Khalida Ismail

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.

Systematic review and meta-analysis of randomised controlled trials of psychological interventions to improve glycaemic control in patients with type 2 diabetes.

BACKGROUND Adherence difficulties and psychological problems are associated with poor glycaemic control in diabetes. We undertook a systematic review and meta-analysis of psychological therapies to assess their effectiveness in improving glycaemic control in type 2 diabetes. METHODS We searched MEDLINE, PsychINFO, EMBASE, and the Cochrane Central Register of Controlled Trials up to January, 2003. Eligible studies were randomised controlled trials that involved people with type 2 diabetes and evaluated a psychological therapy (counselling, cognitive behaviour therapy, or psychodynamic therapy) to improve diabetes control. We extracted the number of participants, their age, duration of diabetes, glycaemic control, type of psychological therapy, its mode of delivery, and type of intervention in the control group. The main outcome was long-term glycaemic control measured by percentage of glycated haemoglobin. Blood glucose concentration, weight, and psychological distress were also measured. Pooled standardised effect sizes were calculated. FINDINGS 25 trials were eligible for the review. In 12 trials, the mean percentage glycated haemoglobin was lower in people assigned a psychological intervention than in the control group (usual care, education, waiting list, or attention control); the pooled mean difference was -0.32 (95% CI -0.57 to -0.07) equivalent to an absolute difference of -0.76%. There were non-significant differences in blood glucose concentration (eight trials; -0.11 [-0.65 to 0.42]) and weight gain (nine trials; 0.37 [-0.18 to 0.93]). Psychological distress was significantly lower in the intervention groups (five trials; -0.58 [-0.95 to -0.20]). INTERPRETATION In type 2 diabetes, there are improvements in long-term glycaemic control and psychological distress but not in weight control or blood glucose concentration in people who receive psychological therapies.

Type 2 diabetes mellitus as a risk factor for the onset of depression: a systematic review and meta-analysis

Aims/hypothesisAn earlier meta-analysis showed that diabetes is a risk factor for the development and/or recurrence of depression. Yet whether this risk is different for studies using questionnaires than for those relying on diagnostic criteria for depression has not been examined. This study examined the association of diabetes and the onset of depression by reviewing the literature and conducting a meta-analysis of longitudinal studies on this topic.MethodsEMBASE, MEDLINE and PsycInfo were searched for articles published up to September 2009. All studies that examined the relationship between type 2 diabetes and the onset of depression were included. Pooled relative risks were calculated using fixed and random effects models.ResultsEleven studies met our inclusion criteria for this meta-analysis. Based on the pooled data, including 48,808 cases of type 2 diabetes without depression at baseline, the pooled relative risk was 1.24 (95% CI 1.09–1.40) for the random effects model. This risk was significantly higher for studies relying on diagnostic criteria of depression than for studies using questionnaires. However, this difference was no longer significant when controlled for year of publication.Conclusions/interpretationCompared with non-diabetic controls, people with type 2 diabetes have a 24% increased risk of developing depression. The mechanisms underlying this relationship are still unclear and warrant further research.

Psychological interventions to improve glycaemic control in patients with type 1 diabetes: systematic review and meta-analysis of randomised controlled trials

Abstract Objective To determine whether psychological interventions have any effect on glycaemic control in people with type 1 diabetes. Design Systematic review and meta-analysis of psychological therapies to assess their effectiveness in improving glycaemic control in type 1 diabetes. Data sources Medline, PsycINFO, Embase, and Cochrane central register of controlled trials searched to September 2004. Review methods All included studies were randomised controlled trials in children (including adolescents) or adults with type 1 diabetes that evaluated the effect of a psychological therapy (counselling, cognitive behaviour therapy, family systems therapy, and psychodynamic therapy) on control of diabetes. Data were extracted on sample size, age, duration of diabetes, type of psychological therapy, its mode of delivery, and type of intervention in control group. Main outcome measures Glycaemic control measured by percentage of glycated haemoglobin and psychological distress. Pooled standardised effect sizes were calculated. Results 29 trials were eligible for the systematic review and 21 trials for the meta-analysis. In the 10 studies of children and adolescents included in the meta-analysis, the mean percentage of glycated haemoglobin was significantly reduced in those who had received a psychological intervention compared with those in the control group (pooled standardised mean difference −0.35 (95% confidence interval −0.66 to −0.04), equivalent to a 0.48% (0.05% to 0.91%) absolute reduction in glycated haemoglobin. In the 11 studies in adults the pooled standardised mean difference was −0.17 (−0.45 to 0.10), equivalent to 0.22% (−0.13% to 0.56%) absolute reduction in glycated haemoglobin. Psychological distress was significantly lower in the intervention groups in children and adolescents (pooled standardised effect size −0.46, −0.83 to −0.10) but not in adults (−0.25, −0.51 to 0.01). Conclusion Psychological treatments can slightly improve glycaemic control in children and adolescents with diabetes but have no effect in adults.

