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Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
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4
MAJOR COHORT STUDIES

This chapter provides an overview of many of the major cohort studies of Gulf War veterans, discusses the general limitations of the studies, and summarizes the findings from each. Some of the cohorts were brought together in the first few years after the Gulf War; others were assembled more recently. Most of the studies compare sizable groups of deployed veterans with groups of nondeployed veterans or with veterans who were deployed to locations other than the Persian Gulf (for example, Bosnia).

The major cohort studies are important for understanding the health of Gulf War veterans; those studies’ findings, on particular health outcomes, are evaluated thoroughly in Chapter 5 along with additional studies’ findings on smaller samples of Gulf War veterans. The largest studies of Gulf War veterans have been conducted in countries that were members of the Gulf War coalition including: the United States, Canada, Denmark, Australia, and the United Kingdom.

Most major cohort studies address several fundamental questions about Gulf War veterans’ health: What are the nature and prevalence of veterans’ symptoms and diagnoses? Do symptoms that do not fit conventional medical diagnoses, and are therefore unexplained, warrant classification as a new syndrome? Are exposures to specific biologic, chemical, and radiologic agents during the Gulf War associated with veterans’ symptoms and illnesses? Those questions are designed to guide the reader through a complex body of research.

Most major cohorts, once established, led to numerous studies that examined more detailed questions about Gulf War veterans’ health; the committee refers to those studies as derivatives. Table 4.1, at the end of this chapter, provides information about each original cohort—for example, method of assembly, the eligible population, the specific study methods, the study population, and the percentage of subjects who were enrolled—and includes the derivative studies. The table lists a derivative study under the original cohort from which it drew its study population and provides additional information, including its purpose, design, enrollment of its subjects, sample size, response rates,1 and other cohort characteristics. The table was vital in guiding the committee through its analysis and evaluation of the studies discussed in Chapter 5. The information helped the committee to identify the populations that have been studied and enabled the committee to understand which studies were independent of each other;

1

Table 4.1 contains the figures given in each study publication, except response rates. For uniformity, the committee calculated response rates with this formula: response rate = number of study participants who responded divided by the number of people who were located (rather than the number of eligible people).

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

that is important because the committee did not want to factor in the health outcomes occurring in the same people repeatedly.

GENERAL LIMITATIONS OF GULF WAR COHORT STUDIES AND DERIVATIVE STUDIES

The 24 major cohort studies of Gulf War veterans and their derivative studies have contributed greatly to our understanding of veterans’ health, but they are beset by limitations that are commonly encountered in epidemiologic studies, including lack of representativeness, selection bias, lack of control for potential confounding factors, self-reports of health outcomes, outcome misclassification, and self-reports of exposure. The committee members read each study carefully and noted the findings and limitations of each study.

The foremost limitation is lack of representativeness, which limits one’s ability to generalize results to the entire population of interest; for example, about half the cohorts focus on groups of veterans that are selected for study according to where they served in the military (a military-unit-based study). Military-unit studies are not representative of all Gulf War veterans with respect to their duties and location during deployment, their military status during the war (active duty, reserves, or National Guard), their military status after the war (active duty, reserves, or discharged), their branch of service (Army, Navy, Air Force, or Marines), or ease of ascertainment (IOM 1999b). The most representative studies are population-based: the cohorts are selected on the basis of where their members reside. In population-based studies of Gulf War veterans, the cohort might be the entire deployed population, as in studies of Canadian and Australian veterans, or a random selection from the population of interest, as in several studies of US and British veterans. The committee, in evaluating major cohort studies, gave greater weight to Gulf War studies that were population-based.

A study’s representativeness, even if it is population-based, can be compromised by low participation rates. Low participation rates can introduce selection bias, for example, when Gulf War veterans who are symptomatic choose to participate more frequently than those who are not symptomatic. Nondeployed veterans, who might be healthier, might be less inclined to participate. In some studies, researchers not only try to measure selection bias by comparing participants with nonparticipants from both deployed and nondeployed populations, but also make adjustments to overcome it, for example, by oversampling nondeployed populations as in the study by Eisen and colleagues (2005).

Selection bias might also occur through the so-called healthy-warrior effect. That form of bias has the potential to occur in most of the major cohorts that compare deployed veterans with nondeployed personnel. The healthy-warrior effect is a form of selection bias insofar as chronically ill or less fit members of the armed forces might be less likely to have been deployed than more fit members. That is, there might have been nonrandom assignment of those selected and not selected for deployment. Some of the best studies attempt to measure the potential for selection bias and adjust for it in the analysis.

A recurrent limitation is that most cohort studies rely on self-reporting of symptoms on questionnaires. Symptom self-reporting potentially introduces reporting bias, which occurs when the group being studied (such as deployed veterans) reports more frequently what it remembers than a comparison group (such as nondeployed veterans). Reporting bias, in this example, would lead to an overestimation of the prevalence of symptoms or diagnoses in the deployed population.

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Symptom self-reporting might sometimes introduce another type of bias known as outcome misclassification, in which there are errors in how symptoms are classified into outcomes and analyzed. One Gulf War study sought to document outcome misclassification by comparing veterans’ symptom reporting on questionnaires with clinical examination about 3 months later (McCauley et al. 1999b). The study found that the extent of misclassification depended on the type of symptom being reported; agreement between questionnaire and clinical examination ranged from 4-79%. The overall problem led the investigators to caution that questionnaire data, in the absence of clinical evaluation or adjustment, might lead to outcome misclassification. Another study also found poor reliability and validity of self-reported diagnoses when compared with medical records (Gray et al. 1999a). In contrast, a study by the Department of Veterans Affairs (VA) (Kang et al. 2000), which verified a random subset of self-reported conditions (n = 4,200) against medical records, found a strong correlation between the two (above 93%). Those data, however, were available only for the 45.2% who signed consent forms that allowed researchers to verify records.

The problem of symptom self-reporting is best addressed through medical evaluations, as was done by VA researchers (e.g., Eisen et al. 2005) and by several other investigators with the resources to conduct medical evaluations. Nevertheless, medical evaluations do not surmount the problem that some outcome measures being studied, such as chronic fatigue syndrome (CFS), are symptom-based syndromes that by definition lack a biologic “gold standard” with which symptoms can be validated. The lack of a diagnostic gold standard or other objective biologic markers poses a particular problem for veterans with fibromyalgia, CFS, and multiple chemical sensitivity (MCS) (IOM 1999a).

Another limitation of most major cohort studies is self-reporting of exposures. Self-reporting of exposures, like self-reporting of symptoms, introduces the possibility of recall bias, the tendency for participants who are symptomatic to overestimate (or underestimate) their exposures compared with those who are not symptomatic. Indeed, a major study from the UK found that Gulf War veterans with more symptoms were likely to report more exposures than those not deployed to the gulf (Unwin et al. 1999). Other complicating factors are exposures often cannot be validated by objective means, often occurred years earlier, and might have been perceived rather than actual. For example, because of the sensitivity of the chemical-warfare monitors, many false alarms might have been perceived by veterans as actual exposures. Enhanced recordkeeping and monitoring of the environment during and after the Gulf War would have averted that problem. Indeed, many expert panels have recommended efforts to improve recordkeeping and environmental monitoring in future deployments (e.g., IOM 1999b; NRC 2000a; NRC 2000b; NRC 2000c).

Other limitations of the body of evidence are that studies might be too narrow in their assessment of health status, the measurement instruments might have been too insensitive to detect abnormalities that affect deployed veterans, and the period of investigation has been too brief to detect health outcomes that have a long latency or require many years to progress to the point where disability, hospitalization, or death occurs. Virtually all US studies are cross-sectional, and this limits the opportunity to learn about symptom duration and chronicity, latency of onset (especially for health conditions with a long latency, such as cancer), and prognosis.

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

ORGANIZATION OF THIS CHAPTER

This chapter organizes numerous major cohort studies by a key feature of study design—how the cohort was assembled. Roughly half the chapter covers cohorts that are population-based, and the rest includes cohorts that are military-unit based.

For each major cohort, we use a uniform format. The cohort methods and major findings regarding symptoms and diagnoses are described first. Then we turn to how symptoms, if unexplained, cluster together (under the heading “Symptom Clustering”). The next section reviews findings of the medical evaluation, if one was conducted. The final section describes what symptom-exposure relationships were found.

This chapter does not cover studies whose sample population is drawn from any of the Gulf War registries, because they lack comparison groups. Registries have been set up in the United States, by the Department of Defense (DOD) and VA, and in the UK by the Ministry of Defence for UK Gulf War. Registries are self-selected case series of veterans who presented for care, so they cannot be and were not intended to be representative of the symptoms and diagnoses of the entire group of Gulf War veterans. Nor were registries designed with control groups or with diagnostic standardization across the multiple sites at which examinations took place (Joseph 1997; Roy et al. 1998). Finally, registries relied on standard diagnostic classifications and were not designed to probe for novel diagnoses2 or to search for biologic correlates. Thus, because of their methodologic limitations, registry studies cannot stand alone as a basis of conclusions or of the conduct of research. But they do provide a glimpse into veterans’ symptoms and the difficulties of fitting those symptoms into standard diagnoses. Registry programs have been a valuable source of information for generating hypotheses that have been tested in rigorous epidemiologic studies with control groups to estimate the health status of Gulf War veterans.

POPULATION-BASED STUDIES

The Iowa Study

The “Iowa study”, a major population-based study of US Gulf War veterans, was a cross-sectional survey of a representative sample of 4,886 military personnel who listed Iowa as their home of record at the time of enlistment (Iowa Persian Gulf Study Group 1997). The study examined the health of military personnel in all branches of service who were still serving or had left service. The sample was randomly selected from and representative of 28,968 military personnel. Of the study subjects who were contacted, 3,695 (90.7%) completed a telephone interview. Study subjects were divided into four groups: Gulf War-deployed regular military, Gulf War-deployed National Guard or Reserve, non-Gulf War-deployed regular military, and non-Gulf War-deployed National Guard or Reserve. Trained examiners using standardized questions, instruments, and scales interviewed the subjects.3 When compared with the groups not

2

Registries rely on the ICD-9-CM (Joseph 1997; Murphy et al. 1999).

3

Sources of questions included the National Health Interview Survey, the Behavioral Risk Factor Surveillance Survey, the National Medical Expenditures Survey, the Primary Care Evaluation of Mental Disorders, the Brief Symptom Inventory, the CAGE questionnaire (for alcoholism), the PTSD (Posttraumatic Stress Disorder)

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

deployed to the Persian Gulf, the two groups of Gulf War military personnel reported roughly twice the prevalence of symptoms suggestive of fibromyalgia, cognitive dysfunction, depression, alcohol abuse, asthma, posttraumatic stress disorder (PTSD), sexual discomfort, and chronic fatigue.4 In a separate analysis, the prevalence of MCS symptoms was about twice the prevalence in the comparison population (Black et al. 2000). Furthermore, in the main cohort study, which used a standardized instrument for assessing functioning (the Medical Outcome Study’s 36-item questionnaire known as the Short Form-36, or SF-36), Gulf War veterans displayed significantly lower scores on all eight subscales for physical and mental health. The subscales profile aspects of quality of life. The subscales for bodily pain, general health, and vitality showed the greatest absolute differences between deployed and nondeployed veterans. In short, this large, well-controlled study demonstrated that some sets of symptoms were more frequent and quality of life poorer among Gulf War veterans than among nondeployed military controls.

Symptom Clustering

The Iowa study was the first major population-based study to group sets of symptoms into categories suggestive of known syndromes or disorders, such as fibromyalgia or depression. Its finding of considerably higher prevalence of symptom groups suggestive of fibromyalgia, depression, and cognitive dysfunction among Gulf War veterans motivated other researchers to examine, through factor analysis, the potential for a new syndrome that would group and classify veterans’ symptoms. Several years later, the Iowa investigators performed a factor analysis on their cohort (Doebbeling et al. 2000). They identified three symptom factors in deployed veterans—somatic distress, psychologic distress, and panic—but the factors were not exclusive to deployed veterans. Thus, the study did not support the existence of a new syndrome (see Chapter 3 for a discussion of factor analysis).

Exposure-Symptom Relationships

The Iowa study assessed exposure-symptom relationships by asking veterans to report on their exposures in the Gulf War. Researchers found that many of the self-reported exposures were significantly associated with health conditions. For example, symptoms of cognitive dysfunction were found to have been associated with self-reports of exposure to solvents or petrochemicals, smoke or combustion products, lead from fuels, pesticides, ionizing or nonionizing radiation, chemical-warfare agents, use of pyridostigmine bromide (PB), infectious agents, and physical trauma. A similar set of exposures were associated with symptoms of depression or fibromyalgia. The study concluded that no exposure to any single agent was related to the conditions that the authors found to be more prevalent in Gulf War veterans (Iowa Persian Gulf Study Group 1997).

Women’s Health

The Gulf War was among the first wars to see a sizable fraction of women in the military. About 7% of military personnel serving in the Persian Gulf were women (Joseph 1997). The Iowa study was one of the few population-based US studies that investigated the health of

Checklist—Military, the Centers for Disease Control and Prevention Chronic Fatigue Syndrome Questionnaire, the Chalder Fatigue Scale, the American Thoracic Society questionnaire, and the Sickness Impact Profile.

4

The conditions listed were not diagnosed, because no clinical examinations were performed. Rather, before conducting their telephone survey, researchers grouped sets of symptoms from their symptom checklists into a priori categories of diseases or disorders. After a veteran identified himself or herself as having the requisite set of symptoms, researchers analyzing responses considered the veteran as having symptoms “suggestive” of or consistent with a particular disorder but not as having a formal diagnosis of the disorder.

