Psychosocial factors and hospitalisations for COVID-19: Prospective cohort study based on a community sample.

BACKGROUND: While certain infectious diseases have been linked to socioeconomic disadvantage, mental health problems, and lower cognitive function, relationships with COVID-19 are either uncertain or untested. Our objective was to examine the association of a range of psychosocial factors with hospitalisation for COVID-19. METHODS: UK Biobank, a prospective cohort study, comprises around half a million people who were aged 40-69 years at study induction between 2006 and 2010 when information on psychosocial factors and covariates were captured. Hospitalisations for COVID-19 were ascertained between 16th March and 26th April 2020. RESULTS: There were 908 hospitalisations for COVID-19 in an analytical sample of 431,051 England-based study members. In age- and sex-adjusted analyses, an elevated risk of COVID-19 was related to disadvantaged levels of education (odds ratio; 95% confidence interval: 2.05; 1.70, 2.47), income (2.00; 1.63, 2,47), area deprivation (2.20; 1.86, 2.59), occupation (1.39; 1.14, 1.69), psychological distress (1.58; 1.32, 1.89), mental health (1.50; 1.25, 1.79), neuroticism (1.19; 1.00, 1.42), and performance on two tests of cognitive function - verbal and numerical reasoning (2.66; 2.06, 3.34) and reaction speed (1.27; 1.08, 1.51). These associations were graded (p-value for trend ≤ 0.038) such that effects were apparent across the full psychosocial continua. After mutual adjustment for these characteristics plus ethnicity, comorbidity, and lifestyle factors, only the relationship between lower cognitive function as measured using the reasoning test and risk of the infection remained (1.98; 1.38, 2.85). CONCLUSIONS: A range of psychosocial factors revealed associations with hospitalisation for COVID-19 of which the relation with cognitive function, a marker of health literacy, was most robust.

Does inflammation provide a link between psychosocial work characteristics and diabetes? Analysis of the role of interleukin-6 and C-reactive protein in the Whitehall II cohort study.

OBJECTIVE: Inflammation may underlie the association between psychological stress and cardiometabolic diseases, but this proposition has not been tested longitudinally. We investigated whether the circulating inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP) mediate the relationship between psychosocial work characteristics and diabetes. METHODS: We used three phases of data at 5 years intervals from the Whitehall II cohort study, originally recruiting 10,308 civil service employees aged 35-55 years. The data included repeat self-reports of job demands, control and social support, IL-6 from plasma samples, CRP from serum samples, and diabetes, ascertained through oral glucose tolerance test, medications, and self-reports of doctor-diagnosed diabetes. RESULTS: Structural equation models with age, sex and occupational position considering men and women combined, showed that low social support at work, but not high job demands or low job control, was prospectively associated with diabetes (standardized ß  =  0.05, 95% confidence interval (CI) 0.01-0.09) and higher levels of IL-6 (ß  =  0.03, CI 0.00-0.06). The inflammatory markers and diabetes were bidirectionally associated over time. A mediation model including workplace social support, IL-6 and diabetes further showed that 10% of the association between social support and diabetes over the three repeat examinations (total effect ß  =  0.08, CI 0.01-0.15) was attributable to a weak indirect effect through IL-6 (ß  =  0.01, CI 0.00-0.02). A similar indirect effect was observed for CRP in men only, while job control was prospectively associated with IL-6 among women. CONCLUSIONS: This study indicates an association between poor workplace support and diabetes that is partially ascribed to an inflammatory response.

Association of objectively measured physical activity with brain structure: UK Biobank study.

BACKGROUND: Physical activity may be beneficial for cognition but mechanisms are unclear. We examined the association between objectively assessed physical activity and brain volume, with a focus on the hippocampus region. METHODS: We used data from UK Biobank (n = 5272; aged 55.4 ± 7.5 years; 45.6% men) collected through 2013-2016. Participants wore the Axivity AX3 wrist-worn triaxial accelerometer for 7 days to assess habitual physical activity. Structural magnetic resonance imaging was performed using a standard Siemens Skyra 3T running VD13A SP4 to obtain images of the brain. RESULTS: There was an association between physical activity (per SD increase) and grey matter volume after adjustment for a range of covariates, although this association was only detected in older adults (>60 years old). We also observed associations of physical activity with both left (B = 0.52, 95% CI, 0.01, 1.03; P = 0.046) and right hippocampal volume (B = 0.59, 95% CI, 0.08, 1.10; P = 0.024) in covariate-adjusted models. CONCLUSION: In summary, physical activity may play a role in the prevention of neurodegenerative diseases.

