5
HEALTH OUTCOMES

In this chapter, the committee evaluates the evidence and draws conclusions about long-term health outcomes associated with serving in the Persian Gulf War. The studies reviewed in this chapter generally compare Gulf War veterans with veterans who, during the same period, were either deployed to the Gulf War or were deployed elsewhere. This chapter draws on information from many of the studies that were described in Chapter 4. The committee presents the health outcomes in order of their ICD-10 codes.1 The committee did not examine health outcomes related to or resulting from infectious and parasitic diseases because another IOM committee2 is examining those outcomes; its report will be released in fall 2006.


For each health outcome presented here, the committee first identifies the primary studies and then the secondary studies, as defined by the committee’s criteria (see Chapter 3). Because many cohort studies in this chapter examine multiple outcomes, a study might be referred to in more than one place. The same study might be deemed a primary study for several health outcomes or a primary study for one outcome and a secondary study for another outcome. The key determinant is how well the study’s health outcomes are defined and measured. For example, a study that was well designed for assessing a neurobehavioral effect might not be as well designed for assessing peripheral neuropathy. In general, only primary studies appear in the tables accompanying the discussions of health outcomes.

With rare exceptions, the chapter excludes studies of participants in Gulf War registries established by the Department of Veterans Affairs (VA) and the Department of Defense (DOD). Registry participants are not representative of all Gulf War veterans in that they are self-selected veterans who come to receive care. The VA and DOD registries were not intended to be representative of the entire group of Gulf War veterans.

CANCER (ICD-10 C00-D48)

Over a million people are diagnosed with cancer each year in the United States. About one of every two American men and one of every three American women will have cancer at

1

The International Statistical Classification of Diseases and Related Health Problems (ICD) provides a detailed description of known diseases and injuries. Every disease (or group of related diseases) is given a unique code. It is periodically revised and the tenth edition is known as the ICD-10.

2

The Committee on Gulf War and Health: Infectious Diseases.



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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 5 HEALTH OUTCOMES In this chapter, the committee evaluates the evidence and draws conclusions about long-term health outcomes associated with serving in the Persian Gulf War. The studies reviewed in this chapter generally compare Gulf War veterans with veterans who, during the same period, were either deployed to the Gulf War or were deployed elsewhere. This chapter draws on information from many of the studies that were described in Chapter 4. The committee presents the health outcomes in order of their ICD-10 codes.1 The committee did not examine health outcomes related to or resulting from infectious and parasitic diseases because another IOM committee2 is examining those outcomes; its report will be released in fall 2006. For each health outcome presented here, the committee first identifies the primary studies and then the secondary studies, as defined by the committee’s criteria (see Chapter 3). Because many cohort studies in this chapter examine multiple outcomes, a study might be referred to in more than one place. The same study might be deemed a primary study for several health outcomes or a primary study for one outcome and a secondary study for another outcome. The key determinant is how well the study’s health outcomes are defined and measured. For example, a study that was well designed for assessing a neurobehavioral effect might not be as well designed for assessing peripheral neuropathy. In general, only primary studies appear in the tables accompanying the discussions of health outcomes. With rare exceptions, the chapter excludes studies of participants in Gulf War registries established by the Department of Veterans Affairs (VA) and the Department of Defense (DOD). Registry participants are not representative of all Gulf War veterans in that they are self-selected veterans who come to receive care. The VA and DOD registries were not intended to be representative of the entire group of Gulf War veterans. CANCER (ICD-10 C00-D48) Over a million people are diagnosed with cancer each year in the United States. About one of every two American men and one of every three American women will have cancer at 1 The International Statistical Classification of Diseases and Related Health Problems (ICD) provides a detailed description of known diseases and injuries. Every disease (or group of related diseases) is given a unique code. It is periodically revised and the tenth edition is known as the ICD-10. 2 The Committee on Gulf War and Health: Infectious Diseases.

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 some point during their lifetime. Cancer can develop at any age, but about 77% of all cancers are diagnosed in people 55 of age and older. Military personnel during the Gulf War were had a mean age of 28 years, thus it is likely too early for the development of most cancers in Gulf War veterans. Cancer strikes Americans of all racial and ethnic groups, and the rate at which new cancers occur (the incidence) varies from group to group (ACS 2006). The mortality and hospitalization studies reviewed later in this chapter do not definitively identify overall increases in cancer among Gulf War veterans. However, there are other studies that have examined the possibility of brain and testicular cancer. Those cancer studies are evaluated in this section. Because few of the studies dealt with specific cancers, this section groups primary and secondary studies together. Primary and Secondary Studies Brain Cancer Brain cancer is relatively rare. The annual age-adjusted incidence of brain cancer in the United States is 6.4 cases per 100,000 men and women. The median age at diagnosis of brain cancer is 55 years; about 22% of cases are diagnosed between the ages of 20-44 years old (Ries et al. 2005). There is one published study of brain cancer in Gulf War veterans. Bullman and colleagues assessed cause-specific mortality among the 100,487 Gulf War veterans identified with the 2000 sarin plume model (described in Chapter 2) as having been subjected to nerve-agent exposure from the March 1991 demolition of weapons at Khamisiyah (Bullman et al. 2005). Compared with 224,980 Gulf War veterans similarly deployed but considered unexposed to the plume, there was an increased risk of brain cancer deaths with followup through December 31, 2000 (relative risk [RR] 1.94, 95% confidence interval [CI] 1.12-3.34). There was also a suggestion of a dose-response relationship, with the risk increasing from those who were unexposed to those exposed for 1 day to those exposed for 2 days. Specific subtypes of brain cancer were not considered. Because brain cancer is considered to have a latent period of 10-20 years, and the study included less than 9 years of followup, the results should be interpreted with caution. Further followup is necessary to draw any conclusions about the risk of brain cancer among Gulf War veterans. Testicular Cancer Two articles have focused specifically on testicular cancer. Testicular cancer is relatively uncommon in the United States. The annual age-adjusted incidence is 5.3 cases per 100,000 men. However, it is one of the few cancers whose usual age of onset is in the same range as the age of the Gulf War veterans, about 20 to 44 years old (Ries et al. 2005). In general, little is known about environmental risk factors for testicular cancer. Knoke and colleagues (1998) examined testicular cancer among US servicemen on active duty during the time of the Gulf War (August 8, 1990, through July 31, 1991) and who remained on active duty at the end of the deployment period. Eligible servicemen included 517,223 people deployed to the gulf and 1,291,323 nondeployed. The authors identified cases of all first-hospital admissions, in US military hospitals worldwide, for a principal diagnosis of testicular cancer from the period of July 31, 1991 through April 1, 1996. Cases were identified by examining the DOD hospitalization database through April 1, 1997. A total of 505 cases were ascertained: 134 among the deployed and 371 among the nondeployed. In Cox proportional-hazards models adjusted for race and ethnicity, age, and occupation, no association with deployment status was

