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Abstract Background Few studies evaluated the use of Household Disinfectant and Cleaning Products (HDCPs) during the COVID-19 pandemic, but no population-based cohorts used longitudinal data. We studied changes in HDCPs during the first lockdown, based on longitudinal data from the French population-based NutriNet-Santé and CONSTANCES cohorts. Methods Based on standardized questionnaires on household cleaning tasks in 2018–2019 and around the first lockdown in France (March17-May3 2020), we compared the duration of weekly use of HDCPs ( 30 min/week) and the household cleaning help (yes/no) before and during the lockdown period by Bhapkar and McNemar’s tests. Moreover, we assessed self-reported changes in the frequency of HDCPs during the lockdown from before (unchanged/increased). Results Analyses were carried on 31,105 participants of NutriNet-Santé (48 years, 75% women, 81% ≥ high school diploma) and 49,491 of CONSTANCES (47 years, 51% women, 87% ≥ high school diploma). During the lockdown, compared with 2018–2019, duration of HDCPs use increased (> 30 min; NutriNet-Santé: 44% versus 18%; CONSTANCES: 63% versus 16%) and household help decreased (NutriNet-Santé: 5% versus 40%; CONSTANCES: 3% versus 56%). Regarding the frequency of HDCPs use, 55% of participants of NutriNet-Santé (57% women/49% men) and 83% of CONSTANCES (86% women/81% men) reported an increased use since the beginning of the lockdown, significantly higher among women (p

Abstract The demographical history of France remains largely understudied despite its central role toward understanding modern population structure across Western Europe. Here, by exploring publicly available Europe-wide genotype datasets together with the genomes of 3234 present-day and six newly sequenced medieval individuals from Northern France, we found extensive fine-scale population structure across Brittany and the downstream Loire basin and increased population differentiation between the northern and southern sides of the river Loire, associated with higher proportions of steppe vs. Neolithic-related ancestry. We also found increased allele sharing between individuals from Western Brittany and those associated with the Bell Beaker complex. Our results emphasise the need for investigating local populations to better understand the distribution of rare (putatively deleterious) variants across space and the importance of common genetic legacy in understanding the sharing of disease-related alleles between Brittany and people from western Britain and Ireland.

Abstract Background Healthy lifestyles are inversely associated with the risk of noncommunicable diseases, which are leading causes of death. However, few studies have used longitudinal data to assess the impact of changing lifestyle behaviours on all-cause and cancer mortality. Methods Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, lifestyle profiles of 308,497 cancer-free adults (71% female) aged 35–70 years at recruitment across nine countries were assessed with baseline and follow-up questionnaires administered on average of 7 years apart. A healthy lifestyle index (HLI), assessed at two time points, combined information on smoking status, alcohol intake, body mass index, and physical activity, and ranged from 0 to 16 units. A change score was calculated as the difference between HLI at baseline and follow-up. Associations between HLI change and all-cause and cancer mortality were modelled with Cox regression, and the impact of changing HLI on accelerating mortality rate was estimated by rate advancement periods (RAP, in years). Results After the follow-up questionnaire, participants were followed for an average of 9.9 years, with 21,696 deaths (8407 cancer deaths) documented. Compared to participants whose HLIs remained stable (within one unit), improving HLI by more than one unit was inversely associated with all-cause and cancer mortality (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.81, 0.88; and HR: 0.87; 95% CI: 0.82, 0.92; respectively), while worsening HLI by more than one unit was associated with an increase in mortality (all-cause mortality HR: 1.26; 95% CI: 1.20, 1.33; cancer mortality HR: 1.19; 95% CI: 1.09, 1.29). Participants who worsened HLI by more than one advanced their risk of death by 1.62 (1.44, 1.96) years, while participants who improved HLI by the same amount delayed their risk of death by 1.19 (0.65, 2.32) years, compared to those with stable HLI. Conclusions Making healthier lifestyle changes during adulthood was inversely associated with all-cause and cancer mortality and delayed risk of death. Conversely, making unhealthier lifestyle changes was positively associated with mortality and an accelerated risk of death.

Background Identifying factors that predict the course of persistent symptoms that occurred during the COVID-19 pandemic is a public health issue. Modifiable factors could be targeted in therapeutic interventions.Objective This prospective study based on the population-based CONSTANCES cohort examined whether the psychological burden associated with incident persistent symptoms (ie, that first occurred from March 2020) would predict having ≥1 persistent symptom 6–10 months later.Methods A total of 8424 participants (mean age=54.6 years (SD=12.6), 57.2% women) having ≥1 incident persistent symptom at baseline (ie, between December 2020 and February 2021) were included. The psychological burden associated with these persistent symptoms was assessed with the Somatic Symptom Disorder-B Criteria Scale (SSD-12). The outcome was having ≥1 persistent symptom at follow-up. Adjusted binary logistic regression models examined the association between the SSD-12 score and the outcome.Findings At follow-up, 1124 participants (13.3%) still had ≥1 persistent symptom. The SSD-12 score at baseline was associated with persistent symptoms at follow-up in both participants with (OR (95% CI) for one IQR increase: 1.42 (1.09 to 1.84)) and without SARS-CoV-2 infection prior to baseline (1.39 (1.25 to 1.55)). Female gender, older age, poorer self-rated health and infection prior to baseline were also associated with persistent symptoms at follow-up.Conclusions The psychological burden associated with persistent symptoms at baseline predicted the presence of ≥1 persistent symptom at follow-up regardless of infection prior to baseline.Clinical implications Intervention studies should test whether reducing the psychological burden associated with persistent symptoms could improve the course of these symptoms.

Abstract Background Work circumstances can substantially negatively impact health. To explore this, large occupational cohorts of free-text job descriptions are manually coded and linked to exposure. Although several automatic coding tools have been developed, accurate exposure assessment is only feasible with human intervention. Methods We developed OPERAS, a customizable decision support system for epidemiological job coding. Using 812,522 entries, we developed and tested classification models for the Professions et Catégories Socioprofessionnelles (PCS)2003, Nomenclature d’Activités Française (NAF)2008, International Standard Classifications of Occupation (ISCO)-88, and ISCO-68. Each code comes with an estimated correctness measure to identify instances potentially requiring expert review. Here, OPERAS’ decision support enables an increase in efficiency and accuracy of the coding process through code suggestions. Using the Formaldehyde, Silica, ALOHA, and DOM job-exposure matrices, we assessed the classification models’ exposure assessment accuracy. Results We show that, using expert-coded job descriptions as gold standard, OPERAS realized a 0.66–0.84, 0.62–0.81, 0.60–0.79, and 0.57–0.78 inter-coder reliability (in Cohen’s Kappa) on the first, second, third, and fourth coding levels, respectively. These exceed the respective inter-coder reliability of expert coders ranging 0.59–0.76, 0.56–0.71, 0.46–0.63, 0.40–0.56 on the same levels, enabling a 75.0–98.4% exposure assessment accuracy and an estimated 19.7–55.7% minimum workload reduction. Conclusions OPERAS secures a high degree of accuracy in occupational classification and exposure assessment of free-text job descriptions, substantially reducing workload. As such, OPERAS significantly outperforms both expert coders and other current coding tools. This enables large-scale, efficient, and effective exposure assessment securing healthy work conditions.