Job strain as a risk factor for clinical depression: systematic review and meta-analysis with additional individual participant data.

BACKGROUND: Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression. METHOD: We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol. RESULTS: We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47-2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04-1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94-1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81-1.32). CONCLUSIONS: Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.

History, politics and vulnerability: explaining excess mortality in Scotland and Glasgow.

OBJECTIVES: High levels of excess mortality (i.e. that not explained by deprivation) have been observed for Scotland compared with England & Wales, and especially for Glasgow in comparison with similar post-industrial cities such as Liverpool and Manchester. Many potential explanations have been suggested. Based on an assessment of these, the aim was to develop an understanding of the most likely underlying causes. Note that this paper distils a larger research report, with the aim of reaching wider audiences beyond Scotland, as the important lessons learnt are relevant to other populations. STUDY DESIGN: Review and dialectical synthesis of evidence. METHODS: Forty hypotheses were examined, including those identified from a systematic review. The relevance of each was assessed by means of Bradford Hill's criteria for causality alongside-for hypotheses deemed causally linked to mortality-comparisons of exposures between Glasgow and Liverpool/Manchester, and between Scotland and the rest of Great Britain. Where gaps in the evidence base were identified, new research was undertaken. Causal chains of relevant hypotheses were created, each tested in terms of its ability to explain the many different aspects of excess mortality. The models were further tested with key informants from public health and other disciplines. RESULTS: In Glasgow's case, the city was made more vulnerable to important socioeconomic (deprivation, deindustrialisation) and political (detrimental economic and social policies) exposures, resulting in worse outcomes. This vulnerability was generated by a series of historical factors, processes and decisions: the lagged effects of historical overcrowding; post-war regional policy including the socially selective relocation of population to outside the city; more detrimental processes of urban change which impacted on living conditions; and differences in local government responses to UK government policy in the 1980s which both impacted in negative terms in Glasgow and also conferred protective effects on comparator cities. Further resulting protective factors were identified (e.g. greater 'social capital' in Liverpool) which placed Glasgow at a further relative disadvantage. Other contributory factors were highlighted, including the inadequate measurement of deprivation. A similar 'explanatory model' resulted for Scotland as a whole. This included: the components of the Glasgow model, given their impact on nationally measured outcomes; inadequate measurement of deprivation; the lagged effects of deprivation (in particular higher levels of overcrowding historically); and additional key vulnerabilities. CONCLUSIONS: The work has helped to further understanding of the underlying causes of Glasgow's and Scotland's high levels of excess mortality. The implications for policy include the need to address three issues simultaneously: to protect against key exposures (e.g. poverty) which impact detrimentally across all parts of the UK; to address the existing consequences of Glasgow's and Scotland's vulnerability; and to mitigate against the effects of future vulnerabilities which are likely to emerge from policy responses to contemporary problems which fail sufficiently to consider and to prevent long-term, unintended social consequences.

Depressive symptoms and obesity: instrumental variable analysis using mother-offspring pairs in the 1970 British Cohort Study.

BACKGROUND: The extent to which depression and obesity are causally related remains to be determined. We used intergenerational data on mother-offspring pairs in an instrumental variable analysis to examine the longitudinal association between adolescent depressive symptoms and body mass index (BMI) in adulthood. METHODS: A total of 4733 mother-offspring pairs were identified from the 1970 British Cohort Study. Mothers completed the Malaise Inventory to assess depressive symptoms on three occasions across their offsprings' childhood/adolescence (aged 5, 10 and 16 years). Height and weight were recorded in mother and offspring (aged 16 years). Measures of height, weight and the Malaise Inventory were repeated in the participant at the age of 42 years. RESULTS: Maternal malaise score was associated with offspring malaise score, thus confirming the validity of the chosen instrumental variable. A higher mother's malaise score was associated with higher offspring BMI at follow-up (B=0.043; 95% confidence interval (CI): 0.013, 0.072). There was a higher risk of adulthood offspring obesity in mothers with two or three episodes of depression compared with one or none (odds ratio, 1.42; 95% CI: 1.14, 1.76). The maternal malaise-offspring BMI association remained (P=0.003) after adjustment for offspring malaise score, suggesting that maternal mental health influences offspring obesity through mechanisms other than depression. Results from standard and instrumental variable analyses did not support a causal pathway in a direction from BMI to depression. CONCLUSIONS: Our data support a causal pathway linking adolescent depressive symptoms to adiposity in adulthood over 26 years follow-up. The reverse direction, that is, adiposity to depression, was not supported.

