Sarin exposure, mortality and cancer incidence in UK military veterans involved in human experiments at Porton Down: 52-year follow-up.

OBJECTIVES: We investigated whether UK military personnel exposed to sarin during the 'Service Volunteer Programme' at Porton Down had increased rates of mortality or cancer incidence over a 52-year follow-up. METHODS: A historical cohort study assembled from UK military records, comprising male veterans exposed to sarin during the 'Service Volunteer Programme' at Porton Down, UK (n=2975) and a comparison group of similar veterans who did not attend (n=2919). Mortality and cancer incidence data were obtained from national registries up to December 2019. Analysis was conducted using Cox regression adjusted for age, year of birth and service characteristics. RESULTS: Over a median follow-up of 52.2 years (range 2 days to 74.6 years), 1598 (53.7%) sarin-exposed veterans and 1583 (54.3%) non-exposed veterans died. Adjusted HRs for all-cause mortality were raised for any sarin exposure (HR=1.08, 95% CI 1.01 to 1.16), two or more exposures (HR=1.25, 95% CI 1.04 to 1.49) and higher doses (air >15 mg.min/m3) (HR=1.15, 95% CI 1.02 to 1.30). For cause-specific mortality, sarin exposure was associated with deaths from 'other' circulatory diseases (excludes ischaemic and cerebrovascular diseases) (HR=1.41, 95% CI 1.06 to 1.87) and alcohol-attributable deaths (HR=2.66, 95% CI 1.40 to 5.07). There was no association between sarin exposure and overall cancer incidence (HR=1.01, 95% CI 0.93 to 1.10), but cancer incidence was higher for alcohol-related neoplasms (HR=1.24, 95% CI 1.01 to 1.51). CONCLUSIONS: Sarin exposure was associated with increased rates of mortality over a 50-year follow-up. The strongest associations were observed for deaths attributable to alcohol and 'other' circulatory diseases.

Resilience resources for mental health among people living with HIV: a mixed-method systematic review.

People living with HIV (PLWH) experience a disproportionate burden of mental health problems compared to people living without HIV. This systematic review aims to depict the spectrum of resilience resources that may promote the mental health of PLWH at the individual, interpersonal, organisational, community and policy levels. A systematic literature search was conducted in PsycINFO, Scopus, Medline and advanced Google Scholar. The quality of included studies was assessed using the Mixed Methods Appraisal Tool (MMAT). Of the 591 studies identified, fourteen were included representing a total of 5,142 PLWH from China, Ghana, Nepal, Spain, Tanzania and the USA. Resilience resources were identified at the individual level (self-efficacy, self-esteem, acceptance, hope, optimism, religiosity/spirituality, belief in fate, mindfulness, strength and self-responsibility); interpersonal level (social support and parental monitoring); and community level (attending HIV clinic support groups and access to healthcare). All quantitative studies were cross-sectional, limiting inferences about causation or directionality. Future research should focus on resilience resources at the organisational and policy levels and incorporate longitudinal designs.

Mortality and cancer incidence in UK military veterans involved in human experiments at Porton Down: 48-year follow-up.

BACKGROUND: We investigated whether military personnel involved in chemical warfare agent research at Porton Down had increased rates of mortality or cancer incidence. METHODS: This was a historical cohort study comprising male UK veterans who participated in the 'Service Volunteer Programme', 1941-89, identified from Porton Down experiment books, and a comparison group of similar 'non-Porton Down' veterans identified from military personnel files. Of 19 233 records retrieved for each group, 18 133 (94%) Porton Down and 17 591 (92%) non-Porton Down were included in our analytical sample. Mortality and cancer incidence data were obtained from national registries up to December 2019. RESULTS: Over a median follow-up of 48.1 years, 10 935 Porton Down veterans (60.3%) and 10 658 non-Porton Down veterans (60.6%) had died. After adjustment for age, year of birth and military service characteristics, overall, Porton Down veterans had a 6% higher rate of all-cause mortality compared with non-Porton Down veterans [hazard ratio (HR) = 1.06, 95% confidence interval (CI) 1.03-1.09]. For cause-specific mortality, Porton Down veterans had higher rates of death from genitourinary diseases (HR = 1.34, 95% CI 1.05-1.70) and deaths attributable to alcohol (HR = 1.44, 95% CI 1.07-1.94), with weaker associations observed for deaths from infectious and parasitic diseases (HR = 1.32, 95% CI 0.99-1.78), lung cancer (HR = 1.10, 95% CI 1.01-1.20) and external causes (HR = 1.15, 95% CI 1.00-1.32). Associations with all-cause mortality were stronger for veterans who attended Porton Down between 1960 and 1964 (HR = 1.34, 95% CI 1.19-1.50); likelihood-ratio test, P = 0.006. There was no association between attendance at Porton Down and overall cancer incidence (HR = 1.00, 95% CI 0.95-1.03). CONCLUSIONS: Overall, mortality rates were slightly higher in Porton Down veterans, but there was no difference in cancer incidence. Associations for mortality were stronger in Porton Down veterans who attended in the early 1960s.