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

women separately (Carney et al. 2003). Women were less likely to participate in combat than men, but 71% of women had at least one combat exposure. Women also reported similar rates of exposure to environmental agents, such as diesel fuel and smoke from oil-well fires. Their patterns of health-care use varied from that of men: they had significantly more outpatient, as well as inpatient, health care 5 years after the war. They were also more likely than men to receive VA compensation (17% vs 7%), although their level of disability was similar.

Department of Veterans Affairs Study

A major population-based study of US veterans was mandated by Public Law 103-446. The study is a retrospective cohort design conducted by VA. Its purpose is to estimate the prevalence of symptoms and other health outcomes (including reproductive outcomes in spouses and birth defects in children) in Gulf War veterans vs non-Gulf War veterans. This population-based survey had three phases. In the first, a questionnaire was mailed to 30,000 veterans. The second phase validated self-reported data with medical-record review and analyzed characteristics of those who did not respond to the mailed survey. The third phase was a comprehensive medical examination and laboratory testing of a random sample of 2,000 veterans drawn from the Gulf War population and a comparison group.

The study was designed to be representative of the nearly 700,000 US veterans sent to the Persian Gulf and 800,680 non-Gulf War veterans of the same era. Questionnaires were mailed to a stratified random sample of 15,000 Gulf War and 15,000 non-Gulf War veterans identified by DOD and representing various units and branches of the military. The questionnaires contained a list of 48 symptoms and questions about chronic medical conditions, functional limitations, and other items from the National Health Interview Survey. A questionnaire about exposures was also included. The overall response rate was about 70%.

Survey Findings (Phases I and II)

The investigation found significantly higher symptom prevalence of all 48 symptoms among Gulf War veterans (Kang et al. 2000). Four of the most frequently reported symptoms were runny nose, headache, unrefreshing sleep, and anxiety (Table 4.2). Numerous chronic medical conditions—such as sinusitis, gastritis, and dermatitis—were reported more frequently among Gulf War veterans; many were reported twice as often. Ten symptoms and 12 medical conditions were remarkably similar in prevalence to those in a UK cohort (Unwin et al. 1999). Gulf War veterans reported significantly higher rates of functional impairment (27.8% vs 14.2%), limitations of employment (17.2% vs 11.6%), and health-care use as assessed by clinic visits (50.8% vs 40.5%) or hospitalizations (7.8% vs 6.4%) compared with nondeployed veterans. In a randomly selected subset of veterans, medical-record reviews verified more than 90% of self-reported reasons for clinic visits or hospitalizations. A separate analysis of the VA cohort found that 10% of them, compared with 4% of controls, met symptom-based criteria for PTSD, and 4.9% (vs 1.2%) met symptom-based criteria for CFS (Kang et al. 2003).

Symptom Clustering

The VA study searched for potentially new syndromes through factor analysis. A separate article by Kang and colleagues (2002) found that 47 symptoms reported by veterans yielded six factors, only one of which contained a cluster of neurologic symptoms that did not load on any factors in the non-Gulf War deployed veterans. The symptoms in the cluster were loss of balance or dizziness, speech difficulty, blurred vision, and tremors or shaking. A group of

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

277 deployed veterans (2.4%) vs 43 nondeployed veterans (0.45%) met a case definition subsuming all four symptoms. The authors interpreted their findings as suggesting a possible unique neurologic syndrome related to Gulf War deployment that requires objective supporting clinical evidence.

TABLE 4.2 Results of VA Study

Most Common Self-Reported Symptomsa

Prevalence in Gulf War Veterans (%)

Prevalence in Non-Gulf War Veterans (%)

Runny nose

56

43

Headache

54

37

Unrefreshing sleep

47

24

Anxiety

45

28

Joint pain

45

27

Back pain

44

30

Fatigue

38

15

Ringing in ears

37

23

Heartburn

37

25

Difficulty in sleeping

37

21

Depression

36

22

Difficulty in concentrating

35

13

5 Most Common Self-Reported Chronic Medical Conditionsa

Prevalence in Guld War Veterans (%)

Prevalence in Non-Gulf War Veterans (%)

Sinusitis

38.6

28.1

Gastritis

25.2

11.7

Dermatitis

25.1

12.0

Arthritis

22.5

16.7

Frequent diarrhea

21.2

5.9

a Subjects were asked whether symptoms were recurring or persistent during previous 12 months. Differences in prevalence are all statistically significant (p < 0.05).

SOURCE: Kang et al. 2000.

Exposure-Symptom Relationships

A nested case-control analysis (see Chapter 3) was performed on those who met the case definition for the possible neurologic syndrome to determine which of 23 self-reported exposures were more common among cases than among controls (not deployed to the Gulf War) (Kang et al. 2002). Exposures to a variety of chemical agents were reported to be higher among cases than controls; the exposures noted were to chemical-agent-resistant compound paint, depleted uranium, nerve gas, food contaminated with oil or smoke, and bathing in or drinking water contaminated with oil or smoke. Dose-response relationships were not studied because of the nature of the dataset regarding self-reported exposure.

Another cohort study (Kang et al. 2000) did not assess exposure-symptom relationships. It reported on exposures only by compiling the percentages of veterans who reported each of 23 environmental exposures and nine vaccine or prophylactic exposures (such as to PB). The five most common environmental exposures reported by more than 60% of survey participants were

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

to diesel, kerosene, or other petrochemical fumes; to local food other than that provided by the armed forces; to chemical protective gear; to smoke from oil-well fires; and to burning trash or feces.

Medical Evaluation Findings (Phase III)

Three studies have reported on physical examinations of a subsample of the cohort that assayed for general medical status (Eisen et al. 2005), distal symmetric polyneuropathy (Davis et al. 2004), and pulmonary function (Karlinsky et al. 2004). The examinations were conducted in 2001, about 10 years after the Gulf War.

Eisen and colleagues (2005) examined 12 primary health outcome-measures and physical functioning on SF-36. Outcome measures were chosen by the authors to cover the most common symptoms reported by veterans, such as musculoskeletal pain, fatigue, rashes, and neuropathy (as noted in Kang et al 2000).

The study evaluated 1,061 Gulf War and 1,128 non-Gulf War veterans who had been randomly selected from 11,441 Gulf War-deployed and 9,476 non-Gulf War-deployed veterans who previously had participated in a 1995 questionnaire survey (Kang et al. 2000). Researchers were blind to deployment status. Despite three waves of recruitment into the study, the participation rate in the 2005 study was low: only 60.9% of Gulf War veterans and 46.2% of non-Gulf War veterans participated. To determine nonparticipation bias, the study authors obtained previously collected findings from participants and nonparticipants from the DOD Manpower Data Center and gathered sociodemographic and self-reported health findings from the 1995 VA study (Kang et al. 2000).

Four of 12 conditions were more prevalent among GW veterans: fibromyalgia (2.0% vs 1.2%; odds ratio [OR] 2.32, 95% confidence interval [CI] 1.02-5.27), CFS (1.6% vs 0.1%; OR 40.6, 95% CI 10.2-161.15), dermatologic conditions (34.6% vs 26.8 %; OR 1.38, 95% CI 1.06-1.80), and dyspepsia (9.1% vs 6.0%; OR 1.87, 95% CI 1.16-2.99). Fibromyalgia was diagnosed according to the 1990 criteria developed by the American College of Rheumatology (Wolfe et al. 1990). CFS was diagnosed according to the case definition developed by the International Chronic Fatigue Syndrome Study Group (Fukuda et al. 1994). The rate of CFS in the nondeployed veterans was similar to that of the US population. For dermatologic diagnoses, the study created two categories, one of which had a higher OR (see discussion in Chapter 5). A dyspepsia diagnosis required a history or symptoms of frequent heartburn and recurrent abdominal pain, and the use of antacids or other medications.

Gulf War veterans reported worse physical health on the SF-36 (49.3 vs 50.8; p < 0.001), but the magnitude of the difference, although statistically significant, was not clinically significant. The analyses adjusted for age, sex, race, years of education, cigarette smoking history, duty type (active vs reserves or National Guard), service branch (Army or Marines vs Navy or Air Force), and rank (enlisted vs officer). The limitations of the study were its performance 10 years after the 1991 Gulf War, which precludes diagnoses that have already resolved, and low participation rates (60.9% Gulf War and 46.2% non-Gulf War), which introduce the possibility of participation bias.

In the study by Davis et al. (2004), the presence of distal symmetric polyneuropathy was evaluated with a history, physical examination, and standardized electrophysiologic assessment of motor and sensory nerves in 1,061 deployed veterans and 1,128 nondeployed veterans. Spouses of deployed and nondeployed veterans were also used as controls. A population of 244

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Khamisiyah-exposed deployed veterans was also tested. Blood studies were performed to rule out metabolic causes of neuropathy. The diagnosis of peripheral neuropathy was defined as a distal sensory or motor neuropathy identified on the basis of the neurologic examination, nerve conduction study, or both. No difference in adjusted population prevalence of distal symmetric polyneuropathy between deployed and nondeployed veterans was found with electrophysiology (3.7% vs 6.3%; p = 0.07), neurologic examination (3.1% vs 2.6%; p = 0.60), or the two methods combined (6.3% vs 7.3%; p = 0.47). The prevalence of distal symmetric polyneuropathy in the spouses of deployed and nondeployed veterans did not differ (2.7% vs 3.2 %; p = 0.64). Veterans exposed to the Khamisiyah ammunition-depot explosion did not differ significantly from nonexposed deployed veterans in prevalence of polyneuropathy.

Karlinsky and colleagues (2004) reported results of pulmonary-function tests (PFTs) on the same VA population as Eisen and colleagues. PFT results were classified into five categories: normal pulmonary function, nonreversible airway obstruction, reversible airway obstruction, restrictive lung physiology, and small-airway obstruction. The pattern of PFT results was similar in deployed and nondeployed veterans, with no statistically significant differences. The pattern of PFT results was also reported to be similar in those exposed and not exposed (according to DOD exposure estimates developed in 2002) to nerve agents from destruction of munitions at the storage site at Khamisiyah in 1991. Prevalences of self-reported pulmonary symptoms were higher in deployed veterans; however, self-reported diagnoses, use of asthma medications, and self-reported physician visits and hospitalizations for pulmonary conditions were similar in deployed and nondeployed. Although no adjustments were made for covariates, demographic variables were similar in the two groups, and a history of tobacco-smoking was more common in deployed than in nondeployed (51.1% vs 44.4%; p = 0.03).

Oregon and Washington Veteran Studies

Veterans from Oregon or Washington were studied in a series of analyses by investigators of the Portland Environmental Hazards Research Center (McCauley et al. 1999b). A questionnaire was sent to a random sample (n = 2,343) of 8,603 Gulf War veterans who listed Oregon or Washington as their home state of record at the time of deployment, according to data provided by the DOD Manpower Data Center. The response rate was 48.4%. The study found high rates (21-60%) of self-reported symptoms, including cognitive-psychologic symptoms, unexplained fatigue, musculoskeletal pain, gastrointestinal complaints, and rashes. However, in the next phase of the study, the clinical-examination component, the first 225 participants displayed differences between the symptoms they reported on questionnaires and the symptoms they reported at clinical examination. The greatest differences were in rash or lesions (4% agreement between questionnaire and clinical examination), gastrointestinal complaints (20% agreement), and musculoskeletal pain (35% agreement). The authors interpreted those findings as suggesting the likelihood of outcome misclassification when self-administered questionnaires were relied on.

Symptom Clustering

Investigators studied clusters of unexplained symptoms by creating a new case definition for unexplained illness (Storzbach et al. 2000). Using questionnaire data, potential cases were identified as those reporting at least one of the following symptoms: musculoskeletal pain; cognitive-psychological changes, gastrointestinal complaints; skin or mucous membrane lesions; or unexplained fatigue. Veterans whose symptom clusters remained unexplained at clinical

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

examination (after exclusion of established diagnoses) were defined as constituting cases. Controls were those who at the time of clinical examination had no history of case-defining symptoms during or after their service in the Gulf War. In an analysis of the 241 cases vs 113 controls, investigators found, at medical evaluation, small but statistically significant deficits in cases on some neurobehavioral tests of memory, attention, and response speed. Cases also were significantly more likely to report increased distress and psychiatric symptoms (Storzbach et al. 2000). Finally, more than half the veterans with unexplained musculoskeletal pain met symptom-based criteria for fibromyalgia, and a large proportion met symptom-based criteria for CFS (Bourdette et al. 2001). Bourdette and colleagues also undertook a factor analysis, which yielded three symptom-based factors: cognitive-psychologic, mixed somatic, and musculoskeletal. These case-control studies and others from this cohort are reviewed further in Chapter 5.

Exposure-Symptom Relationships

Another nested case-control analysis of the population-based cohort examined exposures that might account for cases of unexplained illness (Spencer et al. 2001). The sample consisted of 241 veterans with unexplained illness and 113 healthy controls. In multivariate analysis, exposures most highly associated with unexplained illness were combat conditions, heat stress, and having sought medical attention during the Gulf War. Exposure to PB, insecticides and repellents, and stress was not statistically significantly associated with unexplained illness when multiple simultaneous exposures were controlled for. Those findings led investigators to conclude that unexplained illnesses were not associated with cholinesterase-inhibiting neurotoxic chemicals. One strength of this study was its elimination of numerous self-reported exposures (such as anthrax and botulinum toxoid vaccines) with questionable validity as determined by lack of test-retest reliability or time-dependent information (for example, chemical weapon exposure reported by precombat veterans or postcombat veterans who could not have been so exposed) (McCauley et al. 1999a).

