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Key Points Question Are alcohol-induced loss of consciousness and heavy weekly alcohol consumption associated with increased risk of future dementia? Findings In this multicohort study of 131 415 adults, a 1.2-fold excess risk of dementia was associated with heavy vs moderate alcohol consumption. Those who reported having lost consciousness due to alcohol consumption, regardless of their overall weekly consumption, had a 2-fold increased risk of dementia compared with people who had not lost consciousness and were moderate drinkers. Meaning The findings of this study suggest that alcohol-induced loss of consciousness is a long-term risk factor for dementia among both heavy and moderate drinkers., Importance Evidence on alcohol consumption as a risk factor for dementia usually relates to overall consumption. The role of alcohol-induced loss of consciousness is uncertain. Objective To examine the risk of future dementia associated with overall alcohol consumption and alcohol-induced loss of consciousness in a population of current drinkers. Design, Setting, and Participants Seven cohort studies from the UK, France, Sweden, and Finland (IPD-Work consortium) including 131 415 participants were examined. At baseline (1986-2012), participants were aged 18 to 77 years, reported alcohol consumption, and were free of diagnosed dementia. Dementia was examined during a mean follow-up of 14.4 years (range, 12.3-30.1). Data analysis was conducted from November 17, 2019, to May 23, 2020. Exposures Self-reported overall consumption and loss of consciousness due to alcohol consumption were assessed at baseline. Two thresholds were used to define heavy overall consumption: greater than 14 units (U) (UK definition) and greater than 21 U (US definition) per week. Main Outcomes and Measures Dementia and alcohol-related disorders to 2016 were ascertained from linked electronic health records. Results Of the 131 415 participants (mean [SD] age, 43.0 [10.4] years; 80 344 [61.1%] women), 1081 individuals (0.8%) developed dementia. After adjustment for potential confounders, the hazard ratio (HR) was 1.16 (95% CI, 0.98-1.37) for consuming greater than 14 vs 1 to 14 U of alcohol per week and 1.22 (95% CI, 1.01-1.48) for greater than 21 vs 1 to 21 U/wk. Of the 96 591 participants with data on loss of consciousness, 10 004 individuals (10.4%) reported having lost consciousness due to alcohol consumption in the past 12 months. The association between loss of consciousness and dementia was observed in men (HR, 2.86; 95% CI, 1.77-4.63) and women (HR, 2.09; 95% CI, 1.34-3.25) during the first 10 years of follow-up (HR, 2.72; 95% CI, 1.78-4.15), after excluding the first 10 years of follow-up (HR, 1.86; 95% CI, 1.16-2.99), and for early-onset (, This cohort study examines the association of overall consumption of alcohol and resultant loss of consciousness with risk for dementia.

Few risk prediction scores are available to identify people at increased risk of work disability, particularly for those with an existing morbidity. We examined the predictive performance of disability risk scores for employees with chronic disease. We used prospective data from 88,521 employed participants (mean age 43.1) in the Finnish Public Sector Study including people with chronic disorders: musculoskeletal disorder, depression, migraine, respiratory disease, hypertension, cancer, coronary heart disease, diabetes, comorbid depression and cardiometabolic disease. A total of 105 predictors were assessed at baseline. During a mean follow-up of 8.6 years, 6836 (7.7%) participants were granted a disability pension. C-statistics for the 8-item Finnish Institute of Occupational Health (FIOH) risk score, comprising age, self-rated health, number of sickness absences, socioeconomic position, number of chronic illnesses, sleep problems, BMI, and smoking at baseline, exceeded 0.72 for all disease groups and was 0.80 (95% CI 0.80–0.81) for participants with musculoskeletal disorders, 0.83 (0.82–0.84) for those with migraine, and 0.82 (0.81–0.83) for individuals with respiratory disease. Predictive performance was not significantly improved in models with re-estimated coefficients or a new set of predictors. These findings suggest that the 8-item FIOH work disability risk score may serve as a scalable screening tool in identifying individuals with increased risk for work disability.

Background: The excess risk of cardiovascular disease associated with a wide array of infectious diseases is unknown. We quantified the short- and long-term risk of major cardiovascular events in people with severe infection and estimated the population-attributable fraction. Methods: We analyzed data from 331 683 UK Biobank participants without cardiovascular disease at baseline (2006-2010) and replicated our main findings in an independent population from 3 prospective cohort studies comprising 271 329 community-dwelling participants from Finland (baseline 1986-2005). Cardiovascular risk factors were measured at baseline. We diagnosed infectious diseases (the exposure) and incident major cardiovascular events after infections, defined as myocardial infarction, cardiac death, or fatal or nonfatal stroke (the outcome) from linkage of participants to hospital and death registers. We computed adjusted hazard ratios (HRs) and 95% CIs for infectious diseases as short- and long-term risk factors for incident major cardiovascular events. We also calculated population-attributable fractions for long-term risk. Results: In the UK Biobank (mean follow-up, 11.6 years), 54 434 participants were hospitalized for an infection, and 11 649 had an incident major cardiovascular event at follow-up. Relative to participants with no record of infectious disease, those who were hospitalized experienced increased risk of major cardiovascular events, largely irrespective of the type of infection. This association was strongest during the first month after infection (HR, 7.87 [95% CI, 6.36-9.73]), but remained elevated during the entire follow-up (HR, 1.47 [95% CI, 1.40-1.54]). The findings were similar in the replication cohort (HR, 7.64 [95% CI, 5.82-10.03] during the first month; HR, 1.41 [95% CI, 1.34-1.48] during mean follow-up of 19.2 years). After controlling for traditional cardiovascular risk factors, the population-attributable fraction for severe infections and major cardiovascular events was 4.4% in the UK Biobank and 6.1% in the replication cohort. Conclusions: Infections severe enough to require hospital treatment were associated with increased risks for major cardiovascular disease events immediately after hospitalization. A small excess risk was also observed in the long-term, but residual confounding cannot be excluded. CC BY 4.0Correspondence to: Pyry Sipilä, Clinicum, Department of Public Health, PO Box 20, FI-00014 University of Helsinki, Finland. Email pyry.sipila@helsinki.fiAcknowledgmentsThis research was conducted using data from the UK Biobank (https://www.ukbiobank.ac.uk/) via application 60565.Sources of FundingThis work was funded in whole, or in part, by grants from NordForsk (75021), Academy of Finland (329202 and 350426), Helsinki Institute of Life Science, Emil Aaltonen Foundation, Finnish Medical Foundation, Päivikki and Sakari Sohlberg Foundation, Finnish Foundation for Cardiovascular Research (a86898), US National Institute on Aging (R01AG056477, 1R56AG052519-01, and 1R01AG052519-01A1), UK Medical Research Council (MRC S011676/1, R024227/1, and MR/P023444/1), and Wellcome Trust (201440/Z/16/Z and 221854/Z/20/Z). The funders had no role in study design, data collection, analysis, or interpretation, or writing of the report or decision to submit it for publication.DisclosuresDr Sipilä reports grant support during the conduct of the study from NordForsk (75021), Academy of Finland (311492 and 329202), Helsinki Institute of Life Science, Emil Aaltonen Foundation, and Finnish Medical Foundation. Dr Lindbohm reports grant support during the conduct of the study from the Academy of Finland (339568) and Päivikki and Sakari Sohlberg Foundation. Dr Batty reports grant support from the UK Medical Research Council (MR/P023444/1) and US National Institute on Aging (1R56AG052519-01 and 1R01AG052519-01A1). Dr Vahtera reports grant support from the Academy of Finland (321409 and 329240) and NordForsk (75021). Dr Nyberg reports grant support from NordForsk (75021). Dr Warren-Gash reports support from Wellcome Fellowship (201440/Z/16/Z). Dr Kivimäki reports grant support during the conduct of the study from NordForsk (75021), UK Medical Research Council (MRC S011676/1 and R024227/1), US National Institute on Aging (R01AG056477), Academy of Finland (329202 and 350426), Finnish Foundation for Cardiovascular Research (a86898), Finnish Work Environment Fund (190424), and Wellcome Trust (221854/Z/20/Z). The other authors report no conflicts.

