veterans, 715 participated in the study and 675 of the 1,449 nondeployed veterans made up the comparison group.
From page 166...
... . These VA health care users represent 46% of all deployed Gulf War veterans and 36% of all nondeployed era veterans.
From page 167...
... 8) age- and sex-matched NDVs self-report retarded wound healing 6.0% vs 1.7%, confounders questionnaire p < 0.01; in multivariate other forms of skin problems 17.1% vs analysis 5.2%, p < 0.001; hair loss or hair disease 4.2% vs 0.9%, p < 0.01; sweaty, clammy, or damp hands 7.9% vs 3.9%, p < 0.05 NOTE: CI = confidence interval; GWV = Gulf War veteran; NDV = nondeployed veteran; OR = odds ratio; UK = United Kingdom; U.S.
From page 168...
... Diagnostic criteria for CFS, fibromyalgia, and rheumatic disorders such as rheumatoid arthritis and osteoarthritis are distinct, but the conditions have overlapping symptoms and in some cases may be difficult to distinguish from each other and from related conditions such as chronic widespread pain (CWP) and Gulf War illness, which are seen in many Gulf War veterans.
From page 169...
... . One study in Australian Gulf War veterans showed that CFS and complaints of unexplained chronic fatigue were increased in deployed vs nondeployed veterans (CFS OR = 1.2, 95% CI 0.5–2.9; chronic fatigue lasting more than 6 months OR = 1.9, 95% CI 1.4–2.7)
From page 170...
... In Volume 4, only one study used the full ACR case definition of fibromyalgia (Eisen et al., 2005) , including criteria based on physical examination and found significantly more deployed Gulf War veterans than nondeployed veterans diagnosed with fibromyalgia (OR = 2.32, 95% CI 1.02–5.27)
From page 171...
... The Volume 8 committee identified five new primary studies that looked at hospitalization discharge diagnoses of some form of musculoskeletal disease in Gulf War veterans, but specific diagnoses were not provided in any of the studies. Those studies showed no increased risk of hospitalization for musculoskeletal system conditions among Gulf War deployed veterans compared with their nondeployed counterparts.
From page 172...
... More than half of both deployed and nondeployed veterans reported those symptoms. Finally, with regard to musculoskeletal disorders, the follow-up study asked more specific questions than the baseline study, so longitudinal comparisons were not made.
From page 173...
... This was also true for having a CFS-like illness in the past 12 months for obese nondeployed veterans but not for obese deployed veterans. Further assessment of these veterans found that having a self-reported CFS-like illness was also more prevalent among deployed and era Gulf War veterans with problem drinking than those without problem drinking.
From page 174...
... (2015) found that deployed veterans reported greater pain intensity and more disability than nondeployed veterans, but the differences were not statistically significant; however, deployed veterans reported statistically significant more pain in more body areas, and Dursa et al.
From page 175...
... symptoms of CFS (Kang et al., 2000) Kelsall Cross-sectional 1,424 Australian Association of CFS in deployed veterans Age, service branch, Relatively large et al., survey male GWVs, unexplained chronic vs control groups OR = 1.2 rank; also education, study with national 2006 1,548 male NDVs fatigue and CFS (95% CI 0.5–2.9)
From page 176...
... random sample of must have Phase 2 response rate disabled phase 2 physical disability 67% for GWVs, 55% responders (less than 72.2 on and 43% for Bosnia SF-36 physical and era veterans, functioning scale respectively. from phase 1 54% of GWVs with survey)
From page 177...
... 8) from August 1991 diseases in DoD 1992: OR < 1.0 (95% CI branch, marital to DoD hospitals, through September hospital system < 1.0)
From page 178...
... , veterans branch, occupation, DoD facilities only Gulf War theater of a musculoskeletal of southwest Asia at slightly and predeployment (n = 455,465) ; system disease (ICD-9 increased risk (HR = 1.06, hospitalization; southwest Asia codes 710–739)
From page 179...