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 observed (RR 1.05, 95% CI 0.86-1.29). The deployed did have an increased risk in the early months after the end of the deployment period; it persisted, but did not increase, for about 3 years. The initial increased risk was originally reported in a study of all hospitalizations in the cohort (Gray et al. 1996). However, by the end of the followup period (1996), the cumulative probability of hospitalization of the two groups was the same (0.034% for deployed and 0.035% for nondeployed). There was no interaction between covariates and deployment status. The authors also assessed the association of testicular cancer with specific occupations. The highest RRs were observed for electronic-equipment repair (RR 1.56, 95% CI 1.23-2.00), construction-related trades (RR 1.42, 95% CI 0.93-2.17), and electrical or mechanical repair (RR 1.26, 95% CI 1.01-1.58). To assess whether the transient increase in risk among the deployed servicemen was related to factors associated with service (for example, the healthy warrior effect), the authors repeated the analysis beginning with followup on January 1, 1990. The rate of hospitalization among the deployed was lower during the prewar and deployment period, increased after the deployment period, and then decreased again. That suggests a healthy warrior effect. The overall relative risk for deployment in this analysis (which used the earlier followup date) was 0.89 (95% CI 0.75-1.06). In conclusion, Knoke and colleagues did not observe an association of Gulf War service with a risk of testicular cancer (RR 1.05, 95% CI 0.86-1.29) during almost 5 years of followup. The followup period was short for a cancer assessment, but it did include the age-range (22-31 years) when the disease might appear. No specific Gulf War exposures were assessed although risk by occupational group was calculated. There was some evidence of an association of testicular cancer with Gulf War deployment in a pilot cancer-registry-based study. Levine et al. (2005) matched a cohort of 697,000 Gulf War veterans (all personnel on active duty, in the reserves, and in the National Guard deployed to the Persian Gulf) and 746,248 non-Persian Gulf-region veterans (a stratified random sample of military personnel serving at the time of the conflict but not deployed) with the central cancer registries of New Jersey and the District of Columbia. Between 1991 and 1999, testicular cancer cases were identified in 17 deployed and 11 nondeployed for a crude proportional incidence rate (PIR) of 3.05 (95% CI 1.47-6.35). After adjustment for state of residence, deployment status, race, and age, the PIR was reduced to 2.33 (95% CI 0.95-5.70). The excess in the number of cases peaked 4-5 years after deployment, as opposed to the findings in the Knoke et al. study, where the excess was seen in the first few months after the soldiers returned home. The numbers of cancers included in this study are small, and no definitive conclusions can be made until additional registries are added to the overall study. All Cancers Macfarlane and colleagues (2003) assessed all first diagnoses of malignant cancer in a cohort of UK armed-services personnel. The deployed group consisted of all military personnel who served in the Persian Gulf in the period September 1990-June 1991 (n = 51,721). The comparison group was randomly selected from members of the armed services who were in service on January 1, 1991 but not deployed in the Persian Gulf, and was stratified to match the Persian Gulf cohort on age, sex, service branch, rank, and level of fitness for active service (n = 50,755). Followup was from April 1, 1991 until diagnosis of cancer, emigration, death, or July 31, 2002, whichever was earlier. Cancers were identified through the National Health Service Central Register. During followup, 270 incident cases of cancer among the Gulf War veterans

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 and 269 among the nondeployed group were identified; the RR—after adjustment for sex, age group, service branch, and rank—was 0.99 (95% CI 0.83-1.17). Thus, there was no evidence of an association of Gulf War Service with site-specific cancers. In subgroups of cohort members who participated in morbidity surveys that yielded more information on potential risk factors (28,518 Gulf War veterans and 20,829 nondeployed veterans), the RR was 1.11 (95% CI 0.86-1.44). That result did not change after adjustment for smoking or alcohol use, and there was no evidence of associations with exposure to pesticides; multiple vaccinations against anthrax, plague, and pertussis; or reported exposure to depleted uranium. See Table 5.1 for a summary of the cancer studies. Summary and Conclusion There is no consistent evidence of a higher overall incidence of cancer in Gulf War veterans than in nondeployed veterans. However, many veterans are young for cancer diagnosis and, for most cancers, the followup period after the Gulf War is probably too short to expect the onset of cancer. The incidence of and mortality from cancer in general, and brain and testicular cancer in particular, have been assessed in cohort studies. An association of brain-cancer mortality with possible nerve-agent exposure (as modeled by DOD’s exposure model of 2000) was observed in one study (Bullman et al. 2005). As discussed in more detail in Chapter 2, there are many uncertainties in the exposure model. Further followup is warranted to see whether the association with brain cancer holds up with time. Results for testicular cancer were mixed: one study concluded that there was no evidence of an excess risk, and another, a small registry-based study, suggested that there may be an increased risk. Although the results are inconsistent, the committee believes that followup is warranted to see whether such an association exists when more time has passed, as it is still early for the development of most cancers in Gulf War veterans.

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 TABLE 5.1 Cancer Outcomes Reference Design Population Outcomes Results Adjustments Comments or Limitations Brain cancer Bullman et al. 2005 (population from same source as Kang and Bullman 1996; Kang and Bullman 2001) Cohort mortality study US GWVs, grouped on basis of exposure to Khamisiyah chemical-munitions destruction (sarin gas) determined by 2000 plume model Exposed (n= 100,487) Unexposed (n=224,980) Unknown (n =25,574) Cause-specific mortality ascertained from BIRLS and NDI, followup from date left Gulf through 12/31/2000 Exposed (cases = 25) vs unexposed (cases = 27) Adj RR 1.94(95% CI 1.12-3.34); GWVs: Exposed 2+ days: RR 3.26 (95% CI 1.33-7.96) Exposed 1day: RR 1.72 (95% CI 0.95-3.10) 12.2 deaths/100,000 for each day exposure (95% CI 4.8-19.7) vs general population: Exposed 2+ days: SMR 2.13 (95% CI 0.78-4.63) Unexposed SMR 0.71 (95% CI 0.46-1.04) [similar results when limited to medical-record confirmed cases] Age at entry, race, sex, unit component and rank Latent period too soon (risk increases with time since exposure); multiple comparisons; death certificate diagnosis Testicular cancer Levine et al. 2005 Population-based survey—pilot study US, all personnel (including reserves) deployed to Gulf War (GWVs) and random sample of NDVs; GWVs (n=697,000) NDVs (n = 746,248) Cancers diagnosed 1991-1999 and registered by DC Cancer Registry or NJ State Cancer Registry GWVs (cases = 17) vs NDVs (cases = 11) (358 males with cancer) Crude PIR 3.05 (95% CI 1.47-6.35) Adj PIR 2.33 (95% CI 0.95-5.70) SIR (compared with SEER) for GWVs 1.42, NDVs 0.94; GWVs peaked 1995-1996, NDVs constant Age, state of residence, deployment status, race   Knoke et al. 1998 (followup of Cohort study US, all regular, active-duty male service members First diagnosis of testicular cancer at US military GWVs (cases = 134) vs NDVs (cases = 371) RR 1.05 (95% CI 0.86-1.29) Race or ethnicity, age, occupation Short followup time, but right age range;

