Evaluation of neuromuscular symptoms in UK Gulf War veterans: a controlled study.

OBJECTIVES: To determine whether Gulf War veterans with neuromuscular symptoms that included weakness and fatigue had either 1) objective correlates for muscle weakness or fatigue; or 2) any etiologic explanation for such symptoms; and if so, 3) whether such objective measures or etiologic mechanisms were specific to Gulf War service. METHODS: Forty-nine ill Gulf War veterans with more than four neuromuscular symptoms (Gulf-ill) were compared with 26 Gulf-well veterans, 13 symptomatic Bosnian veterans (Bosnia-ill), and 22 symptomatic troops who were not deployed to the Gulf (Era-ill). Quantitative myometry was used to objectively measure weakness and fatigue. Subjects had an ischemic forearm exercise test, a subanaerobic bicycle exercise test, and a muscle biopsy. RESULTS: Quantitative strength and fatigue measures did not correlate with self-perception of weakness or fatigue for any of our groups. No specific muscle biopsy abnormalities were found. There was no defect of adenylate deaminase or glycogenolysis found. Gulf-ill subjects did find the subanaerobic bicycle exercise more effortful and generated significantly higher plasma lactate concentrations compared with Gulf-well subjects. CONCLUSION: Because complaints of weakness and fatigue in unwell servicemen do not correlate with actual weakness or fatigue, explanations for these symptoms must lie outside of the neuromuscular system. Increased lactate production during subanaerobic bicycle exercise reflects mitochondrial inefficiency, but it is unclear whether this reflects mitochondrial damage sustained during Gulf War service or inactivity secondary to ill health.

Risk factors for continued illness among Gulf War veterans: a cohort study.

BACKGROUND: There are no prospective cohort studies of prognostic factors on the outcome of Gulf War veterans. We aimed to test the hypotheses that Gulf War veterans who were older; had more severe symptoms; had more exposures during deployment; had increased psychological distress and believed they had 'Gulf War syndrome' would experience greater fatigue and poorer physical functioning at follow-up. METHOD: Gulf War veterans who responded to an earlier retrospective cohort study were followed with a postal survey. More symptomatic individuals were oversampled. Outcome was measured on the Chalder fatigue questionnaire, the General Health Questionnaire and the Medical Outcome Study Short-Form 36. RESULTS: Of those surveyed, 73.8% responded. We found some evidence for four of the five hypotheses. More self-reported exposures at baseline were not associated with poorer outcome, but older people, those with more severe symptoms at baseline, those with psychological distress and who believed they were suffering from 'Gulf War syndrome' had more fatigue at follow-up. Officer status was associated with a better outcome. A similar lack of association was found for exposures and physical functioning and GHQ-12 score. 'Gulf War syndrome' attribution was associated with a worse outcome for GHQ-12 and physical functioning even after controlling for severity of symptoms at baseline. CONCLUSIONS: This study suggests that while multiple vaccination and military exposures are important risk factors for the onset of symptoms in Gulf War veterans, these are not important risk factors for persistence of such symptoms. Instead the severity of the initial symptoms; psychological distress and attributions may be more important determinants of outcome.

Stability of recall of military hazards over time. Evidence from the Persian Gulf War of 1991.

BACKGROUND: War time traumatic events are related to subsequent psychological and physical health, but quantifying the association is problematic. Memory changes over time and is influenced by psychological status. AIMS: To use a large, two-stage cohort study of members of the UK armed forces to study changes in recall of both traumatic and 'toxic' hazards. METHOD: A questionnaire-based follow-up study assessed 2370 UK military personnel, repeating earlier questions about exposure to military hazards. RESULTS: The k statistics for reporting of hazards were good for some exposures, but very low for others. Gulf veterans reported more exposures over time (no significant rise in the Bosnia cohort). In the Gulf cohort only, reporting new exposures was associated with worsening health perception, and forgetting previously reported exposures with improved perception. We found no association between physical health, psychological morbidity or post-traumatic stress disorder symptoms and endorsement or non-endorsement of exposures. CONCLUSIONS: Reporting of military hazards after a conflict is not static, and is associated with current self-rated perception of health. Self-report of exposures associated with media publicity needs to be treated with caution.

The health effects of peace-keeping in the UK Armed Forces: Bosnia 1992-1996. Predictors of psychological symptoms.