... for only Gulf health outcomes vs 318,458 War veterans who and exposure to nonexposed, remained on active nerve agents according to duty after the war (follow-up of Gray revised DoD et al., 1999b) exposure model NOTE: CCEP = Comprehensive Clinical Evaluation Program; CDC = Centers for Disease Control and Prevention; CFS = chronic fatigue syndrome; CI = confidence interval; COSHPD = California Office of Statewide Health Planning and Development; CWP = chronic widespread pain; DMDC = Defense Manpower Data Center; DoD = Department of Defense; GWV = Gulf War veteran; HR = hazard ratio; ICD = International Classification of Diseases; IPGWSG = Iowa Persian Gulf War Study Group; NDV = nondeployed veteran; OR = odds ratio; PB = pyridostigmine bromide; PMR = proportional morbidity ratio; RR = risk ratio; UK = United Kingdom; U.S.
From page 180...
... (2006) assessed the difference between deployed and nondeployed veterans, and two other studies examined the effects of environmental exposures to nerve agents or oil-well fires among Gulf War veterans (Smith et al., 2002, 2003)
From page 181...
... . Gulf War veterans consistently reported an increased prevalence of sexual problems when compared with nondeployed veterans.
From page 182...
... Conclusions The studies cited in Volume 8, particularly the secondary studies, found that Gulf War veterans reported more conditions and symptoms of the genitourinary system. The one secondary study identified by the Volume 10 committee indicated that deployed veterans were slightly but not significantly more likely to report having had a disease of the kidney or bladder.
From page 183...
... 8) NDVs with no significant difference in occurrence of rank routine nonnormal diagnoses detected in any other Pap smears age group conducted in 1994 Gray Retrospective 547,076 active- Hospital- Any genitourinary disease (exact values Prewar Very short followet al., cohort, DoD duty GWVs, discharge not given)
From page 184...
... Smith Retrospective Active-duty Postdeployment Compared with GWVs, veterans of Bosnia Sex, age, marital Lower hazard et al., cohort study personnel hospitalization showed reduced risk (HR = 0.60, 95% CI status, pay grade, ratio observed in 2006 of DoD with a single events (1991– 0.51–0.70) , and veterans of southwest Asia race/ethnicity, veterans of Bosnia (Vol.
From page 185...
... ; vs 318,458 system War veterans who analysis nonexposed, (ICD-9-CM remained on active of health according to codes 580–629) duty after the war; outcomes and revised DoD no adjustment exposure to exposure model for confounding nerve agents exposures (follow-up of Gray et al., 1999b)
From page 186...
... Few cases made detection of any differences between birth defect risks in deployed and nondeployed veterans difficult. Overall, studies of Gulf War service and congenital malformations were problematic because specific birth defects are relatively rare, multiple comparisons were performed, and sample sizes were small when divided by timing of exposure (before or after conception)
From page 187...
... Thus, the Volume 4 committee found it difficult to conclude whether there is a higher prevalence of adverse pregnancy outcomes in Gulf War deployed than in nondeployed veterans. Two secondary studies of self-reported adverse birth outcomes indicated possible increased risks of miscarriage, spontaneous abortions, and stillbirths among pregnancies to fathers deployed to the Gulf War, but results were not consistent between the studies (Doyle et al., 2004; Kang et al., 2001)
From page 188...
... . It found no evidence of significant differences in concentrations of male reproductive hormones between deployed and nondeployed Gulf War veterans.
From page 189...
... Of the 1,456 eligible deployed veterans, 715 participated in the study and 675 of the 1,449 nondeployed veterans provided the comparison group. Based on self-reported pregnancy and fertility information collected since 1992, more deployed veterans reported difficulty fathering a pregnancy (RR = 1.44, 95% CI 1.05–1.99)
From page 190...
... TABLE 4-23  Birth Defects, Adverse Pregnancy Outcomes, and Fertility 190 Study Design Population Outcomes Results Adjustments Comments Volume 4 and 8 Primary Studies Birth Defects Araneta Retrospective Infants of military 48 birth defects Postwar conceptions, GWVs vs NDVs State, maternal California limited et al., 2003 cohort, using personnel born identified by (unadjusted RRs) : and paternal to diagnoses (Vol.
From page 191...
