Pain in veterans of the Gulf War of 1991: a systematic review

BackgroundVeterans of the Persian Gulf War of 1991 have reported a range of adverse health symptoms. This systematic review aims to identify all studies that have compared the prevalence of symptoms of pain in veterans of the Gulf War to that in a non-Gulf military comparison group, and to determine whether Gulf War veterans are at increased risk of reporting pain.MethodsStudies published between January 1990 and May 2004 were identified by searching a large number of electronic databases. Reference lists and websites were also searched and key researchers were contacted. Studies were included if they reported the prevalence of any symptom or condition that included the word "pain" in Gulf War veterans and in a comparison group of non-Gulf veterans. 2401 abstracts were independently reviewed by two authors.ResultsTwenty studies fulfilled the inclusion criteria. Five main sites of pain were identified (muscle, joint, chest/heart, back and abdominal pain) and separate meta-analyses were performed to summarise the results related to each site. A greater proportion of Gulf veterans reported symptoms at each site of pain when compared to a non-Gulf military group. Gulf deployment was most strongly associated with abdominal pain, with Gulf veterans being more than three times more likely to report such pain than a comparison group (OR 3.23; 95%CI 2.31–4.51). Statistical heterogeneity between study estimates was significant, probably due to variation in measured periods of prevalence and symptom measurement methods. higher proportion of veterans of the Persian Gulf War of 1991 reported symptoms of pain than military comparison groups. This is consistent with previously demonstrated increased reporting of more general symptoms (fatigue, multiple chemical sensitivity, post traumatic stress disorder) in these veterans compared with non-Gulf military groups. However, the primary studies were heterogeneous and varied greatly in quality.

Related papers:

title: Musculoskeletal manifestations, pain, and quality of life in Persian Gulf War veterans referred for rheumatologic evaluation.
abstract: Pain in the joints and other areas has been a frequent complaint among veterans of Operation Desert Storm who are experiencing unexplained illness. We characterized the rheumatic manifestations of a group of veterans of the Persian Gulf War who were referred to a rheumatology clinic.



Consecutive South Texas veterans of the Persian Gulf War who were referred for evaluation of rheumatic manifestations underwent a comprehensive evaluation of their musculoskeletal symptoms, pain, and health related quality of life.



Of 928 veterans evaluated in a screening clinic for unexplained symptoms, 145 had rheumatic manifestations (15.6%) and were referred to a rheumatology clinic. The most common diagnosis was fibromyalgia, present in 49 patients (33.8%), followed by various soft tissue problems in 25 (17.2%), nonspecific arthralgias in 14 (9.6%), and clinical or radiographic osteoarthritis in 16 (11.0%). In 39 patients (26.9%), no symptoms were present at the time of the evaluation, a careful musculoskeletal examination and laboratory tests were normal, and no diagnosis was possible. Two patients had Reiter's syndrome. Four had a positive rheumatoid factor and 3 had antinuclear antibodies, but none of these had clinical evidence of rheumatoid arthritis or systemic lupus erythematosus. Pain was present in nearly all patients and was widely distributed, with no body area spared in this group of patients. The most frequent painful areas were the knees in > 65%, the lower back in > 60%, the shoulders in 50%, and the hands and wrists in 35%. Widespread body pain was present in 65.1% of the veterans. Average values of all 8 scales measured by the SF-36 health survey were below the 25th percentile of published national norms, with pain and the number of nonarticular rheumatic symptoms explaining most of the decreased health related quality of life in the veterans we evaluated.



No specific rheumatic diagnosis is characteristic of Gulf War veterans with unexplained illness referred to a rheumatology clinic. However, pain is common and widespread in these patients, and their health related quality of life is poor. Further research is necessary to determine the cause of the symptoms of veterans of the Gulf War.

title: Chronic multisymptom illness affecting Air Force veterans of the Gulf War.
abstract: Gulf War (GW) veterans report nonspecific symptoms significantly more often than their nondeployed peers. However, no specific disorder has been identified, and the etiologic basis and clinical significance of their symptoms remain unclear.



To organize symptoms reported by US Air Force GW veterans into a case definition, to characterize clinical features, and to evaluate risk factors.



Cross-sectional population survey of individual characteristics and symptoms and clinical evaluation (including a structured interview, the Medical Outcomes Study Short Form 36, psychiatric screening, physical examination, clinical laboratory tests, and serologic assays for antibodies against viruses, rickettsia, parasites, and bacteria) conducted in 1995.



The cross-sectional questionnaire survey included 3723 currently active volunteers, irrespective of health status or GW participation, from 4 air force populations. The cross-sectional clinical evaluation included 158 GW veterans from one unit, irrespective of health status.



Symptom-based case definition; case prevalence rate for GW veterans and nondeployed personnel; clinical and laboratory findings among veterans who met the case definition.