BACKGROUND: Peace-keeping duties are associated with unique stresses for military personnel. There have been few reports on the effects of peace-keeping on psychological health. METHOD: We used data from a cross-sectional study originally established to examine health effects of service in the Gulf War, which included a control group who had been deployed in Bosnia (N= 2049). This group was examined to establish which demographic, occupational, and deployment-related risk factors were associated with psychological distress measured on the General Health Questionnaire (GHQ-12) and stress symptoms akin to a post-traumatic stress reactions. RESULTS: The main risk factors for stress symptoms in the Bosnia group were--lower rank, being deployed early in the campaign, having more deployment-related exposures, and serving on staff duties. There was no protective effect of previous deployments to the Falklands or Northern Ireland, and time off following deployment was not protective. For GHQ-12 cases, the main risk factors were: female gender, lower rank, increased deployment-related exposures and serving on staff duties. CONCLUSIONS: This study suggests that stress symptoms and GHQ-12 cases, are strongly predicted both by experiences during deployment and demographic factors.

Neurophysiologic analysis of neuromuscular symptoms in UK Gulf War veterans: a controlled study.

BACKGROUND: UK veterans who were deployed to the Gulf in 1990 to 1991 reported higher prevalence of neuromuscular symptoms. OBJECTIVE: To investigate whether these Gulf War-related symptoms were associated with objective evidence of neuromuscular dysfunction. METHODS: Forty-nine Gulf War veterans with more than four neuromuscular symptoms (Gulf-ill), 26 Gulf-well veterans, 13 symptomatic Bosnian veterans (Bosnia-ill), and 22 symptomatic veterans who were not deployed to the Gulf (Era-ill) underwent detailed neurophysiologic assessment: nerve conduction studies, quantitative sensory and autonomic testing, and concentric needle and single-fiber electromyography (EMG). RESULTS: Nerve conduction studies detected carpal tunnel syndrome in two Gulf-ill, two Gulf-well, one Bosnia-ill, and three Era-ill veterans. Ulnar neuropathy was detected in one Gulf-ill and two Era-ill veterans. However, results of detailed nerve conduction studies of the Gulf-ill veterans were comparable with results observed in the other three groups. Quantitative sensory and autonomic assessments also failed to show any specific abnormalities in the Gulf-ill group. Similarly, quantitative assessment of concentric needle and single-fiber EMG detected no chronic denervation or myopathic changes or any abnormalities of neuromuscular transmission in the Gulf-ill veterans. CONCLUSION: Gulf War-related neuromuscular symptoms are not associated with specific impairments of peripheral nerves, neuromuscular junctions, or skeletal muscles.

Cognitive functioning and disturbances of mood in UK veterans of the Persian Gulf War: a comparative study.

BACKGROUND: Complaints of poor memory and concentration are common in veterans of the 1991 Persian Gulf War as are other symptoms. Despite a large research effort, such symptoms remain largely unexplained. METHOD: A comprehensive battery of neuropsychological tests and rating scales was administered to 341 UK servicemen who were returnees from the Gulf War and peace keeping duties in Bosnia, plus non-deployed military controls. All were drawn from a large randomized survey. Most were selected on the basis of impaired physical functioning defined operationally. RESULTS: Group comparisons revealed an association between physical functioning and symptoms of depression, post-traumatic stress reactions, increased anger and subjective cognitive failures. Poorer performance on some general cognitive measures, sequencing and attention was also seen in association with being 'ill' but virtually all differences disappeared after adjusting for depressed mood or multiple comparisons. Deployment was also associated with symptoms of post-traumatic stress and subjective cognitive failures, independently of health status, as well as minor general cognitive and constructional impairment. The latter remained significantly poorer in the Gulf group even after adjusting for depressed mood. CONCLUSIONS: Disturbances of mood are more prominent than quantifiable cognitive deficits in Gulf War veterans and probably lead to subjective underestimation of ability. Task performance deficits can themselves be explained by depressed mood although the direction of causality cannot be inferred confidently. Reduced constructional ability cannot be explained in this way and could be an effect of Gulf-specific exposures.

Antinuclear autoantibodies (ANA) in Gulf War-related illness and chronic fatigue syndrome (CFS) patients.

It is established that veterans of the 1991 Gulf War have an increased frequency of experiencing multiple symptoms. The underlying mechanism of these ailments is unclear, although they do not correspond to any clearly defined syndrome. The most common symptoms overlap with those of chronic fatigue syndrome (CFS). CFS was recently associated with a novel subtype of antinuclear autoantibody (ANA) that reacts with nuclear envelope (NE) antigens. NE autoantibodies are not known to be linked with any distinct clinical condition, but have been observed in patients with unusual mixed chronic autoimmune disorders and connective tissue diseases. In this study we examined whether NE ANAs are a feature of patients with CFS and symptomatic Gulf War veterans (sGWV). We studied the prevalence of ANA in 130 sGWV, 90 well Gulf War veterans (wGWV), 128 symptomatic Bosnia and Era veterans (sBEV), 100 CFS patients, and 111 healthy control subjects matching for age and sex. We found no significant difference in the prevalence of ANAs between any of the groups. None of the patients/or veterans we studied had ANA of the NE type. Our results show that multisymptom illness due to CFS or related to Gulf War service is not associated with antinuclear autoimmunity.

