Work stress may be an important determinant of CHD among working-age populations, which is mediated through indirect effects on health behaviours and direct effects on neuroendocrine stress pathways.

There is a common perception that excess adiposity, commonly approximated by body mass index (BMI), is associated with reduced cancer survival. A number of studies have emerged challenging this by demonstrating that overweight and early obese states are associated with improved survival. This finding is termed the “obesity paradox” and is well recognized in the cardio-metabolic literature but less so in oncology. Here, we summarize the epidemiological findings related to the obesity paradox in cancer. Our review highlights that many observations of the obesity paradox in cancer reflect methodological mechanisms including the crudeness of BMI as an obesity measure, confounding, detection bias, reverse causality, and a specific form of the selection bias, known as collider bias. It is imperative for the oncologist to interpret the observation of the obesity paradox against the above methodological framework and avoid the misinterpretation that being obese might be “good” or “protective” for cancer patients.

Short sleep duration and increased sleep disturbances are independently associated with diurnal slope in cortisol secretion of a large community-based cohort of middle-aged men and women.

Positive affective states are associated with favorable health outcomes, but the underlying mechanisms are poorly understood. The authors assessed associations between positive affect, cortisol sampled over the day, and inflammatory markers (C-reactive protein and interleukin-6) among 2,873 healthy members of the Whitehall II study. Data for this study were collected in 2002-2004 in London, United Kingdom. Saliva free cortisol was assessed on waking, 30 minutes later, and four times over the day and evening. Positive affect was indexed by aggregating ecological momentary assessments of positive mood over the day. Salivary cortisol averaged over the day was inversely associated with positive affect after controlling for age, gender, income, ethnicity, body mass index, waist/hip ratio, smoking, paid employment, time of waking in the morning, and depression (p ¼ 0.003). There was no association with cortisol responses to waking. The adjusted odds of C-reactive protein 3.00 mg/liter was 1.89 (95% confidence interval: 1.08, 3.31) in low-compared with high-positive-affect women, and plasma interleukin-6 was also inversely related to positive affect in women (p ¼ 0.016). Neither inflammatory marker was related to positive affect in men. These results confirm findings from smaller studies relating cortisol with positive affect while suggesting that in women, positive affect is associated with reduced levels of inflammatory markers. adrenal cortex hormones; affect; C-reactive protein; happiness; interleukin-6 Abbreviations: CES-D, Center for Epidemiologic Studies Depression; CRP, C-reactive protein; IL-6, interleukin-6; SD, standard deviation.Positive affective states and positive well-being are associated with reduced risk of physical disease and prolonged healthy life expectancy (1). Associations have been described between positive psychological states and greater longevity, reduced risk of death due to stroke and coronary heart disease, and delayed onset of disability and hypertension (2-8), stimulating the search for mediating biologic and behavioral pathways.Direct associations with neuroendocrine, inflammatory, and immune processes may be present. Positive affect has been shown to predict reduced risk of upper respiratory infectious illness following experimentally administered virus (9) and greater antibody responses to hepatitis B vaccination (10). In an earlier study with a subsample from the Whitehall II cohort (n ¼ 216), we assessed positive affect by aggregating ecological momentary assessments of positive affect over a working day and evening (11). Positive affect was associated with lower salivary free cortisol over the working day independently of age, gender, socioeconomic status, smoking, body mass index, and negative affect. Similar findings were observed over a weekend day, and effects were replicated at 3-year follow-up (12). Positive affect was also related to reduced fibrinogen responses to acute mental stress. These cortisol differences have been observed in Correspondence to Dr.