Kansas Veteran Study

The state of Kansas established the Kansas Persian Gulf War Veterans Health Initiative to determine the patterns of veterans’ health problems in the state. Using lists of eligible veterans from DOD, Steele and colleagues (2000) conducted a population-based survey of veterans who listed Kansas as their home state of record. A stratified random sample of 3,138 was selected, from which 2,396 were located with instate contact information. The survey, mailed out in 1998, asked about 16 specific medical or psychiatric conditions, 37 symptoms, service branch, locations during the Gulf War (including whether the veterans were notified about the Khamisiyah demolitions), and vaccinations. Kansas Gulf War veterans, in comparison with Kansas nondeployed veterans, reported greater prevalence of 10 physician-diagnosed conditions: skin conditions, stomach or intestinal conditions, depression, arthritis, migraine headaches, CFS, bronchitis, PTSD, asthma, and thyroid condition. Using their own definition of Gulf War illness, which was similar to that used by the Centers for Disease Control and Prevention (CDC) (Fukuda et al. 1998), the investigators found that its prevalence was most associated with the period and location in the gulf in which veterans served. It was least prevalent in the period before the war, for example. Overall, the multisymptom illness was found in 34% of deployed, 12% of nondeployed who had received vaccines, and 4% of nondeployed who did not receive vaccines. The study concluded that excess morbidity is tied to characteristics of Gulf War service and that vaccine exposure might contribute to onset of multisymptom illness.

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Canadian Veteran Study

The findings of a 1997 survey (Goss Gilroy Inc. 1998)5 mailed to the entire cohort of Canadian Gulf War veterans were similar to those of the Iowa study. Respondents from Canada who had been deployed to the Gulf War (n = 3,113) were compared with respondents deployed elsewhere (n = 3,439) during the same period. Of the Gulf War veterans responding, 2,924 were male, 189 female. Deployed forces had higher rates of self-reported chronic conditions and symptoms of a variety of clinical outcomes than controls. Those outcomes and symptoms include chronic fatigue, cognitive dysfunction, MCS, major depression, PTSD, chronic dysphoria, anxiety, and respiratory diseases. The greatest differences between deployed and nondeployed forces were in the first three. The symptom grouping with the highest overall prevalence was cognitive dysfunction, which occurred in 34-40% of Gulf War veterans and 10-15% of control veterans. Gulf War veterans also reported significantly more visits to health-care practitioners, greater dissatisfaction with their health status, and greater health-related reductions in recent activity.

Symptom Clustering

The Canadian study did not search for potentially new syndromes.

Exposure-Symptom Relationships

In Canadian Gulf War veterans, the greatest number of symptom groupings was associated with self-reported exposures to psychologic stressors and physical trauma. Several symptom groupings also were associated with exposure to chemical-warfare agents, absence of routine immunizations, sources of infectious diseases, and ionizing or nonionizing radiation. Nevertheless, a subset of Canadian veterans who, because they were based at sea, could not have been exposed to many of the agents reported symptoms as frequently as did land-based veterans.

United Kingdom Veteran Studies

The UK sent over 53,000 personnel to the Gulf War. From the pool of veterans, two teams of researchers each studied a separate, nonoverlapping, stratified random sample of Gulf War veterans. The first team was from the University of London (Guy’s, King’s, and St. Thomas’s Medical Schools), the second team from the University of Manchester. A third team of researchers from the London School of Hygiene and Tropical Medicine surveyed the entire cohort of 53,000 veterans for a more narrowly focused study of birth defects and other reproductive outcomes.

University of London Veteran Studies

Unwin and collaborators (1999) at the University of London investigated the health of servicemen from the UK in a population-based study. The study used a random sample of the entire UK contingent deployed to the Gulf War6 and two comparison groups. One of the comparison groups was deployed to the conflict in Bosnia (n = 2,620); this made the study the only one to use a comparison population with combat experience during the time of the Gulf War.

5

In January 1997, Goss Gilroy Inc. was contracted by the Canadian Department of National Defence to carry out an epidemiologic survey of Canadians who served in the Gulf War to establish the overall health status of Gulf War personnel.

6

UK military personnel in the Gulf War were somewhat different from US personnel in demographics, combat experience, and exposures to particular agents (UK Ministry of Defence, 2000).

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
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The second comparison group (n = 2,614) was deployed to other noncombat locations outside the UK in the same period. As opposed to what was done in some studies, this nondeployed control group was recruited from among the subset of nondeployed service members who were fit for combat duty and thus avoided selection bias related to the healthy-warrior effect. Through a mailed questionnaire, the investigators asked about symptoms (50 items), medical disorders (39 items), exposure history (29 items), functional capacity, and other topics. The findings on the Gulf War cohort and comparison cohorts were compared through calculation of ORs. The study controlled for potential confounding factors (including sociodemographic and lifestyle factors) by logistic regression analysis. Only male veterans’ results were analyzed, because female veterans’ roles and symptoms were distinct enough to warrant separate consideration.

The Gulf War-deployed veterans (n = 2,961) reported higher prevalences of symptoms and diminished functioning than did either comparison group. Gulf War veterans were 2-3 times more likely than comparison subjects to have met symptom-based criteria for chronic fatigue, posttraumatic stress reaction, and “chronic multisymptom illness”, the label for the first case definition7 developed by CDC researchers to probe for the existence of a potential new syndrome among Gulf War veterans (Fukuda et al. 1998). It should be noted, that the Bosnia cohort, which also had been deployed to a combat setting, reported fewer symptoms than the Gulf War cohort suggests that combat deployment itself does not account for higher symptom reporting.

A separate analysis of this UK Gulf War cohort found that the prevalence of self-reported symptoms of MCS8 was 1.3%, statistically significantly greater than in the comparison groups. The prevalence of CFS, 2.1%, was not statistically significantly greater than in the nondeployed Gulf War-era cohort but was greater than in the Bosnian cohort (Reid et al. 2001). Results of this and other studies with respect to, for example, PTSD and other psychiatric disorders, are discussed and evaluated in Chapter 5.

A followup study using a postal survey was sent 11 years after the war to a stratified random sample of participants from the first study. The followup study found modestly lower prevalence of fatigue symptoms and psychologic distress but slightly higher prevalence of physical symptoms on the SF-36 in the Gulf War cohort than in the earlier study. Gulf War veterans were still more symptomatic than nondeployed controls (Hotopf et al. 2003a).

Symptom Clustering

In a companion study using the UK dataset, Ismail and colleagues (1999) set out to determine whether the symptoms that occurred with heightened prevalence in UK Gulf War veterans constituted a new syndrome. By applying factor analysis, they identifed three fundamental factors, which they classified as related to mood, the respiratory system, and the peripheral nervous system. The pattern of symptom reporting by Gulf War veterans differed little from the patterns by Bosnia and Gulf War-era comparison groups, although the Gulf War cohort had a higher frequency of symptom reporting and greater severity of symptoms. Furthermore, the study did not identify in this cohort the six factors characterized by Haley and colleagues (1997b) in their factor-analysis study described in the next section. The UK authors interpreted their results as evidence against the existence of a unique Gulf War syndrome. Nevertheless, in a

7

A case is defined as having one or more chronic symptoms in at least two of these three categories: fatigue, mood-cognition (for example, depression or difficulty in remembering or concentrating), and musculoskeletal (joint pain, joint stiffness, or muscle pain). This case definition was developed as a research tool to organize veterans’ unexplained symptoms into a potentially new syndrome.

8

Based on criteria of Simon and colleagues (1993).

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
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later study of veterans’ beliefs, the authors found that 17.3% of UK Gulf War veterans believed that they had a condition known as Gulf War syndrome (Chalder et al. 2001).

Exposure-Symptom Relationships

In the UK Gulf War cohort, most self-reported exposures were associated with all the health outcomes; that was also true in the two comparison cohorts (Unwin et al. 1999). The authors interpreted that finding as evidence that the exposures were not uniquely associated with Gulf War illnesses. Veterans with symptoms, regardless of deployment status, were more likely to report a wide variety of exposures than those without symptoms. Within the Gulf War cohort, two vaccine-related exposures—vaccination against biologic-warfare agents and multiple vaccinations—were associated with the case definition of “chronic multisymptom illness” developed by CDC researchers (Fukuda et al. 1998). A later analysis of the data on a subcohort of UK veterans found that receiving multiple vaccinations during deployment was weakly associated with five of the six health outcomes examined, including “chronic multisymptom illness” as defined by CDC (Hotopf et al. 2003a). Another separate analysis of a subgroup of veterans meeting case criteria for MCS symptoms found that they were significantly more likely to report several types of pesticide exposures. Veterans meeting case criteria for CFS were not more likely to report pesticide exposure but were more likely to report combat-related injury (Reid et al. 2001).

University of Manchester Veteran Study

The University of Manchester study used a random sample of UK veterans 7 years after the Gulf War (Cherry et al. 2001a; Cherry et al. 2001b). The cohort was deliberately separate from that studied by Unwin and colleagues (1999). Two groups of veterans deployed to the Gulf War (n = 8,210, a main cohort and a validation cohort) were compared with veterans who were not deployed but whose health would not have prevented deployment (n = 3,981). Veterans were sent a questionnaire about the extent to which they were burdened by 95 symptoms in the previous month. By asking them to mark their answers on a visual analogue scale, investigators sought to determine the degree of symptom severity. Investigators also sought to determine areas of peripheral neuropathy by asking veterans to shade body areas on two mannequins in which they were experiencing pain or numbness and tingling. On almost all 95 symptoms, deployed veterans reported greater symptom severity. The overall mean symptom severity scores of the two Gulf War cohorts were similar and significantly greater than that of the non-Gulf War cohort. For 14 symptoms—including memory, concentration, and mood problems—the severity scores of deployed veterans were at least twice those of the nondeployed veterans. Numbness and tingling were reported by about 13% of deployed and about 7% of nondeployed. Widespread pain was also reported more frequently (12.2% vs 6.5%).

Symptom Clustering

Through factor analysis, the investigators identified seven factors which accounted for 48% of the variance. Deployed veterans’ scores were significantly different on five factors: psychologic, peripheral, respiratory, gastrointestinal, and concentration. No difference was found in the neurologic factor; and appetite, the final factor, was significantly lower than in the non-Gulf War cohort. None of the factors was exclusive to Gulf War veterans, so the investigators concluded that their findings did not support a new syndrome (Cherry et al. 2001a).

Exposure-Symptom Relationships

The two UK Gulf War cohorts completed a second questionnaire with details of the dates when they were sent to each location and the exposures they had experienced. The exposure

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
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questionnaire contained 14 exposures. The main analysis involved a multiple regression of each of the seven factors identified through factor analysis on all exposures and other potential confounders. Many of the reported exposures correlated with one another. In the multivariate regression analysis, the number of days on which veterans handled pesticides was related to the overall severity score and to the peripheral and neurologic factors. The number of days on which they applied insecticide to their skin was related to severity and to the peripheral, respiratory, and appetite factors. The number of inoculations was associated with skin and musculoskeletal symptoms. There was a marked dose-response gradient for the association between insect repellents and the peripheral and respiratory factors. A dose-response gradient for the association of handling pesticides with the peripheral factor was present but less robust. The handling of pesticides and side effects of handling nerve-agent prophylaxis were associated with peripheral neuropathy (OR 1.26; p < 0.001), and the use of insect repellent was associated with widespread pain (OR 1.15; p < 0.001) (Cherry et al. 2001b).

London School of Hygiene and Tropical Medicine Veteran Study

The third British study was a very large mail survey conducted by researchers from the London School of Hygiene and Tropical Medicine (Maconochie et al. 2003; Simmons et al. 2004). It was designed largely to assess reproductive outcomes among Gulf War veterans, but it contained open-ended questions about their general health. The exposed cohort consisted of all UK Gulf War veterans, and the unexposed cohort consisted of a random sample of nondeployed UK military personnel from the same period. Although the numbers of surveys returned in the study were large (25,084 by Gulf War veterans and 19,003 by non-Gulf War veterans), the participation rates were low (47.3% and 37.5% of male and female Gulf War veterans, respectively, and 57.3% and 45.6% of male and female nondeployed veterans). The survey included a broad variety of items on reproductive and child health, exposure histories, current health, and health of sexual partners, and was supplemented by examination of medical records for pregnancies, live births, and outcomes. Maconochie et al. (2003) reported that 42-46% of participants had conceived or had attempted to conceive a child by 2001. In a subanalysis restricted to male respondents (24,379 Gulf War veterans and 18,439 nondeployed veterans), Simmons et al. (2004) reported that 61% of Gulf War veterans reported at least one new medical symptom or disease since 1990 compared with 37% of nondeployed veterans. The symptoms most strongly associated with Gulf War deployment were mood swings, memory loss or lack of concentration, night sweats, general fatigue and sexual dysfunction. Overall, 6% of the Gulf War veterans believed that they had “Gulf War syndrome”; that belief was associated with the highest reporting of new symptoms or diseases.

Danish Peacekeeper Studies

Military personnel from Denmark were involved primarily in peacekeeping or humanitarian roles after the end of the Gulf War. They were studied in a series of population-based cohort studies (Ishoy et al. 1999b; Suadicani et al. 1999). A total of 821 Danes were eligible by virtue of having been deployed at any time in the period between August 1990 to December 1997. The Gulf War veterans were matched by age, sex, and profession to 400 members of the Danish armed forces who were not deployed to the Gulf War. Symptom and exposure questionnaires and health and laboratory examinations were used. Findings of health examinations were not used in the study’s analysis of exposure-symptom relationships.

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Of 22 neuropsychologic symptoms, 17 were significantly more prevalent among Gulf War veterans than among controls. Many of the symptoms were correlated with one another. Headache and fatigue-related symptoms were present in about 20% of deployed vs up to 10% of nondeployed. Gastrointestinal symptoms and diseases and symptoms related to the skin or allergy were more frequent in deployed veterans, but gastrointestinal symptoms, which were suggestive of irritable bowel syndrome (Ishoy et al. 1999b), were no more prevalent in Gulf War veterans than in Danish troops that had been previously deployed overseas. The pattern of symptoms, except musculoskeletal symptoms (which were not more prevalent), was similar to the patterns seen in the UK, VA, and Canadian cohorts. The investigators also examined male participants for sexual dysfunction. Decreased libido or nonorganic erectile dysfunction was reported by 12% of Gulf War veterans and 3.7% of nondeployed troops. An extensive examination of serum sex hormones failed to detect clinically significant differences. Predictors of male sexual dysfunction were feeling threatened and bathing in or drinking contaminated water (Ishoy et al. 2001b). The investigators concluded that the overlap of symptoms between veterans deployed during and after the war indicated the existence of common risk factors independent of exposure to war itself.