... Study Design Population Outcomes Results Adjustments Comments Doyle Retrospective All UK GWVs and Fetal death: Adjusted ORs GWVs vs NDVs: Stratum Response rates: et al., 2004 cohort randomly selected early and late fathers: all miscarriages matched on GWVs: men 53%, (Vol.
From page 192...
... ; stratified on NDVs, 57.8% 215 NDVs libido) ; measured reproductive hormones, deployment Limited control male reproductive no significant difference; organization, for confounding, hormones: serum suspected oligospermia, FSH ≥ 10 duration of small numbers for concentrations IU/L, inhibin B £ 80 pg/mL, 1.6% deployment study of fertility of LH, FSH, vs 1.6%; fertility rates, spontaneous rates, congenital testosterone, inhibin abortion, congenital malformations: malformations; B no differences objective measurement of hormones
From page 193...
... but not for a shorter or longer period Birth defects were not associated with any other exposures NOTE: BMI = body mass index; CDC = Centers for Disease Control and Prevention; CI = confidence interval; DU = depleted uranium; FSH = follicle-stimulating hormone; GW = Gulf War; GWV = Gulf War veteran; HFM = hemifacial microsomia; LH = luteinizing hormone; NDV = nondeployed veteran; NIFS = Nuclear Industry Family Study; OR = odds ratio; RR = risk ratio.
From page 194...
... In Volumes 4 and 8, only external causes of mortality were considered as a separate outcome; information on disease-related mortality was considered for each organ system when available. However, given the small number of new studies that have assessed mortality from any cause, this committee believed that it was reasonable to consider all causes of mortality in one section, the better to determine if deployed Gulf War veterans were at increased risk of dying compared with nondeployed veterans or with the general U.S.
From page 195...
... Although there were no statistically significant findings after adjustment for age, sex, race, and year of death, some studies suggested a modest increase in transportation-related deaths among deployed Gulf War veterans compared with nondeployed veterans in the first several years after the war (DASA, 2005; Kang and Bullman, 1996, 2001; Macfarlane et al., 2000; Writer et al., 1996)
From page 196...
... literature easier. 8 A summary mortality rate ratio is a summary statistic reflecting the comparison of mortality rates of deployed and nondeployed veterans, whereas an SMR represents a ratio of frequencies (observed deaths in either deployed or nondeployed veterans vs expected number of deaths derived from rates occurring in a reference population, usually the general U.S.
From page 197...
... In the Australian Gulf War Veterans' Follow Up Health Study (Sim et al., 2015) the all-cause mortality and all-external cause mortality were lower for both veterans cohorts compared with the Australian male population, but the differences were statistically significant only for the era veterans (all-cause SMR = 0.59, 95% CI 0.45–0.76; all external causes SMR = 0.61, 95% CI 0.41–0.92)
From page 198...
... veterans. After adjusting for age, sex, race, branch of service, and unit component, deployed veterans had a statistically significantly lower rate of death from all disease-related causes compared with nondeployed veterans (MRR = 0.96, 95% CI 0.94–0.98)
From page 199...
... compared cancer mortality rates between deployed and nondeployed veterans as well as between each veteran cohort and the age-adjusted Australian male population. Among deployed veterans, observed cancer deaths were slightly higher than expected compared with the age-matched Australian male population, but this difference was not statistically significant.
From page 200...
... Conclusions Two new primary studies on mortality from cancer in Gulf War veterans were reviewed. Even after following Gulf War deployed and era veterans for 22 years, no statistically significant differences in mortality were found in either the primary or secondary studies, which is consistent with the findings from Volumes 4 and 8.
From page 201...
... (2009) did not find any increase in ALS mortality in Gulf War veterans compared with nondeployed veterans (MRR = 0.96, 95% CI 0.56–1.62; adjusted for sex, race, type of unit, and age)
From page 202...
... In the one secondary study that presented mortality information on conditions of the nervous system, no statistically significant differences were observed between the deployed and nondeployed veterans. T  herefore, the Volume 10 committee concludes that there is insufficient/inadequate evidence of an association between deployment to the Gulf War and mortality from neurologic conditions, specifically multiple sclerosis, Alzheimer's disease, and Parkinson's disease.
From page 203...