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 Reference Design Population Outcomes Results Adjustments Comments or Limitations Gray et al. 1996)   GWVs (n = 517,223) NDVs (n = 1,291,323) hospitals worldwide 7/31/1991-4/1/1996     no specific exposures evaluated; military hospitals only Gray et al. 1996 Cohort study US, regular, active-duty military personnel deployed in gulf and randomly selected nondeployed personnel GWVs (n = 579,931) NDVs (n = 700,000) Cause-specific hospitalizations in military hospitals 10/1/1988-7/31/1990, 8/1/1991-12/31/1991, 1992, 1/1/1993-9/30/1993 1991 followup period GWVs (cases = 29) vs NDVs (cases = 14) RR 2.12 (95% CI 1.11-4.02) Later followup periods No excess risk Age, sex Active duty personnel only; short followup All cancers Macfarlane et al. 2003 (followup of Macfarlane et al. 2000) Cohort study UK armed service personnel GWVs (n = 51,721) NDVs (n = 50,755); Subgroup participated in morbidity study with information on risk factors and exposures (GWVs = 28,518, NDVs = 20,829) First diagnosis of cancer 4/1/1991-7/31/2002 identified through NHSCR GWVs (cases = 270) vs NDVs (cases = 269) Main study: RR 0.99 (95% CI 0.83-1.17) Morbidity study subgroup: RR 1.12 (95% CI 0.86-1.45) Main analysis:. sex, age group, service branch, rank; Morbidity study: smoking, alcohol Short followup; low age; grouped all cancer sites because of small numbers Kang and Bullman 2001 (also in Gray et al. 1996—followup thru 1993) Cohort mortality study US, all military personnel in Gulf before 3/1/1991 and random sample of nondeployed GWV (n = 621,902) NDV (n = 746,248) Cause specific mortality ascertained from BIRLS, death certificates and NDI; followup from date left gulf through 12/31/1997 Males: GWVs (cases = 477) vs controls (cases = 860): adjusted RR 0.90 (95% CI 0.81-1.01) Females: GWVs (cases= 49) vs controls (cases = 103): adjusted RR 1.11 (95% CI 0.78-1.57) Age, race, branch of service, unit component, marital status Short latency; low age range; Death certificates

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 NOTE: BIRLS = Beneficiary Identification Records Locator System; GWV = Gulf War veteran; NDI =National Death Index; NDV = nondeployed veteran; NHSCR = National Health Service Central Register; PIR = proportional incidence ratio; SEER = Surveillance Epidemiology and End Results; SIR = standardized incidence ratio; SMR = standardized mortality ratio.

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 MENTAL AND BEHAVIORAL DISORDERS (ICD-10 F00-F99) War is a known health risk for psychiatric conditions (Pizarro et al. 2006; Wessely 2005). The description of the extent and type of psychiatric affliction and its course has depended on the development of modern psychiatric diagnostic systems and epidemiologic methods. The development of a structured diagnostic system and diagnostic instruments has facilitated the diagnosis of behavioral disorders. Moreover, the prevalence of psychiatric disorders in epidemiologic samples drawn from the general population has become available (Kessler et al. 2005) and provides baseline data with which to compare data from specific inquiries. Thus, after the Persian Gulf War, many methodologic and scientific details were in place to support a sound assessment of the psychologic consequences of war. The Persian Gulf War was highly unusual in that the air war lasted 40 days and the ground war concluded in 5 days, so there was a limited theater and set of conditions amenable in many respects to scientific study. In fact, each of the large cohort studies of Gulf War veterans, described in Chapter 4, included items pertaining to mental health. Nested within them was analysis of mental health characteristics based on direct interview techniques or validated symptom scales. Types of psychiatric ill health that could be associated with the Gulf War, particularly posttraumatic stress disorder (PTSD), were predicted on the basis of their descriptions from previous wars (O'Toole et al. 1996; Roy-Byrne et al. 2004). As background, psychiatric disorders in the general population are common, as well as disabling and chronic (Department of Health and Human Services 1999). Diagnosable psychiatric disorders are found in about 20% of the US population, but their prevalence in military populations is lower, largely as a result of the healthy-warrior effect. Psychiatric disorders can be grouped into several large classes, for example, mood disorders (that is, depression and bipolar disorder); anxiety disorders (that is, generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, and social phobia); and substance use disorders (for example, abuse of drugs and/or alcohol). The specification of characteristics of mental diagnoses has made research on their incidence and prevalence possible (Tasman et al. 2003). Depression, a type of mood disorder, is characterized by lifelong vulnerability to episodes of depressed mood and loss of interest and pleasure in daily activities. Some symptoms of clinical depression include sleeping too little or too much, reduced appetite and weight loss or increased appetite and weight gain, restlessness, irritability, difficulty concentrating, feeling guilty, hopeless or worthless, and thoughts of suicide or death. Depression is categorized as major depressive disorder (MDD) or, when it accompanies mania, as bipolar disorder. PTSD is a subtype of anxiety disorder; it occurs after exposure to a traumatic event and is diagnosed when a person manifests severe distress on recollection of the event, avoids the situation, and suffers symptoms of anxiety in daily life. Substance abuse is defined as a maladaptive pattern of substance use (there are many types of abused substances) that results in a failure to fulfill major social roles (such as work or family-care performance), that involves use of the substance despite physical hazards and in association with legal consequences, and that involves use despite deleterious social and interpersonal consequences. The prevalence of those disorders in the general population is addressed in the US National Comorbidity Survey Replication, a nationally representative face-to-face household

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 survey conducted in the period February 2001-April 2003 (Kessler et al. 2005). The data show that the prevalence estimates for all anxiety disorders were 28.8% (lifetime) and 18.1% (in the last 2 months); for all mood disorders, 20.8% (lifetime) and 9.5% (in the last 12 months); and for substance use disorders, 14.6% (lifetime) and 3.8% (in the last 12 months). Those prevalence estimates are generally higher than those in deployed veterans exposed to war and much higher than in the control veteran populations. It is expected, however, that the military population is healthier than a broad epidemiologic population-based sample, given their age, general health, and military screening. Primary Studies In general, each of the large epidemiologic studies of Gulf War veterans’ health included items pertaining to mental health. Moreover, there was often a nested case-control study of mental health characteristics in the primary epidemiologic cohort studies that used direct interview techniques. The studies reviewed here drew their data from the direct-interview studies from the large Gulf War cohort studies reviewed in Chapter 4, and often used validated instruments to complement the interview. Black et al. (2004b) reanalyzed the population-based, telephone interviews from the Iowa cohort of 4,886 randomly selected veterans (military and reserve), deployed and nondeployed (Iowa Persian Gulf Study Group 1997). The initial cohort study had uncovered higher than anticipated levels of anxiety; therefore, this analysis of the interview data looked more carefully into the features of anxiety in that population. The original cohort was interviewed by telephone using the Primary Care Evaluation of Mental Disorders (PRIME-MD). The Post Traumatic Stress Disorder Checklist-Military (PCL-M) was used for the diagnosis of PTSD (Blanchard et al. 1996; Dobie et al. 2002; Forbes et al. 2001; Weathers and Ford 1996); the CAGE3 was used to estimate alcoholism, and structured questions identified medical conditions and military preparedness. The study identified over a twofold increase in the prevalence of generalized anxiety disorder, panic disorder, PTSD, and any anxiety disorder in veterans deployed to the Gulf War vs the nondeployed. Nearly 6% of deployed veterans met criteria for having any anxiety disorder, compared with nearly 3% of nondeployed veterans (odds ratio [OR] 2.3, 95% CI 1.5-3.5). Participation in combat was an important independent risk factor for the development of anxiety disorders, particularly PTSD (OR 2.1, 95% CI 1.7-4.2). Anxious Gulf War veterans were more likely to have had a pre-existing psychiatric condition, to have taken medications associated with a psychiatric diagnosis, or to have had a previous psychiatric hospitalization. Anxiety conditions occurred with several psychiatric and some medical conditions. In a separate analysis of the same population based on the telephone survey data, Barrett et al. (2002) used the PCL-M to examine PTSD in the Gulf War veterans. Each of 17 items was rated on a 1-5 severity scale and the scores were summed. A score of 50 or more defined PTSD. Symptoms of physical health were solicited and recognition assessment of medical problems was obtained. PTSD-positive veterans had a mean score of 58.7, whereas those without PTSD had a mean score of 19.7. The PTSD score was significantly associated with the magnitude of other physical illness and negative emotional characteristics. 3 CAGE = acronym for four questions: Have you ever thought you should Cut down on your drinking? Have you ever felt Annoyed by others’ criticism of your drinking? Have you ever felt Guilty about your drinking? Do you have a morning Eye-opener?