Sarcopenic obesity and risk of new onset depressive symptoms in older adults: English Longitudinal Study of Ageing.

BACKGROUND: We examined the role of sarcopenic obesity as a risk factor for new-onset depressive symptoms over 6-year follow-up in a large sample of older adults. METHODS: The sample comprised 3862 community dwelling participants (1779 men, 2083 women; mean age 64.6±8.3 years) without depressive symptoms at baseline, recruited from the English Longitudinal Study of Ageing. At baseline and 4-year follow-up, handgrip strength (kg) of the dominant hand was assessed using a hand-held dynamometer, as a measure of sarcopenia. The outcome was new onset depressive symptoms at 6-year follow-up, defined as a score of ⩾4 on the 8-item Centre of Epidemiological Studies Depression scale. Sarcopenic obesity was defined as obese individuals (body mass index ⩾30 kg m(-)(2)) in the lowest tertile of sex-specific grip strength (<35.3 kg men; <19.6 kg women). RESULTS: Using a multivariable logistic regression model, the risk of depressive symptoms was greatest in obese adults in the lowest tertile of handgrip strength (odds ratio (OR), 1.79, 95% confidence interval (CI), 1.10, 2.89) compared with non-obese individuals with high handgrip strength. Participants who were obese at baseline and had a decrease of more than 1 s.d. in grip strength over 4-year follow-up were at greatest risk of depressive symptoms (OR=1.97, 95% CI, 1.22, 3.17) compared with non-obese with stable grip strength. CONCLUSIONS: A reduction in grip strength was associated with higher risk of depressive symptoms in obese participants only, suggesting that sarcopenic obesity is a risk factor for depressive symptoms.

Severity of depressive symptoms as a predictor of mortality: the English longitudinal study of ageing.

BACKGROUND: Major depressive disorder and subthreshold depression have been associated with premature mortality. We investigated the association between depressive symptoms and mortality across the full continuum of severity. METHOD: We used Cox proportional hazards models to examine the association between depressive symptom severity, assessed using the eight-item Center for Epidemiological Studies Depression Scale (CES-D; range 0-8), and the risk of all-cause mortality over a 9-year follow-up, in 11 104 members of the English Longitudinal Study of Ageing. RESULTS: During follow-up, one fifth of study members died (N = 2267). Depressive symptoms were associated with increased mortality across the full range of severity (p trend < 0.001). Relative to study members with no symptoms, an increased risk of mortality was found in people with depressive symptoms of a low [hazard ratio (HR) for a score of 2 was 1.59, 95% confidence interval (CI) 1.40-1.82], moderate (score of 4: HR 1.80, 95% CI 1.52-2.13) and high (score of 8: HR 2.27, 95% CI 1.69-3.04) severity, suggesting risk emerges at low levels but plateaus thereafter. A third of participants (36.4%, 95% CI 35.5-37.3) reported depressive symptoms associated with an increased mortality risk. Adjustment for physical activity, physical illnesses, and impairments in physical and cognitive functioning attenuated this association (p trend = 0.25). CONCLUSIONS: Depressive symptoms are associated with an increased mortality risk even at low levels of symptom severity. This association is explained by physical activity, physical illnesses, and impairments in physical and cognitive functioning.

Interleukin-6 as a predictor of symptom resolution in psychological distress: a cohort study.

BACKGROUND: Elevated levels of interleukin-6 (IL-6) have been associated with the development of common mental disorders, such as depression, but its role in symptom resolution is unclear. METHOD: We examined the association between IL-6 and symptom resolution in a non-clinical sample of participants with psychological distress. RESULTS: Relative to high IL-6 levels, low levels at baseline were associated with symptom resolution at follow-up [age- and sex-adjusted risk ratio (RR) = 1.15, 95% confidence interval (CI) 1.06-1.25]. Further adjustment for covariates had little effect on the association. Symptomatic participants with repeated low IL-6 were more likely to be symptom-free at follow-up compared with those with repeated high IL-6 (RR = 1.21, 95% CI 1.03-1.41). Among the symptomatic participants with elevated IL-6 at baseline, IL-6 decreased along with symptom resolution. CONCLUSIONS: IL-6 is potentially related to the mechanisms underlying recovery from symptoms of mental ill health. Further studies are needed to examine these mechanisms and to confirm the findings in relation to clinical depression.

Association of metabolically healthy obesity with depressive symptoms: pooled analysis of eight studies.