First- v. second-generation antipsychotics and risk for diabetes in schizophrenia: systematic review and meta-analysis

BACKGROUND The increased prevalence of diabetes in schizophrenia is partly attributed to antipsychotic treatment, in particular second-generation antipsychotics, but the evidence has not been systematically reviewed. AIMS Systematic review and meta-analysis comparing diabetes risk for different antipsychotics in people with schizophrenia. METHOD We searched MEDLINE, PsycINFO, EMBASE, International Pharmaceutical Abstracts, CINAHL and Web of Knowledge until September 2006. Studies were eligible for inclusion if the design was cross-sectional, case-control, cohort or a controlled trial in individuals with schizophrenia or related psychotic disorders, where second-generation antipsychotics (defined as clozapine, olanzapine, risperidone and quetiapine) were compared with first-generation antipsychotics and diabetes was an outcome. Data were pooled using random effects inverse variance weighted meta-analysis. RESULTS Of the studies that met the inclusion criteria (n=14), 11 had sufficient data to include in the meta-analysis. Four of these were retrospective cohort studies. The relative risk of diabetes in patients with schizophrenia prescribed one of the second-generation v. first-generation antipsychotics was 1.32 (95% CI 1.15-1.51). There were insufficient data to include aripiprazole, ziprasidone and amisulpride in this analysis. CONCLUSIONS There is tentative evidence that the second-generation antipsychotics included in this study are associated with a small increased risk for diabetes compared with first-generation antipsychotics in people with schizophrenia. Methodological limitations were found in most studies, leading to heterogeneity and difficulty interpreting data. Regardless of type of antipsychotic, screening for diabetes in all people with schizophrenia should be routine.

Is there a Gulf War syndrome

Summary 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. Lancet 1999; 353: 179‐82 See Commentary page ???

A Cohort Study of People With Diabetes and Their First Foot Ulcer The role of depression on mortality

OBJECTIVE—The aim was to evaluate over 18 months whether depression was associated with mortality in people with their first foot ulcer. RESEARCH DESIGN AND METHODS—A prospective cohort design was used. Adults with their first diabetic foot ulcer were recruited from foot clinics in southeast London, U.K. At baseline, the Schedules for Clinical Assessment in Neuropsychiatry 2.1 was used to define those who met DSM (Diagnostic and Statistical Manual of Mental Disorders)-IV criteria for minor and major depressive disorders. Potential covariates were age, sex, marital status, socioeconomic status, smoking, antidepressant use, A1C, macro- and microvascular complications, and University of Texas classification–based severity and size of ulcer. The main outcome was mortality 18 months later, and A1C was the secondary outcome. The proportion who had an amputation, had recurrence, and whose ulcer had healed was recorded. RESULTS—A total of 253 people with their first diabetic foot ulcer were recruited. The prevalence of minor and major depressive disorder was 8.1% (n = 21) and 24.1% (n = 61), respectively. There were 40 (15.8%) deaths, 36 (15.5%) amputations, and 99 (43.2%) recurrences. In the adjusted Cox regression analysis, minor and major depressive disorders were associated with an approximately threefold hazard risk for mortality compared with no depression (3.23 [95% CI 1.39–7.51] and 2.73 [1.38–5.40], respectively). There was no association between minor and major depression compared with no depression and A1C (P = 0.86 and P = 0.43, respectively). CONCLUSIONS—One-third of people with their first diabetic foot ulcer suffer from clinical depression, and this is associated with increased mortality.

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

Abstract 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.