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 In a nested case-comparison study, Black et al. (2004a) conducted face-to-face interviews with 602 veterans in 1999-2002. They used the Structured Clinical Interview for DSM-IV (SCID) with a random group of veterans drawn from strata of the PRIME-MD-interviewed group who reported one or more of the following symptom-based conditions during their previous interview: depression (major or minor depression), widespread chronic pain (established criteria for generalized, severe, and chronic pain), and cognitive dysfunction (amnesia or cognitive impairment of a moderate and prolonged intensity). Veterans were stratified by each symptom combination (one, two, or all) and by deployed or non-deployed status. Controls did not have any of those conditions and might have been deployed or not deployed. The veterans were selected randomly for interview from each stratum to optimize the match between cases and controls; interviewers were trained in the use of the diagnostic instruments. Personality disorders were assessed with the SNAP (Schedule for Nonadaptive and Adaptive Personality). Level of functioning was assessed using the SF-36 (36-Item Short-Form Health Survey). The Whiteley Index was used to determine hypochondriasis. The study found a 32% rate of lifetime depression diagnosis (all types) and that was the same in deployed and nondeployed veterans. There were few diagnostic differences between the depressed deployed and the depressed nondeployed veterans, except for PTSD (27.3% in deployed, 5.0% in non-deployed), anxiety disorders (51.5% deployed and 25.0% non-deployed) and any disorder (68.2% deployed and 51.7% non-deployed). The deployed depressed veterans were more likely to have a diagnosis of any substance-use disorder (69.7% in deployed vs 51.7% in non-deployed). What was most surprising about the direct interview analysis was that there was so little difference between the deployed and the nondeployed veterans in aspects of depression (36.6% vs 30.3%). Most differences were found in anxiety disorder (51.5% vs 25.0%) as noted above. Kang et al. (2003) conducted a population-based stratified random sample of 15,000 US Gulf War troops compared to a similar sample of troops deployed elsewhere. Phase 1 was a mail survey and phase 2 was a telephone-based survey of PTSD symptoms and chronic fatigue (CFS) symptoms. In the interview cohort, 12.1% of Gulf War veterans and 4.3% of other veterans had symptoms of PTSD, with an adjusted OR of 3.1 (95% CI 2.7-3.4) for PTSD in the Gulf War group; and 6% of the Gulf War veterans and 1.2% of the other veterans (OR 4.8) had CFS symptoms. It was interesting to note that PTSD symptoms showed a monotonic relationship to intensity of war stress, whereas the CFS symptoms did not show any relationship to war stress. The rates of PTSD tracked rates of stressors closely. Deployment, but not war stress, was associated with CFS symptoms. Wolfe et al. (1999a; 1999b), and Proctor et al. (1998) examined cohorts of veterans randomly sampled and stratified from the Fort Devens and New Orleans-deployed Gulf War veterans, as well as a cohort deployed to Germany (a noncombat area). The Gulf War-deployed veterans from Fort Devens were followed longitudinally from the day of their arrival home from the gulf (time 1) to about 2 years later (time 2) with a 78% participation rate. The Fort Devens cohort was mainly male, Caucasian, and National Guard; rates of PTSD measured at time 1 were 3%. From those cohorts, stratified random samples were selected for closer study with direct interview (220 of the Fort Devens cohort, 73 of the New Orleans cohort, and 48 of the Germany-deployed). The researchers used questionnaires (the 52-item expanded Health Symptoms Checklist [HSC] and the Expanded Combat Exposure Scale), a neuropsychologic test battery, an environmental interview, and psychiatric diagnostic instruments (the Clinician-Administered

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 PTSD Scale [CAPS] or the Mississippi Scale for Combat-Related PTSD) (Proctor et al. 1998). Current PTSD (time 2) was diagnosed in 8.1% of the Fort Devens group, 7.6% of the New Orleans group, and none of the Germany group. Health status and function were lower in the Fort Devens cohort. The three most prevalent symptoms in the Fort Devens group were “forgetfulness,” “fatigue,” and “unsatisfactory sleep.” Wolfe et al. (1999b) also recruited cases from the Fort Devens and Germany cohorts with a stratified random-sampling strategy (148 from the Fort Devens group, 73 from the New Orleans group, and 48 from the Germany group). They used the Laufer Combat Scale to assess exposure to combat situations and the Mississippi Scale for Combat-Related PTSD to assess PTSD. The deployed Fort Devens group had higher levels of current and lifetime PTSD and current and lifetime MDD than the Germany group; little else regarding psychiatric function was different between the groups. Compared with the PTSD prevalence in the general population (7.8%) (Kessler et al. 1995), the Germany group (controls) had much lower rates of PTSD. However, the low prevalence estimates in the controls increases from zero to 5-8% when the veterans are deployed to active war situations. A strength of this study is that it is characterized by direct interview. A different study of the cohort examined above (Wolfe et al. 1999a) looked at the course and predictors of PTSD and found that there was a higher rate of PTSD at time 2 (8%) than at time 1 (3%), indicating the development of new cases. Responders at time 2 were more likely to be younger, belong to racial minorities, and be deployed; however, the absence of differences in PTSD rates due to those characteristics indicates a lack of selection bias at time 2. Women were significantly more likely to have PTSD (OR 3.2 at time 1; OR 2.3 at time 2), although their numbers were very low at each assessment. Brailey et al. (1998) studied Gulf War veterans on their return from service (an average of 9 months after their return) with a face-to-face debriefing and psychologic assessment, comparing Gulf War-deployed (n = 876) with nondeployed veterans (n = 396 mobilized but not deployed), including National Guard and reserve troops. A subset of 349 received a followup assessment an average of 16 months later. They used standard psychiatric rating scales for their assessments including: the Beck Depression Inventory (BDI), the State Anger, State Anxiety, the Brief Symptom Inventory (BSI) Depression, BSI Anxiety, BSI Hostility, and the Health Symptom Checklist (HSC). The deployed veterans had higher scores than the nondeployed on the BDI, the State Anger, the BSI Anxiety, and the HSC. When the Gulf War-deployed veterans were reassessed on average of 16 months later, they showed increases on all scales, including the BDI, the State Anger, the BSI Anxiety, the BSI Hostility, HSC, and on both PTSD scales (the 17-item DSM-III R PTSD Checklist and the Mississippi Scale for Desert Storm War Zone Personnel). They showed increased rates of depression (6.9% to 13.8%), PTSD (2.3% to 10.6%), and hostility (4.9% to 13.8%). The authors correlated war stress with those symptoms and found that the higher the war-zone stress, the more severe the depressive and anxiety symptoms. Troops who were assigned to high-risk activities, such as grave registration, showed a high prevalence of PTSD (46%), depression (25%), and substance abuse (13%). Goss Gilroy et al. (1998) assessed all 3,113 Canadian Gulf War veterans deployed to the war zone and a comparison group of nondeployed veterans with a mail questionnaire; the methodologic details are in Chapter 4. Using the PCL-M, the investigators found that symptoms of PTSD were 2.5 times more prevalent in the deployed than in the nondeployed veterans (OR 2.69, 95% CI 1.7-4.2). Using the PRIME-MD, the investigators found that the deployed had