Reported chemical sensitivities in a health survey of United Kingdom military personnel.

OBJECTIVE: To report the prevalence of self reported chemical sensitivities in three cohorts of United Kingdom service personnel. METHOD: Cross sectional postal survey of three cohorts of United Kingdom military personnel comprising Gulf veterans (n=3531), those who had served in Bosnia (n=2050), and those serving during the Gulf war but not deployed there (Era cohort, n=2614). RESULTS: Sensitivity to at least one everyday chemical was reported by a considerable proportion of all three cohorts, and particularly by veterans of the Gulf war (Era: 14%; Bosnia: 13%; Gulf: 28%). CONCLUSION: Reported chemical sensitivities were common in all three military cohorts. Our understanding of chemical sensitivities remains limited and objective evidence for a causal link between low level exposures to chemicals and reported symptoms is lacking. Given their frequency in the population, further work in this area is necessary.

Prevalence of Gulf war veterans who believe they have Gulf war syndrome: questionnaire study.

OBJECTIVES: To determine how many veterans in a random sample of British veterans who served in the Gulf war believe they have "Gulf war syndrome," to examine factors associated with the presence of this belief, and to compare the health status of those who believe they have Gulf war syndrome with those who do not. DESIGN: Questionnaire study asking British Gulf war veterans whether they believe they have Gulf war syndrome and about symptoms, fatigue, psychological distress, post-traumatic stress, physical functioning, and their perception of health. PARTICIPANTS: 2961 respondents to questionnaires sent out to a random sample of 4250 Gulf war veterans (69.7%). MAIN OUTCOME MEASURE: The proportion of veterans who believe they have Gulf war syndrome. RESULTS: Overall, 17.3% (95% confidence interval 15.9 to 18.7) of the respondents believed they had Gulf war syndrome. The belief was associated with the veteran having poor health, not serving in the army when responding to the questionnaire, and having received a high number of vaccinations before deployment to the Gulf. The strongest association was knowing another person who also thought they had Gulf war syndrome. CONCLUSIONS: Substantial numbers of British Gulf war veterans believe they have Gulf war syndrome, which is associated with psychological distress, a high number of symptoms, and some reduction in activity levels. A combination of biological, psychological, and sociological factors are associated with the belief, and these factors should be addressed in clinical practice.

Multiple chemical sensitivity and chronic fatigue syndrome in British Gulf War veterans.

The objective of this study was to measure the prevalence of multiple chemical sensitivity (MCS) and chronic fatigue syndrome (CFS) in British Gulf War veterans and to investigate their association with reported exposures and psychologic morbidity. In 1997--1998, the authors undertook a cross-sectional survey of three cohorts of British military personnel comprising Gulf veterans (n = 3,531), those who had served in Bosnia (n = 2,050), and those serving during the Gulf War but not deployed there (Era cohort, n = 2,614). MCS and CFS were defined according to operational criteria. The prevalence of MCS in the Gulf, Bosnia, and Era cohorts was 1.3%, 0.3%, and 0.2%, respectively. For CFS, the prevalence was 2.1% (Gulf cohort), 0.7% (Bosnia cohort), and 1.8% (Era cohort). In Gulf veterans, MCS was strongly associated with exposure to pesticides (adjusted odds ratio = 12.3, 95% confidence interval: 5.1, 30.0). Both syndromes were associated with high levels of psychologic morbidity. These findings suggest that CFS and MCS account for some of the medically unexplained illnesses reported by veterans after deployment to the Gulf. MCS was particularly associated with Gulf deployment and self-reported exposure to pesticides, findings that merit further exploration given the controversial status of this diagnosis and the potential for recall bias in a questionnaire survey.

Occupational risk factors for ill health in Gulf veterans of the United Kingdom.