Abstract Background Few population‐based studies have described allergic rhinitis (AR) according to the Allergic Rhinitis and its Impact on Asthma (ARIA) classification, and none have assessed the impact of asthma on this classification. Our aims were to 1) describe AR according to four ARIA classes and 2) within each of the four ARIA classes, compare participants with AR alone versus those with AR and asthma. Methods Cross‐sectional analyses were performed using data from the 2014 annual follow‐up questionnaire of the French adult population‐based cohort Constances. Current AR was defined by the report of sneezing, runny, or blocked nose in the last 12 months and the report of nasal allergies. Following ARIA recommendations, rhinitis was classified according to its severity (mild or moderate‐severe) and duration (intermittent or persistent). Ever asthma was also defined by a questionnaire. Results Among the 4675 participants with AR (57% women, mean age 50.2 ± 12.7 years), 44% were classified as mild/intermittent, 16% mild/persistent, 25% moderate‐severe/intermittent, and 15% moderate‐severe/persistent. Within each of the four ARIA classes, compared to participants with rhinitis alone, participants with rhinitis and asthma had significantly more severe symptoms, more conjunctivitis, a higher mean eosinophil count and more treatments with intra‐nasal corticosteroids and oral antihistamines co‐medication. Conclusions This is a paradigm shift study as for the first time this large population‐based study in adults showed that asthma status has a profound effect on the ARIA classification. Rhinitis alone and rhinitis with asthma represent two distinct phenotypes. These results reinforce the need to include asthma status in the ARIA classification and guidelines.

Abstract Background This study examined prospective associations between atypical working hours with subsequent tobacco, cannabis and alcohol use as well as sugar and fat consumption. Methods In the French population-based CONSTANCES cohort, 47,288 men and 53,324 women currently employed included between 2012 and 2017 were annually followed for tobacco and cannabis use. Among them, 35,647 men and 39,767 women included between 2012 and 2016 were also followed for alcohol and sugar and fat consumption. Three indicators of atypical working hours were self-reported at baseline: working at night, weekend work and non-fixed working hours. Generalized linear models computed odds of substance use and sugar and fat consumption at follow-up according to atypical working hours at baseline while adjusting for sociodemographic factors, depression and baseline substance use when appropriate. Results Working at night was associated with decreased smoking cessation and increased relapse in women [odds ratios (ORs) of 0.81 and 1.25], increased cannabis use in men [ORs from 1.46 to 1.54] and increased alcohol use [ORs from 1.12 to 1.14] in both men and women. Weekend work was associated with decreased smoking cessation in women [ORs from 0.89 to 0.90] and increased alcohol use in both men and women [ORs from 1.09 to 1.14]. Non-fixed hours were associated with decreased smoking cessation in women and increased relapse in men [ORs of 0.89 and 1.13] and increased alcohol use in both men and women [ORs from 1.12 to 1.19]. Overall, atypical working hours were associated with decreased sugar and fat consumption. Conclusions The potential role of atypical working hours on substance use should be considered by public health policy makers and clinicians in information and prevention strategies.

Objectives Distinguish the respective effects of social position, work environment and unemployment on cardiovascular and cancer risks.Design A cross-sectional and retrospective observational study.Setting A population-based French cohort (CONSTANCES).Participants 130 197 adults enrolled between 2012 and 2021 without missing values.Primary outcome measures The associations of social position, work environment and unemployment exposure with the prevalence of cardiovascular events and cancers simultaneously tested using logistic regression models adjusting for common risk factors.Results While social position, work environment and unemployment exposure are strongly inter-related with each other, they are not linked to the same cardiovascular and cancer outcomes. Low social position and long unemployment duration are significantly associated with an increased prevalence of angina pectoris, myocardial infarction and peripheral arterial disease (OR=1.22 to 1.90, p

Background: The specific compounds that make ambient fine particulate matter (PM2.5) carcinogen remain poorly identified. Some metals contribute to ambient PM2.5 and possibly to its adverse effects. But the challenge of assessing exposure to airborne metals limits epidemiological studies. Objective: To analyze the relationships between several airborne metals and risk of cancer in a large population. Methods: We estimated the individual exposure to 12 airborne metals of ∼ 12,000 semi-urban and rural participants of the French population-based Gazel cohort using moss biomonitoring data from a 20-year national program. We used principal component analyses (PCA) to derive groups of metals, and focused on six single carcinogenic or toxic metals (arsenic, cadmium, chromium, lead, nickel, and vanadium). We used extended Cox models with attained age as time-scale and time-varying weighted average exposures, adjusted for individual and area-level covariables, to analyze the association between each exposure and all-site combined, bladder, lung, breast, and prostate cancer incidence. Results: We identified 2,401 cases of all-site cancer between 2001 and 2015. Over the follow-up, median exposures varied from 0.22 (interquartile range (IQR): 0.18–0.28) to 8.68 (IQR: 6.62–11.79) µg.g−1 of dried moss for cadmium and lead, respectively. The PCA yielded three groups identified as “anthropogenic”, “crustal”, and “marine”. Models yielded positive associations between most single and groups of metal and all-site cancer, with e.g. hazard ratios of 1.08 (95% CI: 1.03, 1.13) for cadmium or 1.06 (95% CI: 1.02,1.10) for lead, per interquartile range increase. These findings were consistent across supplementary analyses, albeit attenuated when accounting for total PM2.5. Regarding specific site cancers, we estimated positive associations mostly for bladder, and generally with large confidence intervals. Conclusion: Most single and groups of airborne metals, except vanadium, were associated with risk of cancer. These findings may help identify sources or components of PM2.5 that may be involved in its carcinogenicity.

Background A higher burden of cardiovascular disease risk factors has been reported in sexual minority populations. Primordial prevention may therefore be a relevant preventative strategy. The study's objectives are to estimate the associations of Life's Essential 8 (LE8) and Life's Simple 7 (LS7) cardiovascular health scores with sexual minority status. Methods and Results The CONSTANCES is a nationwide French epidemiological cohort study that recruited randomly selected participants older than 18 years in 21 cities. Sexual minority status was based on self‐reported lifetime sexual behavior and categorized as lesbian, gay, bisexual, or heterosexual. The LE8 score includes nicotine exposure, diet, physical activity, body mass index, sleep health, blood glucose, blood pressure, and blood lipids. The previous LS7 score included 7 metrics without sleep health. The study included 169 434 cardiovascular disease–free adults (53.64% women; mean age, 45.99 years). Among 90 879 women, 555 were lesbian, 3149 were bisexual, and 84 363 were heterosexual. Among 78 555 men, 2421 were gay, 2748 were bisexual, and 70 994 were heterosexual. Overall, 2812 women and 2392 men declined to answer. In multivariable mixed effects linear regression models, lesbian (β=−0.95 [95% CI, −1.89 to −0.02]) and bisexual (β=−0.78 [95% CI, −1.18 to −0.38]) women had a lower LE8 cardiovascular health score compared with heterosexual women. Conversely, gay (β=2.72 [95% CI, 2.25–3.19]) and bisexual (β=0.83 [95% CI, 0.39–1.27]) men had a higher LE8 cardiovascular health score compared with heterosexual men. The findings were consistent, although of smaller magnitudes for the LS7 score. Conclusions Cardiovascular health disparities exist in sexual minority adults, particularly lesbian and bisexual women, who may represent a priority population for primordial cardiovascular disease prevention.