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 Doyle P, Maconochie N, Davies G, Maconochie I, Pelerin M, Prior S, Lewis S. 2004. Miscarriage, stillbirth and congenital malformation in the offspring of UK veterans of the first Gulf war. International Journal of Epidemiology 33(1):74-86. Draxler RR, McQueen JT, Stunder BJB. 1994. An evaluation of air pollutant exposures due to the 1991 Kuwait oil fires using a Lagrangian model. Atmospheric Environment 28(13):2197-2210. Eisen SA, Kang HK, Murphy FM, Blanchard MS, Reda DJ, Henderson WG, Toomey R, Jackson LW, Alpern R, Parks BJ, Klimas N, Hall C, Pak HS, Hunter J, Karlinsky J, Battistone MJ, Lyons MJ. 2005. Gulf War veterans' health: Medical evaluation of a US cohort. Annals of Internal Medicine 142(11):881-890. Epstein KR. 1995. The chronically fatigued patient. Medical Clinics of North America 79(2):315-327. Everitt B, Ismail K, David AS, Wessely S. 2002. Searching for a Gulf War syndrome using cluster analysis.Psychological Medicine 32(8):1371-1378. Fiedler N, Kipen H, Natelson B, Ottenweller J. 1996. Chemical sensitivities and the Gulf War: Department of Veterans Affairs Research Center in basic and clinical science studies of environmental hazards. Regulatory Toxicology and Pharmacology 24(1 Pt 2):S129-S138. Forbes AB, McKenzie DP, Mackinnon AJ, Kelsall HL, McFarlane AC, Ikin JF, Glass DC, Sim MR. 2004. The health of Australian veterans of the 1991 Gulf War: Factor analysis of self-reported symptoms. Occupational and Environmental Medicine 61(12):1014-1020. Forbes D, Creamer M, Biddle D. 2001. The validity of the PTSD checklist as a measure of symptomatic change in combat-related PTSD. Behaviour Research and Therapy 39(8):977-986. Franse LV, Valk GD, Dekker JH, Heine RJ, van Eijk JT. 2000. 'Numbness of the feet' is a poor indicator for polyneuropathy in Type 2 diabetic patients. Diabetic Medicine 17(2):105-110. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. 1994. The chronic fatigue syndrome: A comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Annals of Internal Medicine 121(12):953-959. Fukuda K, Nisenbaum R, Stewart G, Thompson WW, Robin L, Washko RM, Noah DL, Barrett DH, Randall B, Herwaldt BL, Mawle AC, Reeves WC. 1998. Chronic multisymptom illness affecting Air Force veterans of the Gulf War. Journal of the American Medical Association 280(11):981-988. Gackstetter G, DeBakey S, Cowan D, Paxton M, Weaver R, Lange J, Kang H, Bullman T, Lincoln A, Hooper T. 2002. Fatal motor vehicle crashes among veterans of the gulf war era: A nested case-control study. Annals of Epidemiology 12(7):509. Gillespie N, Kirk KM, Heath AC, Martin NG, Hickie I. 1999. Somatic distress as a distinct psychological dimension. Social Psychiatry and Psychiatric Epidemiology 34(9):451-458. Goldenberg DL. 1999. Fibromyalgia syndrome a decade later: What have we learned? Archives of Internal Medicine 159(8):777-785. Goldstein G, Beers SR, Morrow LA, Shemansky WJ, Steinhauer SR. 1996. A preliminary neuropsychological study of Persian Gulf veterans. Journal of the International Neuropsychological Society 2(4):368-371.

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 Goshorn RK. 1998. Chronic fatigue syndrome: A review for clinicians. Seminars in Neurology 18(2):237-242. Goss Gilroy Inc. 1998. Health Study of Canadian Forces Personnel Involved in the 1991 Conflict in the Persian Gulf. Ottawa, Canada: Goss Gilroy Inc. Department of National Defence. Graveling RA, Pilkington A, George JP, Butler MP, Tannahill SN. 1999. A review of multiple chemical sensitivity. Occupational and Environmental Medicine 56(2):73-85. Gray GC, Coate BD, Anderson CM, Kang HK, Berg SW, Wignall FS, Knoke JD, Barrett-Connor E. 1996. The postwar hospitalization experience of U.S. veterans of the Persian Gulf War. New England Journal of Medicine 335(20):1505-1513. Gray GC, Kaiser KS, Hawksworth AW, Hall FW, Barrett-Connor E. 1999a. Increased postwar symptoms and psychological morbidity among U.S. Navy Gulf War veterans. American Journal of Tropical Medicine and Hygiene 60(5):758-766. Gray GC, Smith TC, Knoke JD, Heller JM. 1999b. The postwar hospitalization experience of Gulf War Veterans possibly exposed to chemical munitions destruction at Khamisiyah, Iraq. American Journal of Epidemiology 150(5):532-540. Gray GC, Smith TC, Kang HK, Knoke JD. 2000. Are Gulf War veterans suffering war-related illnesses? Federal and civilian hospitalizations examined, June 1991 to December 1994. American Journal of Epidemiology 151(1):63-71. Gray GC, Reed RJ, Kaiser KS, Smith TC, Gastanaga VM. 2002. Self-reported symptoms and medical conditions among 11,868 Gulf War-era veterans: The Seabee Health Study. American Journal of Epidemiology 155(11):1033-1044. Haley RW. 2003. Excess incidence of ALS in young Gulf War veterans. Neurology 61(6):750-756. Haley RW, Hom J, Roland PS, Bryan WW, Van Ness PC, Bonte FJ, Devous MD Sr, Mathews D, Fleckenstein JL, Wians FH Jr, Wolfe GI, Kurt TL. 1997a. Evaluation of neurologic function in Gulf War veterans. A blinded case-control study. Journal of the American Medical Association 277(3):223-230. Haley RW, Kurt TL, Hom J. 1997b. Is there a Gulf War Syndrome? Searching for syndromes by factor analysis of symptoms. Journal of the American Medical Association 277(3):215-222. Haley RW, Billecke S, La Du BN. 1999. Association of low PON1 type Q (type A) arylesterase activity with neurologic symptom complexes in Gulf War veterans. Toxicology and Applied Pharmacology 157(3):227-233. Haley RW, Luk GD, Petty F. 2001. Use of structural equation modeling to test the construct validity of a case definition of Gulf War syndrome: Invariance over developmental and validation samples, service branches and publicity. Psychiatry Research 102(2):175-200. Haley RW, Fleckenstein JL, Marshall WW, McDonald GG, Kramer GL, Petty F. 2000a. Effect of basal ganglia injury on central dopamine activity in Gulf War syndrome: Correlation of proton magnetic resonance spectroscopy and plasma homovanillic acid levels. Archives of Neurology 57(9):1280-1285. Haley RW, Marshall WW, McDonald GG, Daugherty MA, Petty F, Fleckenstein JL. 2000b. Brain abnormalities in Gulf War syndrome: Evaluation with 1H MR spectroscopy. Radiology 215(3):807-817.