We defined a case as having 1 or more chronic symptoms from at least 2 of 3 categories (fatigue, mood-cognition, and musculoskeletal). The prevalence of mild-to-moderate and severe cases was 39% and 6%, respectively, among 1155 GW veterans compared with 14% and 0.7% among 2520 nondeployed personnel. Illness was not associated with time or place of deployment or with duties during the war. Fifty-nine clinically evaluated GW veterans (37%) were noncases, 86 (54%) mild-to-moderate cases, and 13 (8%) severe cases. Although no physical examination, laboratory, or serologic findings identified cases, veterans who met the case definition had significantly diminished functioning and well-being.



Among currently active members of 4 Air Force populations, a chronic multisymptom condition was significantly associated with deployment to the GW. The condition was not associated with specific GW exposures and also affected nondeployed personnel.

title: Prevalence of chronic benign pain disorder among adults: a review of the literature
abstract: In this review epidemiological studies concerning chronic benign pain among adults are discussed. To this end, studies focusing on chronic pain, reporting prevalences at a population or primary health care level, including subjects aged between 18 and 75 years have been collected and analyzed. Focus of analysis was on research methods, definitions of chronic benign pain used, and reported prevalences. Prevalences varied between 2% and 40% of the population. Nor method used (telephone survey, postal survey, nor definition of chronicity (>1 month; >3 months; >6 months) clearly explained the differences in prevalence in the various studies. Implications for future research are discussed.

title: Epidemiology of illness and injury among U.S. Navy and Marine Corps female training populations.
abstract: Evidence suggests that female military populations are at greater risk than their male counterparts for certain training- and combat-related illnesses and injuries. The objective of this prospective, multisite, epidemiological study was to define the patterns of illness and injury in military women during training. We developed a computer-based outpatient tracking system for prospective data collection of all outpatient encounters for use at (1) Officer Candidate School (OCS), Quantico; (2) Marine Corps Recruit Depot (MCRD), Parris Island; and (3) Recruit Training Command (RTC), Great Lakes. During the study period, 85.8% of OCS candidates (260 of 303), 72.4% of MCRD recruits (2,002 of 2,766), and 83.4% of RTC recruits (7,395 of 8,865) had at least one medical encounter during training. The most common category of medical encounters at all three sites was musculoskeletal injury, followed by respiratory and dermatological disorders. This study establishes high morbidity rates and identifies medical priorities for preventive interventions in Marine Corps and Navy female trainees.

title: Gulf War unexplained illnesses: persistence and unexplained nature of self-reported symptoms.
abstract: Most published reports of health symptoms among Gulf War (GW) veterans have been based on self-reported questionnaire data. The presence of these symptoms at the time of a clinical evaluation and the unexplained nature of the symptoms have not been described. We report the findings of a sample of symptomatic veterans that were examined as part of a population-based case-control study of GW unexplained illnesses. Participants in the case-control study were selected from responders to a cross-sectional survey of a random sample of GW veterans residing in the northwestern United States. The initial survey questionnaire solicited information on the presence of fatigue and psychological/cognitive, gastrointestinal, musculoskeletal, and dermatological problems. The persistence of the symptoms and possible explanatory diagnoses were explored at the time of the clinical evaluation. Findings from the first 225 participants who completed clinical examinations indicate significant differences between self-reported symptoms on the survey questionnaire and those confirmed at the time of clinical exam. The agreement between symptoms reported both on the survey and at the time of examination varies across the symptom groups. While self-reported unexplained fatigue was confirmed at the time of clinical encounter in 79% of participants, self-reported gastrointestinal symptoms were confirmed at the clinical encounter in only 20% of participants. Differences between symptoms reported on the survey questionnaire and those confirmed at the time of clinical encounter were attributable to finding a clinical diagnosis for the symptom, resolution of symptom(s) between time of questionnaire and clinical exam, and inadvertent endorsement of the symptom on the questionnaire. These findings suggest that due to the possibility of outcome misclassification, inappropriate conclusions may be drawn about the association between exposures and unexplained illnesses in GW veterans from data derived solely from self-administered questionnaires.

title: Psychiatric disorder in veterans of the Persian Gulf War of 1991
abstract: Veterans of the Persian Gulf War of 1991 have reported symptoms attributed to their military service.  To review all studies comparing the prevalence of psychiatric disorders in Gulf War veterans and in a comparison group of service personnel not deployed to the Gulf War.  Studies of military personnel deployed to the Gulf published between 1990 and 2001 were identified from electronic databases. Reference lists and websites were searched and key researchers were contacted for information. Atotal of 2296 abstracts and 409 complete articles were reviewed and data were extracted independently by two members of the research team.  The prevalence of psychiatric disorder in 20 studies of Gulf War veterans was compared with the prevalence in the comparison group. Prevalence of post-traumatic stress disorder (PTSD) and common mental disorder were higher in the Gulf War veterans. Heterogeneity between studies was significant, but all reported this increased prevalence.  Veterans of the Persian Gulf War reported an increased prevalence of PTSD and common mental disorder compared with other active service personnel not deployed to the Gulf. These findings are attributable to the increase in psychologically traumatic events in wartime.