Background Obstructive sleep apnoea (OSA) is associated with increased morbidity and mortality. Although the disorder has been well studied in selected high-risk populations, few data exist on its prevalence in the general population. We aimed to assess the prevalence and determinants of OSA in France. Methods Data from participants of the French population-based CONSTANCES cohort aged 18–69 years at inclusion and being treated for sleep apnoea or screened for OSA in 2017 using the Berlin Questionnaire were analysed. Weighted analyses were performed to provide recent and representative results in the general population. Results Among 20 151 participants, the prevalence of treated sleep apnoea was 3.5% (95% CI 3.0–3.9%). The prevalence of untreated subjects with a positive Berlin Questionnaire was 18.1% (95% CI 17.3–19.2%) for a total weighted prevalence of treated sleep apnoea or high risk of OSA of 20.9% (95% CI 20.0–21.9%). Regarding prevalence of OSA symptoms, it was 37.2% (95% CI 36.1–38.3%) for severe snoring and 14.6% (95% CI 13.8–15.5%) for hypersomnolence. In multivariable logistic regression analysis, male sex, age, previous cardiovascular events, smoking, low educational level, low physical activity and depressive symptoms were associated with having either treated sleep apnoea or a positive Berlin Questionnaire. Conclusion In this large French population-based cohort, one in five participants had a high likelihood of OSA, whereas only 3.5% were treated for the disorder, suggesting major underdiagnosis in the general population. OSA diagnosis should be considered more often in people with risk factors such as depressive symptoms as well as unhealthy behaviours and socioeconomic conditions.

Abstract Many studies have investigated the impact of the COVID-19 pandemic on mental health. Throughout the pandemic, time spent at home increased to a great extent due to restrictive measures. Here we set out to investigate the relationship between housing conditions and the mental health of populations across European countries. We analyzed survey data collected during spring 2020 from 69,136 individuals from four cohorts from Denmark, France, and the UK. The investigated housing conditions included household density, composition, and crowding, access to outdoor facilities, dwelling type, and urbanicity. The outcomes were loneliness, anxiety, and life satisfaction. Logistic regression models were used, and results were pooled using random-effects meta-analysis. In the meta-analysis, living alone was associated with higher levels of loneliness (OR = 3.08, 95% CI 1.87–5.07), and lower life satisfaction (OR = 1.27, 95% CI 1.05–0.55), compared to living with others. Not having access to an outdoor space and household crowding were suggestively associated with worse outcomes. Living in crowded households, living alone, or lacking access to outdoor facilities may be particularly important in contributing to poor mental health during a lockdown. Addressing the observed fundamental issues related to housing conditions within society will likely have positive effects in reducing social inequalities, as well as improving preparedness for future pandemics.

Abstract Background Rheumatoid arthritis (RA) is characterized by increased cardiovascular (CV) mortality. CV events are particularly high in patients with RA-specific autoimmunity, including rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), raising the question whether RA-specific autoimmunity itself is associated with CV events. Methods New CV events (myocardial infarction, stroke or death by CV cause) were recorded in 20,625 subjects of the Electricité de France – Gaz de France (GAZEL) cohort. Self-reported RA cases in the GAZEL cohort were validated by phone interview on the basis of a specific questionnaire. In 1618 subjects, in whom plasma was available, RF and ACPA were measured. A piecewise exponential Poisson regression was used to analyze the association of CV events with presence of RA as well as RA-specific autoimmunity (without RA). Results CV events in GAZEL were associated with age, male sex, smoking, hypertension, hyperlipidemia, and diabetes mellitus (HR from 1.06 to 1.87, p

Abstract We examined the prospective association of physical exertion at work with subsequent tobacco, cannabis, alcohol use, and sugar and fat consumption. Volunteers of the French population-based CONSTANCES cohort currently employed were included from 2012 to 2017 for tobacco and cannabis outcomes (n = 100,612), and from 2012 to 2016 for alcohol and sugar and fat outcomes (n = 75,414). High level of physical exertion at work was defined as a score ≥ 12 at the Rating Perceived Exertion Borg scale. Substance use was self-reported and diet rich in sugar and fat was obtained from principal component analysis and analyzed as quartiles. Generalized linear models computed odds of substance use and sugar and fat consumption at follow-up according to baseline physical exertion at work, while adjusting for sociodemographic factors, depressive symptoms and baseline level of consumption. High physical exertion was associated with tobacco use with dose-dependent relationships. It was also associated with increased odds of cannabis use at least once per month compared to no use in the past and with increased odds of diet rich in sugar and fat. Hence, the role of physical exertion at work on tobacco and cannabis use and diet rich in sugar and fat should be tackled for information and prevention strategies.

BackgroundTattooing, whose popularity is growing worldwide, is an invasive body art that involves the injection of chemical mixtures, the tattoo ink, into the upper layer of the dermis. Although these inks may contain environmental toxins, including known human carcinogens, their long-term health effects are poorly studied. To conduct the urgently required epidemiological studies on tattoos and their long-term health effects, a validated method for assessing the complex tattoo exposure is needed. ObjectiveWe aimed to develop and validate the Epidemiological Tattoo Assessment Tool (EpiTAT), a questionnaire to self-assess tattoo ink exposure in tattooed populations suitable for application in large epidemiological cohort studies. MethodsOne of 3 preliminary versions of the EpiTAT using one of the alternative tattoo measurement units hand surface, credit card, or body schemes was randomly filled in by tattooed volunteers in Lyon, France. To identify the most suitable unit of tattoo self-assessment, a validation study was conducted with the selected respondents (N=97) to compare the self-assessments of tattoo surface, color, and coverage with validation measurements made by trained study personnel. Intraclass correlation, the Kendall rank correlation, and 2-tailed t tests were used to statistically compare tattoo size, color area, and tattoo coverage separately for each questionnaire version. Participants’ opinions on the alternative measurement units were also considered in the overall evaluation. For quality control of the validation measures, digital surface analysis of 62 photographs of selected tattoos was performed using Fiji/ImageJ. ResultsIn general, the results revealed overestimation of self-assessed measures compared with validation measures (eg, mean tattooed body surface 1768, SD 1547, cm2 vs 930, SD 1047, cm2, respectively, for hand surface; P

Background and Aim: Few studies have reported the association between air pollution exposure with different dimensions of depression. We aimed to explore this association across different dimensions of depressive symptoms in a large population. Methods: Data from the enrollment phase of the French CONSTANCES cohort (2012–2020) were analyzed cross-sectionally. Annual concentrations of particulate matter with a diameter

Abstract This study provides trends in obesity prevalence in adults from 2013 to 2016 in France. 63,582 men and women from independent samples upon inclusion from the Constances cohort were included. Anthropometrics were measured at Health Screening Centers and obesity defined as a Body mass index (BMI) ≥ 30 kg/m2; obesity classes according to BMI are as follows: class 1 [30–34.9]; class 2 [35–39.9]; class 3 [≥ 40 kg/m2]. Linear trends across obesity classes by sex and age groups were examined in regression models and percentage point change from 2013 to 2016 for each age category calculated. All analyses accounted for sample weights for non-response, age and sex-calibrated to the French population. Prevalence of obesity ranged from 14.2 to 15.2% and from 14 to 15.3% in women and men respectively from 2013 to 2016. Class 1 obesity category prevalence was the only one to increase significantly across survey years in both men and women (p for linear trend = 0.04 and 0.01 in women and men respectively). The only significant increase for obesity was observed in the age group 18–29 y in both women and men (+ 2.71% and + 3.26% point increase respectively, equivalent to an approximate rise of 50% in women and 93% in men, p = 0.03 and 0.02 respectively). After adjustment for survey non-response and for age and sex distribution, the results show that class 1 obesity prevalence has significantly increased in both women and men from 2013 to 2016, and only in young adults in a representative sample of the French population aged 18–69 years old.

Summary: 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. Funding: Medical Research Council, National Institute on Aging, NordForsk, Academy of Finland, Finnish Work Environment Fund.