Symptom Clustering

The authors did not use factor analysis, but they did use a multiple logistic regression analysis with adjustments for age and sex to find the most relevant neuropsychologic symptoms (Suadicani et al. 1999). Only five of the 17 symptoms remained significant after adjustment for the interrelationship of variables. About 21% of Gulf War veterans vs 6.2% of controls reported a clustering of three to five of the relevant symptoms (p < 0.001). Relevant symptoms included concentration or memory problems, repeated headache, balance disturbances or dizziness, abnormal fatigue not caused by physical activity, and problems in sleeping all night. The symptoms excluded from further analysis included numbness or tingling in hands and feet, suddenly diminished muscular power, and tingling or shivering of arms, legs, or other parts of the body.

Exposure-Symptom Relationships

One of the analyses investigated whether 22 neuropsychologic symptoms were associated with 18 self-reported environmental exposures9 (Suadicani et al. 1999). Most exposures were significantly associated with three to five relevant neuropsychologic symptoms in a univariate analysis. One psychologic exposure (“having watched colleagues or friends threatened or shot at”) and environmental exposures, especially “bathing in or drinking contaminated water (fumes, oil, chemicals)”, remained significant after adjustment in a multiple logistic model that adjusted for associations of exposures with one another. A separate multivariate analysis of gastrointestinal symptoms found them to be associated with two exposures: burning of waste or manure and exposure to insecticide against cockroaches (Ishoy et al. 1999a).

Australian Veteran Studies

Investigators from Monash University conducted a cohort study of Australian service personnel who had or had not been deployed to the gulf as part of the multinational force. The exposed cohort comprised 1,456 participants, the nonexposed cohort 1,588. Participation rates

9

Exposures did not include PB or vaccinations against chemical- or biologic-warfare agents, because Danish veterans had a peacekeeping role and thus were not at risk for chemical or biologic warfare.

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

were 80.5% and 56.8%, respectively (Kelsall et al. 2004a). In the Australian contingent sent to the Gulf War, members of the Navy were heavily overrepresented (86.5%). Very few experienced direct combat. Despite their lack of combat exposure, deployment was a stressful event: deployed veterans experienced higher rates of fear and threat of entrapment, attack (including nerve-agent warfare), and death or injury (Ikin et al. 2004). Participants completed a mailed questionnaire, which consisted of a physical and mental health screening questionnaire (SF-12), a test for nonpsychotic psychologic illness (GHQ-12), a PTSD checklist (PCL-S), and a questionnaire about military service and exposures. Thirty-one percent of Gulf War veterans had developed DSM-IV diagnoses since the Gulf War compared with 21% of non-Gulf War veterans. Significant excesses were seen in PTSD, depression, and substance-use disorders. A more recent study of Australian Navy Gulf War veterans noted that those veterans reported many stressful experiences, including fear of death and perceived threat of attack, more frequently in relation to the Gulf War than other military services (Ikin et al. 2005). The study population was the entire cohort of 1,579 veterans deployed to the 1991 Gulf War, but in the final analysis, results were restricted to 1,232 male participants.

Kelsall et al. (2004a) stated that participants in the exposed cohort reported a higher prevalence of all symptoms and reported more severe symptoms. McKenzie et al. (2004) reported that Gulf War veterans had poorer psychologic health and that the number of stressful exposures correlated with poorer scores on three standard instruments used to measure functioning and psychologic health.

Symptom Clustering

Forbes et al. (2004) used factor analysis to attempt to group symptom complexes for this cohort. Three factors emerged as more prominent in Gulf War veterans—psychophysiologic distress, somatic distress, and arthroneuromuscular distress and the symptoms in those complexes were more severe in Gulf War than in non-Gulf War veterans. This well-designed study confirms the extent and greater severity of symptoms in Gulf War veterans, even in a predominantly naval population with few direct military attacks, no deaths, and few casualties. The results suggest a deployment effect in the absence of actual combat.

Exposure-Symptom Relationships

Greater symptom severity was associated with 10 or more immunizations, use of PB, pesticides, insect repellents, presence in a chemical-weapons area, and reporting of stressful military service (Kelsall et al. 2004a).

MILITARY-UNIT-BASED STUDIES

Ft. Devens and New Orleans Cohort Studies

The symptom experience of two deployed cohorts of Gulf War veterans was studied by Boston-based researchers. One of the cohorts, an Army cohort based in Ft. Devens, Massachusetts, was surveyed longitudinally at three times (1991, 1993-1994, and 1997), and underwent psychiatric interviews and other clinical evaluations at the second time (e.g., White et al. 2001). A second deployed cohort from New Orleans was also studied at the second time, as was a non-Gulf War-deployed unit sent to Germany. The Germany-deployed unit was an air ambulance company of National Guard from Maine that had been deployed to Germany for handling wounded personnel evacuated from the gulf.

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
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In comparison with veterans deployed to Germany during the Gulf War era, stratified random samples of both Gulf War cohorts (Ft. Devens and New Orleans) had increased prevalence of 51 of 52 items on a health-symptom checklist (Proctor et al. 1998). The greatest differences in prevalence of reported symptoms were of dermatologic symptoms (such as rash, eczema, and skin allergies), neuropsychologic symptoms (such as difficulty in concentrating and difficulty in learning new material), and gastrointestinal symptoms (such as stomach cramps and excessive gas). With a separate checklist, researchers found a higher prevalence of PTSD, according to the Clinician-Administered PTSD Scale (CAPS) (5% Ft. Devens, 7% New Orleans, and 0% Germany). The study’s nearly 300 subjects represented a stratified random sample of 2,949 troops from Ft. Devens and 928 from New Orleans; both groups consisted of active-duty, reserve, and National Guard troops. The comparison group was Germany-deployed veterans from an air ambulance company (n = 48). The cohorts were also the focus of several studies of stress-related disorders, such as PTSD, depression, and substance abuse (see Chapter 5).

Symptom Clustering

Symptom clustering among the Ft. Devens cohort was studied in 1997 with CDC's case definition of multisymptom illness (Wolfe et al. 2002). The case definition was applied to findings from the 52-item health checklist. About 60% of respondents met the CDC case definition. That group was roughly evenly divided between “mild to moderate” and “severe” cases. On the basis of logistic regression, many of the exposures were associated with meeting the case definition, including anti-nerve-gas pills, anthrax vaccination, tent heaters, exposure to oil-fire smoke, and chemical odors.

Exposure-Symptom Relationships

In 1994-1996, Proctor (1998) surveyed the deployed cohorts (Ft. Devens and New Orleans) on about eight exposures, and asked respondents to rate each on a scale of 0-2, (0 = no exposure; 1 = exposed; 2 = exposed and felt sick at the time). Using standardized regression, they found the strongest associations between several exposures—debris from SCUDS, chemical and biologic warfare agents—and musculoskeletal, neurologic, neuropsychologic and psychologic symptoms.

Seabee Reserve Battalion Studies

Haley and collaborators (1997b) studied members of one battalion of naval reservists called to active duty for the Gulf War. The battalion was a mobile construction battalion for other branches of the military. More than half the battalion had left the military by the time of the study. Participants were recruited from those for whom investigators had addresses and from veterans’ meetings. Of those participating, 70% reported having had a serious health problem since returning from the Gulf War. A telephone survey of a random sample of nonparticipants found that, while they were demographically similar to participants, fewer (43%) reported having serious health problems since the war. Eleven percent of participants and only 3% of nonparticipants were unemployed. Participation rate was low (41.1% of 606 males in the battalion; 58.0% of those located), and there was no comparison cohort of nondeployed veterans. All those features strongly suggest selection bias, which could lead to overestimation of health effects among participants.

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
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Symptom Clustering

The study was the first to cluster symptoms into new syndromes by applying factor analysis. Through standardized symptom questionnaires and two-stage factor analysis, the investigators defined what they considered to be either six syndromes or six variants of a single syndrome, which they labeled impaired cognition, confusion-ataxia, arthromyoneuropathy, phobia-apraxia, fever-adenopathy, and weakness-incontinence. One-fourth of the veterans in this uncontrolled study (n = 63) were classified as having one of the six syndromes. The first three syndromes had the strongest factor clustering of symptoms.

In a followup study of the same cohort, Haley and colleagues (1997a) used a case-control design to examine neurologic function. They chose as cases the 23 veterans who had scored highest on the three syndromes with the strongest factor clustering. Controls consisted of two small groups of healthy veterans, of which one (n = 10) was deployed to the Gulf War and the other (n = 10) was not. The results of extensive neurologic and neurobehavioral testing demonstrated that cases had significantly greater evidence of neurologic dysfunction compared with controls. Investigators concluded that the three syndromes, derived from factor analysis of symptoms, might signify variant forms of expression of a generalized injury to the nervous system.10 In a later study, cases with one of the three syndromes were more likely than healthy controls to exhibit vestibular dysfunction (Roland et al. 2000). Related research on the same subset of veterans found evidence of basal ganglia and brainstem neuronal loss through magnetic resonance spectroscopy (Haley et al. 2000b). Those studies are discussed further in Chapter 5.

Exposure-Symptom Relationships

The three syndromes identified by Haley and colleagues (1997a) were the focus of another case-control study that examined their relationship to self-reported exposures to neurotoxicants. The study tested the hypothesis that exposure to organophosphates and related chemicals that inhibit cholinesterase are responsible for the three nervous system-based syndromes (Haley and Kurt 1997). Each of the syndromes was associated with a distinct set of risk factors. The “impaired-cognition syndrome” was found, through multiple logistic regression, to be associated with jobs in security and the wearing of flea-and-tick collars. The “confusion-ataxia syndrome” was associated with self-reports of having been involved in a chemical-weapons attack and of having advanced adverse effects of PB. Finally, “arthromyoneuropathy” was associated with higher scores on the scale of advanced adverse effects of PB and with an index created by the investigators to enable veterans to self-report the amount and frequency of their use of government-issued insect repellent. The authors concluded that some Gulf War veterans had delayed chronic nervous system syndromes as a result of exposure to combinations of neurotoxic chemicals (Haley and Kurt 1997).

Another study by Haley and collaborators (1999) examined whether genetic susceptibility could play a role in placing some veterans at risk for neurologic damage by organophosphate chemicals. They hypothesized that neurologic symptoms in ill veterans might be explained by their having genetic polymorphisms (variations) in metabolizing enzymes. One set of polymorphisms could impair their ability to quickly detoxify organophosphorus compounds,

10

Neuropsychologic or neurologic impairments have been the focus of several smaller studies as well. Some found subtle changes in nerve-conduction velocity and cold sensation (Jamal et al. 1996) and in some tests of finger dexterity and executive functioning (Axelrod and Milner 1997); others found no significant differences in measures of nerve conduction and neuromuscular functioning (Amato et al. 1997) or neuropsychologic performance (Goldstein et al. 1996).

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
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such as sarin, soman, and some pesticides. The investigators studied 45 veterans: 25 with chronic neurologic symptoms identified through their earlier factor-analysis study and 20 healthy controls from the same battalion. They measured blood butyrylcholinesterase and two types, or allozymes, of paraoxonase/arylesterase-1 (PON1). The genotypes encoding the allozymes were also studied. The investigators found that veterans who were ill had blood butyrylcholinesterase concentrations similar to those of control subjects; however, ill veterans had lower type Q paraoxonase/arylesterase, the allozyme that hydrolyzes sarin rapidly. They also were more likely to have the type R genotype, which encodes the allozyme that has low hydrolyzing activity for sarin. The authors interpreted their findings as suggesting that reduced ability to detoxify organophosphorus chemicals might have contributed to the onset of neurologic symptoms in some Gulf War veterans. Contrary evidence was provided by Hotopf and colleagues (2003b), who did not find differences in PON1 activity among symptomatic vs healthy Gulf War veterans in a more representative, population-based sample.

Larger Seabee Cohort Studies

The first in a series of studies by Gray and collaborators (1999a) surveyed active-duty Seabees who remained on active duty for at least 3 years after the Gulf War. The Seabees were from 14 Seabee commands at two locations (Port Hueneme, California, and Gulfport, Mississippi). Those who were deployed to the Gulf War were in mobile construction battalions serving in the same tasks and at the same sites as did the reserve Seabee battalion studied by Haley and collaborators. During the Gulf War, Seabees built airports, supply points, and roads. Unlike Haley et al., Gray et al. excluded Gulf War veterans who were no longer active at the time of the study.

Gray and colleagues enrolled 1,497 study subjects, 527 of whom were Gulf War veterans and 970 nondeployed veterans. Study subjects filled out symptom and exposure questionnaires and answered additional questions screening for PTSD, CFS, and various psychologic symptom domains; they had serum tested for acute-phase reactants and had handgrip strength tested.

The deployed veterans reported greater prevalence of 35 of 41 symptoms. In a subset of veterans, symptom reporting was not reliable when retested several months later, and it lacked validity on the basis of checks with medical records. Gulf War veterans were more likely to report symptoms of PTSD (OR 1.8, 95% CI 1.3-2.5). They also had a small but significant decrease in handgrip strength.

Symptom Clustering

Knoke and colleagues (2000) reported a factor analysis of the active-duty Seabee study in response to a factor analysis conducted by Haley et al. (1997b). Knoke and colleagues found that three factors were more common among Seabees who had been deployed—somatization, depression, and obsessive-compulsive symptoms—and that they affected 20% of Gulf War veterans. Their findings were similar to those of Doebbling et al. (2000), Fukuda (1998), and Ismail et al. (2002) and consistent with findings in a civilian population with CFS (Nisenbaum et al. 1998). They concluded, unlike Haley after the study of Seabee reservists from one reserve battalion, that there was no evidence of a unique spectrum of neurologic injury.