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 Haley RW, Vongpatanasin W, Wolfe GI, Bryan WW, Armitage R, Hoffmann RF, Petty F, Callahan TS, Charuvastra E, Shell WE, Marshall WW, Victor RG. 2004. Blunted circadian variation in autonomic regulation of sinus node function in veterans with Gulf War syndrome. American Journal of Medicine 117(7):469-478. Hallman WK, Kipen HM, Diefenbach M, Boyd K, Kang H, Leventhal H, Wartenberg D. 2003. Symptom patterns among Gulf War registry veterans. American Journal of Public Health 93(4):624-630. Hardt J, Buchwald D, Wilks D, Sharpe M, Nix WA, Egle UT. 2001. Health-related quality of life in patients with chronic fatigue syndrome: An international study. Journal of Psychosomatic Research 51(2):431-434. Higgins EM, Ismail K, Kant K, Harman K, Mellerio J, Du Vivier AW, Wessely S. 2002. Skin disease in Gulf war veterans. QJM 95(10):671-676. Holmes DT, Tariot PN, Cox C. 1998. Preliminary evidence of psychological distress among reservists in the Persian Gulf War. Journal of Nervous and Mental Disease 186(3):166-173. Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S, et al. 1988. Chronic fatigue syndrome: A working case definition. Annals of Internal Medicine 108(3):387-389. Hom J, Haley RW, Kurt TL. 1997. Neuropsychological correlates of Gulf War syndrome. Archives of Clinical Neuropsychology 12(6):531-544. Horner RD, Kamins KG, Feussner JR, Grambow SC, Hoff-Lindquist J, Harati Y, Mitsumoto H, Pascuzzi R, Spencer PS, Tim R, Howard D, Smith TC, Ryan MA, Coffman CJ, Kasarskis EJ. 2003. Occurrence of amyotrophic lateral sclerosis among Gulf War veterans. Neurology 61(6):742-749. Hotopf M, Mackness MI, Nikolaou V, Collier DA, Curtis C, David A, Durrington P, Hull L, Ismail K, Peakman M, Unwin C, Wessely S, Mackness B. 2003. Paraoxonase in Persian Gulf War veterans. Journal of Occupational and Environmental Medicine 45(7):668-675. Hotopf M, David A, Hull L, Nikalaou V, Unwin C, Wessely S. 2004. Risk factors for continued illness among Gulf War veterans: A cohort study. Psychological Medicine 34(4):747-754. Hull L, Farrin L, Unwin C, Everitt B, Wykes T, David AS. 2003. Anger, psychopathology and cognitive inhibition: A study of UK servicemen. Personality and Individual Differences 35(5):1211. Ikin JF, Sim MR, Creamer MC, Forbes AB, McKenzie DP, Kelsall HL, Glass DC, McFarlane AC, Abramson MJ, Ittak P, Dwyer T, Blizzard L, Delaney KR, Horsley KWA, Harrex WK, Schwarz H. 2004. War-related psychological stressors and risk of psychological disorders in Australian veterans of the 1991 Gulf War. British Journal of Psychiatry 185:116-126. Iowa Persian Gulf Study Group. 1997. Self-reported illness and health status among Gulf War veterans: A population-based study. Journal of the American Medical Association 277(3):238-245. Ishoy T, Suadicani P, Guldager B, Appleyard M, Gyntelberg F. 1999a. Risk factors for gastrointestinal symptoms. The Danish Gulf War Study. Danish Medical Bulletin 46(5):420-423.

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 Ishoy T, Suadicani P, Guldager B, Appleyard M, Hein HO, Gyntelberg F. 1999b. State of health after deployment in the Persian Gulf. The Danish Gulf War Study. Danish Medical Bulletin 46(5):416-419. Ishoy T, Andersson AM, Suadicani P, Guldager B, Appleyard M, Gyntelberg F, Skakkebaek NE, Danish Gulf War Study. 2001a. Major reproductive health characteristics in male Gulf War Veterans. The Danish Gulf War Study. Danish Medical Bulletin 48(1):29-32. Ishoy T, Suadicani P, Andersson A-M, Guldager B, Appleyard M, Skakkebaek N, Gyntelberg F. 2001b. Prevalence of male sexual problems in the Danish Gulf War Study. Scandinavian Journal of Sexology 4(1):43-55. Ismail K, Blatchley N, Hotopf M, Hull L, Palmer I, Unwin C, David A, Wessely S. 2000. Occupational risk factors for ill health in Gulf veterans of the United Kingdom. Journal of Epidemiology and Community Health 54(11):834-838. Ismail K, Everitt B, Blatchley N, Hull L, Unwin C, David A, Wessely S. 1999. Is there a Gulf War syndrome? Lancet 353(9148):179-182. Jason LA, Taylor RR, Kennedy CL. 2000. Chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivities in a community-based sample of persons with chronic fatigue syndrome-like symptoms. Psychosomatic Medicine 62(5):655-663. Joseph TK, Foster L, Pasquina PF. 2004. Decreased prevalence of peripheral nerve pathology by electrodiagnostic testing in Gulf War veterans. Military Medicine 169(11):868-871. Kang HK, Bullman TA. 1996. Mortality among US veterans of the Persian Gulf War. New England Journal of Medicine 335(20):1498-1504. Kang HK, Bullman TA. 2001. Mortality among US veterans of the Persian Gulf War: 7-year follow-up. American Journal of Epidemiology 154(5):399-405. Kang HK, Mahan CM, Lee KY, Magee CA, Murphy FM. 2000. Illnesses among United States veterans of the Gulf War: A population-based survey of 30,000 veterans. Journal of Occupational and Environmental Medicine 42(5):491-501. Kang H, Magee C, Mahan C, Lee K, Murphy F, Jackson L, Matanoski G. 2001. Pregnancy outcomes among US Gulf War veterans: A population-based survey of 30,000 veterans. Annals of Epidemiology 11(7):504-511. Kang HK, Mahan CM, Lee KY, Murphy FM, Simmens SJ, Young HA, Levine PH. 2002. Evidence for a deployment-related Gulf War syndrome by factor analysis. Archives of Environmental Health 57(1):61-68. Kang HK, Natelson BH, Mahan CM, Lee KY, Murphy FM. 2003. Post-traumatic stress disorder and chronic fatigue syndrome-like illness among Gulf War veterans: A population-based survey of 30,000 veterans. American Journal of Epidemiology 157(2):141-148. Karlinsky JB, Blanchard M, Alpern R, Eisen SA, Kang H, Murphy FM, Reda DJ. 2004. Late prevalence of respiratory symptoms and pulmonary function abnormalities in Gulf War I Veterans. Archives of Internal Medicine 164(22):2488-2491. Kelsall HL, Sim MR, Forbes AB, Glass DC, McKenzie DP, Ikin JF, Abramson MJ, Blizzard L, Ittak P. 2004a. Symptoms and medical conditions in Australian veterans of the 1991 Gulf War: Relation to immunisations and other Gulf War exposures. Occupational and Environmental Medicine 61(12):1006-1013.