Summary: Background: Many patients report persistent symptoms after COVID-19. Our aim was to determine whether some of these symptoms were more associated with past SARS-CoV-2 infection compared to other conditions. Methods: This prospective survey was nested in CONSTANCES, a randomly selected French population-based cohort, started in 2012. All participants being followed-up by internet completed 2 questionnaires during the first wave of the pandemic focusing on the acute symptoms of their COVID-19-like illness. Serological tests for SARS-CoV-2 were then performed (May-Nov 2020). Between December 2020 and January 2021, participants completed a third questionnaire about symptoms that had lasted more than 2 months. Participants were classified into four groups according to both European Center for Diseases Control (ECDC) criteria for COVID-19 (ECDC+ or ECDC-) and serological SARS-CoV-2 test results (Sero+ or Sero-). To compare the risk of each persistent symptom among the groups, logistic regression models were adjusted for age, sex, educational level, comorbidities, and the number of acute symptoms declared during the first wave of the epidemic. A mediation analysis was performed to estimate the direct effect of the infection on persistent symptoms and its indirect effect via the initial clinical presentation. Findings: The analysis was performed in 25,910 participants. There was a higher risk of persistent dysgeusia/anosmia, dyspnea and asthenia in the ECDC+/Sero+ group than in the ECDC+/Sero- group (OR: 6.83 [4.47–10.42], 1.69 [1.07–2.6] and 1.48 [1.05–2.07], respectively). Abdominal pain, sensory symptoms or sleep disorders were at lower risk in the ECDC+/Sero+ group than in the ECDC+/Sero- group (0.51 [0.24–0.96], 0.40 [0.16–0.85], and 0.69 [0.49–0.95], respectively). The mediation analysis revealed that the association of the serological test results with each symptom was mainly mediated by ECDC symptoms (proportion mediated range 50–107%). Conclusion: A greater risk of persistent dysgeusia/anosmia, dyspnea and asthenia was observed in SARS-CoV-2 infected people. The initial clinical presentation substantially drives the association of positive serological test results with persistent symptoms. Funding: French National Research Agency

AimsTo examine the longitudinal associations between cannabis use and risks of short (28 days) sickness absences at one-year follow-up.Methods87,273 participants aged 18-65 years from the French CONSTANCES cohort reported their frequency of cannabis use at inclusion between 2012 and 2018. Sickness absences occurring during one year of follow-up were collected from national medico-administrative registries. Multivariable generalized linear regressions were used to compute the Odds Ratios (OR) with their 95% Confidence Intervals (CI) of having at least one sickness absence at follow-up compared to no sickness absence, while controlling for sociodemographic factors, chronic conditions and occupational factors.ResultsCannabis use more than once a month was associated with an increased risk of short (OR, [95% CI]: 1.56 [1.32–1.83]) and medium (1.29 [1.07–1.54]) sickness absences at one-year follow-up, with dose-dependent relationships for short sickness absences (1.13 [1.08–1.18], p-for-trend

Summary: Background: Asthma is an inflammatory heterogeneous disease. Asthma inflammatory phenotypes based on blood eosinophil and neutrophil counts have never been identified and characterized in population-based studies. Methods: Adults with current asthma and available blood eosinophil and neutrophil counts from the French population-based CONSTANCES cohort were included. Current asthma was defined by reports of asthma attacks, symptoms or treatments in the last 12 months. Inflammatory phenotypes were based on low (L) and high (H) blood (B) eosinophil (E) (LBE/HBE:

Background Social position and work environment are highly interrelated and their respective contribution to cardiovascular risk is still debated. Methods and Results In a cohort of 20 625 French workers followed for 25 years, discrete‐time survival analysis with reciprocal mediating effects, adjusted for sex, age, and parental history of early coronary heart disease, was performed using Bayesian structural equation modeling to simultaneously investigate the extent to which social position mediates the effect of work environment and, inversely, the extent to which work environment mediates the effect of social position on the incidence of common cardiovascular risk factors. Depending on the factor, social position mediates 2% to 53% of the effect of work environment and work environment mediates 9% to 87% of the effect of social position. The mediation by work environment is larger than that by social position for the incidence of obesity, hypertension, dyslipidemia, diabetes, sleep complaints, and depression (mediation ratios 1.32–41.5, 6.67 when modeling the 6 factors together). In contrast, the mediation by social position is larger than that by work environment for the incidence of nonmoderate alcohol consumption, smoking, and leisure‐time physical inactivity (mediation ratios 0.16–0.69, 0.26 when modeling the 3 factors together). Conclusions The incidence of behavioral risk factors seems strongly dependent on social position whereas that of clinical risk factors seems closely related to work environment, suggesting that preventive strategies should be based on education and general practice for the former and on work organization and occupational medicine for the latter.

Background: The current evidence on health effects of long-term exposure to outdoor airborne black carbon (BC) exposure remains scarce. Objectives: To examine the association between long-term exposure to BC and mortality in a large population-based French cohort, with 28 years of follow-up. Methods: Data from the GAZEL cohort were collected between 1989 and 2017. Land use regression model with temporal extrapolation wa used to estimate yearly BC and PM2.5 exposure at the residential addresses from 1989 until censoring for 19,906 participants. Time-varying Cox models with attained age as time-scale was used to estimate the associations between BC and all-cause and cardiovascular mortality, after adjusting for individual and area-level covariates. To handle confounding by PM2.5, we used the residual of BC regressed on PM2.5 as an alternate exposure variable. For all-cause mortality, we also examined effect modification by sex, smoking status, BMI and fruit/vegetable intake. Results: The median of 20-year moving average of BC exposure was 2.02 10−5/m in study population. We found significant associations between BC exposure and all-cause mortality (n = 2357) using both 20-year moving average of BC and residual of BC, with corresponding hazard ratios (HR) of 1.14 (95 %CI: 1.07–1.22) and 1.17 (95 %CI: 1.10–1.24) for an inter-quartile range (IQR) increase (0.86 10−5/m for BC and 0.57 10−5/m for residual of BC). We found a similar association between BC and cardiovascular mortality (n = 277) with a HR of 1.15 (95 %CI: 0.95–1.38). The dose–response relationship between BC and all-cause mortality was monotonic but nonlinear with a steeper slope at high BC levels. In addition, the effect of BC was higher among never-smokers and among those having fruit/vegetables less than twice a week. Conclusions: There was a positive association between long-term exposure to BC and increased mortality risk, reinforcing the emerging evidence that BC is a harmful component of PM2.5.

Background: Rhinitis is one of the most common disease worldwide with a high and increasing prevalence. There is limited knowledge on the link between long-term exposure to air pollution and rhinitis. Objectives: We aim to study the associations between long-term exposure to air pollutants and self-reported current rhinitis among adults from Constances, a large French population-based cohort. Methods: Current rhinitis was defined at inclusion from questionnaire by the presence of sneezing, runny or blocked nose in the last 12 months without a cold or the flu. Annual concentrations of nitrogen dioxide (NO2), particulate matter ≤ 2.5 µm (PM2.5) and black carbon (BC) were estimated at the participants' residential address by European land-use regression models. Cross-sectional associations between annual exposure to each air pollutant and current rhinitis were estimated using logistic models adjusted for age, sex, smoking, education level and French deprivation index. The health prevention centers were taken into account by marginal models with generalized estimating equations. Several supplementary analyses were performed. Results: Analyses were performed on 127,108 participants (47 years old on average, 54% women, 19% current smokers). The prevalence of current rhinitis, allergic (AR) and non-allergic (NAR) rhinitis were 36%, 25% and 11% respectively. Adjusted ORs for current rhinitis were 1.13 (1.08, 1.17), 1.12 (1.07, 1.17), and 1.11 (1.06, 1.17) per one interquartile range increase of PM2.5 (4.85 µg/m3), BC (0.88 · 10−5 m−1) and NO2 (17.3 µg/m3) respectively. Significant and positive associations were also found for both AR and NAR. Results were similar in men and women, and in the different smoking strata, and were consistent with meta-analysis or after imputing missing covariates. Discussion: An increase of modeled annual average residential exposure to PM2.5, BC, and NO2 was significantly associated with an increase of prevalence of current rhinitis in adults in the French general population. The results suggest that among air pollutants, BC may be of special interest.