OBJECTIVES: To study the association between occupational factors specific to the Armed Forces (rank, functional roles, Service, regular or reservist status and deployment factors) and symptomatic health problems in Gulf veterans, after sociodemographic and lifestyle factors have been accounted for. DESIGN: A postal cross sectional survey of randomly selected UK Gulf veterans was conducted six to seven years after the Gulf conflict. Physical ill health was measured using the Fatigue Questionnaire and a measure of the Centers for Disease Control and Prevention (CDC) multi-symptom syndrome. Psychological ill health was measured using the General Health Questionnaire and a post-traumatic stress measure. SETTING: Population of servicemen who were serving in the UK Armed Forces during the Gulf conflict between 1 September 1990 and 30 June 1991. PARTICIPANTS: 3297 Gulf veterans. MAIN RESULTS: In multivariate logistic regression, there was an inverse relation between higher rank and psychological and physical ill health (test of trend: General Health Questionnaire, p=0.004; post-traumatic stress, p=0.002; fatigue, p=0.015; CDC case, p=0.002). Having left the Armed Forces was associated with a two to three times increase in reporting ill health. Of the deployment factors, there was a weak association between being deployed as an individual reinforcement in a combat role and post-traumatic stress but there was no association between receiving pre-deployment training or post-deployment leave and ill health. Marital status and smoking were associated with psychological and physical ill health. CONCLUSIONS: Rank was the main occupational factor associated with both psychological and physical ill health in Gulf veterans. This may parallel the associations between socioeconomic status and morbidity in civilian populations. Ill health seems to be greater in those who return to civilian life. Sociodemographic factors also seem to be important in ill health in Gulf veterans.

Role of vaccinations as risk factors for ill health in veterans of the Gulf war: cross sectional study.

OBJECTIVES: To explore the relation between ill health after the Gulf war and vaccines received before or during the conflict. To test the hypothesis that such ill health is limited to military personnel who received multiple vaccines during deployment and that pesticide use modifies any effect. DESIGN: Cross sectional study of Gulf war veterans followed for six to eight years after deployment. SETTING: UK armed forces. PARTICIPANTS: Military personnel who served in the Gulf and who still had their vaccine records. MAIN OUTCOME MEASURES: Multisymptom illness as classified by the Centers for Disease Control and Prevention; fatigue; psychological distress; post-traumatic stress reaction; health perception; and physical functioning. RESULTS: The response rate for the original survey was 70.4% (n=3284). Of these, 28% (923) had vaccine records. Receipt of multiple vaccines before deployment was associated with only one of the six health outcomes (post-traumatic stress reaction). By contrast five of the six outcomes (all but post-traumatic stress reaction) were associated with multiple vaccines received during deployment. The strongest association was for the multisymptom illness (odds ratio 5.0; 95% confidence interval 2.5 to 9.8). CONCLUSION: Among veterans of the Gulf war there is a specific relation between multiple vaccinations given during deployment and later ill health. Multiple vaccinations in themselves do not seem to be harmful but combined with the "stress" of deployment they may be associated with adverse health outcomes. These results imply that every effort should be made to maintain routine vaccines during peacetime.

Health of UK servicemen who served in Persian Gulf War.

BACKGROUND: Various symptoms in military personnel in the Persian Gulf War 1990-91 have caused international speculation and concern. We investigated UK servicemen. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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.

Is there a Gulf War syndrome?

BACKGROUND: UK veterans of the Gulf War report more ill health than servicemen who were not deployed to the Gulf War. We investigated whether the pattern of symptom reporting by veterans of the Gulf War differed from that in active servicemen who had not fought in the Gulf War or who had fought in other conflicts. METHODS: We used a population-based cross-sectional design. We sent a standardised survey that asked about 50 physical symptoms to three UK military cohorts; men who had served in the Gulf War, those who had served in the Bosnia conflict, and men who had been in active service but not deployed to the Gulf War (Era cohort). We used exploratory factor analysis to identify underlying factors and describe the factor structure of the symptoms reported in the Gulf War cohort. Confirmatory factor analysis was used to test the fit of this factor structure in the Bosnia and Era cohorts. FINDINGS: Three factors in the Gulf War cohort together accounted for about 20% of the common variance. We labelled the factors mood, respiratory system, and peripheral nervous system, according to the symptoms that loaded on to them. In the confirmatory factor analysis, the factor structure identified in the Gulf War cohort fitted reasonably well in the Bosnia and Era cohorts. INTERPRETATION: Although results from complex modelling procedures need to be interpreted with caution, our findings do not support a unique Gulf War syndrome. The mechanisms behind increased self-reporting of symptoms need further investigation.

A randomized controlled trial and economic evaluation of counselling in primary care.