The hypothesis of metabolically healthy obesity posits that adverse health effects of obesity are largely avoided when obesity is accompanied by a favorable metabolic profile. We tested this hypothesis with depressive symptoms as the outcome using cross-sectional data on obesity, metabolic health and depressive symptoms. Data were extracted from eight studies and pooled for individual-participant meta-analysis with 30,337 men and women aged 15-105 years (mean age=46.1). Clinic measures included height, weight and metabolic risk factors (high blood pressure, high triglycerides, low high-density lipoprotein cholesterol, high C-reactive protein and high glycated hemoglobin). Depressive symptoms were assessed using clinical interview or standardized rating scales. The pooled sample comprised 7673 (25%) obese participants (body mass index ⩾30 kg m(-2)). Compared to all non-obese individuals, the OR for depressive symptoms was higher in metabolically unhealthy obese individuals with two or more metabolic risk factors (1.45; 95% confidence interval (CI)=1.30, 1.61) and for metabolically healthy obese with ⩽1 metabolic risk factor (1.19; 95% CI=1.03, 1.37), adjusted for sex, age and race/ethnicity. Metabolically unhealthy obesity was associated with higher depression risk (OR=1.23; 95% CI=1.05, 1.45) compared with metabolically healthy obesity. These associations were consistent across studies with no evidence for heterogeneity in estimates (all I(2)-values<4%). In conclusion, obese persons with a favorable metabolic profile have a slightly increased risk of depressive symptoms compared with non-obese, but the risk is greater when obesity is combined with an adverse metabolic profile. These findings suggest that metabolically healthy obesity is not a completely benign condition in relation to depression risk.

Is personality associated with cancer incidence and mortality? An individual-participant meta-analysis of 2156 incident cancer cases among 42,843 men and women.

BACKGROUND: The putative role of personality in cancer risk has been controversial, and the evidence remains inconclusive. METHODS: We pooled data from six prospective cohort studies (British Household Panel Survey; Health and Retirement Study; Household, Income, and Labour Dynamics in Australia; Midlife in the United Survey; Wisconsin Longitudinal Study Graduate; and Sibling samples) for an individual-participant meta-analysis to examine whether personality traits of the Five Factor Model (extraversion, neuroticism, agreeableness, conscientiousness, and openness to experience) were associated with the incidence of cancer and cancer mortality in 42,843 cancer-free men and women at baseline (mean age 52.2 years, 55.6% women). RESULTS: During an average follow-up of 5.4 years, there were 2156 incident cancer cases. In random-effects meta-analysis adjusted for age, sex, and race/ethnicity, none of the personality traits were associated with the incidence of all cancers or any of the six site-specific cancers included in the analysis (lung, colon, breast, prostate, skin, and leukaemia/lymphoma). In the three cohorts with cause-specific mortality data (421 cancer deaths among 21,835 participants), none of the personality traits were associated with cancer mortality. CONCLUSIONS: These data suggest that personality is not associated with increased risk of incident cancer or cancer-related mortality.

Job strain and the risk of severe asthma exacerbations: a meta-analysis of individual-participant data from 100 000 European men and women.

BACKGROUND: Many patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations in working-age European men and women. METHODS: We analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident severe asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. RESULTS: During a median follow-up of 10 years, 1 109 individuals experienced a severe asthma exacerbation (430 with asthma as the primary diagnostic code). In the age- and sex-adjusted analyses, job strain was associated with an increased risk of severe asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR: 1.27, 95% confidence interval, CI: 1.00, 1.61). This association attenuated towards the null after adjustment for potential confounders (HR: 1.22, 95% CI: 0.96, 1.55). No association was observed in the analyses with asthma defined using any diagnostic code (HR: 1.01, 95% CI: 0.86, 1.19). CONCLUSIONS: Our findings suggest that job strain is probably not an important risk factor for severe asthma exacerbations leading to hospitalization or death.

Is bipolar disorder more common in highly intelligent people? A cohort study of a million men.