Objectives To determine whether the terrorist attacks occurring in Paris on November 2015 have changed benzodiazepine use in the French population.Design Interrupted time series analysis.Setting National population-based cohort.Participants 90 258 individuals included in the population-based CONSTANCES cohort from 2012 to 2017.Outcome measures Benzodiazepine use was evaluated according to two different indicators using objective data from administrative registries: weekly number of individuals with a benzodiazepine delivered prescriptions (BDP) and weekly number of defined daily dose (DDD). Two sets of analyses were performed according to sex and age (≤50 vs >50). Education, income and area of residence were additional stratification variables to search for at-risk subgroups.Results Among women, those with younger age (incidence rate ratios (IRR)=1.18; 95% CI=1.05 to 1.32 for BDP; IRR=1.14; 95% CI=1.03 to 1.27 for DDD), higher education (IRR=1.23; 95% CI=1.03 to 1.46 for BDP; IRR=1.23; 95% CI=1.01 to 1.51 for DDD) and living in Paris (IRR=1.27; 95% CI=1.05 to 1.54 for BDP) presented increased risks for benzodiazepine use. Among participants under 50, an overall increase in benzodiazepine use was identified (IRR=1.14; 95% CI=1.02 to 1.28 for BDP and IRR=1.12; 95% CI=1.01 to 1.25 for DDD) and in several strata. In addition to women, those with higher education (IRR=1.22; 95% CI=1.02 to 1.47 for BDP), lower income (IRR=1.17; 95% CI=1.02 to 1.35 for BDP) and not Paris residents (IRR=1.13; 95% CI=1.02 to 1.26 for BDP and IRR=1.13; 95% CI=1.03 to 1.26 for DDD) presented increased risks for benzodiazepine use.Conclusion Terrorist attacks might increase benzodiazepine use at a population level, with at-risk subgroups being particularly concerned. Information and prevention strategies are needed to provide appropriate care after such events.

Background: Long-term exposure to air pollution affects health, but little is known about exposure to atmospheric metals. Estimating exposure to atmospheric metals across large spatial areas remains challenging. Metal concentrations in mosses could constitute a useful proxy. Here, we linked moss biomonitoring and epidemiological data to investigate the associations between long-term exposure to metals and mortality. Methods: We modelled and mapped 13 atmospheric metals from a 20-year national moss biomonitoring program to derive exposure estimates across France. In the population-based Gazel cohort, we included 11,382 participants from low to intermediate population density areas and assigned modelled metals to their residential addresses. We distinguished between airborne metals that are primarily of natural origin and those primarily of anthropogenic origin. Associations were estimated between exposure to metals and mortality (natural-cause, cardiovascular and respiratory), using Cox models, with confounder adjustment at individual level. Findings: Between 1996 and 2017, there were 1313 deaths in the cohort (including 181 cardiovascular and 33 respiratory). Exposure to the anthropogenic metals was associated with an increased risk of natural-cause mortality (hazard ratio of 1.16 [1.08–1.24] per interquartile range of exposure), while metals from natural sources were not. Interpretation: Some atmospheric anthropogenic metals may be associated with excess mortality – even in areas with relatively low levels of exposure to air pollution. Consistent with the previous literature, our findings support the use of moss biomonitoring as a tool to assess health effects of air pollution exposure at individual level.

Abstract Background Data are lacking regarding the prevalence of benzodiazepine long-term use in the general population. Our aim was to examine the prevalence of prescribed benzodiazepine long-term use (BLTU) according to sociodemographic and clinical factors in the French general population. Methods Data came from 4686 men and 4849 women included in 2015 in the French population-based CONSTANCES cohort. BLTU was examined using drug reimbursement administrative registries from 2009 to 2015. Analyses were weighted to provide results representative of the French general population covered by the general health insurance scheme. Weighted prevalence of BTLU and weighted Odds Ratios (OR) of having BTLU were computed with their 95% Confidence Interval (95% CI) according to age, education level, occupational status, occupational grade, household income, marital status, alcohol use disorder risk and depressive symptoms. All the analyses were stratified for gender. Results Weighted prevalence of BLTU were 2.8%(95% CI:2.3–3.4) and 3.8%(95% CI: 3.3–4.5) in men and women, respectively. Compared to men, women had an increased risk of having benzodiazepine long-term use with OR = 1.34(95% CI = 1.02–1.76). Aging, low education, not being at-work, low occupational grade, low income, being alone and depressive state were associated with increased risks of having BTLU. Conclusions BLTU is widespread in the French general population, however this issue may particularly concern vulnerable subgroups. These findings may help in raising attention on this public health burden as well as targeting specific at-risk subgroups in preventive intervention.

OBJECTIVE: Most suicides occur among individuals of working age. Risk is elevated in some occupational groups, however relations between long-term occupational trajectories and suicide are not well known. We describe career-long occupational trajectories and examine their influence on suicide. METHODS: Data come from GAZEL, a French cohort study set among employees of a large national utilities company. Occupational grade was obtained from company records from the time of hiring (1953‒1988). Group-based trajectory models were used to define occupational trajectories over a mean time period of 25.0 (standard deviation 6.5) years. Causes of mortality, coded using the International Classification of Diseases, were recorded from 1993‒2014 and studied using Cox regression models. RESULTS: Of the 20 452 participants included in the study, 73 died by suicide between 1993‒2014. Results suggested an increased risk of suicide [hazard ratio (HR) 2.57, 95% confidence interval (CI) 1.08–6.15] among participants with persistently low occupational grade compared to those with higher occupational grade and career development. After adjustment for all covariates, especially psychological factors, this association was reduced and no longer statistically significant (HR 2.02, 95% CI 0.82–4.95). CONCLUSIONS: Persistently low occupational grade could be related to an elevated risk of suicide. This association partly reflects psychological and health characteristics, which can influence occupational trajectories and be reinforced by unfavorable work conditions.

Background: In response to the COVID-19 pandemic, governments around the world instituted various public-health measures. Our project aimed to highlight the most significant similarities and differences in key mental-health indicators between four Western and Northern European countries, and identify the population subgroups with the poorest mental-health outcomes during the first months of the pandemic. Methods: We analysed time-series survey data of 205,084 individuals from seven studies from Denmark, France, the Netherlands, and the UK to assess the impact of the pandemic and associated lockdowns. All analyses focused on the initial lockdown phase (March–July 2020). The main outcomes were loneliness, anxiety, and COVID-19-related worries and precautionary behaviours. Findings: COVID-19-related worries were consistently high in each country but decreased during the gradual reopening phases. While only 7% of the respondents reported high levels of loneliness in the Netherlands, percentages were higher in the rest of the three countries (13–18%). In all four countries, younger individuals and individuals with a history of mental illness expressed the highest levels of loneliness. Interpretation: The pandemic and associated country lockdowns had a major impact on the mental health of populations, and certain subgroups should be closely followed to prevent negative long-term consequences. Younger individuals and individuals with a history of mental illness would benefit from tailored public-health interventions to prevent or counteract the negative effects of the pandemic. Individuals across Western and Northern Europe have thus far responded in psychologically similar ways despite differences in government approaches to the pandemic. Funding: See the Funding section.