BACKGROUND: Counselling in primary care settings remains largely unevaluated. Such evaluation has been strongly recommended. AIM: To determine the relative effectiveness and cost-effectiveness of generic counselling and usual general practitioner (GP) care for patients with minor mental health problems. METHOD: A randomized controlled trial and health economic evaluation were carried out in nine general practices. Access to generic counselling (brief counselling, generally involving up to six 50-minute sessions) was compared with usual GP care. A total of 162 patients aged 16 years and over with diverse mental health problems (excluding phobic conditions and psychoses) were randomized. The Hospital Anxiety and Depression (HAD) scale, COOP/WONCA (World Organization of Family Doctors) functional health assessment charts, and the delighted-terrible faces scale were used to assess outcome four months after randomization. RESULTS: The two groups were similar at baseline. There were significant improvements in both groups between randomization and follow-up for most outcome measures, but no significant differences between the study arms. The 95% confidence limits were narrow and excluded clinically significant effects. Under various assumptions concerning the cost of secondary care referrals and of counselling time, no clear cost advantage was associated with either intervention. CONCLUSIONS: This pragmatic trial demonstrates no difference in functional or mental health outcome at four months between subjects offered access to counselling and those given usual care by their GP. There is no clear difference in the cost-effectiveness of the two interventions. Purchasers should take account of these findings in allocating resources within primary care.

A review of hospital medical record audits: implications for funding and training.

This paper summarises the findings of coding audits in seven hospitals and one re-audit conducted by the Health Department of Western Australia. The accuracy of the coding in the first audits, as measured by differences in AN-DRG assignment, varied from 83% to 93%. The accuracy of the coding in the re-audited hospital increased by 6% to 94.5%. The major coding problems related to incorrect abstraction of information from the medical record, inaccurate code assignment, non-application of the Australian Coding Standards, or poor documentation. On average, these coding problems resulted in a loss of nearly $400,000 per hospital per year in the surveyed hospitals.

Factors associated with the duration of breastfeeding: analysis of the primary and secondary responders to a self-completed questionnaire.

A cohort of 1192 consecutive newborn infants was followed prospectively for factors possibly affecting the length of time they were breastfed. Following the procedure of a double-blind test, one-third of the cohort received Credé prophylaxis at age 2 h. The duration of breastfeeding (sole or partial) was recorded up to age 6 months and there was a 100% follow-up. Multivariate proportional hazards regression analysis (Cox) of the whole cohort showed that babies being delivered between 21.00 and 24.00 h were associated with a shorter duration of breastfeeding (rate ratio = 1.37, 99% confidence interval = 1.05-1.78). Mother's age (under 21 years), marital status (unmarried) and birthweight (inversely) were factors also independently associated with shorter breastfeeding duration. Boys were breastfed for a shorter time than girls (p < 0.05). In univariate analyses only, the first-born babies had a significantly shorter breastfeeding time, and purulent eyes in the first 24 h was a factor of borderline significance (p < 0.05). Educational level, socioeconomic status and smoking habits of the mothers were not investigated in this study. Owing to the lack of regulations in place at the time of the study (1981-82), it was possible to differentiate between the mothers who responded spontaneously to the self-completion questionnaire (primary responders, 68.5%) and those who required one or two reminders. Short breastfeeding time was the strongest predictor of being a secondary responder, followed by being very young or unmarried. Approaching the secondary responders reduced the prevalence of breastfeeding at 6 months by 5% (from 53.8% to 48.8%).

The impact of tobacco smoking and alcohol consumption on aboriginal mortality in Western Australia, 1989-1991.

OBJECTIVES: To compare the estimated death rates associated with alcohol and tobacco use for Australian Aboriginals in Western Australia with those for non-Aboriginals. METHOD: Deaths attributable to tobacco smoking and alcohol consumption were estimated for 1989-1991 with the aetiological fractions method, using data from the Health Department of Western Australia's mortality database. RESULTS: Tobacco smoking was responsible for 15.4% of all deaths and 13.9% of Aboriginal deaths, and alcohol consumption for 5% and 9.2%, respectively. The age-standardised death rates per 100,000 person-years for tobacco and alcohol were: Aboriginal males, 271 and 152; other males, 113 and 29; Aboriginal females, 118 and 56; and other females, 32 and 15. Of those who died as a result of tobacco use, 49% of Aboriginal males and 48% of Aboriginal females died before 55 years of age, compared with 11% and 10%, respectively, in non-Aboriginal males. For alcohol-related deaths, 62% of Aboriginal males and 70% of Aboriginal females died before 55 years of age, compared with 35% and 23%, respectively, in non-Aboriginals. CONCLUSION: During 1989-1991 tobacco smoking and alcohol consumption were responsible for much higher death rates among Aboriginals than among non-Aboriginals in Western Australia.