Association Between Lifetime Affective Symptoms and Premature Mortality.

Importance: Associations between affective symptoms and mortality have been evaluated, but studies have not examined timing or cumulative exposure to affective symptoms over the life course. Objectives: To examine how lifetime accumulation and timing of affective symptoms are associated with mortality and identify potential explanatory factors. Design, Setting, and Participants: Data were obtained from the MRC National Survey of Health and Development (1946 British birth cohort), a socially stratified, population-based sample originally consisting of 5362 singleton births in England, Wales, and Scotland during March 1946. The cohort has been followed up 24 times, most recently in 2014-2015. Eligible participants included those flagged for mortality with affective symptom data available at a minimum of 3 time points (n = 3001). Data analysis was conducted from July 2016 to January 2019. Exposures: Affective symptoms were assessed at ages 13 to 15 years (teacher-rated questionnaire), 36 years (Present State Examination clinical semistructured interview), 43 years (Psychiatric Symptom Frequency questionnaire), and 53 years (General Health Questionnaire-28). Case-level affective symptoms were determined by those scoring in the top 16th percentile (ie, suggestive of a clinical diagnosis). Main Outcomes and Measures: Mortality data were obtained from the UK National Health Service Central Register from age 53 to 68 years. Results: Of 3001 study members (1509 [50.3%] female, 1492 [49.7%] male), 235 individuals (7.8%) died over a 15-year follow-up. After adjustment for sex, those who experienced case-level affective symptoms 1, 2, and 3 to 4 times had 76%, 87%, and 134% higher rates of premature mortality, respectively, compared with those who never experienced case-level symptoms. Case-level symptoms in adolescence only (ages 13-15 years) were associated with a 94% increased rate of mortality, which was unexplained after full adjustment for covariates (hazard ratio, 1.73; 95% CI, 1.10-2.72). Associations between participants with case-level symptoms multiple (2-4) times and mortality were predominately explained by adult health indicators and behaviors. For example, associations for those with case-level symptoms 3 to 4 times were most strongly attenuated by number of health conditions (32.1%), anxiolytic use (28.4%), lung function (24.6%), physical activity (23.9%), smoking (24.6%), antidepressant use (20.1%), diet (16.4%), pulse rate (12.7%), and adult social class (11.2%). Conclusions and Relevance: Lifetime accumulation of affective symptoms may be associated with an increased rate of mortality, with explanatory pathways dependent on the duration and timing of symptoms. Future research into causal pathways and potential points of intervention should consider affective symptom history.

Increased risk of depression in non-depressed HIV infected men with sleep disturbance: Prospective findings from the Multicenter AIDS Cohort Study.

OBJECTIVE: Sleep disturbance is a known risk factor for depression, but it is not known whether sleep disturbance contributes to greater risk of depression in those infected with human immunodeficiency virus (HIV+) as compared to those uninfected with HIV (HIV-). METHODS: Using data from the Multicenter AIDS Cohort Study, a population-based prospective study of men who have sex with men (MSM), self-reported sleep disturbance (>2 weeks) and depressive symptoms (Clinical Epidemiologic Scale for Depression, CES-D) were assessed every 6 months over 12 years of follow-up. Adjusted mixed effects logistic regression analyses tested whether sleep disturbance predicted depression (CES-D ≥ 16) at the immediate subsequent visit, and so on over 12 years, in non-depressed HIV+(N = 1054; 9556 person-visits) and non-depressed HIV- (N = 1217; 12,680 person-visits). In HIV+ vs. HIV- MSM, linearly estimated average incidence of depression and normalized cumulative rate of depression over 12 years were compared. RESULTS: In the HIV+ MSM, sleep disturbance was associated with a significant increase in depression 6 months later (OR = 1.6; 95% CI, 1.30, 1.96), which was significantly greater (P < .05) than in HIV- MSM (OR = 1.16; 95% CI, 0.94, 1.44). HIV status and sleep disturbance interacted (P < .001), such that incidence of depression and normalized cumulative rate of depression were greater in HIV+ with sleep disturbance than in HIV+ without sleep disturbance and HIV- groups (all P's < 0.001). CONCLUSIONS: HIV+ persons who report sleep disturbance represent a high risk group to be monitored for depression, and possibly targeted for insomnia treatment to prevent depression. FUND: National Institute of Allergy and Infectious Diseases.

Adolescent affective symptoms and mortality.