The study aimed to assess the proportion mediated by the duration of exposure to ergonomic factors at work on the relationship between socioeconomic position (SEP) and low walking speed. This cross-sectional study was performed on data collected at baseline on 19,704 men and 20,273 women 45–70 years old, currently or previously employed, enrolled in the Constances cohort. SEP was assigned through current or last occupation, categorized in three classes, based on the European Socioeconomic Classification. Walking speed was assessed through one measurement of normal walking for 3 m and dichotomized at the lowest quintile of the sex- and age- (5-year) specific distribution. Self-reported workplace exposure throughout working life to repetitive work, intense physical work, and lifting/carrying heavy loads was used to assess the duration of exposure to each factor, categorized in four classes. Through Poisson regression models, adjusted for BMI, smoking, alcohol intake, hypertension, physical activity, diabetes, cardiovascular diseases, and a cognitive score, the attenuation in the prevalence ratio (PR) of low walking speed by SEP produced by the inclusion of duration of exposure to each factor was evaluated. The mediating effect of work ergonomic exposures on the relationship between SEP and low walking speed was assessed using the weighted method by Vanderweele. In the fully adjusted model without ergonomic exposures, both men and women in the middle and the lowest SEP had a significantly increased risk of low walking speed compared with those in the highest SEP (men: PR = 1.30 and PR = 1.46, respectively; women: PR = 1.24 and PR = 1.45, respectively). The inclusion in separate regression models of exposure duration to repetitive work, intense physical work, and handling of heavy loads produced modest risk attenuations in both men and women, all smaller or around 10%. Mediation analysis revealed in both sexes significant mediation effects for most ergonomic exposures considered, although also with low mediation effects. Significant differences in walking speed by SEP were observed in this large sample, but the proportion of such differences explained by the duration of exposure to ergonomic factors at work was low using either the risk attenuation or the mediation analysis methods.

Introduction Early management of chronic respiratory diseases (CRDs) and frailty have been identified as key targets towards healthy ageing, but the association between CRDs and frailty has been poorly investigated. We studied the association between asthma and frailty in adults of the GAZEL cohort using different definitions of asthma over the 26 years of follow-up.Methods Current asthma definitions are based on yearly self-reports of symptoms or medication (in 2015, constant reports or at least one report between 1990 and 2015), or on a detailed respiratory symptoms questionnaire in 2002. Frailty definition is based on weakness, fatigue, unintentional weight loss, low physical activity and mobility in 2015. Frail participants had three criteria or more, pre-frail 1 or 2, and robust 0. Multinomial regression models adjusted for age, sex, body mass index, smoking, education, marital status and comorbidities were performed.Results In 2015, 12 345 adults (73% men, 61 to 77 years old) were included: 3% of them reported current asthma, 1.6% had constant reports during the follow-up and 9% reported current asthma at least once. In 2015, 6% were frail, 34% pre-frail and 13% of current asthmatics and 6% of non-asthmatics were frail (adjusted OR (aOR) 2.19 (1.44 to 3.34)). Significant associations were also found with the 2002 definition (aOR 2.24 (1.73 to 2.90)), constant reports (aOR 3.67 (1.70 to 7.93)) or at least once (aOR 1.50 (1.15 to 1.98)). Current asthma was also associated with pre-frailty with the 2002 definition (aOR 1.46 (1.26 to 1.68)).Discussion Participants with asthma had increased risk of frailty. A better understanding of their relationship could help to define and evaluate strategies for a better ageing of asthmatics.

Funded by the European Commission Horizon 2020 programme, the Lifepath research consortium aimed to investigate the effects of socioeconomic inequalities on the biology of healthy aging. The main research questions included the impact of inequalities on health, the role of behavioral and other risk factors, the underlying biological mechanisms, the efficacy of selected policies, and the general implications of our findings for theories and policies. The project adopted a life-course and comparative approach, considering lifetime effects from childhood and adulthood, and pooled data on up to 1.7 million participants of longitudinal cohort studies from Europe, USA, and Australia. These data showed that socioeconomic circumstances predicted mortality and functional decline as strongly as established risk factors currently targeted by global prevention programmes. Analyses also looked at socioeconomically patterned biological markers, allostatic load, and DNA methylation using richly phenotyped cohorts, unraveling their association with aging processes across the life-course. Lifepath studies suggest that socioeconomic circumstances are embedded in our biology from the outset—i.e., disadvantage influences biological systems from molecules to organs. Our findings have important implications for policy, suggesting that (a) intervening on unfavorable socioeconomic conditions is complementary and as important as targeting well-known risk factors, such as tobacco and alcohol consumption, low fruit and vegetable intake, obesity and a sedentary lifestyle, and that (b) effects of preventive interventions in early life integrate interventions in adulthood. The report has an executive summary that refers to the different sections of the main paper.

ObjectivesDespite the recent awareness of the environment impact on brain ageing, the influence of the neighbourhood socioeconomic status on cognitive impairment remains unclear. Here, we investigated the effects of individual and neighbourhood deprivation on cognitive impairment in middle-aged and young-old people.DesignCross-sectional study.Settings21 Health Screening Centres in the entire French metropolitan territory.ParticipantsA total of 44 648 participants (age range: 45 to 69 years) from the French CONSTANCES cohort were included in the analyses.Main outcomesAssociations between the overall cognitive score (based on a standardised battery of cognitive tests administered by neuropsychologists) and individual deprivation (Evaluation of Deprivation and Inequalities in Health Screening Centres; EPICES score) and geographical deprivation (French Deprivation Index; FDep index).ResultsBased on the EPICES score (validated cut-off ≥30.17), 12% of participants were considered to be deprived. After mutual adjustment, individual and geographical deprivation were associated with higher cognitive impairment in a multilevel logistic regression analysis that was also adjusted for sociodemographic, lifestyle and health factors. Specifically, individual deprivation was associated with an odds increase of 55% (OR=1.55, 95% CI: 1.45 to 1.66). The risk of global cognitive impairment progressively increased with the neighbourhood deprivation level, evaluated by the FDep index (reference Q1; Q2: OR=1.09, 95% CI: 0.98 to 1.20; Q3: OR=1.15, 95% CI: 1.04 to 1.27; Q4: OR=1.15, 95% CI: 1.04 to 1.28; Q5: OR=1.25, 95% CI: 1.13 to 1.39).ConclusionOur results suggest that the neighbourhood socioeconomic deprivation level is associated with cognitive impairment, independently of the individual deprivation level. A better understanding of this association could help to define new prevention strategies to target high-risk residents and high-risk geographical areas in order to reduce social health inequalities.