Publisher Copyright: © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under CC BY-NC-ND 4.0 license Background: High emotional demands at work can affect employees’ health and there is a need to understand whether such an association might be modified by other working conditions. We aimed to examine emotional demands at work as a risk factor for long-term sickness absence and analyse whether influence, possibilities for development, role conflicts, and physical demands at work might modify this risk. Methods: We did a nationwide, population-based, prospective cohort study in Denmark and included employed individuals who were residing in Denmark in 2000, aged 30–59 years, who had complete data on age, sex, and migration background, with information on emotional demands and possible effect modifiers from job exposure matrices, and covariates and outcome (sickness absence) from population registers. Individuals with long-term sickness absence (≥6 weeks of consecutive sickness absence) between Jan 1, 1998, and Dec 31, 2000, and self-employed individuals were excluded. We assessed long-term sickness absence during a 10-year period from Jan 1, 2001, to Dec 31, 2010. Using Cox regression, we estimated hazard ratios (HRs) and 95% CIs and tested interaction as departure from additivity, estimating relative excess risk due to interaction (RERI). Multivariable adjusted models included sex, age, cohabitation, migration background, and income. Findings: 1 521 352 employed individuals were included and contributed data between Jan 1, 2000, and Dec 31, 2010. During 11 919 021 person-years (mean follow-up 7·8 years), we identified 480 685 new cases of long-term sickness absence. High emotional demands were associated with increased risk of long-term sickness absence compared with low emotional demands, after adjusting for age, sex, cohabitation, migration background, income, and the four possible effect modifiers (adjusted HR 1·55 [95% CI 1·53–1·56]). The association between high emotional demands and risk of long-term sickness absence was stronger in a synergistic way when individuals were also exposed to low possibilities for development (RERI 0·35 [95% CI 0·22–0·47]; 28·9 additional cases per 1000 person-years) and high role conflicts (0·13 [0·11–0·15]; 22·0 additional cases per 1000 person-years). No synergy was observed for influence and physical demands at work. Interpretation: People in occupations with high emotional demands were at increased risk of long-term sickness absence. Our findings on synergistic interactions suggest that, in emotionally demanding occupations, increasing possibilities for development and reducing work-related role conflicts might reduce long-term sickness absence. Further interventional studies are needed to confirm or refute this hypothesis. Funding: Danish Work Environment Research Fund, NordForsk.

BACKGROUND: Observational studies have identified a link between unfavourable neighbourhood characteristics and increased risk of morbidity, but it is unclear whether changes in neighbourhoods affect future disease risk. We used a data-driven approach to assess the impact of neighbourhood modification on 79 health outcomes. METHODS: In this prospective cohort study, we used pooled, individual-level data from two Finnish cohort studies: the Health and Social Support study and the Finnish Public Sector study. Neighbourhood characteristics (mean educational level, median income, and employment rate of residents, and neighbourhood green space) and individual lifestyle factors of community-dwelling individuals were assessed at baseline (at different waves starting between 1998 and 2013). We repeated assessment of neighbourhood characteristics and lifestyle factors approximately 5 years from each baseline assessment, after which follow-up began for health conditions diagnosed according to the WHO International Classification of Diseases for 79 common health conditions using linkage to electronic health records. We used Cox proportional hazard regression models to compute adjusted hazard ratios (HRs) of incident disease associated with neighbourhood characteristics and changes in neighbourhood characteristics over time and logistic regression analysis to compute adjusted odds of association between changes in neighbourhood characteristics and individual lifestyle factors. FINDINGS: 114 786 individuals (87 012 [75·8%] women; mean age 44·4 years [SD 11·1]) had complete data and were included in this cohort study. During 1·17 million person-years at risk, we recorded 164 368 new-onset health conditions and 3438 deaths. Favourable changes in neighbourhood characteristics were associated with reduced risk of all-cause mortality and incidence of 19 specific health conditions. Unfavourable changes were correspondingly associated with increased risk of mortality and 27 specific health conditions. Among participants who did not move residence during the observation period, relative to individuals who continually lived in disadvantaged neighbourhoods, those who experienced favourable modifications in neighbourhood characteristics had a lower risk of future diabetes (HR 0·84, 95% CI 0·75-0·93), stroke (0·49, 0·29-0·83), skin disease (0·72, 0·53-0·97), and osteoarthritis (0·87, 0·77-0·99). Living in a neighbourhood with improving characteristics was also associated with improvements in individual-level health-related lifestyle factors. Among participants who lived in advantaged residential environments at baseline, unfavourable changes in neighbourhood characteristics were associated with an increased risk of diabetes, stroke, skin disease, and osteoarthritis compared with individuals who lived in advantaged neighbourhoods throughout the study period. INTERPRETATION: Favourable modifications to residential neighbourhoods showed robust, longitudinal associations with a range of improvements in health outcomes, including improved health behaviours and reduced risk of cardiometabolic, infectious, and orthopaedic conditions. FUNDING: UK Medical Research Council, US National Institute on Aging, NordForsk, and Academy of Finland. CC BY 4.0

Few risk prediction scores are available to identify people at increased risk of work disability, particularly for those with an existing morbidity. We examined the predictive performance of disability risk scores for employees with chronic disease. We used prospective data from 88,521 employed participants (mean age 43.1) in the Finnish Public Sector Study which included people with chronic disorders: musculoskeletal disorder, depression, migraine, respiratory disease, hypertension, cancer, coronary heart disease, diabetes and comorbid depression and cardiometabolic disease. 105 predictors were assessed at baseline and participants were linked to a national disability pension register. During a mean follow-up of 8.6 years, 6836 (7.7%) participants got a disability pension, the incidence varying between 9.9% among participants with migraine and 27.7% in those with comorbid depression and cardiometabolic disease. C-statistics for an 8-item risk score, comprising age, self-rated health, number of sickness absences, socioeconomic position, number of chronic illnesses, sleep problems, BMI, and smoking at baseline, was 0.80 (95%CI: 0.80-0.81) for musculoskeletal disorders (N=33,601), 0.83 (0.82-0.84) for migraine (N=22,065), 0.82 (0.81-0.83) for respiratory disease (N=15,372) and exceeded 0.72 for other disease groups. With 30% estimated risk as a threshold, a positive test detection rate and false positive rate ranged from 42.2% and 18.8% (cancer) to 79.8% and 45.2% (comorbid depression and cardiometabolic disease). Predictive performance was not improved in models with a new set of predictors or re-estimated coefficients. In conclusion, the 8-item work disability risk score may serve as a scalable screening tool in identifying individuals with increased risk for work disability.