Anecdotal and biographical reports have long suggested that bipolar disorder is more common in people with exceptional cognitive or creative ability. Epidemiological evidence for such a link is sparse. We investigated the relationship between intelligence and subsequent risk of hospitalisation for bipolar disorder in a prospective cohort study of 1,049,607 Swedish men. Intelligence was measured on conscription for military service at a mean age of 18.3 years and data on psychiatric hospital admissions over a mean follow-up period of 22.6 years was obtained from national records. Risk of hospitalisation with any form of bipolar disorder fell in a stepwise manner as intelligence increased (P for linear trend <0.0001). However, when we restricted analyses to men with no psychiatric comorbidity, there was a 'reversed-J' shaped association: men with the lowest intelligence had the greatest risk of being admitted with pure bipolar disorder, but risk was also elevated among men with the highest intelligence (P for quadratic trend=0.03), primarily in those with the highest verbal (P for quadratic trend=0.009) or technical ability (P for quadratic trend <0.0001). At least in men, high intelligence may indeed be a risk factor for bipolar disorder, but only in the minority of cases who have the disorder in a pure form with no psychiatric comorbidity.

Childhood socioeconomic position, adult socioeconomic position and social mobility in relation to markers of adiposity in early adulthood: evidence of differential effects by gender in the 1978/79 Ribeirao Preto cohort study.

BACKGROUND: Longitudinal studies drawn from high-income countries demonstrate long-term associations of early childhood socioeconomic deprivation with increased adiposity in adulthood. However, there are very few data from resource-poor countries where there are reasons to anticipate different gradients. Accordingly, we sought to characterise the nature of the socioeconomic status (SES)-adiposity association in Brazil. METHODS: We use data from the Ribeirao Preto Cohort Study in Brazil in which 9067 newborns were recruited via their mothers in 1978/79 and one-in-three followed up in 2002/04 (23-25years). SES, based on family income (salaries, interest on savings, pensions and so on), was assessed at birth and early adulthood, and three different adiposity measures (body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR)) ascertained at follow-up. The association between childhood SES, adult SES and social mobility (defined as four permutations of SES in childhood and adulthood: low-low, low-high, high-low, high-high), and the adiposity measures was examined using linear regression. RESULTS: There was evidence that the association between SES and the three markers of adiposity was modified by gender in both adulthood (P<0.02 for all outcomes) and childhood SES (P<0.02 for WC and WHR). Thus, in an unadjusted model, linear regression analyses showed that higher childhood SES was associated with lower adiposity in women (coefficient (95% confidence intervals) BMI: -1.49 (-2.29,-0.69); WC: -3.85 (-5.73,-1.97); WHR: -0.03 (-0.04,-0.02)). However, in men, higher childhood SES was related to higher adiposity (BMI: 1.03 (0.28,-1.78); WC: 3.15 (1.20, 5.09); WHR: 0.009 (-0.001, 0.019)) although statistical significance was not seen in all analyses. There was a suggestion that adult SES (but not adult health behaviours or birthweight) accounted for these relationships in women only. Upward mobility was associated with protection against greater adiposity in women but not men. CONCLUSION: In the present study, in men there was some evidence that both higher childhood and adulthood SES was related to a higher adiposity risk, while the reverse gradient was apparent in women.

Ageing and the prevalence and treatment of mental health problems.

BACKGROUND: Ageing is an important factor in the development of mental health problems and their treatment. We assessed age trajectories of common mental disorders (CMDs) and psychotherapy utilization from adolescence to old age, and examined whether these trajectories were modified by time period or birth cohort effects. METHOD: British Household Panel Survey (BHPS) with an 18-year follow-up between 1991 and 2009 (n=30 224 participants, aged 15­100 years, with an average 7.3 person-observations per person). CMDs were assessed with the 12-item version of the General Health Questionnaire (GHQ). Psychotherapy treatment utilization during the past year was self-reported by the participants. The modifying influences of time period and cohort effects were assessed in a cohort-sequential longitudinal setting. RESULTS: Following a moderate decrease after age 50, the prevalence of GHQ caseness increased steeply from age 75. This increase was more marked in the 2000s (GHQ prevalence increasing from 24% to 43%) than in the 1990s (from 22% to 34%). Psychotherapy utilization decreased after age 55, with no time period or cohort effects modifying the age trajectory. These ageing patterns were replicated in within-individual longitudinal analysis. CONCLUSIONS: Old age is associated with higher risk of CMDs, and this association has become more marked during the past two decades. Ageing is also associated with an increasing discrepancy between prevalence of mental disorders and provision of treatment, as indicated by lower use of psychotherapy in older individuals.

Risk of future depression in people who are obese but metabolically healthy: the English longitudinal study of ageing.