BACKGROUND:Unemployment is associated with a high prevalence of risky health behaviors. Mortality increases with the number of co-occurring risky behaviors but whether these behaviors co-occur with a greater than expected frequency (clustering) among unemployed people is not known. METHODS:Differences according to unemployment status in co-occurrence and clustering of smoking, alcohol abuse, low leisure-time physical activity and unhealthy diet (marked by low fruit and vegetable intake) were assessed in 65,630 salaried workers, aged 18 to 65, who were participants in Constances, a French population-based cohort. Among them, 4573 (7.0%) were unemployed without (n = 3160, 4.8%) or with (n = 1413, 2.1%) past experience of unemployment. RESULTS:Compared to the employed, unemployed participants without or with past experience of unemployment were similarly overexposed to each risky behavior (sex and age adjusted odds-ratios ranging from 1.38 to 2.19) except for low physical activity, resulting in higher rates of co-occurrence of two, three and four behaviors (relative risk ratios, RRR 1.20 to 3.74). Association between behavior co-occurrence and unemployment did not vary across gender, partnership status or income category. Risky behavior clustering, i.e., higher than expected co-occurrence rates based on the prevalence of each behavior, was similar across unemployment status. The same observations can be made in employed participants with past experience of unemployment, although overexposure to risky behaviors (ORs 1.15 to 1.38) and increased rates of co-occurrence (ORs 1.19 to 1.58) were not as pronounced as in the unemployed. CONCLUSIONS:Co-occurrence of risky behaviors in currently and/or formerly unemployed workers is not worsened by behavior clustering. Engagement in each of these behaviors should be considered an engagement in distinct social practices, with consequences for preventive policies.

ObjectiveTo investigate the effects of co-exposure to biomechanical wrist stressors and chemicals on the risk of CTS in a large cohort of French workers.MethodsProspective study using the data collected at baseline and at the first 12 month-follow-up for the 18,018 participants included in the population-based Constances cohort between 2012 and 2015. CTS at follow-up and exposure to biomechanical wrist stressors and chemicals at baseline were assessed using a self-administered questionnaire. Associations between CTS and co-exposure to biomechanical wrist stressors and chemicals were studied using multivariate logistic regression models, adjusted for personal/medical factors.Results184 men (2.1%, 95%CI 1.8-2.4) and 331 women (3.6%, 3.2-3.9) free from chronic hand symptoms at baseline declared suffering from unilateral/bilateral CTS at follow-up. A potentiating effect of co-exposure to biomechanical wrist stressors and chemicals on the risk of CTS was found for both genders, with higher OR in the co-exposure group (OR = 3.38 [2.29-5.01] in men and OR = 4.12 [2.73-6.21] in women) than in the biomechanical exposure group (OR = 2.14 [1.51-3.03] in men and OR = 2.19 [1.72-2.78] in women) compared to no exposure group.ConclusionsThe study showed an association between CTS and co-exposure to biomechanical wrist stressors and chemicals, after adjustment for the main personal and medical factors. This finding should be confirmed using more objective case definition of CTS and assessment of the chemical exposure before drawing conclusions on the possible synergistic effects of mechanical stressors and chemical on the median nerve.

Abstract Background Studies have shown that alcohol intake trajectories differ in their associations with biomarkers of cardiovascular functioning, but it remains unclear if they also differ in their relationship to actual coronary heart disease (CHD) incidence. Using multiple longitudinal cohort studies, we evaluated the association between long-term alcohol consumption trajectories and CHD. Methods Data were drawn from six cohorts (five British and one French). The combined analytic sample comprised 35,132 individuals (62.1% male; individual cohorts ranging from 869 to 14,247 participants) of whom 4.9% experienced an incident (fatal or non-fatal) CHD event. Alcohol intake across three assessment periods of each cohort was used to determine participants’ intake trajectories over approximately 10 years. Time to onset for (i) incident CHD and (ii) fatal CHD was established using surveys and linked medical record data. A meta-analysis of individual participant data was employed to estimate the intake trajectories' association with CHD onset, adjusting for demographic and clinical characteristics. Results Compared to consistently moderate drinkers (males: 1–168 g ethanol/week; females: 1–112 g ethanol/week), inconsistently moderate drinkers had a significantly greater risk of incident CHD [hazard ratio (HR) = 1.18, 95% confidence interval (CI) = 1.02–1.37]. An elevated risk of incident CHD was also found for former drinkers (HR = 1.31, 95% CI = 1.13–1.52) and consistent non-drinkers (HR = 1.47, 95% CI = 1.21–1.78), although, after sex stratification, the latter effect was only evident for females. When examining fatal CHD outcomes alone, only former drinkers had a significantly elevated risk, though hazard ratios for consistent non-drinkers were near identical. No evidence of elevated CHD risk was found for consistently heavy drinkers, and a weak association with fatal CHD for inconsistently heavy drinkers was attenuated following adjustment for confounding factors. Conclusions Using prospectively recorded alcohol data, this study has shown how instability in drinking behaviours over time is associated with risk of CHD. As well as individuals who abstain from drinking (long term or more recently), those who are inconsistently moderate in their alcohol intake have a higher risk of experiencing CHD. This finding suggests that policies and interventions specifically encouraging consistency in adherence to lower-risk drinking guidelines could have public health benefits in reducing the population burden of CHD. The absence of an effect amongst heavy drinkers should be interpreted with caution given the known wider health risks associated with such intake. Trial registration ClinicalTrials.gov, NCT03133689.

Abstract Background The manner in which organizational downsizing is implemented can make a substantial difference as to whether the exposed workers will suffer from psychological ill health. Surprisingly, little research has directly investigated this issue. We examined the likelihood of psychological ill health associated with strategic and reactive downsizing. Methods A cross-sectional survey included 1456 respondents from France, Sweden, Hungary and the United Kingdom: 681 employees in stable workplaces (reference group) and 775 workers from downsized companies. Reactive downsizing was exemplified by the exposures to compulsory redundancies of medium to large scale resulting in job loss or surviving a layoff while staying employed in downsized organizations. The workforce exposed to strategic downsizing was represented by surplus employees who were internally redeployed and supported through their career change process within a policy context of “no compulsory redundancy”. Symptoms of anxiety, depression and emotional exhaustion were assessed in telephone interviews with brief subscales from Hospital Anxiety Scale (HADS-A), Hopkins Symptom Checklist (SCL-CD6) and Maslach Burnout Inventory (MBI-GS). Data were analyzed using logistic regression. Results We observed no increased risk of psychological ill health in the case of strategic downsizing. The number of significant associations with psychological ill health was the largest for the large-scale reactive downsizing: surviving a layoff was consistently associated with all three outcome measures; returning to work after the job loss experience was related to anxiety and depression, while persons still unemployed at interview had elevated odds of anxiety. After reactive medium-scale downsizing, unemployment at interview was the only exposure associated with anxiety and depression. Conclusions The manner in which organizational downsizing is implemented can be important for the psychological wellbeing of workers. If downsizing is unavoidable, it should be achieved strategically. Greater attention is needed to employment and health policies supporting the workers after reactive downsizing.

OBJECTIVES: The aim of this study was to investigate the individual, joint and interactive effects of job strain and informal caregiving on long-term sickness absence with special attention to gender differences. METHODS: The study comprised a prospective cohort study of 6798 working adults from France, 14 727 from Finland, and 5275 from the UK. A total of 26 800 participants, age 52 (interquartile range 47–56) years participated in the study. Job strain was assessed using the demand–control model. Informal caregiving was defined as care for a sick, disabled, or elderly person. Long-term sickness absence spells defined as absence >14 consecutive days were registered during two years follow-up. We used recurrent-events Cox regression in random-effects meta-analyses. RESULTS: A total of 12% men and 21% women had ≥1 long-term sickness absence spell. Among women, both high job strain [hazard ratio (HR) 1.08, 95% confidence interval (95% CI) 1.00–1.17] and informal caregiving (HR 1.13, 95% CI 1.04–1.23) were associated with a modestly higher risk of sickness absence. Women doubly exposed to high job strain and informal caregiving also showed a moderately higher risk of sickness absence (HR 1.20, 95% CI 1.03–1.41), but the excess risk was not more than expected from joint exposure to caregiving and job strain. Neither job strain nor informal caregiving predicted sickness absence for men. CONCLUSIONS: High job strain and informal caregiving predicted long-term sickness absence among women. However there was no noticeable interaction in the presence of both exposures.