Summary Background Evaluation of cardiovascular disease risk in primary care, which is recommended every 5 years in middle-aged and older adults (typical age range 40–75 years), is based on risk scores, such as the European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE) and American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease (ASCVD) algorithms. This evaluation currently uses only the most recent risk factor assessment. We aimed to examine whether 5-year changes in SCORE and ASCVD risk scores are associated with future cardiovascular disease risk. Methods We analysed data from the Whitehall II longitudinal, prospective cohort study for individuals with no history of stroke, myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention, definite angina, heart failure, or peripheral artery disease. Participants underwent clinical examinations in 5-year intervals between Aug 7, 1991, and Dec 6, 2016, and were followed up for incident cardiovascular disease until Oct 2, 2019. Levels of, and 5-year changes in, cardiovascular disease risk were assessed using the SCORE and ASCVD risk scores and were analysed as predictors of cardiovascular disease. Harrell's C index, continuous net reclassification improvement, the Akaike information criterion, and calibration analysis were used to assess whether incorporating change in risk scores into a model including only a single risk score assessment improved the predictive performance. We assessed the levels of, and 5-year changes in, SCORE and ASCVD risk scores as predictors of cardiovascular disease and disease-free life-years using Cox proportional hazards and flexible parametric survival models. Findings 7574 participants (5233 [69·1%] men, 2341 [30·9%] women) aged 40–75 years were included in analyses of risk score change between April 24, 1997, and Oct 2, 2019. During a mean follow-up of 18·7 years (SD 5·5), 1441 (19·0%; 1042 [72·3%] men and 399 [27·7%] women) participants developed cardiovascular disease. Adding 5-year change in risk score to a model that included only a single risk score assessment improved model performance according to Harrell's C index (from 0·685 to 0·690, change 0·004 [95% CI 0·000 to 0·008] for SCORE; from 0·699 to 0·700, change 0·001 [0·000 to 0·003] for ASCVD), the Akaike information criterion (from 17 255 to 17 200, change −57 [95% CI −97 to −13] for SCORE; from 14 739 to 14 729, change −10 [–28 to 7] for ASCVD), and the continuous net reclassification index (0·353 [95% CI 0·234 to 0·447] for SCORE; 0·232 [0·030 to 0·344] for ASCVD). Both favourable and unfavourable changes in SCORE and ASCVD were associated with cardiovascular disease risk and disease-free life-years. The associations were seen in both sexes and all age groups up to the age of 75 years. At the age of 45 years, each 2-unit improvement in risk scores was associated with an additional 1·3 life-years (95% CI 0·4 to 2·2) free of cardiovascular disease for SCORE and an additional 0·9 life-years (95% CI 0·5 to 1·3) for ASCVD. At age 65 years, this same improvement was associated with an additional 0·4 life-years (95% CI 0·0 to 0·7) free of cardiovascular disease for SCORE and 0·3 life-years (95% CI 0·1 to 0·5) for ASCVD. These models were developed into an interactive calculator, which enables estimation of the number of cardiovascular disease-free life-years for an individual as a function of two risk score measurements. Interpretation Changes in the SCORE and ASCVD risk scores over time inform cardiovascular disease risk prediction beyond a single risk score assessment. Repeat data might allow more accurate cardiovascular risk stratification and strengthen the evidence base for decisions on preventive interventions. Funding UK Medical Research Council, British Heart Foundation, Wellcome Trust, and US National Institute on Aging.

Introduction Conventional risk factors targeted by prevention (e.g., low education, smoking, and obesity) are associated with a 1.2‐ to 2‐fold increased risk of dementia. It is unclear whether having a physical disease is an equally important risk factor for dementia. Methods In this exploratory multicohort study of 283,414 community‐dwelling participants, we examined 22 common hospital‐treated physical diseases as risk factors for dementia. Results During a median follow‐up of 19 years, a total of 3416 participants developed dementia. Those who had erysipelas (hazard ratio = 1.82; 95% confidence interval = 1.53 to 2.17), hypothyroidism (1.94; 1.59 to 2.38), myocardial infarction (1.41; 1.20 to 1.64), ischemic heart disease (1.32; 1.18 to 1.49), cerebral infarction (2.44; 2.14 to 2.77), duodenal ulcers (1.88; 1.42 to 2.49), gastritis and duodenitis (1.82; 1.46 to 2.27), or osteoporosis (2.38; 1.75 to 3.23) were at a significantly increased risk of dementia. These associations were not explained by conventional risk factors or reverse causation. Discussion In addition to conventional risk factors, several physical diseases may increase the long‐term risk of dementia.

Objectives This study aimed to examine the association between job strain and incident coronary heart disease (CHD) in Denmark, while accounting for changes of job strain. Methods We included all employees residing in Denmark in 2000, aged 30-59 years with no prevalent CHD (N=1660 150). We determined exposure to job strain from 1996-2009 using a job exposure matrix (JEM) with annual updates. Follow-up for incident CHD was from 2001-2010 via linkage to health records. We used Cox regression to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between job strain and incident CHD. Results During 16.1 million person-years, we identified 24 159 incident CHD cases (15.0 per 10 000 person-years). After adjustment for covariates, job strain in 2000 predicted onset of CHD during a mean follow-up of 9.71 years (HR 1.10, 95% CI 1.07-1.13). When analyzing changes in job strain from one year to the next and CHD in the subsequent year, persistent job strain (HR 1.07, 95% CI 1.03-1.10), onset of job strain (HR 1.20, 95% CI 1.12-1.29) and removal of strain (HR 1.20, 95% CI 1.12-1.28) were associated with higher CHD incidence compared to persistent no job strain. Associations were similar among men and women. Conclusions Job strain is associated with a higher risk of incident CHD in Denmark. As we used a JEM, we can rule out reporting bias. However, under- or overestimation of associations is possible due to non-differential misclassification of job strain and residual confounding by socioeconomic position.

Background Heavy alcohol consumption increases the risk of several chronic diseases. In this multicohort study, we estimated the number of life-years without major chronic diseases according to different characteristics of alcohol use. Methods In primary analysis, we pooled individual-level data from up to 129,942 adults across 12 cohort studies with baseline data collection on alcohol consumption, drinking patterns, and history between 1986 and 2005 (the IPD-Work Consortium). Self-reported alcohol consumption was categorised according to UK guidelines - non-drinking (never or former drinkers); moderate consumption (1-14 units); heavy consumption (>14 units per week). We further subdivided moderate and heavy drinkers by binge drinking pattern (alcohol-induced loss of consciousness). In addition, we assessed problem drinking using linked data on hospitalisations due to alcohol abuse or poisoning. Follow-up for chronic diseases for all participants included incident type 2 diabetes, coronary heart disease, stroke, cancer, and respiratory disease (asthma and chronic obstructive pulmonary disease) as ascertained via linkage to national morbidity and mortality registries, repeated medical examinations, and/or self-report. We estimated years lived without any of these diseases between 40 and 75 years of age according to sex and characteristics of alcohol use. We repeated the main analyses using data from 427,621 participants in the UK Biobank cohort study. Findings During 1.73 million person-years at risk, 22,676 participants in IPD-Work cohorts developed at least one chronic condition. From age 40 to 75 years, never-drinkers [men: 29.3 (95%CI 27.9-30.8) years, women 29.8 (29.2 - 30.4) years)] and moderate drinkers with no binge drinking habit [men 28.7 (28.4-29.0) years, women 29.6 (29.4-29.7) years] had the longest disease-free life span. A much shorter disease-free life span was apparent in participants who experienced alcohol poisoning [men 23.4 (20.9-26.0) years, women 24.0 (21.4-26.5) years] and those with self-reported heavy overall consumption and binge drinking [men: 26.0 (25.3-26.8), women 27.5 (26.4 - 28.5) years]. The pattern of results for alcohol poisoning and self-reported alcohol consumption was similar in UK Biobank. In IPD-Work and UK Biobank, differences in disease-free years between self-reported moderate drinkers and heavy drinkers were 1.5 years or less. Interpretation Individuals with alcohol poisonings or heavy self-reported overall consumption combined with a binge drinking habit have a marked 3- to 6-year loss in healthy longevity. Differences in disease-free life between categories of self-reported weekly alcohol consumption were smaller. CC BY 4.0Corresponding author at: Clinicum, Department of Public Health, Faculty of Medicine, University of Helsinki, Tukholmankatu 8B, FI-00014 Helsingin yliopisto, Helsinki, Finland. E-mail address: solja.nyberg@helsinki.fi (S.T. Nyberg).Funding Medical Research Council, National Institute on Aging, NordForsk, Academy of Finland, Finnish WorkEnvironment Fund.