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 Kelsall HL, Sim MR, Forbes AB, McKenzie DP, Glass DC, Ikin JF, Ittak P, Abramson MJ. 2004b. Respiratory health status of Australian veterans of the 1991 Gulf War and the effects of exposure to oil fire smoke and dust storms. Thorax 59(10):897-903. Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. 1995. Posttraumatic stress disorder in the National Comorbidity Survey. Archives of General Psychiatry 52(12):1048-1060. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. 2005. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62(6):617-627. Kipen HM, Fiedler N. 2002. Environmental factors in medically unexplained symptoms and related syndromes: The evidence and the challenge. Environmental Health Perspectives 110 (S4):597-599. Knoke JD, Gray GC. 1998. Hospitalizations for unexplained illnesses among US veterans of the Persian Gulf War. Emerging Infectious Diseases 4(2):211-219. Knoke JD, Gray GC, Garland FC. 1998. Testicular cancer and Persian Gulf War service. Epidemiology 9(6):648-653. Knoke JD, Smith TC, Gray GC, Kaiser KS, Hawksworth AW. 2000. Factor analysis of self-reported symptoms: Does it identify a Gulf War syndrome? American Journal of Epidemiology 152(4):379-388. Komaroff AL, Fagioli LR, Doolittle TH, Gandek B, Gleit MA, Guerriero RT, Kornish RJ 2nd, Ware NC, Ware JE Jr, Bates DW. 1996. Health status in patients with chronic fatigue syndrome and in general population and disease comparison groups. American Journal of Medicine 101(3):281-90. Kreutzer R, Neutra RR, Lashuay N. 1999. Prevalence of people reporting sensitivities to chemicals in a population-based survey. American Journal of Epidemiology 150(1):1-12. Kroenke K, Koslowe P, Roy M. 1998. Symptoms in 18,495 Persian Gulf War veterans. Latency of onset and lack of association with self-reported exposures. Journal of Occupational and Environmental Medicine 40(6):520-528. Lange G, Tiersky LA, Scharer JB, Policastro T, Fiedler N, Morgan TE, Natelson BH. 2001. Cognitive functioning in Gulf War Illness. Journal of Clinical and Experimental Neuropsychology 23(2):240-249. Lange JL, Schwartz DA, Doebbeling BN, Heller JM, Thorne PS. 2002. Exposures to the Kuwait oil fires and their association with asthma and bronchitis among gulf war veterans. Environmental Health Perspectives 110(11):1141-1146. Levine PH, Young HA, Simmens SJ, Rentz D, Kofie VE, Mahan CM, Kang HK. 2005. Is testicular cancer related to Gulf War deployment? Evidence from a pilot population-based study of Gulf War era veterans and cancer registries. Military Medicine 170(2):149-153. Lezak M, Loring D, Howieson D. 2004. Neuropsychological Assessment. New York: Oxford University Press. Lindem K, Heeren T, White RF, Proctor SP, Krengel M, Vasterling J, Sutker PB, Wolfe J, Keane TM. 2003a. Neuropsychological performance in Gulf War era veterans: Traumatic stress symptomatology and exposure to chemical-biological warfare agents. Journal of Psychopathology and Behavioral Assessment 25(2):105-119.

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 Lindem K, Proctor SP, Heeren T, Krengel M, Vasterling J, Sutker PB, Wolfe J, Keane TM, White RF. 2003b. Neuropsychological performance in Gulf War era veterans: Neuropsychological symptom reporting. Journal of Psychopathology and Behavioral Assessment 25(2):121-127. Lindem K, White RF, Heeren T, Proctor SP, Krengel M, Vasterling J, Wolfe J, Sutker PB, Kirkley S, Keane TM. 2003c. Neuropsychological performance in Gulf War era veterans: Motivational factors and effort. Journal of Psychopathology and Behavioral Assessment 25 (2):129-138. Lucchini R, Albini E, Benedetti L, Alessio L. 2005. Neurobehavioral science in hazard identification and risk assessment of neurotoxic agents—what are the requirements for further development? International Archives of Occupational and Environmental Health 78(6):427-437. Macfarlane GJ, Thomas E, Cherry N. 2000. Mortality among UK Gulf War veterans. Lancet 356(9223):17-21. Macfarlane GJ, Biggs AM, Maconochie N, Hotopf M, Doyle P, Lunt M. 2003. Incidence of cancer among UK Gulf war veterans: Cohort study. British Medical Journal 327 (7428):1373-1375. Mackness B, Mackness MI, Arrol S, Turkie W, Durrington PN. 1997. Effect of the molecular polymorphisms of human paraoxonase (PON1) on the rate of hydrolysis of paraoxon. British Journal of Pharmacology 122(2):265-268. Maconochie N, Doyle P, Carson C. 2004. Infertility among male UK veterans of the 1990-1 Gulf war: Reproductive cohort study. British Medical Journal 329(7459):196-201. Magruder KM, Frueh BC, Knapp RG, Davis L, Hamner MB, Martin RH, Gold PB, Arana GW. 2005. Prevalence of posttraumatic stress disorder in Veterans Affairs primary care clinics. General Hospital Psychiatry 27(3):169-179. Matarazzo JD. 1972. Wechsler's Measurement and Appraisal of Adult Intelligence. 5th ed. Baltimore, Md: Williams and Wilkins McCauley LA, Joos SK, Lasarev MR, Storzbach D, Bourdette DN. 1999. Gulf War unexplained illnesses: Persistence and unexplained nature of self-reported symptoms. Environmental Research 81(3):215-223. McCauley LA, Lasarev M, Sticker D, Rischitelli DG, Spencer PS. 2002. Illness experience of Gulf War veterans possibly exposed to chemical warfare agents. American Journal of Preventive Medicine 23(3):200-206. McGuire V, Longstreth WT Jr, Koepsell TD, van Belle G. 1996a. Incidence of amyotrophic lateral sclerosis in three counties in western Washington state. Neurology 47(2):571-573. McKenzie DP, Ikin JF, McFarlane AC, Creamer M, Forbes AB, Kelsall HL, Glass DC, Ittak P, Sim MR. 2004. Psychological health of Australian veterans of the 1991 Gulf War: An assessment using the SF-12, GHQ-12 and PCL-S. Psychological Medicine 34(8):1419-1430. McQueen JT, Draxler RR. 1994. Evaluation of model back trajectories of the Kuwait oil fires smoke plume using digital satellite data. Atmospheric Environment 28(13):2159-2174. Merck Manuals Online Medical Library. Polyneuropathy: Peripheral Nerve Disorders. [Online]. Available: http://www.merck.com/mmhe/sec06/ch095/ch095h.html [accessed July 11, 2006].