A randomised controlled trial of cognitive behaviour therapy and motivational interviewing for people with Type 1 diabetes mellitus with persistent sub-optimal glycaemic control: a Diabetes and Psychological Therapies (ADaPT) study.

OBJECTIVES To determine whether (i) motivational enhancement therapy (MET) + cognitive behaviour therapy (CBT) compared with usual care, (ii) MET compared with usual care, (iii) or MET + CBT compared with MET was more effective in improving glycaemic control when delivered by general nurses with additional training in these techniques. DESIGN A three-arm parallel randomised controlled trial as the gold standard design to test the effectiveness of psychological treatments. SETTING The recruiting centres were diabetes clinics in seven acute trusts in south-east London and Greater Manchester. PARTICIPANTS Adults (18-65 years) with a confirmed diagnosis of type 1 diabetes for a minimum duration of 2 years and a current glycated (or glycosylated) haemoglobin (HbA1c) value between 8.2% and 15.0%. INTERVENTIONS The control arm consisted of usual diabetes care which varied between the hospitals, but constituted at least three monthly appointments to diabetes clinic. The two treatments arms consisted of usual care with MET and usual care with MET + CBT. MAIN OUTCOME MEASURES The primary outcome was HbA1c at 12 months from randomisation. Secondary outcome measures were 1-year costs measured by the Client Service Receipt Inventory at baseline, 6 months and 12 months; quality of life-years [quality-adjusted life-years (QALYs)] measured by the SF-36 (Short Form-36 Health Survey Questionnaire) and EQ-5D (European Quality of Life-5 Dimensions) at baseline and 12 months. RESULTS One thousand six hundred and fifty-nine people with type 1 diabetes were screened and 344 were randomised to MET + CBT (n = 106), MET (n = 117) and to usual care (n = 121). The 12-month follow-up rate for HbA1c was 88% (n = 305). The adjusted mean 12-month HbA1c was 0.45% lower in those treated with MET + CBT [95% confidence interval (CI) 0.16% to 0.79%, p = 0.008] than for usual care; 0.16% lower in those treated with MET (95% CI 0.20% to 0.51%, p = 0.38) than for usual care; and 0.30% lower with MET + CBT than with MET (95% CI -0.07% to 0.66%, p = 0.11). The higher the HbA1c, and the younger the participant at baseline, the greater was the reduction in HbA1c. The interventions had no effect on secondary outcomes such as depression and quality of life. The economic evaluation was inconclusive. Both interventions were associated with increased health care costs than for usual care alone. There was no significant difference in social costs. Cost effectiveness ratios, up to one year, varied considerably according to whether QALY estimates were based on EQ-5D or SF-36 and whether imputed or complete data were used in the analyses. CONCLUSIONS A combination of MET and CBT may be useful for patients with persistent sub-optimal diabetic control. MET alone appears less effective than usual care. Economic evaluation was inconclusive. TRIAL REGISTRATION Current Controlled Trials ISRCTN77044517.

A systematic review and meta-analysis of the association between depression and insulin resistance.

OBJECTIVE Depression is associated with the onset of type 2 diabetes. A systematic review and meta-analysis of observational studies, controlled trials, and unpublished data was conducted to examine the association between depression and insulin resistance (IR). RESEARCH DESIGN AND METHODS Medline, EMBASE, and PsycINFO were searched for studies published up to September 2011. Two independent reviewers assessed the eligibility of each report based on predefined inclusion criteria (study design and measure of depression and IR, excluding prevalent cases of diabetes). Individual effect sizes were standardized, and a meta-analysis was performed to calculate a pooled effect size using random effects. Subgroup analyses and meta-regression were conducted to explore any potential source of heterogeneity between studies. RESULTS Of 967 abstracts reviewed, 21 studies met the inclusion criteria of which 18 studies had appropriate data for the meta-analysis (n = 25,847). The pooled effect size (95% CI) was 0.19 (0.11–0.27) with marked heterogeneity (I2 = 82.2%) using the random-effects model. Heterogeneity between studies was not explained by age or sex, but could be partly explained by the methods of depression and IR assessments. CONCLUSIONS A small but significant cross-sectional association was observed between depression and IR, despite heterogeneity between studies. The pathophysiology mechanisms and direction of this association need further study using a purposively designed prospective or intervention study in samples at high risk for diabetes.