Gray et al. (2002) re-examined the question of symptoms and exposures by expanding their deployed and nondeployed cohorts to include all Seabees who had been on active duty during the time of the Gulf War regardless of whether they remained on active duty, were in the reserve, or had separated from service. There were 11,868 participants and a 67.4% participation

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

rate. Participants were divided into three exposure groups: 3,831 who had been deployed to the Gulf War, 4,933 who had been deployed elsewhere, and 3,104 who had not been deployed. Those who had been deployed to the gulf reported more poor health, missed work, cognitive failure, hospitalizations, digestive diseases, and depression. They also reported a greater frequency of leishmaniasis, CFS, PTSD, MCS, and irritable bowel syndrome. Overall, 22.1% of Gulf War veterans met a working definition of Gulf War syndrome. Being defined as a case was associated with participation in a federal Gulf War veteran registry, being female, a reservist, or a member of two Seabee battalions, or having a nontraditional Seabee occupation. There were also weak associations (OR < 2.0) with 12 specific exposures.

Exposure-Symptom Relationships

Deployed veterans reported more frequent exposure to 26 of the 30 possible agents. The agents reported were somewhat different from those reported in a Seabee reserve battalion (Haley and Kurt 1997; Haley et al. 1997b). For example, the reserve battalion reported wearing pet flea collars and being exposed to chemical weapons, but the active-duty Seabees in this study did not. The authors chose to dichotomize the 26 exposures artificially; they carried out further analyses only on the subset of the 11 agents which the OR for exposure between Gulf War veterans and nondeployed veterans was greater than 3, and if more than 5% of Gulf War veterans reported the exposure. The study found many exposure-symptom associations with the 11 agents. The authors apparently carried out multivariate analysis, but they did not report its results. They stated that they “could not isolate or implicate specific war exposures" using their multivariate analysis. Other study limitations were recall bias, moderate-to-low response rate (53%), exclusion of veterans no longer in active service, and lack of representativeness of the entire Gulf War population.

Pennsylvania Air National Guard Study

A large study by Fukuda and colleagues (1998) used factor analysis and other methods to assess the health status of Gulf War veterans in response to requests from DOD, VA, and the state of Pennsylvania to assess the prevalence and causes of an unexplained illness in members of one currently active Air National Guard unit. By studying that unit and three comparison Air Force populations,11 the investigators aimed to organize symptoms into a case definition and to carry out clinical evaluations on participants from the index Air National Guard unit (using a nested case-control design). All the units that were studied had a combination of deployed and nondeployed veterans. For purposes of assessing symptom prevalence, the investigators combined the four units and compared questionnaire responses of deployed and nondeployed. Of 3,723 participants surveyed, those deployed to the Gulf War experienced higher prevalence of chronic symptoms (33 of 35 symptoms of more than 6-month duration were reported to be more prevalent) than nondeployed veterans. For purposes of developing a case definition, the investigators focused, at first, solely on the Pennsylvania index unit. The authors used two broad methods to derive a case definition: (1) a clinical approach in which symptoms had to be reported for 6 months or longer, had to occur in 25% or more of Gulf War veterans, and had to occur at least 2.5 times more frequently in Gulf War veterans than in non-Gulf War veterans; and (2) factor analysis. The two approaches yielded similar case definitions.

11

Air National Guard in Pennsylvania, US Air Force Reserve in Florida, and US Air Force active duty in Florida. Those comparison units were demographically similar to the index unit but had different primary missions.

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
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Symptom Clustering

The authors defined a case of chronic multisymptom illness as having one or more chronic symptoms from at least two of three categories: fatigue, mood-cognition symptoms (for example, depression or difficulty in remembering or concentrating), and musculoskeletal symptoms (joint pain, joint stiffness, or muscle pain). Severe cases were defined as those in which each case-defining symptom had been reported as severe. According to that definition, 39% of Gulf War-deployed veterans and 14% of nondeployed veterans had mild-to-moderate cases, whereas 6% and 0.7%, respectively, had severe cases. On the basis of a total of 158 clinical examinations in one unit, there were no abnormal physical or laboratory findings that differentiated those who met the case definition and those who did not. Cases, however, reported significantly lower functioning and well-being.

A sizable fraction (14%) of nondeployed veterans also met the mild-to-moderate case definition. The investigators concluded that their case definition could not specifically characterize Gulf War veterans with unexplained illnesses. The study, however, had several limitations, the most important of which was its coverage of only current Air Force personnel several years after the Gulf War (including Air National Guard, Air Force Reserve, and active duty), which limits its generalizability to other branches of service and to those who left the service possibly because of illness.

Medical Evaluation

To assess risk factors, the authors performed clinical evaluations on a subset of participants (n = 158), all of whom volunteered for the evaluation and came from the index unit of the Pennsylvania Air Force National Guard. Of the members of this unit, 45% had been deployed to the Gulf War. Overall, there were few abnormal findings from blood, stool, and urine testing among those who met the case definition for chronic multisymptom illness. There were no differences between cases and noncases in the proportion that seroreacted to botulinum toxin, anthrax-protective antigen, leishmanial antigens, and other antigens. This was among the few studies to have assessed exposures (mostly to infectious diseases) via laboratory testing as opposed to self-reports, but the sample undergoing clinical evaluation was relatively small and restricted to Air Force National Guard members.

Exposure-Symptom Relationships

A nested case-control study of the same cohort (n = 1,002) sought to identify self-reported exposures associated with cases of chronic multisymptom illness (Nisenbaum et al. 2000). It found that meeting the case definition of severe and mild-to-moderate illness was associated with use of PB, use of insect repellent, and belief in a threat from biologic or chemical weapons. Having an injury requiring medical attention was also associated with having a severe case of chronic multisymptom illness.

OTHER COHORT STUDIES

The following studies are grouped because they are more narrowly focused than the major cohort studies and often lack analysis of symptom clustering or exposure-symptom relationships.

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Hawaii and Pennsylvania Active Duty and Reserve Study

One of the first epidemiologic studies of US Gulf War veterans was a congressionally mandated study of more than 4,000 active-duty and reserve personnel from bases in Pennsylvania and Hawaii. The main purpose of the study was a focus on psychologic health, but the first publication also dealt with physical health (Stretch et al. 1995). It found that veterans deployed to the Gulf War reported higher prevalence of 21 of 23 symptoms on a symptom checklist than nondeployed veterans. Overall, deployed veterans were about 2-4 times more likely than nondeployed veterans to report each symptom. In a later publication (Stretch et al. 1996a), the authors reported that deployed veterans commonly reported significant levels of stress, including operating in desert climates, long duty days, extended periods in chemical-protective clothing, lack of sleep, crowding, lack of private time, physical workload, and boredom. Another publication examined PTSD as measured by the Impact of Event Scale and the Brief Symptom Inventory (Stretch et al. 1996b). The prevalence of PTSD symptoms in the deployed veterans was 8.0-9.2% vs 1.3-2.1% in the nondeployed. The low overall response rate, 30.6%, limits the generalizability of the three studies.

New Orleans Reservist Studies

A series of studies by Sutker and colleagues analyzed psychologic outcomes in a cohort of New Orleans reservists (n = 1,520). The cohort consisted of Louisiana National Guard and reservists from the Army, Air Force, and Navy. The overall response rate was 83.7%. Of the 1,272 who responded, 876 had been deployed and 396 had not been deployed. Deployed veterans, assessed by survey at an average of 9 months (time 1) after the war, had higher scores on depression and anxiety symptom scales12 than nondeployed veterans (Brailey et al. 1998). Twenty-five months after the war (time 2), the researchers studied only the deployed group (n = 349), which represented 88.1 % of the original group of deployed veterans studied at time 1. Responses at time 2 revealed higher rates of PTSD, depression, and hostility than at time 1. The increasing prevalence of PTSD was linked to symptom clusters of hyperarousal and numbing (Thompson et al. 2004). Hyperarousal and numbing were also associated with development of depression, anxiety, hostility, and physical symptoms. Higher wartime stress exposure vs low-stress exposure was related to PTSD and somatic problems (Brailey et al. 1998; Sutker et al. 1993). The personality and coping factors found to increase the likelihood of PTSD were low personality hardiness, high avoidance coping, and low perceived family cohesion (Sutker et al. 1995b).

Air Force Women Study

Female Air Force veterans were studied by Pierce (1997), who examined a stratified sample of 525 women (active-duty, National Guard, and reserve) drawn from all 88,415 women who served in the Air Force during the Gulf War era. Women deployed to the Gulf War reported rash, cough, depression, unintentional weight loss, insomnia, and memory problems more frequently than women deployed elsewhere. The pattern of symptom reporting was similar to that reported by men and women in other Gulf War studies (Carney et al. 2003; Unwin et al.

12

The authors used the Beck Depression Inventory, the Brief Symptom Inventory for Anxiety and Depression, the PTSD checklist, and the Mississippi Scale for PTSD.

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

2002). In addition, women deployed to the Gulf War were more likely than controls to report sex-specific problems, such as breast cysts and lumps, and abnormal cervical cytology.

Connecticut National Guard

Southwick and colleagues studied two deployed units of the Connecticut National Guard (n = 240) (Morgan et al. 1999; Southwick et al. 1993; Southwick et al. 1995). The focus of the study was on trauma-related symptoms and the course of PTSD. The cohort was studied prospectively at 1 month, 6 months, 2 years, and 6 years. The study was unusual in its frequency of followup, but there was no nondeployed comparison group. Although 240 were eligible to participate, only 119 filled out the first questionnaire and 84 filled out a second questionnaire at the 6-month mark. From 1 month to 6 months, the prevalence of PTSD increased, as did the severity rating of some symptom clusters (for example, hyperarousal). The prevalence varied, depending on the symptom scale and cutoffs being used, but on the average rose from about 3% to 6.5%. The degree of combat exposure was associated with the degree of PTSD symptoms. All veterans who, at 1 month or 6 months, met the criteria for PTSD according to the Mississippi scale, also met the criteria at 2 years (Southwick et al. 1995).

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

TABLE 4.1 Major Cohort Studies (Shaded) and Derivative Studies

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Iowa Persian Gulf Study Group 1997

Iowa listed as home of record on initial military record, and service in regular military or activated National Guard/Reserve sometime from 8/2/1990-7/31/1991, identified by Defense Manpower Data Center, Monterey CA, DOD (n = 28,968)

Population based interview study Stratum random sample with proportional allocation—64 strata (GW, type of military, age, sex, race, rank, branch), Pilot study not eligible

9/1995-5/1996

Total 4,886

4,072 (83.3%)

3,695 (90.7%; 75.6% of eligible)

Limited assessment of selection bias

Derivatives from Iowa Persian Gulf Study Group 1997

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Black et al. 1999

Quality of life and health-services utilization among those with MCS

Cross-sectional survey

Population described in Iowa Persian Gulf Study Group 1997: n = 3,695

 

Black et al. 2000

Prevalence of MCS syndrome

Cross-sectional survey

Population described in Iowa Persian Gulf Study Group 1997: n = 3,695

 

Doebbeling et al. 2000

Definition of Persian Gulf War Syndrome

Factor analysis

Population described in Iowa Persian Gulf Study Group 1997: n = 3,695

 

Zwerling et al. 2000

Prevalence of self-reported postwar injuries

Cross-sectional survey

Population described in Iowa Persian Gulf Study Group 1997: n = 3,695

 

Barrett et al. 2002

Association between PTSD and self-reported physical health status

Cross-sectional survey

Population described in Iowa Persian Gulf Study Group 1997 excluding 13 with missing information

Total: n = 3,682

GWVs: n = 1,889

NDVs: n = 1,793

 

Black et al. 2004b

Prevalence and risk factors for anxiety

Cross-sectional survey

Population described in Iowa Persian Gulf Study Group 1997: n = 3,695

 

Lange et al. 2002

Exposures to Kuwait oil fires and asthma and bronchitis

Cross-sectional survey

Population described in Iowa Persian Gulf Study Group 1997 excluding 336 with unknown exposure information: n = 1,560

 

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Black et al. 2004a

Depression in deployed and nondeployed veterans Cases: report of depression, cognitive dysfunction, or chronic widespread pain Controls: without any of these conditions

Case-comparison study

Total population: 602 veterans interviewed in phase II from original study Iowa Persian Gulf Study Group 1997; cases defined as reporting depression, cognitive dysfunction or chronic widespread pain in phase I; controls defined as free of all 3 conditions

Not a case-control study; comparison of deployed and nondeployed depressed veterans

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Kang et al. 2000

Any person who served in the US military on active duty, in reserves, or in National Guard, irrespective of whether they were still in the service or separated (n = 693,826 deployed; 800,680 not deployed (~50% of all troops in military 9/1990-5/1991 but not in the gulf))

Cross-sectional study, population-based sample; 15,000 troops deployed, 15,000 troops not deployed; “National Health Survey of GW Era Vets and their families”

 

Total: 30,000

GWV: 15,000

NGV: 15,000

30,000

15,225

14,775

20,917 (70%)

11,441 (75%)

9,476 (64%)

Compared survey participants with VA health registry participants (n = 15,891)

Did not list number of missing addresses

From Kang et al. 2002 learned that 225 NGVs were actually GWVs

Some misclassification in original sample of 15,000 each

Assessed selection bias

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Derivatives from Kang et al. 2000 – U.S

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Kang et al. 2002

Factor analysis to define GWS

Factor analysis

Numbers used in factor analysis:

GWVs: n = 10,423

NGVs: n = 8,960

Cases and noncase GWVs analyzed for self-reported exposures: n = 11,441; cases = 277