title: Meta-analysis: Potentials and promise
abstract: The number of papers published on meta-analyses in medical research has increased sharply in the past 10 years (fig 1). The merits and perils of the somewhat mysterious procedure of meta-analysis, however, continue to be debated in the medical  23 What, then, is meta-analysis? A useful definition was given by Huque: “A statistical analysis that combines or integrates the results of several independent clinical trials considered by the analyst to be ‘combinable.’” 4 The terminology, however, is still debated, and expressions used concurrently include “overview,” “pooling,” and “quantitative synthesis.” We believe that the term meta-analysis should be used to describe the statistical integration of separate studies, whereas “systematic review” is most appropriate for denoting any review of a body of data that uses clearly defined methods and criteria (box). Systematic reviews can include meta-analyses, appraisals of single trials, and other sources of  In this article we examine the potentials and promise of meta-analysis of randomised controlled trials. In later articles of this series we will consider the practical steps involved in meta-analysis,7 examine various extensions beyond the calculation of a combined estimate,8 address potential biases and discuss strategies to detect and minimise the influence of these in meta-analysis of randomised trials9 and of observational studies.10 We will conclude with a discussion of unresolved issues and future developments.11 Details of relevant software will appear on the BMJ's website at the end of the series.



Fig 1 
Number of publications about meta-analysis, 1987–96 (results from Medline search using text word and medical subject heading “meta-analysis”)



 The case for “meta-analysis”

The term meta-analysis for statistically combining and analysing data from separate studies is appropriate because:

title: Meta-analysis in clinical trials.
abstract: This paper examines eight published reviews each reporting results from several related trials. Each review pools the results from the relevant trials in order to evaluate the efficacy of a certain treatment for a specified medical condition. These reviews lack consistent assessment of homogeneity of treatment effect before pooling. We discuss a random effects approach to combining evidence from a series of experiments comparing two treatments. This approach incorporates the heterogeneity of effects in the analysis of the overall treatment efficacy. The model can be extended to include relevant covariates which would reduce the heterogeneity and allow for more specific therapeutic recommendations. We suggest a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.

title: War‐Zone Trauma and Stress‐Related Symptoms in Operation Desert Shield/Storm (ODS) Returnees
abstract: A growing literature suggests that human beings are often negatively impacted by participation in military combat, but there have been few attempts to document the psychological effects of war stress in the masses of troops deployed to action. We chose to study the relationship of Operation Desert Shield/Storm (ODS) participation and symptoms of psychological distress in a comparison of 215 Army National Guard and Army Reserve troops who were activated to service in the Persian Gulf and returned to the States without seeking mental health treatment services and 60 troops from these same units who were activated but not deployed overseas. Negative psychological outcomes were measured within four to ten months from homecoming in three domains: negative mood states, symptoms of posttraumatic stress disorder (PTSD), and physical health complaints. Results indicated that as war-zone stress exposure increased, the frequency and severity of psychological symptoms were enhanced, providing correlational evidence of the adverse impact of war stress, at least among a subset of ODS returnees. As many as 16–24% of war zone exposed troops exhibited levels of distress symptomatology sufficiently exaggerated to suggest the presence of mental disorders, specifically clinical depression and PTSD. Psychological symptoms were less frequently reported among troops classified in the lower war-zone stress exposure subset and those activated but not deployed to the Persian Gulf.

title: Is there a Persian Gulf War syndrome? Evidence from a large population-based survey of veterans and nondeployed controls.
abstract: Concerns have been raised about whether veterans of the Gulf War have a medical illness of uncertain etiology. We surveyed veterans to look for evidence of an illness that was unique to those deployed to the Persian Gulf and was not seen in comparable military controls.



A population-based sample of veterans (n = 1,896 from 889 units) deployed to the Persian Gulf and other Gulf War-era controls (n = 1799 from 893 units) who did not serve in the Gulf were surveyed in 1995-1996. Seventy-six percent of eligible subjects, including 91% of located subjects, answered questions about commonly reported and potentially important symptoms. We used factor analysis, a statistical technique that can identify patterns of related responses, on a random subset of the deployed veterans to identify latent patterns of symptoms. The results from this derivation sample were compared with those obtained from a separate validation sample of deployed veterans, as well as the nondeployed controls, to determine whether the results were replicable and unique.