... . Conclusions Consistent with the findings of mortality from cardiovascular disease presented in Volume 8, the Volume 10 committee also failed to find any statistically significant differences in mortality from these conditions between deployed and nondeployed veterans after 20 or more years of follow-up.
From page 204...
... . Conclusions The new literature reviewed by the Volume 10 committee was consistent with the literature reviewed in Volume 8, where few deaths due to respiratory causes were reported and no evidence of different mortality rates were observed between deployed and nondeployed veterans.
From page 205...
... included mortality rates from gastrointestinal conditions for both deployed and era Gulf War veterans. No statistically significant difference was observed between the two groups (MRR = 1.01, 95% CI 0.93–1.11; adjusted for race, sex, age, branch of service, and unit component)
From page 206...
... suggests that the Gulf War deployed veterans are at less risk of developing and dying from infectious or parasitic diseases than nondeployed veterans; however, the committee did not have a category of association to indicate such a relationship. T  herefore, the Volume 10 committee concludes that there is limited/suggestive evidence of no as sociation between deployment to the Gulf War and infectious or parasitic disease-related causes of mortality.
From page 207...
... 8) causes of neoplasms No significant difference in mortality rate was found structure death from for any of the specific classes of malignant neoplasm of the Gulf April 1, 1991, included in the study cohort at to December January 1, 31, 2007 1991 Statistics Retrospective 5,117 Canadian Mortality Cancer mortality, (HR = 0.85, 95% CI 0.38–1.90)
From page 208...
... Brain cancer GWVs (144 cases) vs NDVs (228 cases)
From page 209...
... ; exposure through determined from BIRLS, SSA; the 2000 DoD COD data plume model from NDI Statistics Retrospective 5,117 Canadian Mortality due MRR = 0.49 (95% CI 0.17–1.40) Age, sex, Small sample; Canada, cohort study GWVs; 6,093 to diseases of rank, short follow2005 (cohort based Canadian NDVs, the circulatory marital up; young age (Vol.
From page 210...
... 8) matched by age, system cohort of sex, service branch, moderate size; rank; also fitness no control for for active service confounding in the Army and variables Royal Air Force DASA, Summary 53,409 UK GWVs Mortality due MRR = 0.87 (95% CI 0.70–1.07)
From page 211...
... ; other external causes of branch death from accidental injury (SMR = 1.07, 95% CI 0.74–1.54) ; April 1, 1991, higher deaths from external causes disappeared about to June 30, 10 years after Gulf War 2005 Lincoln Retrospective 1,318 cases of Annual Higher motor vehicle annual mortality rate in deployed Deployed et al., cohort and motor vehicle motor vehicle veterans: 23.56 (95% CI 21.9–25.3)
From page 212...
... 8) causes of of death No significant difference in mortality rate was found structure death from classified for any of the specific external causes of mortality of the gulf April 1, 1991, based on included in the study cohort at to December ICD-10 January 1, 31, 2007 1991 Statistics Retrospective 5,117 Canadian Mortality All external causes (OR = 1.53, 95% CI 0.82–2.86)
From page 213...
... ; NDV SMR = 0.53 (95% CI 0.48–0.59) External causes: 539 vs 505 (RR = 1.06, 95% CI 0.94–1.2)
From page 214...
... on ICD-9 1.39, 95% CI 1.22–1.60) codes Excess mortality decreased with time after deployment except mortality rates for all external causes and motor vehicle events, which remained significantly higher among GWVs compared with NDVs (external causes SMRR = 1.09, 95% CI 1.04–1.14; and motor vehicle SMRR = 1.29, 95% CI 1.18–1.40)
From page 215...
... This small group of Gulf War veterans exposed to DU has been followed biennially for 20 years to identify uranium-related changes in health; findings from these cross-sectional assessments have been routinely published (McDiarmid et al., 2001, 2004, 2006, 2007a,b, 2009, 2011a, 2013, 2015)
From page 216...
... . As a part of the surveillance program for Gulf War veterans exposed to DU, skin reactivity to uranium was examined in 40 deployed Gulf War veterans and 46 controls (patients with no known occupational exposure to DU seen at University of Maryland Dermatology Clinic for evaluation of contact dermatitis who completed a clinical assessment between April–June 2009)