 

Kang et al. 2003

Prevalence of PTSD and CFS

Cross-sectional cohort study

GWVs: n = 11,441

NGVs: n = 9,476

 

Karlinsky et al. 2004

Prevalence of respiratory symptoms and pulmonary-function abnormalities

Cross-sectional medical evaluation survey (including pulmonary-function tests)

Recruited from 5,885 on list of matched GWVs and NDVs

GWVs: n = 1,036

NDVs: n = 1,103

No details on participation rates

Davis et al. 2004

Prevalence of symptoms suggesting distal symmetric polyneuropathy in GWVs and spouses

Cross-sectional clinical and lab assessment “VA Medical Evaluation” Eligible population selected randomly from Kang population and likely to live close to examination center

GWVs: n = 1,996

Spouses: n = 745

NGVs: n = 2,883

Spouses: n = 846

 

GWVs: 1,061 (53.2%)

Spouses: 484 (65%)

NGVs: 1,128 (39.1%)

Spouses: 533 (63%)

Total number of spouses eligible not given, number located not given, response rates from total eligible

Eisen et al. 2005

Prevalence of fibromyalgia, CFS, dermatologic conditions, dyspepsia, SF-36, hypertension, obstructive lung disease, arthralgias, peripheral neuropathy 10 years after deployment

Cross-sectional medical evaluation survey “VA Medical Evaluation” Eligible population selected randomly from Kang population

GWVs: n = 1,996

NGVs: n = 2,883

1,741 (87.2%)

2,444 (84.8%)

GWVs: 1,061 (60.9%; 53.2% of eligible)

NGVs: 1,128 (46.2%; 39.1% of eligible)

Even though veterans with CFS were more likely to participate, bias was nondifferential Authors adjusted for problem of generalizability by correcting for overrepresentation

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Eligible population

Type of study/methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Unwin et al. 1999

UK military who served in gulf region 9/1/1990-6/30/1991, excluding special forces (n = 53,462); comparison populations: personnel served in Bosnia 4/1/1992-2/6/1997 (n = 39,217); Era cohort, in military but not gulf 1/1/1991 (n = 250,000)

Cross-sectional survey, stratified random sample (service, sex, age, service status, rank, fitness, as appropriate for population), oversampled women

8-9/1997 through 11/11/1998

Total

GWV

Bosnia

NGV

12,592 (12,744; 152 unknown addresses)

4,246

4,250

4,248

8,195 (65.1%) (calculated from numbers listed in text of study)

2,961 (69.7%)

2,620 (61.6%)

2,614 (61.5%)

Authors note that 800 Bosnia veterans later moved to GWV group; extensive assessment of selection bias

Derivatives from Unwin et al. 1999: UK Gulf War veterans – University of London

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Ismail et al. 1999

Is there a GWS?

Factor analysis

Total cohort: n = 3,214

Says men only, from Unwin et al. looks as though women are included

Chalder et al. 2001

Prevalence of belief of GWS and comparison of health with other veterans

Cross-sectional cohort study

GWVs only: n = 2,961

 

Reid et al. 2001

Prevalence of MCS and CFS, association with exposures and psychologic morbidity

Cross-sectional cohort study

GWVs: n = 3,531

Bosnia: n = 2,050

Era: n = 2,614

Report that they attempted 5,046 GWVs—more than reported in Unwin et al.

Reid et al. 2002

Prevalence of specific chemical sensitivities

Cross-sectional cohort study

GWVs: n = 3,531

Bosnia: n = 2,050

Era: n = 2,614

Case = report ≥1 trigger

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Ismail et al. 2002

Prevalence of psychiatric disorders in veterans with and without unexplained physical disability

(Two-phase) cohort study, medical assessment 1/1999-9/2000

Disabled GWVs: n = 406

Nondisabled GWVs: n = 3,047

Disabled Bosnia: n = 138

Disabled Era: n = 278

166

158

98

184

111 (67%)

98 (62%)

54 (55%)

79 (43%)

Report in text that 740 cohort members were eligible, but only 607 were contacted; does not explain why

Hotopf et al. 2003a

Describe changes in health

Cohort study

Eligible: all responders except 503 who refused future contact and 449 who did not complete relevant parts of questionnaire

Selected all women, all male veterans with fatigue score > 8, for GWVs 50% sample of those with scores 4-8, all 4-8s in Bosnia and Era, 1 in 8 sample of veterans with scores < 4

GWVs: 1,472

Bosnia: 909

Era: 924

1089 (74.0%)

638 (70.2%)

643 (69.6%)

Report 8,196 reported to first survey (Unwin et al.: n = 8,195)

Nisenbaum et al. 2004

Patterns of symptom reporting

Factor analysis

GWVs: n = 3,454

Bosnia: n = 1,979

Era: n = 2,577

US 1991 GWVs from four Air Force units: n = 1,163

US veterans from Fukuda et al. 1998

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Everitt et al. 2002

Patterns of symptom reporting

Cluster analysis

500 veterans randomly selected from each group

Reports that there had been 3,529 responses in GWV group (as opposed to 3,531)

Hotopf et al. 2000

Ill health and vaccinations

Cross-sectional study

Servicemen who served in gulf: n = 3,284

Included those with vaccination records: n = 923

 

David et al. 2002

Poor memory and concentration

Case-control study, medical evaluation – case definition Cutoff: 1st decile of distribution of SF36-PF subscale in Era cohort

Recruited 12-18 months after phase 1

GWV: n = 406

Bosnia: n = 138

Era: n = 278

GWV well: n = 3,047

738 randomly selected and contacted

GWV ill: 111 (66.9%)

Era ill: 78 (42.5%)

Bosnia ill: 54 (56.8%)

GWV well: 98 (62.4%)

Excluded three randomly selected eligibles with current serious physical illness

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Cherry et al. 2001a; Cherry et al. 2001b

UK military who served in gulf region 9/1990-6/1991, excluding special forces identified by MOD Comparison population—not deployed, in military 1/1/1991 No overlap with Unwin et al. population

Cross-sectional survey, Stratified by sex, age, service, rank; GWV stratum matched with randomly selected sample for NGVs, three stratified random samples; main and validation cohort selected; mail and personal visits depending on service group

1st site visits 12/1997, followup until 9/1999

Total

14,254

12,191 (85.5%); 11,914 usable questionnaires (83.6%)

Macfarlane et al. study of mortality on same group

Analysis on 7,971 GWVs who reported having been in the gulf, useful questionnaires and contacted outside MOD medical assistance

Gulf–Main

4,755

4,076 (85.7%)

Gulf–Validation

4,750

4,134 (87.0%)

Non-gulf

4,749

3,981 (83.8%)

Assessed selection bias

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Maconochie et al. 2003

UK military who served in gulf 8/1990-6/1991 excluding special services identified by MOD (n = 52,811)

Comparison population – not deployed, appropriately fit, in military 1/1/1991 (n = 52,924)

Retrospective cohort study of reproductive outcomes Comparison group stratum matched on service, sex, age, serving status, rank

8/1998-3/2001

Total

GWV men

GWV women

NGV men

NGV women

105,735

51,581

1,230

51,688

1,236

44,087 (41.7%, 48.5% adjusted)

24,379 (47.3%, 53% adjusted)

705 (57.3%, 72% adjusted)

18,439 (35.7%, 42% adjusted)

564 (45.6%, 60% adjusted)

Adjusted response rate—accounts for undelivered

Assessed selection bias

Derivatives from Maconochie et al. 2003: UK Gulf War veterans – Reproductive study

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Doyle et al. 2004

Miscarriage, stillbirth, congenital malformation in offspring

Retrospective cohort study

As reported in Maconochie et al.

 

Simmons et al. 2004

Incidence of self-reported adult ill health

Retrospective cohort study, comparison of deployed and nondeployed and among those who believe theyhave GWS

Men only: n = 42,818

 

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Kelsall et al. 2004a

All Australian veterans served in gulf 8/2/1990-9/4/1991 Comparison group—randomly selected from Australian Defense Force personnel in

Postal questionnaire and comprehensive health assessment

Comparison group frequency matched by

8/2000-4/2002

Total

4,795

GWV

4,604 recruitable (96.0%)

1,808

3,044 (66.1% of recruitable; 63.5% of eligible)

1,456 (80.5% of

Assessed selection bias using telephone-survey-only results

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

 

operational units at time but not deployed (n = 26,411)

service type, sex, age, rank

 

1,871

NGV

2,924

recruitable (96.6%)

2,796 recruitable (95.6%)

recruitable; 77.8% of eligible); 1,414 with both instruments (78.2% of recruitable; 75.6% of eligible)

1,588 (56.8% of recruitable; 54.3% of eligible); 1,411 with both instruments (50.5% of recruitable; 48.3% of eligible)

 

Derivatives from Kelsall et al. 2004a: Australian cohort

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Forbes et al. 2004

Self-reported symptoms

Factor analysis

GWVs with complete data on 62 symptoms: n = 1,322

NGVs with complete data: n = 1,459

 

McKenzie et al. 2004

Psychologic health, SF-12

Cross-sectional study

Male GWVs: n = 1,424; 1,374 with complete data

Male NGVs: n = 1,548; 1,513 with complete data

 

Ikin et al. 2004

Psychologic disorders and association with exposure to GW-related psychologic stressors

Cross-sectional study

Male GWVs: n = 1,424; 1,381 with psychologic health interview)

Male NGVs: n = 1,548; 1,377 with psychologic health interview)

 

Kelsall et al. 2004b

Respiratory health status, exposure to oil-fire smoke and dust storms

Cross-sectional study

Full cohort as described in Kelsall et al. 2004a

 

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

McCauley et al. 1999b

Veterans deployed to gulf 8/1/1990-7/31/1991 who listed Oregon or Washington as home state of record at deployment and currently reside in either state (n = 8,603), identified from ODSS database, DOD

Population-based case-control study

Phase I: mail survey of randomly selected population, reservists oversampled, all women selected

Phase II: case-control study

Mail survey: 11/1995-1/1998, this report is through 6/1997

Total 2,343 (by 6/1997 only mailed: 1651)

GWVs with unexplained illnesses (cases)

Healthy GWVs (controls)

1,396 (84.6% of eligible mailed by 6/1997)

Potential cases of unexplained illnesses: 297 Potential controls: 130

675 (48.4%; 40.9% of total eligible); 454 eligible for clinical study (32.5%; 27.5% of total eligible)

158 (53.2%)

67 (51.5%)

Report only on first 225 clinical examinations of potential cases

Limited assessment of selection bias

Derivatives from McCauley et al. 1999b

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Spencer et al. 1998

Differential exposures and persistent unexplained illness

Case-control study

1,084 returned survey by 6/1/1998, 567 (52.3%) agreed to participate

Cases: n = 244

Controls: n = 113

Case and control numbers same as finals listed in Bourdette et al. 2001

Anger et al. 1999

Neurobehavioral deficits

Case-control study

Tested by 12/1996

Cases: n = 66

Controls: n = 35

Appears to be from before survey was completed

Binder et al. 1999

Subjective cognitive complaints, affective distress, objective cognitive performance among cases of unexplained illness

Cross-sectional study

Cases with psychologic complaints: n = 100

 

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Storzbach et al. 2000

Psychologic differences between veterans with and without GW unexplained symptoms

Case-control study

Cases: n = 241

Controls: n = 113

Number of cases reported as both 244 and 241

Storzbach et al. 2001

Neurobehavioral deficits, defined by ODTP

Case-control study

Cases: n = 239 with ODTP data available

Controls: n = 112 with ODTP data available

 

Binder et al. 2001

CFS and cognitive deficits on computerized cognitive testing

Case-control study

Cases: those who met revised definition of CFS and had AFQT data available: n = 32

Controls: with AFQT data available: n = 62

 

Ford et al. 2001

PTSS and unexplained illness

Case-control study

Cases: n = 237

Controls: n = 112

 

McCauley et al. 2002a

Chronic fatigue

Case-control study

Final numbers from Bourdette et al. 2001

Cases: n = 103 who met fatigue case definition (ICF n = 59, CFS-94 n = 44)

Controls: n = 113

Analyzed subgroup of cases from main study, specifically looking at chronic fatigue

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Bourdette et al. 2001

As above

As above, including symptom factor analysis Case definition: ≥ 1 of (a) cognitive or psychologic changes including memory loss, confusion, inability to concentrate, mood swings, and/or somnolence; (b) gastrointestinal distress; (c) fatigue; (d) muscle andjoint pain; (e) skin or mucous

Mail survey: 11/1995-1/1998

Total

2,343 sample;

2,022 eligible

GWVs with unexplained illnesses (cases)

1,760 (75.1% of total sample; 87.0% of total eligible)

Potential: 336

1,119 (63.6%; 55.3% of total eligible) (799 eligible for clinical study, 443 examined)

244 met definition

Subject numbers differ for derivative studies: Binder et al. 2001: 801 eligible for clinical study

Storzbach et al. 2000: 517 cases and 213 controls contacted by telephone

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

 

 

membrane lesions

Symptoms began during or after deployment, persisted ≥1 month, occurred during 3 months before to recruitment

 

Healthy GWV (controls)

Potential: 107

113 met definition

Misclassified some cases and controls

Limited assessment of selection bias—clinical sample not representative of nonresponders

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

McCauley et al. 2002b

Active or reserve Army or National Guard deployed in gulf or on active duty but not deployed 1/1/1991-3/31/1991 and residents of Oregon, Washington, California, Georgia, or North Carolina Khamisiyah-exposed GWVs (n = 5,328)

Non-Khamisiyah-exposed

GWVs

(n = 143,910)

NDVs

(n = 814,331)

Cohort study, telephone survey

1999

Total

3,219

Khamisiyah-exposed GWVs 923

Non-Khamisiyah-exposed GWVs 927

NDVs 1,369

2,918 (90.6%)