We aimed to examine the association between exposure to work stress and chronic disease incidence and loss of chronic disease-free life years in the Danish workforce. The study population included 1,592,491 employees, aged 30 to 59 in 2000 and without prevalent chronic diseases. We assessed work stress as the combination of job strain and effort-reward imbalance using job exposure matrices. We used Cox regressions to estimate risk of incident hospital-diagnoses or death of chronic diseases (i.e., type 2 diabetes, coronary heart disease, stroke, cancer, asthma, chronic obstructive pulmonary disease, heart failure, and dementia) during 18 years of follow-up and calculated corresponding chronic disease-free life expectancy from age 30 to age 75. Individuals working in occupations with high prevalence of work stress had a higher risk of incident chronic disease compared to those in occupations with low prevalence of work stress (women: HR 1.04 (95% CI 1.02 to 1.05), men: HR 1.12 (95% CI 1.11 to 1.14)). The corresponding loss in chronic disease-free life expectancy was 0.25 (95% CI -0.10 to 0.60) and 0.84 (95% CI 0.56 to 1.11) years in women and men, respectively. Additional adjustment for health behaviours attenuated these associations among men. We conclude that men working in high-stress occupations have a small loss of years lived without chronic disease compared to men working in low-stress occupations. This finding appeared to be partially attributable to harmful health behaviours. In women, high work stress indicated a very small and statistically non-significant loss of years lived without chronic disease.

Background: The accumulation of disparate diseases in complex multimorbidity makes prevention difficult if each disease is targeted separately. We aimed to examine obesity as a shared risk factor for common diseases, determine associations between obesity-related diseases, and examine the role of obesity in the development of complex multimorbidity (four or more comorbid diseases). Methods: We did an observational study and used pooled prospective data from two Finnish cohort studies (the Health and Social Support Study and the Finnish Public Sector Study) comprising 114 657 adults aged 16–78 years at study entry (1998–2013). A cohort of 499 357 adults (aged 38–73 years at study entry; 2006–10) from the UK Biobank provided replication in an independent population. BMI and clinical characteristics were assessed at baseline. BMIs were categorised as obesity (≥30·0 kg/m2), overweight (25·0–29·9 kg/m2), healthy weight (18·5–24·9 kg/m2), and underweight (CC BY 4.0© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseCorrespondence to: Prof Mika Kivimäki, Department of Epidemiology and Public Health, University College London, London WC1E 6BT, UK m.kivimaki@ucl.ac.uk; @MikaKivimakiFunding Wellcome Trust, Medical Research Council, National Institute on Aging.

Background: Studies on the association between long working hours and health have captured only a narrow range of outcomes (mainly cardiometabolic diseases and depression) and no outcome-wide studies on this topic are available. To achieve wider scope of potential harm, we examined long working hours as a risk factor for a wide range of disease and mortality endpoints. Methods: The data of this multicohort study were from two population cohorts from Finland (primary analysis, n=59 599) and nine cohorts (replication analysis, n=44 262) from Sweden, Denmark, and the UK, all part of the Individual-participant Meta-analysis in Working Populations (IPD-Work) consortium. Baseline-assessed long working hours (≥55 hours per week) were compared to standard working hours (35-40 h). Outcome measures with follow-up until age 65 years were 46 diseases that required hospital treatment or continuous pharmacotherapy, all-cause, and three cause-specific mortality endpoints, ascertained via linkage to national health and mortality registers. Findings: 2747 (4·6%) participants in the primary cohorts and 3027 (6·8%) in the replication cohorts worked long hours. After adjustment for age, sex, and socioeconomic status, working long hours was associated with increased risk of cardiovascular death (hazard ratio 1·68; 95% confidence interval 1·08-2·61 in primary analysis and 1·52; 0·90-2·58 in replication analysis), infections (1·37; 1·13-1·67 and 1·45; 1·13-1·87), diabetes (1·18; 1·01-1·38 and 1·41; 0·98-2·02), injuries (1·22; 1·00-1·50 and 1·18; 0·98-1·18) and musculoskeletal disorders (1·15; 1·06-1·26 and 1·13; 1·00-1·27). Working long hours was not associated with all-cause mortality. Interpretation: Follow-up of 50 health outcomes in four European countries suggests that working long hours is associated with an elevated risk of early cardiovascular death and hospital-treated infections before age 65. Associations, albeit weak, were also observed with diabetes, musculoskeletal disorders and injuries. In these data working long hours was not related to elevated overall mortality. Funding: NordForsk, the Medical Research Council, the National Institute on Aging, the Wellcome Trust, Academy of Finland, and Finnish Work Environment Fund. CC BY-NC-ND 4.0© 2021 The AuthorsCorresponding author: Jenni ErvastiFunding: NordForsk, the Medical Research Council, the National Institute on Aging, the Wellcome Trust, Academy of Finland, and Finnish Work Environment Fund.

Aims: Sleep disturbances exhibit a strong social patterning, and inadequate sleep has been associated with adverse health outcomes, including cardiovascular disorders (CVD). However, the contribution of sleep to socioeconomic inequalities in CVD is unclear. This study pools data from eight European cohorts to investigate the role of sleep duration in the association between life-course socioeconomic status (SES) and CVD. Methods and results: We used cross-sectional data from eight European cohorts, totalling 111 205 participants. Life-course SES was assessed using father’s and adult occupational position. Self-reported sleep duration was categorized into recommended (6–8.5 h/night), long (>8.5 h/night), and short (

Objectives To examine the association between cognitively stimulating work and subsequent risk of dementia and to identify protein pathways for this association. Design Multicohort study with three sets of analyses. Setting United Kingdom, Europe, and the United States. Participants Three associations were examined: cognitive stimulation and dementia risk in 107 896 participants from seven population based prospective cohort studies from the IPD-Work consortium (individual participant data meta-analysis in working populations); cognitive stimulation and proteins in a random sample of 2261 participants from one cohort study; and proteins and dementia risk in 13 656 participants from two cohort studies. Main outcome measures Cognitive stimulation was measured at baseline using standard questionnaire instruments on active versus passive jobs and at baseline and over time using a job exposure matrix indicator. 4953 proteins in plasma samples were scanned. Follow-up of incident dementia varied between 13.7 to 30.1 years depending on the cohort. People with dementia were identified through linked electronic health records and repeated clinical examinations. Results During 1.8 million person years at risk, 1143 people with dementia were recorded. The risk of dementia was found to be lower for participants with high compared with low cognitive stimulation at work (crude incidence of dementia per 10 000 person years 4.8 in the high stimulation group and 7.3 in the low stimulation group, age and sex adjusted hazard ratio 0.77, 95% confidence interval 0.65 to 0.92, heterogeneity in cohort specific estimates I 2 =0%, P=0.99). This association was robust to additional adjustment for education, risk factors for dementia in adulthood (smoking, heavy alcohol consumption, physical inactivity, job strain, obesity, hypertension, and prevalent diabetes at baseline), and cardiometabolic diseases (diabetes, coronary heart disease, stroke) before dementia diagnosis (fully adjusted hazard ratio 0.82, 95% confidence interval 0.68 to 0.98). The risk of dementia was also observed during the first 10 years of follow-up (hazard ratio 0.60, 95% confidence interval 0.37 to 0.95) and from year 10 onwards (0.79, 0.66 to 0.95) and replicated using a repeated job exposure matrix indicator of cognitive stimulation (hazard ratio per 1 standard deviation increase 0.77, 95% confidence interval 0.69 to 0.86). In analysis controlling for multiple testing, higher cognitive stimulation at work was associated with lower levels of proteins that inhibit central nervous system axonogenesis and synaptogenesis: slit homologue 2 (SLIT2, fully adjusted β −0.34, P Conclusions The risk of dementia in old age was found to be lower in people with cognitively stimulating jobs than in those with non-stimulating jobs. The findings that cognitive stimulation is associated with lower levels of plasma proteins that potentially inhibit axonogenesis and synaptogenesis and increase the risk of dementia might provide clues to underlying biological mechanisms.