There is some evidence to suggest that obesity is a risk factor for the development of depression, although this is not a universal finding. This discordance might be ascribed to the existence of a 'healthy obese phenotype'--that is, obesity in the absence of the associated burden of cardiometabolic risk factors. We examined whether the association of obesity with depressive symptoms is dependent on the individual's metabolic health. Participants were 3851 men and women (aged 63.0±8.9 years, 45.1% men) from the English Longitudinal Study of Ageing, a prospective study of community dwelling older adults. Obesity was defined as body mass index ≥30 kg m(-2). Based on blood pressure, high-density lipoprotein cholesterol, triglycerides, glycated haemoglobin and C-reactive protein, participants were classified as 'metabolically healthy' (0 or 1 metabolic abnormality) or 'unhealthy' (≥2 metabolic abnormalities). Depressive symptoms were assessed at baseline and at 2 years follow-up using the 8-item Centre of Epidemiological Studies Depression (CES-D) scale. Obesity prevalence was 27.5%, but 34.3% of this group was categorized as metabolically healthy at baseline. Relative to non-obese healthy participants, after adjustment for baseline CES-D score and other covariates, the metabolically unhealthy obese participants had elevated risk of depressive symptoms at follow-up (odds ratio (OR)=1.50; 95% confidence interval (CI), 1.05-2.15), although the metabolically healthy obese did not (OR=1.38; 95% CI, 0.88-2.17). The association between obesity and risk of depressive symptoms appears to be partly dependent on metabolic health, although further work is required to confirm these findings.

Resting heart rate and the risk of death and cardiovascular complications in patients with type 2 diabetes mellitus.

AIMS/HYPOTHESIS: An association between resting heart rate and mortality has been described in the general population and in patients with cardiovascular disease. There are, however, few data exploring this relationship in patients with type 2 diabetes mellitus. The current study addresses this issue. METHODS: The relationship between baseline resting heart rate and all-cause mortality, cardiovascular death and major cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) was examined in 11,140 patients who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) Study. RESULTS: A higher resting heart rate was associated with a significantly increased risk of all-cause mortality (fully adjusted HR 1.15 per 10 bpm [95% CI 1.08, 1.21], p<0.001), cardiovascular death and major cardiovascular outcomes without adjustment and after adjusting for age and sex and multiple covariates. The increased risk associated with a higher baseline resting heart rate was most obvious in patients with previous macrovascular complications (fully adjusted HR for death 1.79 for upper [mean 91 bpm] vs lowest [mean 58 bpm] fifth of resting heart rate in this subgroup [95% CI 1.28, 2.50], p = .001). CONCLUSIONS/INTERPRETATION: Among patients with type 2 diabetes, a higher resting heart rate is associated with an increased risk of death and cardiovascular complications. It remains unclear whether a higher heart rate directly mediates the increased risk or is a marker for other factors that determine a poor outcome.

Impact of mental health problems on case fatality in male cancer patients.

BACKGROUND: Although mortality rates are elevated in psychiatric patients relative to their healthy counterparts, little is known about the impact of mental health on survival in people with cancer. METHODS AND RESULTS: Among 16 498 Swedish men with cancer, survival was worse in those with a history of psychiatric hospital admissions: multiply-adjusted hazard ratio (95% confidence interval) comparing cancer mortality in men with and without psychiatric admissions: 1.59 (1.39, 1.83). CONCLUSION: Survival in cancer patients is worse among those with a history of psychiatric disease. The mechanisms underlying this association should be further explored.

Association of body mass index in early adulthood and middle age with future site-specific cancer mortality: the Harvard Alumni Health Study.

BACKGROUND: The association between adiposity in early adulthood and subsequent development of specific malignancies is unclear. Further, the potential for mediation by adiposity in middle age has not been well examined. In a rare study, we investigated the association of body mass index (BMI) in early adulthood with mortality from several site-specific cancers. DESIGN: In the Harvard Alumni Health Study cohort, 19 593 males had a physical examination at the university between 1914 and 1952 (mean age: 18.4 years) and returned a questionnaire in 1962 or 1966 (mean age = 45.1 years). BMI was computed using weight (kg)/height(2) (m(2)) at both time points. Vital status follow up continued for a maximum of 82 years. RESULTS: Positive early adulthood cancer mortality gradients by BMI were found for all malignancies combined (adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI]: 1.05-1.17 for a one standard deviation increase in early adulthood BMI), and for lung (HR = 1.24; 95% CI = 1.10-1.40) and skin (HR = 1.29; 95% CI = 0.96-1.75) cancers. There were also apparent associations for cancers of the oesophagus and urogenital sites. Mediation by BMI in middle age was found to be minimal. CONCLUSION: Higher BMI in early adulthood appears to be a direct risk factor for selected malignancies several decades later.