846 contacted

841 contacted

1,231 contacted

Final sample: 1,779 (61.0%; 55.3% of eligible)

653 (77.2% of contacted; 70.7% of eligible)

610 (72.5% of contacted; 65.8% of eligible)

516 (41.9% of contacted; 37.7% of eligible)

Khamisiyah exposure defined as in 50-km radius of Khamisiyah 3/4/1991-3/13/1991 Enrolled=interviewed and met exposure definition

No formal assessment of selection bias (previously reported on selection bias-(McCauley et al. 1999b))

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Steele 2000

Kansas residents on active duty 8/1990-7/1991, separated or retired from military, or currently serving in reserve component (total n = 16,566; GWVs: n = 6,235; NGVs: n = 10,331)

Telephone interview, cross-sectional survey

2/1998-8/1998

Total 3,138

GWVs

NGVs

2,396 (76.3%) located, 2,211 (70.5%) invited

1,665 invited

546 invited

2,030 (91.8% of invited; 64.7% of total)

1,548 (93% of invited)

482 (88% of invited)

No assessment of selection bias

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Proctor et al. 1998

Devens cohort: US Army active, reserve and National Guard veterans followed since return to United States; initial survey spring 1991 (n = 2,949, or 60% of 4,915 per Wolfe et al. 1999b); Second survey in winter 1992/spring 1993 (n = 2,313); those who completed HSC eligible for this study (n = 2021)

New Orleans cohort: active, reserve, and National Guard, US Army, Navy, Marine, and Air Force troops deployed to gulf (n = 928), initial survey within 9 months of return in 1991; those who completed

Cross-sectional study from larger cohorts followed longitudinally

Stratified random sample from GWV cohorts designed to give equal representation of higher and lower symptom reporters; oversampled women Self-reported symptoms

Devens: spring 1994-fall 1996

New Orleans: summer 1994-fall 1995

Germany: spring 1995

Total 645

444 (68.8%)

343 (77.3%; 53.2% of eligible)

participated 300 (67.6%; 46.5% of eligible)

completed questionnaires 332 (74.8%; 51.5% of eligible)

environmental interview 254 (57.2%; 39.4% of eligible) in-person neuropsychologic testing and psychologic diagnostic interview

Germany group not longitudinal, only studied at time 2.

300 who completed Devens questionnaire were analyzed in this study

Assessed selection bias

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

 

HSC eligible for study (n = 818)

Germany-deployed cohort: Maine National Guard air ambulance unit sent to Germany during GW (12/1990-8/1991), personnel whose intended mission was handling and transport of wounded from GW

 

 

Devens 353

New Orleans 194

259 (73.3%)

126 (64.9%)

220 (84.9% of located and contacted; 62.3% of eligible) 186 (71.8%; 52.7% of eligible)

completed questionnaire, 213 (82.2%; 60.3% of eligible)

environmental interview, 148 (57.1%; 41.9% of eligible)

psychologic test 73 (58% of located and contacted; 37.6% of eligible) 66 (52.4%; 34.0% of eligible)

completed questionnaire, 71 (56.3%; 36.6% of eligible)

environmental interview, 58 (46.0%; 29.9% of eligible)

psychologic test

 

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

 

 

 

 

Germany 98

59 (60.2%)

50 (84.7% of located and contacted; 51.0% of eligible)

48 (81.4%; 49.0% of eligible)

completed questionnaire, environmental interview and psychologic test

 

Derivatives from Proctor et al. 1998

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Wolfe et al. 1999a

Relationship of psychiatric status with health problems

Cross-sectional study

Complete data from diagnostic interviews and questionnaires

Devens cohort: n = 148

New Orleans cohort: n = 56

Germany cohort: n = 48

 

White et al. 2001

Neurobehavioral effects

Cross-sectional study

Devens = 142

New Orleans cohort: n = 51

Germany cohort: n = 47

 

Proctor et al. 2001

Chemical sensitivity and chronic fatigue

Cross-sectional study

Devens cohort: n = 180

Germany cohort: n = 46

 

Lindem et al. 2003b

Neuropsychologic performance, traumatic stress symptomatology and exposure to chemical and biologic-warfare agents

Cross-sectional study

Participants who completed all evaluations (including full neuropsychological and PTSD evaluations)

Devens cohort: n = 141

New Orleans cohort: n = 37

Germany cohort: n = 47

 

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Lindem et al. 2003a

Neuropsychologic performance compared with neuropsychologic symptom reporting

Cross-sectional study

Devens cohort: n = 142

New Orleans cohort: n = 51

Germany cohort: n = 47

Does not describe how numbers were obtained

Studies using Devens time 1 and time 2 survey responders only

Wolfe et al. 1999b

Course and predictors of PTSD

Longitudinal cohort study

Time 1- 1991:

Devens survey responders: n = 2,949 (60.0% of 4,915)

Time 2- 1993-1994:

Devens survey: n = 2,313 (78.4% of 2,949)

Nonresponders at time 2 were more likely to be younger, member of minority group, and deployed from active duty, but there were no differences in PTSD rates, indicating a lack of selection bias at time 2

Wagner et al. 2000

PTSD impact on physical health

Cross-sectional study

Devens survey responders with complete data on PTSD (main dependent variable) on time 2 survey: n = 2,301

 

Wolfe et al. 2002

Multisymptom illness

Cross-sectional study

Devens survey responders: n = 2,949 (contact information on 2,903 available (98.4%))

Responders to new questionnaire (3/1997-3/1998): n = 1,290 (full data n = 945 (73.3%))

 

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Ishoy et al. 1999b

Danish Gulf War Study

All Danish Gulf War veterans stationed in gulf 8/2/1990-12/31/1997, peacekeeping UN force, officers, noncommissioned officers, enlisted privates

Comparison group—members of Danish Armed Forces employed according to contract who could have been but had not been deployed in gulf

Cross-sectional study with medical examinations

Comparison group matched on sex, age, profession, randomly selected at end of 1996

Enrolled by questionnaire, health examination

Enrollment comparison group in 1996, health examinations 2/1997-1/1998

GWVs: 821

NGVs: 400

 

686 (83.6%)

231 (57.8%)

No explanation for why 400 NGVs were

selected as comparison group

Limited assessment of selection bias (spot tests showed that most frequent reason for not participating was lack of time)

Derivatives from Ishoy et al. 1999b: Danish Peacekeeping Veterans

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Ishoy et al. 1999a

Gastrointestinal symptoms attributable to physical, chemical, or biologic exposures

Cross-sectional study

GWVs: n = 686

NGVs: n = 257

26 more NGVs than reported in Ishoy et al. 1999b, sample size reported in abstract only, appears that only data on GWVs were analyzed

Suadicani et al. 1999

Determinants of long-term neuropsychologic symptoms

Cross-sectional study

GWVs: n = 686 (667 in tables)

NGVs: n = 257

See above

Ishoy et al. 2001a

Male reproductive-health characteristics

Cross-sectional study, serum levels of reproductive hormones

Male GWVs: n = 661

Male NGVs: n = 215

 

Ishoy et al. 2001b

Male sexual problems

Cross-sectional study

Male GWVs: n = 661

Male NGVs: n = 215

 

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Haley et al. 1997b

Active and retired members of 24th Reserve Naval Mobile Construction Battalion, called to active duty in GW, living in Alabama, Georgia, Tennessee, South Carolina, North Carolina in 11/1994 (n = 606)

Cross-sectional survey, factor analysis

1994, 1995

606

429 located with address and telephone number (70.8%); approximately 350 contacted

249 (58.0% of located; 41.1% of eligible)

No assessment of selection bias

Derivatives from Haley et al. 1997b

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Haley and Kurt 1997

Self-reported exposure to neurotoxic chemical combinations and association with factor-analysis-defined syndrome

Cross-sectional study

GWVs: n = 249

 

Haley et al. 2001

Structural equation modeling to test construct validity of case definition of GWS

Validation study

Original sample: n = 249 (as described in Haley et al. 1997b)

Validation sample: GWVs living in north Texas, registered with Gulf War clinic of Dallas VA Medical Center and responders to advertisements in area (n = 335)

 

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Haley et al. 1997a

Neurologic function in cases and controls

Case-control study, controls of similar age, sex, education to syndrome 2

Cases: three strong syndromes, veterans with highest factor scores on factor 1 (impaired cognition), on factor 2 (confusion-ataxia), on factor 3 (arthro-myo-neuropathy): n = 23 (5 with syndrome 1, 13 with syndrome 2, 5 with syndrome 3)

Deployed controls: GWVs who reported no serious health problems: n = 10 selected from 70 eligible

Nondeployed controls: members of the battalion not deployed: n = 10 selected from 150 eligible

Not true nested case-control studies; selection of cases was, appropriately, from original cohort, but selection of controls was not; 10 of 20 controls were from 150 newly discovered members of battalion who had not been deployed; those 10 were not from original cohort and there is no indication that they were tested for “caseness”

Hom et al. 1997

Neuropsychologic correlates of GWS

Case-control study, controls of similar age, sex, education as cases

Cases: highest factor scores from six syndrome factors: n = 26

Controls: n = 20 (10 deployed who reported no serious health problems, 10 nondeployed)

Assume same population as prior studies, plus 3 new cases; no information on how selected

Haley et al. 1999

Association of low PON1 type Q arylesterase activity with neurologic symptom complexes

Case-control study

n = 45 of 46 in case-control study with blood samples available (missing 1 case)

Assume same population as prior studies, plus 3 new cases; no information on how selected

Roland et al. 2000

Vestibular dysfunction in GWS

Case-control study

Cases: n = 23

Controls: n = 20

As described in Haley et al. 1997a

 

Haley et al. 2000b

Effect of basal ganglia injury on central dopamine activity

Case-control study

Cases and controls from Haley et al. 1997a

Cases with “confusion ataxia”: n = 12

Deployed controls: n = 8

Nondeployed controls: n = 7

 

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Haley et al. 2000a

Brain abnormalities in GWS

Case-control study, subjects with proton (hydrogen 1) magnetic resonance spectroscopy

As described in Haley et al. 1997a

Cases: n = 22 (from the 23, 1 excluded because of multiple myeloma)

Deployed controls: n = 9 (from the 10, 1 declined)

Nondeployed controls: n = 9 (from the 10, 1 declined)

 

Haley et al. 2004

Measurements of abnormalities of autonomic nervous system

Case-control study

As described in Haley et al. 1997a

Cases: n = 22

Deployed controls: n = 9

Nondepoyed controls: n = 9

(17 controls and 21 cases in final analysis because of Holter availability and illness)

 

Kurt 1998

GW illness and exposures to anticholinesterases

Review

Total: n = 249

23 cases, 10 deployed controls, 10 nondeployed controls

 

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Fukuda et al. 1998

Index population: ANG unit in Lebanon, Pennsylvania

Comparison populations: 3 Air Force populations:

Unit A: ANG unit from Pennsylvania, similar demographics to index but different primary mission

Unit B: US Air Force Reserve and

Unit C: active-duty Air Force, similar missions to index, from Florida

Any member on base was eligible

Cross-sectional survey, in-person interviews, factor analysis

Clinical evaluation of GWVs from index unit (4-5/1995)

1-3/1995

Total

Index

Unit A

Unit B

Unit C

6,151

1,083

1,520

1,141

2,407

3,723 (60.5%)

667 (61.6%)

538 (35.4%)

838 (73.4%)

1,680 (69.8%)

Numbers deployed to gulf: index, 47%; A, 22%; B, 32%; C, 28%; Total, 31%

Not clear who was on active duty during war Started out as cluster investigation in Lebanon

“Located” is everyone on base when survey conducted

No assessment of selection bias

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Gray et al. 2002

All regular and Reserve Navy personnel who had served on active duty in Seabee commands for ≥30 days 8/1/1990-7/31/1991 (n = 18,945)

Cross-sectional survey

5/1997-7/1/1999

Total 18,945

GW Seabees

Deployed elsewhere

Nondeployed

17,599 (92.9%)

12,049 (68.6%; 63.6% of total eligible); 11,868 actually completed (67.4%; 62.6% of total eligible)

3,831

4,933

3,104

No information on response rates by subgroup

Assessed selection bias (telephone survey)

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Gray et al. 1999a

Active-duty Seabees in Navy after war and serving in one of two large Seabee centers (Port Hueneme, California and Gulfport, Mississippi)

Cross-sectional survey

Clinical evaluations late 1994, early 1995

Total

GWVs

NDVs

 

1,497 (53%)

527

970

Assessed selection bias

Derivatives from Gray et al. 1999a: Seabee study

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Knoke et al. 2000

Self-reported symptoms to identify syndrome

Factor analysis

Same population as Gray et al. 1999a

GWVs: n = 528

NDVs: n = 968

Sample size not exactly same as Gray et al. 1999a

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Gray et al. 1996

Active-duty Army, Navy (including Marine Corps), or

Air Force deployed in GW ≥1 day 8/8/1990-7/31/1991 (n = 579,931)

Comparison group of randomly selected active-duty military personnel on rosters as of 9/30/1990 but not in PG before 7/31/1991 (n = 700,000)

Retrospective cohort study, hospitalization experience obtained from computerized hospitalization records of DOD

4 years of study before war: 10/1/1988-7/31/1990;

1991: 8/1/1991-12/31/1991;

1992: 1-12/1992;

1993: 1-9/30/1993

Numbers for each period = those on whom data complete and on active duty on 1st day of period

Before war 1,279,931

1991 1,165,411

1992 1,075,430

1993 839,389

Selection bias not an issue (hospitalization records)

Derivatives from Gray et al. 1996: Hospitalization study

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Knoke et al. 1998

Testicular cancer

Retrospective cohort study, followup through 4/1/1996 (reported by 4/1/1997)