BACKGROUND: Infections have been hypothesised to increase the risk of dementia. Existing studies have included a narrow range of infectious diseases, relied on short follow-up periods, and provided little evidence for whether the increased risk is limited to specific dementia subtypes or attributable to specific microbes rather than infection burden. We aimed to compare the risk of Alzheimer's disease and other dementias across a wide range of hospital-treated bacterial and viral infections in two large cohorts with long follow-up periods. METHODS: In this large, multicohort, observational study, the analysis was based on a primary cohort consisting of pooled individual-level data from three prospective cohort studies in Finland (the Finnish Public Sector study, the Health and Social Support study, and the Still Working study) and an independent replication cohort from the UK Biobank. Community-dwelling adults (≥18 years) with no dementia at study entry were included. Follow-up was until Dec 31, 2012, in the Health and Social Support study, Dec 31, 2016, in the public sector study and the Still Working study, and Feb 7, 2018, in the replication cohort. Through record linkage to national hospital inpatient registers, we ascertained exposure to 925 infectious diseases (using the International Classification of Diseases 10th Revision codes) before dementia onset, and identified incident dementia from hospital records, medication reimbursement entitlements, and death certificates. Hazard ratios (HRs) for the associations of each infectious disease or disease group (index infection) with incident dementia were assessed by use of Cox proportional hazards models. We then repeated the analysis after excluding incident dementia cases that occurred during the first 10 years after initial hospitalisation due to the index infection. FINDINGS: From March 1, 1986, to Jan 1, 2005, 260 490 people were included in the primary cohort, and from Dec 19, 2006, to Oct 1, 2010, 485 708 people were included in the replication cohort. In the primary cohort analysis based on 3 947 046 person-years at risk (median follow-up 15·4 years [IQR 9·8-21·0]), 77 108 participants had at least one hospital-treated infection before dementia onset and 2768 developed dementia. Hospitalisation for any infectious disease was associated with increased dementia risk in the primary cohort (adjusted HR [aHR] 1·48 [95% CI 1·37-1·60]) and replication cohort (2·60 [2·38-2·83]). The association remained when analyses were restricted to new dementia cases that occurred more than 10 years after infection (aHR 1·22 [95% CI 1·09-1·36] in the primary cohort, the replication cohort had insufficient follow-up data for this analysis), and when comorbidities and other dementia risk factors were considered. There was evidence of a dose-response association between the number of episodes of hospital-treated infections and dementia risk in both cohorts (ptrend=0·0007). Although the greatest dementia risk was seen for central nervous system (CNS) infections versus no infection (aHR 3·01 [95% CI 2·07-4·37]), excess risk was also evident for extra-CNS infections (1·47 [1·36-1·59]). Although we found little difference in the infection-dementia association by type of infection, associations were stronger for vascular dementia than for Alzheimer's disease (aHR 2·09 [95% CI 1·59-2·75] versus aHR 1·20 [1·08-1·33] in the primary cohort and aHR 3·28 [2·65-4·04] versus aHR 1·80 [1·53-2·13] in the replication cohort). INTERPRETATION: Severe infections requiring hospital treatment are associated with long-term increased risk of dementia, including vascular dementia and Alzheimer's disease. This association is not limited to CNS infections, suggesting that systemic effects are sufficient to affect the brain. The absence of infection specificity combined with evidence of dose-response relationships between infectious disease burden and dementia risk support the hypothesis that increased dementia risk is driven by general inflammation rather than specific microbes. FUNDING: UK Medical Research Council, US National Institute on Aging, Wellcome Trust, NordForsk, Academy of Finland, and Helsinki Institute of Life Science. CC BY 4.0Correspondence to: Dr Pyry N Sipilä, Clinicum, Department of Public Health, University of Helsinki, Helsinki FI-00014, Finland pyry.sipila@helsinki.fiFunding: UK Medical Research Council, US National Institute on Aging, Wellcome Trust, NordForsk, Academy of Finland, and Helsinki Institute of Life Science.

Working hours is a ubiquitous exposure given that most adults are employed, and one that is modifiable via legislative change if not always through individual-level choice. According to a recent report from the World Health Organization (WHO) and International Labour Organization (ILO), there is currently sufficient evidence to conclude that long working hours (i.e., >= 55 h per week) elevate the risk of fatal and non-fatal ischaemic heart disease to a clinically meaningful extent. After assessing the data used by the ILO/WHO, we feel that the expert group has not correctly applied their own framework for assessing the strength of the evidence. In the meta-analysis of observational studies in the report, the association between long working hours and incident heart disease appeared stronger in lower quality cohort studies with a high risk of bias (minimally-adjusted hazard ratio 1.20, 95% CI 1.01-1.41, compared to standard 35-40 weekly hours) than in the superior-quality studies with a lower risk of bias for which the estimate was not significantly different from the null (1.08, 95% CI 0.93-1.25). There was also marked effect modification, such that there was no increase in ischaemic heart disease for those working long hours in high socioeconomic status occupations, a finding also reported in analyses of a recent census-based cohort study which was not included in the report. Our meta-analysis of all these studies confirm that the findings are not consistent but differ between subgroups and that the summary age- and sex-adjusted hazard ratio for long working hours in high socioeconomic status occupations does not support excess risk: 0.85, 95% CI 0.63-1.13 (Pinteraction = 0.005, total N = 451,982). For these and other reasons detailed in this commentary, we advance a more cautious interpretation of the existing evidence. The conclusions should be restricted to low socioeconomic status occupations only and more research is still needed to confirm or refute harmfulness and determine clinical relevance.