One half (50%) of the deployed veterans and 14% of the nondeployed controls reported health problems that they attributed to military service during 1990-1991. Compared with the nondeployed controls, the deployed veterans had significantly greater prevalences of 123 of 137 (90%) symptoms; none was significantly lower. Factor analysis identified three replicable symptom factors (or patterns) in the deployed veterans (convergent correlations > or =0.85). However, these patterns were also highly replicable in the nondeployed controls (convergent correlations of 0.95 to 0.98). The three factors also accounted for similar proportions of the common variance among the deployed veterans (35%) and nondeployed controls (30%).



The increased prevalence of nearly every symptom assessed from all bodily organ systems among the Gulf War veterans is difficult to explain pathophysiologically as a single condition. Identification of the same patterns of symptoms among the deployed veterans and nondeployed controls suggests that the health complaints of Gulf War veterans are similar to those of the general military population and are not consistent with the existence of a unique Gulf War syndrome.

title: Health-related quality of life in Gulf War era military personnel.
abstract: The Gulf War's impact on veterans' health-related quality of life (HRQL) remains unclear. The authors examined the HRQL of military personnel deployed to the Gulf War Theater compared with those not deployed. In 1995-1996, a structured, population-based telephone survey was conducted 5 years postconflict among a cohort originally from Iowa on active duty during the conflict. The sample included 4,886 eligible subjects stratified by deployment and military status and proportionately distributed within five substrata. The Medical Outcome Study Short Form-36 (SF-36) assessed HRQL, and multivariable linear regression identified pre- and perideployment risk factors. A total of 3,695 respondents (76%) participated. Nondeployed participants reported excellent health more often than deployed participants (31% vs. 21%, p < 0.01). SF-36 scores for deployed participants were poorer than those for nondeployed controls across all health domains. Modifiable factors such as smoking and military preparedness, and other factors such as predeployment physical and mental health morbidity, were independent risk factors for poorer HRQL after deployment. Deployed veterans reported slightly poorer HRQL even after the authors adjusted for other risk factors. Further investigation of factors influencing postdeployment HRQL is needed. Routine collection of health information by using standardized instruments pre- and perideployment should be implemented.

title: Health-related quality of life in Persian Gulf War Veterans.
abstract: The objective of this investigation is to describe the health-related quality of life of Persian Gulf War (GW) veterans and to examine the effects of current chronic medical conditions and psychiatric status on physical functioning.



To measure health-related quality of life, the Medical Outcomes Short Form Survey (SF36) was administered approximately 4 years after the GW to a stratified, random sample of New England-area GW-deployed veterans and a group of military personnel deployed to Germany during the GW. The SF36 scores for the GW-deployed study population (N = 141) were compared with those for the Germany-deployed group (N = 46) and with published U.S. population norms. Multiple linear regression analyses were performed to identify risk factors associated with lower physical health functioning in the GW-deployed study group.



Functional health status was significantly lower in the GW-deployed group compared with the Germany-deployed group for each of the SF36 subscales and the two summary scores (Physical Component Summary [PCS] and Mental Component Summary). Compared with the general U.S. population, the GW-deployed group median was between the 25th and 50th percentile for the Physical Functioning subscale and the PCS score. Within the GW-deployed group, lower education, psychological symptomatology, and a higher number of chronic self-reported medical conditions were significant predictors of the PCS score.



GW-deployed veterans report lower functional health status compared with a group of Germany-deployed veterans and published general U.S. population norms. Within the group of GW-deployed veterans, several current medical and psychological conditions predictive of lower physical functioning levels were identified.

title: State of health after deployment in the Persian Gulf. The Danish Gulf War Study.
abstract: Multiple symptoms have been reported in American Gulf War Veterans including headache, fatigue, impaired short-term memory, sleep disturbances, agitation, respiratory symptoms, muscle and joint pain, diseases of the skin, and intermittent fever. The Danish Gulf War Study was performed to clarify if a corresponding pattern existed among Danes having served in the Persian Gulf during and mainly after the conflict.



A cross-sectional study was performed during the period January 1997 to January 1998 which included 821 subjects who had been deployed in the Persian Gulf within the period August 2 1990 until December 31 1997. Of 686 (83.6%) subjects who participated in the study, 95% had been engaged in peace keeping operations after the war. A group consisting of randomly selected age- and gender matched controls, comprised 231 of 400 potential participants (57.7%). All participants underwent clinical and paraclinical examinations, and had an interview based on a previously completed questionnaire.



Unspecific symptoms such as repeated fits of headache, fatigue, memory and concentration difficulties, sleep disturbances, agitation, dyspnea, diseases of the skin, and intermittent fever, were significantly more frequent among Danish Gulf War Veterans, p < 0.05, than among controls; no association was found with respect to muscle and joint pain. The higher symptom prevalence among Gulf War Veterans was observed for conditions which had made their first appearance during or after the Gulf War. The prevalence of symptoms which made their first appearance before August 2 1990 was similar for both groups.