Context:Evidence for an association of smoking status with cortisol secretion is mixed.Objective: The objective of the study was to assess the relationship between smoking status and salivary cortisol.Design: This was a cross-sectional study of smoking status and cortisol secretion from phase 7 (2002-2004) of the Whitehall II study.Setting: An occupational cohort was originally recruited in [1985][1986][1987]. Participants:The study population consisted of 3103 men (1514 never-smokers, 1278 ex-smokers, and 311 smokers) and 1128 women (674 never-smokers, 347 ex-smokers, and 107 smokers). Information was collected on smoking status, average number of cigarettes smoked, and additional covariates.Outcome Measures: Saliva samples were taken on waking; waking ϩ 0.5, 2.5, 8, and 12 h; and bedtime for the assessment of cortisol. Results:Smoking status was significantly associated with increased salivary cortisol release throughout the day (P Ͻ 0.001) adjusted for covariates; this was apparent for the cortisol awakening response (P Ͻ 0.001) when examined separately. Compared with never-smokers, smokers had higher release of total cortisol (P ϭ 0.002), whereas no difference was observed between never-smokers and ex-smokers (P ϭ 0.594): mean release per hour (nanomoles per liter), neversmokers, 4.13 [confidence interval (CI) 4.02-4.24]; ex-smokers, 4.21 (CI 4.08 -4.35); smokers, 4.63 (CI 4.35-4.93). There was no significant relationship between number of cigarettes smoked and total cortisol release. However, a difference was observed for the cortisol awakening response: mean release by tertiles of cigarettes smoked (nanomoles per liter): high, 13.49 medium, low,, P ϭ 0.029. Conclusion:Salivary cortisol is increased in current smokers, compared with nonsmokers; no differences were observed between exsmokers and never-smokers, suggesting that smoking has a shortterm effect on the neuroendocrine system.

Diurnal salivary cortisol profiles are valuable indicators of adrenocortical functioning in epidemiological research and clinical practice. However, normative reference values derived from a large number of participants and across a wide age range are still missing. To fill this gap, data were compiled from 15 independently conducted field studies with a total of 104,623 salivary cortisol samples obtained from 18,698 unselected individuals (mean age: 48.3 years, age range: 0.5 to 98.5 years, 39% females). Besides providing a descriptive analysis of the complete dataset, we also performed mixed-effects growth curve modeling of diurnal salivary cortisol (i.e., 1 to 16 hours after awakening). Cortisol decreased significantly across the day and was influenced by both, age and sex. Intriguingly, we also found a pronounced impact of sampling season with elevated diurnal cortisol in spring and decreased levels in autumn. However, the majority of variance was accounted for by between-participant and between-study variance components. Based on these analyses, reference ranges (LC/MS-MS calibrated) for cortisol concentrations in saliva were derived for different times across the day, with more specific reference ranges generated for males and females in different age categories. This integrative summary provides important reference values on salivary cortisol to aid basic scientists and clinicians in interpreting deviations from the normal diurnal cycle.

BackgroundMultimorbidity is common in primary care populations. Within cardiovascular disease, important differences in disease prevalence and risk factor management by ethnicity are recognised.

Aims/hypothesis The evidence on the association between pioglitazone use and bladder cancer is contradictory, with many studies subject to allocation bias. The aim of our study was to examine the effect of exposure to pioglitazone on bladder cancer risk internationally across several cohorts. The potential for allocation bias was minimised by focusing on the cumulative effect of pioglitazone as the primary endpoint using a time-dependent approach.Methods Prescription, cancer and mortality data from people with type 2 diabetes were obtained from six populations across the world (British Columbia, Finland, Manchester, Rotterdam, Scotland and the UK Clinical Practice Research Datalink). A discrete time failure analysis using Poisson regression was applied separately to data from each centre to model the effect of cumulative drug exposure on bladder cancer incidence, with time-dependent adjustment for ever use of Electronic supplementary material The online version of this article (doi:10.1007/s00125-014-3456-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users. -014-3456-9 pioglitazone. These were then pooled using fixed and random effects meta-regression. Results Data were collated on 1.01 million persons over 5.9 million person-years. There were 3,248 cases of incident bladder cancer, with 117 exposed cases and a median follow-up duration of 4.0 to 7.4 years. Overall, there was no evidence for any association between cumulative exposure to pioglitazone and bladder cancer in men (rate ratio [RR] per 100 days of cumulative exposure, 1.01; 95% CI 0.97, 1.06) or women (RR 1.04; 95% CI 0.97, 1.11) after adjustment for age, calendar year, diabetes duration, smoking and any ever use of pioglitazone. No association was observed between rosiglitazone and bladder cancer in men (RR 1.01; 95% CI 0.98, 1.03) or women (RR 1.00; 95% CI 0.94, 1.07). Conclusions/interpretation The cumulative use of pioglitazone or rosiglitazone was not associated with the incidence of bladder cancer in this large, pooled multipopulation analysis.Diabetologia (2015) 58:493-504 DOI 10.1007/s00125