SummaryBackgroundInfectious diseases have been hypothesised to increase the risk of dementia. However, the evidence is sparse, captures only a limited range of infectious diseases, and relies on short follow-up periods. We assessed a wide range of severe (hospital-treated) bacterial and viral infections and their subtypes as risk factors for dementia in three large cohorts followed up for almost two decades and replicated the main findings in the UK Biobank.MethodsFor primary analysis, we pooled individual-level data from three prospective cohort studies with a median follow up of 19 years (from 1986-2005 to 2012-2016) and a total of 273 125 dementia-free community-dwelling participants. The replication analysis with the UK Biobank was based on 492 146 individuals (median follow-up 9·0 years from 2006-2010 to 2018). We ascertained exposure to infectious diseases and their subtypes before dementia onset using linked records from national hospital inpatient registers. Incident dementia was identified from linked hospital inpatient and outpatient records, medication reimbursement entitlements, and death certificates.FindingsIn the primary analysis based on 5·3 million person-years at risk, 88 099 participants had a hospital-treated infection before dementia onset and 3064 developed dementia. Gram-negative bacterial infections (hazard ratio [HR] 1·64; 95% confidence interval [CI] 1·25–2·14) and herpesvirus infections (HR 1·96; 95% CI 1·31–2·93) were robustly associated with an increased risk of dementia. For these infections, the relative risk of dementia remained similar when reverse causation and ascertainment biases were minimised by assessing only new dementia cases that occurred more than 10 years after the infection, and when comorbidities and potential confounders were considered. The associations were replicated in the UK Biobank with stronger relations observed for vascular dementia than Alzheimer’s disease. In contrast to gram-negative bacterial and herpesvirus infections, the hazard ratio for all bacterial infections combined attenuated from 1·60 (95% CI 1·48–1·72) to 1·27 (95% CI 1·14–1·41) when bias was minimised. For all viral infections, the corresponding attenuation was from HR 1·63 (95% CI 1·32–2·00) to 1·19 (95% CI 0·87–1·62).InterpretationGram-negative bacterial infections and herpesvirus infections were associated with a moderately increased risk of dementia both in the short- and long-term. Hospital-treated bacterial and viral infections in general had only modest long-term associations with incident dementia.FundingUK Medical Research Council, US National Institute on Aging, NordForsk, Academy of Finland, Helsinki Institute of Life Science.Research in contextEvidence before this studyInfectious diseases have been hypothesised in the aetiology of dementia. We searched PubMed on 2 April 2020 for observational studies and systematic reviews using the search terms ((Alzheimer* OR dementia) AND infectio* AND ((systematic[sb]) OR (Observational Study[ptyp])) without restrictions on language or publication date. We also searched the reference lists and citations of relevant articles. In observational studies, infectious diseases in general and specific bacterial (sepsis, septicaemia, bacteraemia, pneumonia, osteomyelitis, urinary tract infection, cellulitis, syphilis, and Borrelia burgdorferi and Chlamydia pneumoniae infections) and viral infections (hepatitis C infection, HIV) are linked to an increased risk of dementia. Additionally, there was suggestive evidence for associations of herpesvirus infections, Toxoplasma gondii parasite infection, and poor oral health with dementia. However, no large-scale studies assessed a wide range of different types of infectious diseases systematically in a single analytical setting and with adequate control for potential sources of bias, such as reverse causation resulting from the systemic changes related to the preclinical stages of dementia that increase susceptibility to infectious diseases.Added value of this studyIn this multicohort study, the primary analysis was based on individual-level data from 273 125 dementia-free community-dwelling participants with a median follow-up of 19 years. We ascertained 528 different infectious diseases before dementia onset using national hospital inpatient records and categorised them by causative microorganism (bacteria, viruses), disease invasiveness (invasive vs localised bacterial infections), and subtype (extracellular vs intracellular lifestyle and cell wall structure of bacteria, and type of virus). When reverse causation was minimised by analysing only infections that occurred more than 10 years before dementia onset, the relative risk of dementia was modest for all bacterial infections combined (hazard ratio [HR] 1·27; 95% confidence interval [CI] 1·14–1·41) and for all viral infections combined (HR 1·19; 95% CI 0·87–1·62). The associations of bacterial infections with dementia did not differ by the invasiveness of the infection (invasive vs localised infections) or extracellular vs intracellular lifestyle of the causative microorganism. In analysis of specific diagnostic groups, robust and stronger long-term associations with dementia were observed for Gram-negative bacterial infections (HR 1·64, 95% CI 1·25–2·14 for full follow-up; HR 1·67, 95% CI 1·13–2·48 from year 10 onwards) and herpesvirus infections (HR 1·96, 95% CI 1.31–2.93 full follow-up; HR 1·92, 95% CI 1·11–3·32 from year 10 onwards). These associations remained after controlling for comorbidities and potential confounders and were replicated in an independent cohort of 492 146 individuals from the UK Biobank (median follow-up 9·0 years) with stronger relations observed for vascular dementia than Alzheimer’s disease.Implications of all the available evidenceGram-negative bacterial infections and herpesvirus infections seem to be robust long-term risk factors for dementia. Further mechanistic and molecular research is warranted to clarify the potential role of Gram-negative bacterial infections and herpesvirus in neurodegeneration and the aetiology of dementia.

BACKGROUND: Socioeconomic disadvantage is a risk factor for many diseases. We characterised cascades of these conditions by using a data-driven approach to examine the association between socioeconomic status and temporal sequences in the development of 56 common diseases and health conditions.METHODS: In this multi-cohort study, we used data from two Finnish prospective cohort studies: the Health and Social Support study and the Finnish Public Sector study. Our pooled prospective primary analysis data comprised 109 246 Finnish adults aged 17-77 years at study entry. We captured socioeconomic status using area deprivation and education at baseline (1998-2013). Participants were followed up for health conditions diagnosed according to the WHO International Classification of Diseases until 2016 using linkage to national health records. We tested the generalisability of our findings with an independent UK cohort study-the Whitehall II study (9838 people, baseline in 1997, follow-up to 2017)-using a further socioeconomic status indicator, occupational position.FINDINGS: During 1 110 831 person-years at risk, we recorded 245 573 hospitalisations in the Finnish cohorts; the corresponding numbers in the UK study were 60 946 hospitalisations in 186 572 person-years. Across the three socioeconomic position indicators and after adjustment for lifestyle factors, compared with more advantaged groups, low socioeconomic status was associated with increased risk for 18 (32·1%) of the 56 conditions. 16 diseases formed a cascade of inter-related health conditions with a hazard ratio greater than 5. This sequence began with psychiatric disorders, substance abuse, and self-harm, which were associated with later liver and renal diseases, ischaemic heart disease, cerebral infarction, chronic obstructive bronchitis, lung cancer, and dementia.INTERPRETATION: Our findings highlight the importance of mental health and behavioural problems in setting in motion the development of a range of socioeconomically patterned physical illnesses. Policy and health-care practice addressing psychological health issues in social context and early in the life course could be effective strategies for reducing health inequalities.FUNDING: UK Medical Research Council, US National Institute on Aging, NordForsk, British Heart Foundation, Academy of Finland, and Helsinki Institute of Life Science.

This cohort study examines disease-free life-years in participants with varying combinations of lifestyle risk factors. Question Are different combinations of lifestyle factors associated with years lived without chronic diseases? Findings In a multicohort study of 116 & x202f;043 participants, a statistically significant association between overall healthy lifestyle score and an increased number of disease-free life-years was noted. Of 16 different lifestyle profiles studied, the 4 that were associated with the greatest disease-free life years included body mass index lower than 25 and at least 2 of 3 factors: never smoking, physical activity, and moderate alcohol consumption. Meaning Various healthy lifestyle profiles appear to be associated with extended gains in life lived without type 2 diabetes, cardiovascular and respiratory diseases, and cancer. Importance It is well established that selected lifestyle factors are individually associated with lower risk of chronic diseases, but how combinations of these factors are associated with disease-free life-years is unknown. Objective To estimate the association between healthy lifestyle and the number of disease-free life-years. Design, Setting, and Participants A prospective multicohort study, including 12 European studies as part of the Individual-Participant-Data Meta-analysis in Working Populations Consortium, was performed. Participants included 116 & x202f;043 people free of major noncommunicable disease at baseline from August 7, 1991, to May 31, 2006. Data analysis was conducted from May 22, 2018, to January 21, 2020. Exposures Four baseline lifestyle factors (smoking, body mass index, physical activity, and alcohol consumption) were each allocated a score based on risk status: optimal (2 points), intermediate (1 point), or poor (0 points) resulting in an aggregated lifestyle score ranging from 0 (worst) to 8 (best). Sixteen lifestyle profiles were constructed from combinations of these risk factors. Main Outcomes and Measures The number of years between ages 40 and 75 years without chronic disease, including type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease. Results Of the 116 & x202f;043 people included in the analysis, the mean (SD) age was 43.7 (10.1) years and 70 & x202f;911 were women (61.1%). During 1.45 million person-years at risk (mean follow-up, 12.5 years; range, 4.9-18.6 years), 17 & x202f;383 participants developed at least 1 chronic disease. There was a linear association between overall healthy lifestyle score and the number of disease-free years, such that a 1-point improvement in the score was associated with an increase of 0.96 (95% CI, 0.83-1.08) disease-free years in men and 0.89 (95% CI, 0.75-1.02) years in women. Comparing the best lifestyle score with the worst lifestyle score was associated with 9.9 (95% CI 6.7-13.1) additional years without chronic diseases in men and 9.4 (95% CI 5.4-13.3) additional years in women (P