Males on active duty

GWVs: n = 517,223

NDVs: n = 1,291,323

Expanded study period from Gray et al. 1996

Gray et al. 1999b

Hospitalization of GWVs possibly exposed to Khamisiyah

Retrospective cohort study, followup 3/1991-9/1995

Army veterans regular and reserve, deployed in GW 3/10-3/13/1991: n = 349,291

Not exposed: n = 224,804

Uncertain low dose: n = 75,717

Specific estimated subclinical exposure—three levels: n = 48,770

Expanded study period from Gray et al. 1996

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Smith et al. 2003

Khamisiyah, postwar hospitalizations revisited

Retrospective cohort study, followup 3/10/1991-12/31/2000

Regular active-duty and reserve Army and Air Force personnel in theater in March 1991: n = 431,762

Demographic and exposure data available on 418,072 (96.8%)

Active duty: n = 333,382; Reserve and National Guard: n = 84,690

Not exposed: n = 318,458

Possibly exposed: n = 99,614

Expanded study period from Gray et al. 1996; hospitalization info limited to active-duty, so Reserves and National Guard only in study until 6/10/1991 (estimated return to civilian operations)

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Knoke and Gray 1998

All active-duty Army, Air Force, Navy, Marine Corps, Coast Guard deployed to GW ≥1 day 8/8/1990-7/31/1991 or not deployed but on active duty for at least part of GW period and remained on active duty at end of period

Retrospective cohort study, admissions (after GW deployment period and before 4/1/1996) to US military hospitals worldwide reported to DOD computerized database

Reported by 10/1/1996

Deployed 552,111

Nondeployed 1,479,751

 

1st hospitalizations: 6,672

1st hospitalizations: 18,823

Selection bias not an issue (hospitalization records)

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Dlugosz et al. 1999

All regular, active-duty Army, Navy, Marine Corps, Air Force personnel who served ≥1 month active duty 8/2/1990-7/31/1991 (n = 1,984,996)

Retrospective cohort study, hospitalizations for mental disorders, reported to DOD (n = 30,539), deployed =1+days 8/2/1990-7/31/1991; followup 6/1/1991-9/30/1993

6/1/1991-9/30/1993

30,539

 

 

Selection bias not an issue (hospitalization records)

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Sutker et al. 1995b

Troops assigned to Marine, Air Force, Navy, Army Reserve, and National Guard units deployed to combat who underwent psychologic debriefing within 1 year of return (n = 1,423), restricted to those who saw war-zone assignment (n = 808)

Discriminant-function analysis

Within 1 year of return from GW

GWVs with appropriate assessment instruments: 775

PTSD cases

No distress

 

97

484

No explanation of how study subjects were selected

No assessment of selection bias

Derivatives from Sutker et al. 1995b and other small studies by same research group

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Benotsch et al. 2000

Longitudinal relationship between resources and emotional distress

Longitudinal study

GWVs: n = 348

 

Brailey et al. 1998

Characterizations of war-zone stressors; documentation of acute and psychologic sequelae to war-zone participation; identification of risk factors predictive of psychologic symptoms

Longitudinal study

GWVs: n = 349

 

Sutker et al. 1995a

Ethnicity and sex comparisons in assessment of psychologic distress

Cross-sectional study

Total: 912 of 1,423 described in Benotsch et al. 2000 (excluded on basis of completion of instruments and measure of intelligence)

Wartime deployed: n = 653

Stateside duty: n = 259

 

Thompson et al. 2004

Early symptom predictors of chronic distress in GWVs

Longitudinal study

GWVs: n = 348 described in Benotsch et al. 2000

 

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Sutker et al. 1993

War-zone trauma and stress-related symptoms

Cross-sectional study

Participants drawn from five National Guard and Army Reserve units deployed in GW and assessed by invitation of Louisiana Army and ANG and US Army Reserve as part of evaluation and debriefing program: n = 306; 215 with complete information

Total responses for analysis: n = 275 (118 of 215 reported up to three of most stressful conditions or events)

 

Sutker et al. 1994a

Psychologic symptoms and psychiatric diagnoses in GW troops serving graves registration duty

Clinical report

Army reservists served on war-zone graves registration duty: n = 24 (of 35-member company)

 

Sutker et al. 1994b

Pyschopathology in war-zone-deployed and -nondeployed GWVs assigned graves registration duty

Clinical report

Army reservists assigned to three quartermaster companies: n = 207 eligible; n = 124 completed assessment and debriefing exercises; n = 63 selected randomly from 207; n = 60 in final sample (3 excluded because of inconsistent responses); of 60, 40 deployed, 20 stateside

 

Sutker et al. 2002

Exposure to war trauma, war-related PTSD and psychologic impact of Hurricane Andrew

Cross-sectional study

Recruited from Marine, Air Force, Army Reserve, National Guard, and Coast Guard units in six southeastern Louisiana parishes; activated in GW (66% saw GW duty); resided in southern Louisiana during 1992 Hurricane Andrew (n = 312)

 

Vasterling et al. 1997

Relationship of intellectual resources to PTSD

Cross-sectional study

Volunteers recruited from enrollment lists of local military units that had mobilized for GW (n = 95; 41 met study eligibility criteria and completed full assessment)

For this study, 18 PTSD diagnosed and 23 psychopathology-free veterans selected

 

Vasterling et al. 1998)

Attention and memory dysfunction in PTSD

Cross-sectional study

As described in Vasterling et al. 1997, but 43 met study criteria

 

Vasterling et al. 2003

Olfactory functioning in GW-era veterans, relationships to war-zone duty, hazards exposures, psychologic distress

Cross-sectional study

Members of south Louisiana National Guard and military reservist units activated for GW duty: n = 105; group recruited as one arm of population described by Brailey et al. 1998: 844 deployed, 326 nondeployed, longitudinal study; n = 319 of these underwent olfactory testing

Deployed to war zone: n = 72

Not deployed to war zone: n = 33

 

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Southwick et al. 1993

Members of two National Guard reserve units, medical company and military police company (n = 240)

Longitudinal study; interviews at two times, eligible if completed psychosocial evaluations

1 month and 6 months after return from gulf

GWVs 160 at 1st meeting (66.7% of total number)

119 completed questionnaire at 1st meeting (74.4%)

84 completed questionnaires 1 month and 6 months after return (70.6%; 52.5% of total at 1st meeting)

No formal assessment of selection bias Investigated where nonresponders were, but no other information was provided

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Stretch et al. 1995

Active-duty and reserve personnel assigned to all Army, Navy, Air Force and Marine units in Hawaii and Pennsylvania (n = 16,167)

Cross-sectional survey distributed to units; Hawaii National Guard did not distribute (n = 2,000)

Enrollment time not available

Total 16,167

Deployed

Nondeployed

14,167 (87.6%)

4,334 (30.6%; 26.8% of eligible)

1,739 (1,524 to gulf, others elsewhere) 2,512

No formal assessment of selection bias (speculated on reasons for nonresponses)

Derivatives from Stretch et al. 1995

Reference

Purpose

Study design

Population

Comments

(where appropriate)

Eligible

Located

Enrolled (Response Rate)

Stretch et al. 1996a

Psychologic health

Cross-sectional survey

Population in Stretch et al. 1995

 

Stretch et al. 1996b

PTSD symptoms

Cross-sectional survey

Population in Stretch et al. 1995

 

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Kang and Bullman 1996

Gulf War veterans (n = 695,516) and other veterans (n = 746,291) identified by Defense Manpower Data Center

Retrospective mortality study

Followup through 1993

 

 

 

Also compared with general population

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Kang and Bullman 2001

GWVs who arrived in the gulf before March 1, 1991 (n = 621,902) and NGVs (n = 746,248)

Retrospective mortality study

Followup began at exit from PG for GWVs and from 5/1/1991 for comparison-group veterans Followup ended 12/31/1997

 

 

 

 

Reference

Eligible population

Type of study or methods

Date(s) of enrollment

Subgroup (n = eligible subjects)

Contacted or Located (% of eligible)

Responded or Enrolled (Response Rate)

Comments

Bullman et al. 2005

GWVs deployed to PG—8/1990-3/1991 (n = 351,041)

Retrospective mortality study; exposure to Khamisiyah defined by 2000 plume model

Followup through 2000

100,487 considered exposed to Khamisiyah plume

 

 

 

NOTE: The committee reported in this table the figures given in each study publication, except response rates. For uniformity, the committee calculated response rates as the number of study participants divided by the number of participants who were located (rather than the number of eligible participants). AFQT = Armed Forces Qualification Test; ANG = Air National Guard; CFS = chronic fatigue syndrome; DOD = Department of Defense; GW = Gulf War;

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

GWS = Gulf War syndrome; GWV = Gulf War veteran; HSC = Health Symptom Checklist; ICF = idiopathic chronic fatigue; MCS = multiple chemical sensitivity; MOD = Ministry of Defence (UK); NDV = nondeployed veteran; NGV = non-Gulf War veteran; ODSS = Operation Desert Shield / Operation Desert Storm; ODTP = Oregon Dual Task Procedures; PG = Persian Gulf; PTSD = posttraumatic stress disorder; PTSS = posttraumatic stress symptomatology; SF-12 = Medical Outcome Study Short Form 12; SF-36 = Medical Outcome Study Short Form 36; SF36-PF = Medical Outcome Study Short Form 36 Physical Functioning; UN = United Nations.

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

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Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Sutker PB, Davis JM, Uddo M, Ditta SR. 1995a. Assessment of psychological distress in Persian Gulf troops: Ethnicity and gender comparisons. Journal of Personality Assessment 64(3):415-427.

Sutker PB, Davis JM, Uddo M, Ditta SR. 1995b. War zone stress, personal resources, and PTSD in Persian Gulf War returnees. Journal of Abnormal Psychology 104(3):444-452.

Sutker PB, Corrigan SA, Sundgaard-Riise K, Uddo M, Allain AN. 2002. Exposure to war trauma, war-related PTSD, and psychological impact of subsequent hurricane. Journal of Psychopathology and Behavioral Assessment 24(1):25-37.

Thompson KE, Vasterling JJ, Benotsch EG, Brailey K, Constans J, Uddo M, Sutker PB. 2004. Early symptom predictors of chronic distress in Gulf War veterans. Journal of Nervous and Mental Disease 192(2):146-152.

United Kingdom Ministry of Defence. 2000. Background to the Use of Medical Countermeasures to Protect British Forces During the Gulf War (Operation Granby). [Online]. Available: http://www.mod.uk/issues/gulfwar/info/medical/ukchemical.htm [accessed September 26, 2003].

Unwin C, Blatchley N, Coker W, Ferry S, Hotopf M, Hull L, Ismail K, Palmer I, David A, Wessely S. 1999. Health of UK servicemen who served in Persian Gulf War. Lancet 353(9148):169-178.

Unwin C, Hotopf M, Hull L, Ismail K, David A, Wessely S. 2002. Women in the Persian Gulf: Lack of gender differences in long-term health effects of service in United Kingdom Armed Forces in the 1991 Persian Gulf War. Military Medicine 167(5):406-413.

Vasterling JJ, Brailey K, Constans JI, Borges A, et al. 1997. Assessment of intellectual resources in Gulf War veterans: Relationship to PTSD. Assessment 4(1):51-59.

Vasterling JJ, Brailey K, Constans JI, Sutker PB. 1998. Attention and memory dysfunction in posttraumatic stress disorder. Neuropsychology 12(1):125-133.

Vasterling JJ, Brailey K, Tomlin H, Rice J, Sutker PB. 2003. Olfactory functioning in Gulf War-era veterans: Relationships to war-zone duty, self-reported hazards exposures, and psychological distress. Journal of the International Neuropsychological Society 9(3):407-418.

Wagner AW, Wolfe J, Rotnitsky A, Proctor SP, Erickson DJ. 2000. An investigation of the impact of posttraumatic stress disorder on physical health. Journal of Traumatic Stress 13(1):41-55.

White RF, Proctor SP, Heeren T, Wolfe J, Krengel M, Vasterling J, Lindem K, Heaton KJ, Sutker P, Ozonoff DM. 2001. Neuropsychological function in Gulf War veterans: Relationships to self-reported toxicant exposures. American Journal of Industrial Medicine 40(1):42-54.

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Wolfe J, Proctor SP, Erickson DJ, Heeren T, Friedman MJ, Huang MT, Sutker PB, Vasterling JJ, White RF. 1999a. Relationship of psychiatric status to Gulf War veterans' health problems. Psychosomatic Medicine 61(4):532-540.

Suggested Citation:"4 Major Cohort Studies." Institute of Medicine. 2006. Gulf War and Health: Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press. doi: 10.17226/11729.
×

Wolfe J, Erickson DJ, Sharkansky EJ, King DW, King LA. 1999b. Course and predictors of posttraumatic stress disorder among Gulf War veterans: A prospective analysis. Journal of Consulting and Clinical Psychology 67(4):520-528.

Wolfe J, Proctor SP, Erickson DJ, Hu H. 2002. Risk factors for multisymptom illness in US Army veterans of the Gulf War. Journal of Occupational and Environmental Medicine 44(3):271-281.

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In 1998, in response to the growing concerns that many returning Gulf War veterans began reporting numerous health problems that they believed to be associated with their service in the Persian Gulf, Congress passed two laws which directed the Secretary of Veterans Affairs to enter into a contract with the National Academy of Sciences. They were tasked to review and evaluate the scientific and medical literature regarding associations between illness and exposure to toxic agents, environmental or wartime hazards, and preventive medicines or vaccines associated with Gulf War service. In addition, the Institute of Medicine of the National Academy of Sciences provided conclusions to these studies that were considered when making decisions about compensation to veterans.

Gulf War and Health Volume 4: Health Effects of Serving in the Gulf War summarizes in one place the current status of health effects in veterans deployed to the Persian Gulf irrespective of exposure information. This book reviews, evaluates, and summarizes both peer-reviewed scientific and medical literature addressing the health status of Gulf War veterans.

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