Except for musculo-skeletal symptoms, this study demonstrated a pattern of symptoms among Danish Gulf War Veterans consistent with the findings among American Gulf War Veterans. Considering that American Gulf War Veterans were predominantly deployed during the armament phase and the brief war phase, and that Danish Gulf War Veterans were predominantly deployed after the war in peace keeping missions, the results indicate the existence of some common risk factors independent of war action.

title: Health of UK servicemen who served in Persian Gulf War
abstract: Various symptoms in military personnel in the Persian Gulf War 1990-91 have caused international speculation and concern. We investigated UK servicemen.



We did a cross-sectional postal survey on a random sample of Gulf War veterans (Gulf War cohort, n=4248) and, stratified for age and rank, servicemen deployed to the Bosnia conflict (Bosnia cohort, n=4250) and those serving during the Gulf War but not deployed there (Era cohort, n=4246). We asked about deployment, exposures, symptoms, and illnesses. We analysed men only. Our outcome measures were physical health, functional capacity (SF-36), the general health questionnaire, the Centers for Disease Control and Prevention (CDC) multisymptom criteria for Gulf War illness, and post-traumatic stress reactions.



There were 8195 (65.1%) valid responses. The Gulf War cohort reported symptoms and disorders significantly more frequently than those in the Bosnia and Era cohorts, which were similar. Perception of physical health and ability were significantly worse in the Gulf War cohort than in the other cohorts, even after adjustment for confounders. Gulf War veterans were more likely than the Bosnia cohort to have substantial fatigue (odds ratio 2.2 [95% CI 1.9-2.6]), symptoms of post-traumatic stress (2.6 [1.9-3.4]), and psychological distress (1.6 [1.4-1.8]), and were nearly twice as likely to reach the CDC case definition (2.5 [2.2-2.8]). In the Gulf War, Bosnia, and Era cohorts, respectively, 61.9%, 36.8%, and 36.4% met the CDC criteria, which fell to 25.3%, 11.8%, and 12.2% for severe symptoms. Potentially harmful exposures were reported most frequently by the Gulf War cohort. All exposures showed associations with all of the outcome measures in the three cohorts. Exposures specific to the Gulf were associated with all outcomes. Vaccination against biological warfare and multiple routine vaccinations were associated with the CDC multisymptom syndrome in the Gulf War cohort.



Service in the Gulf War was associated with various health problems over and above those associated with deployment to an unfamiliar hostile environment. Since associations of ill health with adverse events and exposures were found in all cohorts, however, they may not be unique and causally implicated in Gulf-War-related illness. A specific mechanism may link vaccination against biological warfare agents and later ill health, but the risks of illness must be considered against the protection of servicemen.

title: 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.
abstract: A cross-sectional postal survey was conducted to evaluate the health of a random sample of United Kingdom Armed Forces personnel who were deployed to the 1990-1991 Persian Gulf conflict compared with nondeployed controls and controls deployed to Bosnia. The health of service women was examined and compared with that of United Kingdom service men. The main outcome measures were physical symptoms and ailments, functional capacity on the 36-item Short-Form Health Survey, the 12-item General Health Questionnaire, the Centers for Disease Control and Prevention multisymptom criteria for Gulf War illness, and post-traumatic stress reactions. There were 645 (65.3%) valid responses. The women from the Gulf cohort reported each symptom and the majority of health outcomes more frequently than either control group. No gender differences were found for 32 of the 50 symptoms assessed. Of the remaining 18 symptoms, women reported significantly more than men for only 6 of them, and there were no gender differences in 5 of the 6 principal health outcome measures. Women deployed to the Persian Gulf had similar rates of ill health as their male counterparts. Nothing was found to suggest that, other than for gender-specific health effects, any special considerations need to be made on health grounds for service women in any future deployments.

title: Illnesses among United States veterans of the Gulf War: a population-based survey of 30,000 veterans.
abstract: Despite numerous studies on veterans of the 1990 to 1991 Gulf War, the fundamental questions of how healthy they are and how their health compares with that of their military peers who were not deployed to the Gulf have not been fully answered. We conducted a health survey in which the health outcomes of a population-based sample of 15,000 Gulf veterans representing various military branches and unit components (regular, reserve, National Guard) were compared with those of 15,000 non-Gulf veterans who were randomly sampled to mirror the number in the same military strata in the Gulf veteran group. In comparison with their peers, Gulf veterans had a higher prevalence of functional impairment, health care utilization, symptoms, and medical conditions and a higher rate of low general health perceptions. A longitudinal follow-up of the health of these veterans will be needed to detect changes in health status and to detect diseases with a long latency period.