Background Job strain is implicated in many atherosclerotic diseases, but its role in peripheral artery disease ( PAD ) is unclear. We investigated the association of job strain with hospital records of PAD , using individual‐level data from 11 prospective cohort studies from Finland, Sweden, Denmark, and the United Kingdom. Methods and Results Job strain (high demands and low control at work) was self‐reported at baseline (1985–2008). PAD records were ascertained from national hospitalization data. We used Cox regression to examine the associations of job strain with PAD in each study, and combined the study‐specific estimates in random effects meta‐analyses. We used τ 2 , I 2 , and subgroup analyses to examine heterogeneity. Of the 139 132 participants with no previous hospitalization with PAD , 32 489 (23.4%) reported job strain at baseline. During 1 718 132 person‐years at risk (mean follow‐up 12.8 years), 667 individuals had a hospital record of PAD (3.88 per 10 000 person‐years). Job strain was associated with a 1.41‐fold (95% CI, 1.11–1.80) increased average risk of hospitalization with PAD . The study‐specific estimates were moderately heterogeneous (τ 2 =0.0427, I 2 : 26.9%). Despite variation in their magnitude, the estimates were consistent in both sexes, across the socioeconomic hierarchy and by baseline smoking status. Additional adjustment for baseline diabetes mellitus did not change the direction or magnitude of the observed associations. Conclusions Job strain was associated with small but consistent increase in the risk of hospitalization with PAD , with the relative risks on par with those for coronary heart disease and ischemic stroke.

Individual and Combined Effects of Job Strain Components on Subsequent Morbidity and Mortality

BackgroundAdverse 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.MethodWe 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.ResultsWe 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).ConclusionsJob strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.

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Objectives This systematic review and meta-analysis combined published study-level data and unpublished individual-participant data with the aim of quantifying the relation between long working hours and the onset of depressive symptoms. Methods We searched PubMed and Embase for published prospective cohort studies and included available cohorts with unpublished individual-participant data. We used a random-effects meta-analysis to calculate summary estimates across studies. Results We identified ten published cohort studies and included unpublished individual-participant data from 18 studies. In the majority of cohorts, long working hours was defined as working ≥55 hours per week. In multivariable-adjusted meta-analyses of 189 729 participants from 35 countries [96 275 men, 93 454 women, follow-up ranging from 1-5 years, 21 747 new-onset cases), there was an overall association of 1.14 (95% confidence interval (CI) 1.03-1.25] between long working hours and the onset of depressive symptoms, with significant evidence of heterogeneity (I 2=45.1%, P=0.004). A moderate association between working hours and depressive symptoms was found in Asian countries (1.50, 95% CI 1.13-2.01), a weaker association in Europe (1.11, 95% CI 1.00-1.22), and no association in North America (0.97, 95% CI 0.70-1.34) or Australia (0.95, 95% CI 0.70-1.29). Differences by other characteristics were small. Conclusions This observational evidence suggests a moderate association between long working hours and onset of depressive symptoms in Asia and a small association in Europe. CC BY 4.0

Summary Background Working long hours might have adverse health effects, but whether this is true for all socioeconomic status groups is unclear. In this meta-analysis stratified by socioeconomic status, we investigated the role of long working hours as a risk factor for type 2 diabetes. Methods We identified four published studies through a systematic literature search of PubMed and Embase up to April 30, 2014. Study inclusion criteria were English-language publication; prospective design (cohort study); investigation of the effect of working hours or overtime work; incident diabetes as an outcome; and relative risks, odds ratios, or hazard ratios (HRs) with 95% CIs, or sufficient information to calculate these estimates. Additionally, we used unpublished individual-level data from 19 cohort studies from the Individual-Participant-Data Meta-analysis in Working-Populations Consortium and international open-access data archives. Effect estimates from published and unpublished data from 222 120 men and women from the USA, Europe, Japan, and Australia were pooled with random-effects meta-analysis. Findings During 1·7 million person-years at risk, 4963 individuals developed diabetes (incidence 29 per 10 000 person-years). The minimally adjusted summary risk ratio for long (≥55 h per week) compared with standard working hours (35–40 h) was 1·07 (95% CI 0·89–1·27, difference in incidence three cases per 10 000 person-years) with significant heterogeneity in study-specific estimates ( I 2 =53%, p=0·0016). In an analysis stratified by socioeconomic status, the association between long working hours and diabetes was evident in the low socioeconomic status group (risk ratio 1·29, 95% CI 1·06–1·57, difference in incidence 13 per 10 000 person-years, I 2 =0%, p=0·4662), but was null in the high socioeconomic status group (1·00, 95% CI 0·80–1·25, incidence difference zero per 10 000 person-years, I 2 =15%, p=0·2464). The association in the low socioeconomic status group was robust to adjustment for age, sex, obesity, and physical activity, and remained after exclusion of shift workers. Interpretation In this meta-analysis, the link between longer working hours and type 2 diabetes was apparent only in individuals in the low socioeconomic status groups. Funding Medical Research Council, European Union New and Emerging Risks in Occupational Safety and Health research programme, Finnish Work Environment Fund, Swedish Research Council for Working Life and Social Research, German Social Accident Insurance, Danish National Research Centre for the Working Environment, Academy of Finland, Ministry of Social Affairs and Employment (Netherlands), Economic and Social Research Council, US National Institutes of Health, and British Heart Foundation.

Background: Although overweight and obesity have been studied in relation to individual cardiometabolic diseases, their association with risk of cardiometabolic multimorbidity is poorly understood. Here we aimed to establish the risk of incident cardiometabolic multimorbidity (ie, at least two from: type 2 diabetes, coronary heart disease, and stroke) in adults who are overweight and obese compared with those who are a healthy weight. Methods: We pooled individual-participant data for BMI and incident cardiometabolic multimorbidity from 16 prospective cohort studies from the USA and Europe. Participants included in the analyses were 35 years or older and had data available for BMI at baseline and for type 2 diabetes, coronary heart disease, and stroke at baseline and follow-up. We excluded participants with a diagnosis of diabetes, coronary heart disease, or stroke at or before study baseline. According to WHO recommendations, we classified BMI into categories of healthy (20·0–24·9 kg/m2), overweight (25·0–29·9 kg/m2), class I (mild) obesity (30·0–34·9 kg/m2), and class II and III (severe) obesity (≥35·0 kg/m2). We used an inclusive definition of underweight (2) to achieve sufficient case numbers for analysis. The main outcome was cardiometabolic multimorbidity (ie, developing at least two from: type 2 diabetes, coronary heart disease, and stroke). Incident cardiometabolic multimorbidity was ascertained via resurvey or linkage to electronic medical records (including hospital admissions and death). We analysed data from each cohort separately using logistic regression and then pooled cohort-specific estimates using random-effects meta-analysis. Findings: Participants were 120 813 adults (mean age 51·4 years, range 35–103; 71 445 women) who did not have diabetes, coronary heart disease, or stroke at study baseline (1973–2012). During a mean follow-up of 10·7 years (1995–2014), we identified 1627 cases of multimorbidity. After adjustment for sociodemographic and lifestyle factors, compared with individuals with a healthy weight, the risk of developing cardiometabolic multimorbidity in overweight individuals was twice as high (odds ratio [OR] 2·0, 95% CI 1·7–2·4; pnterpretation: The risk of cardiometabolic multimorbidity increases as BMI increases; from double in overweight people to more than ten times in severely obese people compared with individuals with a healthy BMI. Our findings highlight the need for clinicians to actively screen for diabetes in overweight and obese patients with vascular disease, and pay increased attention to prevention of vascular disease in obese individuals with diabetes. Funding NordForsk, Medical Research Council, Cancer Research UK, Finnish Work Environment Fund, and Academy of Finland.