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 Nelson LM, McGuire V, Longstreth WT Jr, Matkin C. 2000. Population-based case-control study of amyotrophic lateral sclerosis in western Washington State. I. Cigarette smoking and alcohol consumption. American Journal of Epidemiology 151(2):156-163. Nicolson GL, Nasralla MY, Haier J, Pomfret J. 2002. High frequency of systemic mycoplasmal infections in Gulf War veterans and civilians with Amyotrophic Lateral Sclerosis (ALS). Journal of Clinical Neuroscience 9(5):525-529. Nimnuan C, Rabe-Hesketh S, Wessely S, Hotopf M. 2001. How many functional somatic syndromes? Journal of Psychosomatic Research 51(4):549-557. NINDS (National Institute of Neurological Disorders and Stroke). 2006. National Institute of Neurological Disorders and Stroke. [Online]. Available: http://www.ninds.nih.gov/ [accessed January 17, 2006]. Nisenbaum R, Reyes M, Mawle AC, Reeves WC. 1998. Factor analysis of unexplained severe fatigue and interrelated symptoms: Overlap with criteria for chronic fatigue syndrome. American Journal of Epidemiology 148(1):72-77. Nisenbaum R, Ismail K, Wessely S, Unwin C, Hull L, Reeves WC. 2004. Dichotomous factor analysis of symptoms reported by UK and US veterans of the 1991 Gulf War. Population Health Metrics 2(1):8. O'Toole BI, Marshall RP, Grayson DA, Schureck RJ, Dobson M, Ffrench M, Pulvertaft B, Meldrum L, Bolton J, Vennard J. 1996. The Australian Vietnam Veterans Health Study: III. psychological health of Australian Vietnam veterans and its relationship to combat. International Journal of Epidemiology 25(2):331-340. Pearce JM. 2004. Myofascial pain, fibromyalgia or fibrositis? European Neurology 52(2):67-72. Penman AD, Tarver RS, Currier MM. 1996. No evidence of increase in birth defects and health problems among children born to Persian Gulf War Veterans in Mississippi. Military Medicine 161(1):1-6. Petruccelli BP, Goldenbaum M, Scott B, Lachiver R, Kanjarpane D, Elliott E, Francis M, McDiarmid MA, Deeter D. 1999. Health effects of the 1991 Kuwait oil fires: A survey of US army troops. Journal of Occupational and Environmental Medicine 41(6):433-439. Pizarro J, Silver RC, Prause J. 2006. Physical and mental health costs of traumatic war experiences among Civil War veterans. Archives of General Psychiatry 63(2):193-200. Proctor SP, Heeren T, White RF, Wolfe J, Borgos MS, Davis JD, Pepper L, Clapp R, Sutker PB, Vasterling JJ, Ozonoff D. 1998. Health status of Persian Gulf War veterans: Self-reported symptoms, environmental exposures and the effect of stress. International Journal of Epidemiology 27(6):1000-1010. Proctor SP, Heaton KJ, White RF, Wolfe J. 2001. Chemical sensitivity and chronic fatigue in Gulf War veterans: A brief report. Journal of Occupational and Environmental Medicine 43(3):259-264. Proctor SP, White RF, Heeren T, et al. 2003. Neuropsychological Functioning in Danish Gulf War Veterans. Journal of Psychopathology and Behavioral Assessment 25(2):85-93. Reid S, Hotopf M, Hull L, Ismail K, Unwin C, Wessely S. 2001. Multiple chemical sensitivity and chronic fatigue syndrome in British Gulf War veterans. American Journal of Epidemiology 153(6):604-609.

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Gulf War and Health: Health Effects of Serving in the Gulf War, Volume 4 Ries, LAG, Eisner, MP, Kosary, CL, Hankey, BF, Miller, BA, Clegg, L, Mariotto, A, Feuer, EJ, and Edwards, BK, eds. 2005. SEER Cancer Statistics Review, 1975-2002. [Online]. Available: http://seer.cancer.gov/csr/1975_2002/ [accessed 2006]. Rivera-Zayas J, Arroyo M, Mejias E. 2001. Evaluation of Persian Gulf veterans with symptoms of peripheral neuropathy. Military Medicine 166(5):449-451. Roland PS, Haley RW, Yellin W, Owens K, Shoup AG. 2000. Vestibular dysfunction in Gulf War syndrome. Otolaryngology—Head and Neck Surgery 122(3):319-329. Rose MR, Sharief MK, Priddin J, Nikolaou V, Hull L, Unwin C, Ajmal-Ali R, Sherwood RA, Spellman A, David A, Wessely S. 2004. Evaluation of neuromuscular symptoms in UK Gulf War veterans: A controlled study. Neurology 63(9):1681-1687. Rostker, B. 2000. US Demolition Operations at Khamisiyah. [Online]. Available: http://www.gulflink.osd.mil/khamisiyah_ii/ [accessed August 6, 2004]. Rowland LP. 2000. Hereditary and Acquired Motor Neuron Diseases. In: Rowland LP, Editor. Merritt's Neurology. 10th ed. Philadelphia, PA: Lippincott Williams and Wilkins. Pp. 708-714. Roy-Byrne P, Arguelles L, Vitek ME, Goldberg J, Keane TM, True WR, Pitman RK. 2004. Persistence and change of PTSD symptomatology—a longitudinal co-twin control analysis of the Vietnam Era Twin Registry. Social Psychiatry and Psychiatric Epidemiology 39(9):681-685. Shapiro SE, Lasarev MR, McCauley L. 2002. Factor analysis of Gulf War illness: What does it add to our understanding of possible health effects of deployment? American Journal of Epidemiology 156(6):578-585. Sharief MK, Priddin J, Delamont RS, Unwin C, Rose MR, David A, Wessely S. 2002. Neurophysiologic analysis of neuromuscular symptoms in UK Gulf War veterans: A controlled study. Neurology 59(10):1518-1525. Shaw E, Hermansen L, Pugh W, White M. 1991. Disease and Non-Battle Injuries Among Navy and Marine Corps Personnel During Operation Desert Shield/Desert Storm. US: US Naval Health Research Center. Siddique N, Sufit R, Siddique T. 1999. Degenerative Motor, Sensory, and Autonomic Disorders. In: Goetz CG, Pappert EJ, Editors. Textbook of Clinical Neurology. 1st ed. Philadelphia, PA: W.B. Saunders Company. Pp. 695-717. Sillanpaa MC, Agar LM, Milner IB, Podany EC, Axelrod BN, Brown GG. 1997. Gulf War veterans: A neuropsychological examination. Journal of Clinical and Experimental Neuropsychology 19(2):211-219. Simmons R, Maconochie N, Doyle P. 2004. Self-reported ill health in male UK Gulf War veterans: A retrospective cohort study. BMC Public Health 4(1):27. Simon GE, Daniell W, Stockbridge H, Claypoole K, Rosenstock L. 1993. Immunologic, psychological, and neuropsychological factors in multiple chemical sensitivity: A controlled study. Annals of Internal Medicine 119(2):97-103. Smith TC, Gray GC, Knoke JD. 2000. Is systemic lupus erythematosus, amyotrophic lateral sclerosis, or fibromyalgia associated with Persian Gulf War service? An examination of Department of Defense hospitalization data. American Journal of Epidemiology 151(11):1053-1059.

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