title: Factor analysis of self-reported symptoms: does it identify a Gulf War syndrome?
abstract: Active duty US Naval mobile construction battalion personnel (Seabees) were surveyed in 1994 for the presence of a variety of symptoms. Questions were drawn from the Hopkins Symptom Checklist and from a collection of symptoms either defining clinical depression or commonly reported by Persian Gulf War veterans. Of those surveyed, 524 were Gulf War veterans and 935 were nondeployed Gulf War-era veterans. Factor analysis applied to Gulf War veterans yielded five factors, three deriving from the Hopkins Symptom Checklist, one suggesting clinical depression, and one containing symptoms commonly reported by Gulf War veterans. Factor analysis applied to nondeployed veterans yielded five similar factors. Three of the factors yielded statistically significantly greater standardized factor scores for Gulf War veterans than for nondeployed veterans. Four of the factors resembled factors resulting from a previous analysis on a sample of similar Gulf War veterans. Gulf War veterans and nondeployed era veterans reported similar clusters of symptoms and illnesses. However, Gulf War veterans reported these same clusters with greater frequencies than did nondeployed veterans. The authors conclude that, in contrast to a previous report, factor analysis did not identify a unique Gulf War syndrome.

title: Health and exposures of United Kingdom Gulf war veterans. Part I: The pattern and extent of ill health
abstract: To assess the health of United Kingdom Gulf war veterans, to compare their health to that of similar personnel not deployed, to describe patterns of ill health in both groups, and to estimate their extent.  Main Gulf (n=4795) and validation Gulf (n=4793) cohorts were randomly selected within strata from the population deployed to the Gulf and a non-Gulf cohort (n=4790) from those who were not sent. Seven years after the war subjects completed a questionnaire about their health in the past month, including 95 symptom questions and two manikins on which to shade areas of pain or numbness and tingling. Responses were subjected to a principal component analysis with rotation and to a cluster analysis within each cohort. Mean symptom score was used as a measure of severity. Areas shaded on the manikins were coded to indicate widespread pain and possible toxic neuropathy.  A response of 85.5% was achieved. Those who had been to the Gulf were more troubled by every symptom with a mean severity score (3.0) substantially greater than in the non-Gulf cohort (1.7). Seven factors were extracted accounting for 48% of the variance. The scores on five factors (labelled psychological, peripheral, respiratory, gastrointestinal, and concentration) were significantly worse in those who had been to the Gulf. Symptoms suggestive of peripheral neuropathy were found more often (12.5%) in the Gulf than the non-Gulf (6.8%) cohorts. Widespread pain was also found more often (12.2% Gulf; 6.5% non-Gulf). Those who had been to the Gulf were found disproportionately (23.8%) in three clusters with high mean severity scores; only 9.8% of non-Gulf respondents were in these clusters. There was no evidence of an important excess in the use of alcohol, tobacco, or referral to hospital specialists by those who had been to the Gulf. For the same level of reported ill health those who had been to the Gulf were less likely to be referred to specialists than non-Gulf veterans.  Years after the war, the Gulf war veterans were more troubled about their health than those who had not been sent, with a substantial subgroup reporting a pattern of symptoms suggestive of a significant decline in health.

title: Self-reported ill health in male UK Gulf War veterans: a retrospective cohort study
abstract: BackgroundForces deployed to the first Gulf War report more ill health than veterans who did not serve there. Many studies of post-Gulf morbidity are based on relatively small sample sizes and selection bias is often a concern. In a setting where selection bias relating to the ill health of veterans may be reduced, we: i) examined self-reported adult ill health in a large sample of male UK Gulf War veterans and a demographically similar non-deployed comparison group; and ii) explored self-reported ill health among veterans who believed that they had Gulf War syndrome.MethodsThis study uses data from a retrospective cohort study of reproduction and child health in which a validated postal questionnaire was sent to all UK Gulf War veterans (GWV) and a comparison cohort of Armed Service personnel who were not deployed to the Gulf (NGWV). The cohort for analysis comprises 42,818 males who responded to the questionnaire.ResultsWe confirmed that GWV report higher rates of general ill health. GWV were significantly more likely to have reported at least one new medical symptom or disease since 1990 than NGWV (61% versus 37%, OR 2.7, 95% CI 2.5–2.8). They were also more likely to report higher numbers of symptoms. The strongest associations were for mood swings (OR 20.9, 95%CI 16.2–27.0), memory loss/lack of concentration (OR 19.6, 95% CI 15.5–24.8), night sweats (OR 9.9, 95% CI 6.5–15.2), general fatigue (OR 9.6, 95% CI 8.3–11.1) and sexual dysfunction (OR 4.6, 95%CI 3.2–6.6). 6% of GWV believed they had Gulf War syndrome (GWS), and this was associated with the highest symptom reporting.ConclusionsIncreased levels of reported ill health among GWV were confirmed. This study was the first to use a questionnaire which did not focus specifically on the veterans' symptoms themselves. Nevertheless, the results are consistent with those of other studies of post-Gulf war illness and thus strengthen overall findings in this area of research. Further examination of the mechanisms underlying the reporting of ill health is required.