BACKGROUND: Little is known about the relationship between adolescent affective problems (anxiety and depression) and mortality.AimsTo examine whether adolescent affective symptoms are associated with premature mortality, and to assess whether this relationship is independent of other developmental factors. METHOD: Data (n = 3884) was from Britain's oldest birth cohort study - the National Survey of Health and Development. Adolescent affective symptoms were rated by teachers at ages 13 and 15 years: scores were summed and classified into three categories: mild or no, moderate and severe symptoms (1st-50th, 51st-90th and 91st-100th percentiles, respectively). Mortality data were obtained from national registry data up to age 68 years. Potential confounders were parental social class, childhood cognition and illness, and adolescent externalising behaviour. RESULTS: Over the 53-year follow-up period, 12.2% (n = 472) of study members died. Severe adolescent affective symptoms were associated with an increased rate of mortality compared with those with mild or no symptoms (gender adjusted hazard ratio 1.76, 95% CI 1.33-2.33). This association was only partially attenuated after adjustment for potential confounders (fully adjusted hazard ratio 1.61, 95% CI 1.20-2.15). There was suggestive evidence of an association across multiple causes of death. Moderate symptoms were not associated with mortality. CONCLUSIONS: Severe adolescent affective symptoms are associated with an increased rate of premature mortality over a 53-year follow-up period, independent of potential confounders. These findings underscore the importance of early mental health interventions.Declaration of interestNone.

Child maltreatment as a predictor of adult physical functioning in a prospective British birth cohort.

OBJECTIVE: Child maltreatment (abuse and neglect) has established associations with mental health; however, little is known about its relationship with physical functioning. Physical functioning (ie, the ability to perform the physical tasks of daily living) in adulthood is an important outcome to consider, as it is strongly associated with an individual's ability to work, and future disability and dependency. We aimed to establish whether maltreatment was associated with physical functioning, independent of other early-life factors. SETTING: 1958 British birth cohort. PARTICIPANTS: 8150 males and females with data on abuse and who participated at age 50 years. OUTCOME MEASURES: The primary outcome was poor physical functioning at 50 years (<65 on the Short-Form 36 survey physical functioning subscale). Secondary outcomes included mental health and self-reported health at 50 years. RESULTS: 23% of participants reported at least one type of maltreatment; 12% were identified with poor physical functioning. Neglect (ORadj 1.55, 95% CI 1.24 to 1.93), psychological abuse (ORadj 1.49, 1.17-1.88) and sexual abuse (ORadj 2.56, 1.66-3.96) were associated with poor physical functioning independent of other maltreatments and covariates, including childhood social class, birth weight and childhood illness. Odds of poor physical functioning increased with multiple types of maltreatment (ptrend <0.001); ORadj ranged from 1.49 (1.23-1.82) for a single type to 2.09 (1.53-2.87) for those reporting > 3 types of maltreatment, compared with those with none. Associations of similar magnitude were observed for mental and self-reported health outcomes. CONCLUSIONS: Child neglect, psychological and sexual abuse were associated with poor physical functioning at 50 years, with accumulating risk for those with multiple types of maltreatment. Associations were independent of numerous early-life factors and were comparable in magnitude to those observed for mental health and self-rated health. Prevention or alleviation of the ill effects of maltreatment could be an effective policy intervention to promote healthy ageing.

Do depressive symptoms predict cancer incidence?: 17-year follow-up of the Whitehall II study.

OBJECTIVE: To explore the association between depressive symptom history and cancer incidence. METHODS: Affective/emotional depressive symptoms were assessed using the General Health Questionnaire (GHQ-30) depression sub-scale across phase 1 (1985-1988), phase 2 (1989-1990), and phase 3 (1991-1994) of the Whitehall II prospective cohort study; 'chronic'=depressive episode at phase 1, 2 and 3; 'new'=depressive episode at phase 3 only. Cancer incidence was obtained from the National Health Service Central Register with an average follow-up of 15.6 years (range 0.08-17.4). The study sample consisted of 6983 participants, aged 35-55 years at baseline. Results were adjusted for age, sex, socio-economic position, health behaviours, health status/conditions, medication, and social support. RESULTS: Over a 17.4 year follow-up, chronic depressive symptoms did not increase the risk of cancer incidence compared to those who never experienced symptoms (hazard ratio (HR)=1.03, 95% confidence interval (CI): 0.71-1.49). Participants who experienced new depressive symptoms had an increased risk of cancer incidence in the first 9 years of follow-up (HR=1.89, 95% CI: 1.23-2.90) but no increased risk in later years (HR=0.84, 95% CI: 0.52-1.35). CONCLUSION: Chronic depressive symptoms were not associated with cancer incidence. In contrast, new-onset symptoms were associated with a substantially increased risk, possibly due to reverse causality.