BACKGROUND: Epidemiologic evidence for work stress as a risk factor for coronary heart disease is mostly based on a single measure of stressful work known as job strain, a combination of high demands and low job control. We examined whether a complementary stress measure that assesses an imbalance between efforts spent at work and rewards received predicted coronary heart disease. METHODS: This multi-cohort study (the 'IPD-Work' consortium) was based on harmonized individual-level data from 11 European prospective cohort studies. Stressful weappork in 90,164 men and women without coronary heart disease at baseline was assessed by validated effort-reward imbalance and job strain questionnaires. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. Study-specific estimates were pooled by random-effects meta-analysis. RESULTS: At baseline, 31.7% of study members reported effort-reward imbalance at work and 15.9% reported job strain. During a mean follow-up of 9.8 years, 1078 coronary events were recorded. After adjustment for potential confounders, a hazard ratio of 1.16 (95% confidence interval 1.00-1.35) was observed for effort-reward imbalance compared to no imbalance. The hazard ratio was 1.16 (1.01-1.34) for having either effort-reward imbalance or job strain, and 1.41 (1.12-1.76) for having both these stressors compared to having neither effort-reward imbalance nor job strain. CONCLUSIONS: Individuals with effort-reward imbalance at work have an increased risk of coronary heart disease, and this appears to be independent of job strain experienced. These findings support expanding focus beyond just job strain in future research on work stress.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ObjectiveTo examine whether physical inactivity is a risk factor for dementia, with attention to the role of cardiometabolic disease in this association and reverse causation bias that arises from changes in physical activity in the preclinical (prodromal) phase of dementia.DesignMeta-analysis of 19 prospective observational cohort studies.Data sourcesThe Individual-Participant-Data Meta-analysis in Working Populations Consortium, the Inter-University Consortium for Political and Social Research, and the UK Data Service, including a total of 19 of a potential 9741 studies.Review methodThe search strategy was designed to retrieve individual-participant data from prospective cohort studies. Exposure was physical inactivity; primary outcomes were incident all-cause dementia and Alzheimer’s disease; and the secondary outcome was incident cardiometabolic disease (that is, diabetes, coronary heart disease, and stroke). Summary estimates were obtained using random effects meta-analysis.ResultsStudy population included 404 840 people (mean age 45.5 years, 57.7% women) who were initially free of dementia, had a measurement of physical inactivity at study entry, and were linked to electronic health records. In 6.0 million person-years at risk, we recorded 2044 incident cases of all-cause dementia. In studies with data on dementia subtype, the number of incident cases of Alzheimer’s disease was 1602 in 5.2 million person-years. When measured 10 before dementia onset 1.30, 0.79 to 2.14).ConclusionsIn analyses that addressed bias due to reverse causation, physical inactivity was not associated with all-cause dementia or Alzheimer’s disease, although an indication of excess dementia risk was observed in a subgroup of physically inactive individuals who developed cardiometabolic disease.

BACKGROUND: Job insecurity has been associated with certain health outcomes. We examined the role of job insecurity as a risk factor for incident diabetes. METHODS: We used individual participant data from 8 cohort studies identified in 2 open-access data archives and 11 cohort studies participating in the Individual-Participant-Data Meta-analysis in Working Populations Consortium. We calculated study-specific estimates of the association between job insecurity reported at baseline and incident diabetes over the follow-up period. We pooled the estimates in a meta-analysis to produce a summary risk estimate. RESULTS: The 19 studies involved 140 825 participants from Australia, Europe and the United States, with a mean follow-up of 9.4 years and 3954 incident cases of diabetes. In the preliminary analysis adjusted for age and sex, high job insecurity was associated with an increased risk of incident diabetes compared with low job insecurity (adjusted odds ratio [OR] 1.19, 95% confidence interval [CI] 1.09-1.30). In the multivariable-adjusted analysis restricted to 15 studies with baseline data for all covariates (age, sex, socioeconomic status, obesity, physical activity, alcohol and smoking), the association was slightly attenuated (adjusted OR 1.12, 95% CI 1.01-1.24). Heterogeneity between the studies was low to moderate (age- and sex-adjusted model: I2 = 24%, p = 0.2; multivariable-adjusted model: I2 = 27%, p = 0.2). In the multivariable-adjusted analysis restricted to high-quality studies, in which the diabetes diagnosis was ascertained from electronic medical records or clinical examination, the association was similar to that in the main analysis (adjusted OR 1.19, 95% CI 1.04-1.35). INTERPRETATION: Our findings suggest that self-reported job insecurity is associated with a modest increased risk of incident diabetes. Health care personnel should be aware of this association among workers reporting job insecurity.

Background Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. Methods We used individual records from 13 European cohort studies (1985-2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. Findings 30 214 (15%) of 197 473 participants reported job strain. In 1•49 million person-years at risk (mean follow-up 7•5 years [SD 1•7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1•23 (95% CI 1•10-1•37). This effect estimate was higher in published (1•43, 1•15-1•77) than unpublished (1•16, 1•02-1•32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1•31, 1•15-1•48) and 5 years (1•30, 1•13-1•50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3•4%. Interpretation Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. Funding Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health. CODEN: LANCA

BACKGROUND: Guidelines for coronary heart disease (CHD) prevention recommend using multifactorial risk prediction algorithms, particularly the Framingham risk score. We sought to examine whether adding information on job strain to the Framingham model improves its predictive power in a low-risk working population. METHODS: Our analyses are based on data from the prospective Whitehall II cohort study, UK. Job strain among 5533 adults (mean age 48.9 years, 1666 women) was ascertained in Phases 1 (1985-88), 2 (1989-90) and 3 (1991-93). Variables comprising the Framingham score (blood lipids, blood pressure, diabetes and smoking) were measured at Phase 3. In men and women who were CHD free at baseline, CHD mortality and non-fatal myocardial infarction (MI) were ascertained from 5-yearly screenings and linkage to mortality and hospital records until Phase 7 (2002-04). RESULTS: A total of 160 coronary deaths and non-fatal MIs occurred during the mean follow-up period of 11.3 years. The addition of indicators of job strain to the Framingham score increased the C-statistics from 0.725 [95% confidence intervals (95% CIs): 0.575-0.854] to only 0.726 (0.577-0.855), corresponding to a net reclassification improvement of 0.7% (95% CIs: -4.2 to 5.6%). The findings were similar after inclusion of definite angina in the CHD outcome (352 total cases) and when using alternative operational definitions for job strain. CONCLUSION: In this middle-aged low-risk working population, job strain was associated with an increased risk of CHD. However, when compared with the Framingham algorithm, adding job strain did not improve the model's predictive performance.