title: Symptoms and medical conditions in Australian veterans of the 1991 Gulf War: relation to immunisations and other Gulf War exposures
abstract: To investigate whether Australian Gulf War veterans have a higher than expected prevalence of recent symptoms and medical conditions that were first diagnosed in the period following the 1991 Gulf War; and if so, whether these effects were associated with exposures and experiences that occurred in the Gulf War.  Cross-sectional study of 1456 Australian Gulf War veterans and a comparison group who were in operational units at the time of the Gulf War, but were not deployed to that conflict (n = 1588). A postal questionnaire was administered and the likelihood of the diagnosis of self-reported medical conditions was assessed and rated by a medical practitioner.  Gulf War veterans had a higher prevalence of all self-reported health symptoms than the comparison group, and more of the Gulf War veterans had severe symptoms. Increased symptom reporting was associated with several exposures, including having more than 10 immunisations, pyridostigmine bromide tablets, anti-biological warfare tablets, pesticides, insect repellents, reportedly being in a chemical weapons area, and stressful military service experiences in a strong dose-response relation. Gulf War veterans reported psychological (particularly post-traumatic stress disorder), skin, eye, and sinus conditions first diagnosed in 1991 or later more commonly than the comparison group. Over 90% of medical conditions reported by both study groups were rated by a medical practitioner as having a high likelihood of diagnosis.  More than 10 years after the 1991 Gulf War, Australian veterans self-report all symptoms and some medical conditions more commonly than the comparison group. Further analysis of the severity of symptoms and likelihood of the diagnosis of medical conditions suggested that these findings are not due to over-reporting or to participation bias.

title: Increased postwar symptoms and psychological morbidity among U.S. Navy Gulf War veterans.
abstract: To investigate reports on war-related morbidity, 527 active-duty Gulf War veterans and 970 nondeployed veterans from 14 Seabee commands were studied in 1994 with a questionnaire, sera collection, handgrip strength, and pulmonary function testing. The questionnaire assessed postwar symptoms, war exposures, and screened for chronic fatigue syndrome, post-traumatic stress disorder, and psychological symptoms suggesting neurosis (Hopkins Symptom Checklist). Sera were tested with four nonspecific reactant assays: C-reactive protein, transferrin, ferritin, and haptoglobin. Gulf War veterans reported a higher prevalence for 35 of 41 symptoms, scored higher on psychological symptom scales, were more likely to screen for post-traumatic stress disorder, had lower handgrip strength, and had higher serum ferritin assay results. Numerous comparisons of these morbidity outcomes with 30 self-reported exposures demonstrated many associations, but no unique exposure or group of exposures were implicated. Morbidity data are consistent with other postwar observations, but the etiology for morbidity findings remains uncertain.

title: Relationship of psychiatric status to Gulf War veterans' health problems.
abstract: A growing body of research has shown that there are important links between certain psychiatric disorders and health symptom reporting. Two disorders in particular (posttraumatic stress disorder (PTSD) and major depression) have been the most widely implicated to date, and this association has sometimes been used to explain the occurrence of ill-defined medical problems and increased somatic symptoms in certain groups, most recently Gulf War veterans.



Structured psychiatric diagnostic interviews were used to examine the presence of major psychiatric (axis I) disorders and their relation to health symptom reporting in a well-characterized, stratified subset of Gulf War veterans and a non-Gulf-deployed veteran comparison group.



Rates of most psychiatric disorders were substantially lower than national comorbidity estimates, consistent with prior studies showing heightened physical and emotional well-being among active-duty military personnel. Rates of PTSD and major depression, however, were significantly elevated relative to the veteran comparison group. The diagnosis of PTSD showed a small but significant association with increased health symptom reports. However, nearly two-thirds of Gulf participants reporting moderate to high health symptoms had no axis I psychiatric diagnosis.



Results suggest that rates of psychiatric illness were generally low with the exception of PTSD and major depression. Although PTSD was associated with higher rates of reported health problems, this disorder did not entirely account for symptoms reported by participants. Factors other than psychiatric status may play a role in Gulf War health problems.

title: Deployment stressors and a chronic multisymptom illness among Gulf War veterans.
abstract: Unusual health problems have been reported by Gulf War (GW) veterans, but no single etiology has been linked to these illnesses. This study was conducted to determine the association between self-reported GW deployment stressors and an illness defined by a combination of fatigue, mood-cognition, and musculoskeletal symptoms. A total of 1002 GW veterans from this cross-sectional survey of four Air Force units completed a self-administered questionnaire that asked about symptoms, demographic and military characteristics, and stressors during deployment. Severe and mild-moderate illness was positively associated with self-reports of pyridostigmine bromide use, insect repellent use and belief in a threat from biological or chemical weapons. Injuries requiring medical attention were only associated with severe illness. These results suggest a link between self-reported chemical, emotional, and physical exposures, and GW veterans' illness. Further research is needed to determine physiological and psychological mechanisms through which such stressors could have contributed to this symptom complex.

title: Severely disabling chronic pain in young adults: prevalence from a population-based postal survey in North Staffordshire
abstract: BackgroundSeverely disabling chronic pain in the adult population is strongly associated with a range of negative health consequences for individuals and high health care costs, yet its prevalence in young adults is less clear.MethodsAll adults aged 18–25 years old registered with three general practices in North Staffordshire were invited to complete a postal questionnaire containing questions on pain within the last 6 months, pain location and duration. Severity of chronic pain was assessed by the Chronic Pain Grade. Severely disabling chronic pain was defined as pain within the last six months that had lasted for three months or more and was highly disabling-severely limiting (Grade IV).Results858 responses from 2,389 were received (adjusted response = 37.0%). The prevalence of any pain within the previous six months was 66.9% (95%CI: 63.7%, 70.1%). Chronic pain was reported by 14.3% (95%CI: 12.0%, 16.8%) of respondents with severely disabling chronic pain affecting 3.0% (95%CI: 2.0%, 4.4%) of this population. Late responders were very similar to early responders in their prevalence of pain. Cross-checking the practice register against the electoral roll suggested register inaccuracies contributed to non-response.ConclusionPain is a common phenomenon encountered by young adults, affecting 66.9% of this study population. Previously observed age-related trends in severely disabling chronic pain in older adults extend to younger adults. Although a small minority of younger adults are affected, they are likely to represent a group with particularly high health care needs. High levels of non-response in the present study means that these estimates should be interpreted cautiously although there was no evidence of non-response bias.

title: Relationship of Physical Symptoms to Posttraumatic Stress Disorder Among Veterans Seeking Care for Gulf War-Related Health Concerns
abstract: Studies of the relationship of posttraumatic stress disorder (PTSD) to physical symptoms in war veterans consistently show a positive relationship. However, traumatic experiences causing PTSD may correlate with other war exposures and medical illnesses potentially accounting for those symptoms.  We analyzed data obtained from 21,244 Gulf War veterans seeking care for war-related health concerns to assess the relationship of PTSD to physical symptoms independent of environmental exposure reports and medical illness. At assessment, veterans provided demographic information and checklists of 15 common physical symptoms and 20 wartime environmental exposures. Up to seven ICD-9 provider diagnoses were ranked in order of estimated clinical significance. The relationship of provider-diagnosed PTSD to various physical symptoms and to the total symptom count was then determined in bivariate and multivariate analyses.  Veterans diagnosed with PTSD endorsed an average of 6.7 (SD = 3.9) physical symptoms, those with a non-PTSD psychological condition endorsed 5.3 (3.5), those with medical illness endorsed 4.3 (3.4), and a group diagnosed as “healthy” endorsed 1.2 (2.2). For every symptom, the proportion of veterans reporting the symptom was highest in those with PTSD, second highest in those with any psychological condition, third highest in those with any medical illness, and lowest in those labeled as healthy. The PTSD–symptom count relationship was independent of demographic characteristics, veteran-reported environmental exposures, and comorbid medical conditions, even when symptoms overlapping with those of PTSD were excluded.  PTSD diminishes the general health perceptions of care-seeking Gulf War veterans. Clinicians should carefully consider PTSD when evaluating Gulf War veterans with vague, multiple, or medically unexplained physical symptoms.

title: Systematic review of multi-symptom conditions in Gulf War veterans
abstract: Gulf War veterans have a number of health complaints. We therefore decided to carry out a systematic review to identify and summarize the findings from studies that have assessed multi-symptom conditions in Gulf War veterans and in an unexposed comparison group.  Studies published between January 1990 and May 2004 were identified by searching a large number of electronic databases. Reference lists and websites were also searched and key researchers were contacted. Studies were included if they compared the prevalence of chronic fatigue syndrome, multiple chemical sensitivity, CDC-defined chronic multi-symptom illness, fibromyalgia, or symptoms of either fatigue or numbness and tingling in Gulf War veterans and non-Gulf veterans. A total of 2401 abstracts were independently reviewed by two authors.  Twenty-three publications fulfilled the inclusion criteria. Gulf deployment was most strongly associated with chronic fatigue syndrome (OR 3·8, 95% CI 2·2–6·7). Gulf War veterans were also approximately three and a half times more likely than non-Gulf veterans to report multiple chemical sensitivity or chronic multi-symptom illness as defined by CDC. The methodological quality of the studies varied but the later and larger studies were of a high methodological standard with robust sampling strategies, adequate response rates and good adjustment for confounders.  The results support the hypothesis that deployment to the Gulf War is associated with greater reporting of multi-symptom conditions.