Background: To further explain the association between low socioeconomic position and increased risk of poor health, research started to consider life course conditions, including previous occupational positions and patterns of social mobility in the analysis. We describe patterns of intragenerational social mobility and investigate their associations with depressive symptoms. Methods: We use data from the French CONSTANCES study, a population-based cohort and restrict the sample to people aged 45 to 60. Based on detailed retrospective data with annual information on respondents’ occupational position, we assess the modal social class for two time periods – early adulthood (age 25–34) and mid-adulthood (age 35–44). Depressive symptoms are measured by the Centre for Epidemiologic Studies Depression Scale (CES-D), using sex-specific cut-points. Results: Our study reveals that most respondents remained in stable working careers, but these careers were less frequent amongst participants with lower socioeconomic positions compared with higher ones. In contrast to several earlier findings we observe no independent associations of intragenerational social mobility processes and health once the social positions of origin and destination are considered. However, our findings confirm a social gradient in the prevalence of depressive symptoms for stable working careers. Conclusions: Our findings underline the importance of integrating data into analysis on starting and ending points of social mobility processes within entire histories of labor market participation. Keywords: Social mobility, Depressive symptoms, CONSTANCES cohort, Social class, Employment history

BACKGROUND:Substance use is more prevalent among unemployed subjects compared to employed ones. However, quantifying the risk subsequent of job loss at short-term according to substance use remains underexplored as well as examining if this association persist across various sociodemographic and occupational positions previously linked to job loss. We examined this issue prospectively for alcohol, tobacco, cannabis use and their combination, among a large population-based sample of men and women, while taking into account age, gender, overall health status and depressive symptoms. METHODS:From the French population-based CONSTANCES cohort, 18,879 working participants were included between 2012 and 2016. At baseline, alcohol use disorder risk according to the Alcohol Use Disorders Identification Test (mild, dangerous, problematic or dependence), tobacco (non-smoker, former smoker, 1-9, 10-19, >19 cigarettes/day) and cannabis use (never, not in past year, less than once a month, once a month or more) were assessed. Employment status at one-year (working versus not working) was the dependent variable. Logistic regressions provided Odds Ratios(OR(95%CI)) of job loss at one-year, adjusting for age, gender, self-reported health and depressive state (measured with the Center of Epidemiologic Studies Depression scale). Stratified analyses were performed for education, occupational grade, household income, job stress (measured with the Effort-Reward Imbalance), type of job contract, type of work time and history of unemployment. In sensitivity analyses, employment status over a three-year follow-up was used as dependent variable. RESULTS:Alcohol, tobacco and cannabis use were associated with job loss, from the second to the highest category: 1.46(95%CI:1.23-1.73) to 1.92(95%CI:1.34-2.75), 1.26(95%CI:1.09-1.46) to 1.78(95%CI:1.26-2.54) and 1.45(95%CI:1.27-1.66) to 2.68(95%CI:2.10-3.42), respectively, and with dose-dependent relationships (all p for trend

Abstract Background Long-term multicentre studies are subject to numerous factors that may affect the integrity of their conclusions. Quality control and standardization of data collection are crucial to minimise the biases induced by these factors. Nevertheless, tools implemented to manage biases are rarely described in publications about population-based cohorts. This report aims to describe the processes implemented to control biases in the Constances cohort taking lung function results as an example. Methods Constances is a general-purpose population-based cohort of 200,000 participants. Volunteers attend physical examinations at baseline and then every 5 years at selected study sites. Medical device specifications and measurement methods have to comply with Standard Operating Procedures developed by experts. Protocol deviations are assessed by on-site inspections and database controls. In February 2016, more than 94,000 participants yielding around 30 million readings from physical exams, had been covered by our quality program. Results Participating centres accepted to revise their practices in accordance with the study research specifications. Distributors of medical devices were asked to comply with international guidelines and Constances requirements. Close monitoring enhanced the quality of measurements and recordings of the physical exams. Regarding lung function testing, spirometry acceptability rates per operator doubled in some sites within a few months and global repeatability reached 96.7 % for 29,772 acceptable maneuvers. Conclusions Despite Constances volunteers being followed in multiple sites with heterogeneous materials, the investment of significant resources to set up and maintain a continuous quality management process has proved effective in preventing drifts and improving accuracy of collected data.

Summary: Background: Lifestyle factors influence the risk of morbidity and mortality, but the extent to which they are associated with employees' absence from work due to illness is unclear. We examined the relative contributions of smoking, alcohol consumption, high body-mass index, and low physical activity to diagnosis-specific sickness absence. Methods: We did a multicohort study with individual-level data of participants of four cohorts from the UK, France, and Finland. Participants' responses to a lifestyle survey were linked to records of sickness absence episodes, typically lasting longer than 9 days; for each diagnostic category, the outcome was the total number of sickness absence days per year. We estimated the associations between lifestyle factors and sickness absence by calculating rate ratios for the number of sickness absence days per year and combining cohort-specific estimates with meta-analysis. The criteria for assessing the evidence included the strength of association, consistency across cohorts, robustness to adjustments and multiple testing, and impact assessment by use of population attributable fractions (PAF), with both internal lifestyle factor prevalence estimates and those obtained from European populations (PAFexternal). Findings: For 74 296 participants, during 446 478 person-years at risk, the most common diagnoses for sickness absence were musculoskeletal diseases (70·9 days per 10 person-years), depressive disorders (26·5 days per 10 person-years), and external causes (such as injuries and poisonings; 12·8 days per 10 person-years). Being overweight (rate ratio [adjusted for age, sex, socioeconomic status, and chronic disease at baseline] 1·30, 95% CI 1·21–1·40; PAFexternal 8·9%) and low physical activity (1·23, 1·14–1·34; 7·8%) were associated with absences due to musculoskeletal diseases; heavy episodic drinking (1·90, 1·41–2·56; 15·2%), smoking (1·70, 1·42–2·03; 11·8%), low physical activity (1·67, 1·42–1·96; 19·8%), and obesity (1·38, 1·11–1·71; 5·6%) were associated with absences due to depressive disorders; heavy episodic drinking (1·64, 1·33–2·03; 11·3%), obesity (1·48, 1·27–1·72; 6·6%), smoking (1·35, 1·20–1·53; 6·3%), and being overweight (1·20, 1·08–1·33; 6·2%) were associated with absences due to external causes; obesity (1·82, 1·40–2·36; 11·0%) and smoking (1·60, 1·30–1·98; 10·3%) were associated with absences due to circulatory diseases; low physical activity (1·37, 1·25–1·49; 12·0%) and smoking (1·27, 1·16–1·40; 4·9%) were associated with absences due to respiratory diseases; and obesity (1·67, 1·34–2·07; 9·7%) was associated with absences due to digestive diseases. Interpretation: Lifestyle factors are associated with sickness absence due to several diseases, but observational data cannot determine the nature of these associations. Future studies should investigate the cost-effectiveness of lifestyle interventions aimed at reducing sickness absence and the use of information on lifestyle for identifying groups at risk. Funding: NordForsk, British Medical Research Council, Academy of Finland, Helsinki Institute of Life Sciences, and Economic and Social Research Council.

Summary: Background: Obesity increases the risk of several chronic diseases, but the extent to which the obesity-related loss of disease-free years varies by lifestyle category and across socioeconomic groups is unclear. We estimated the number of years free from major non-communicable diseases in adults who are overweight and obese, compared with those who are normal weight. Methods: We pooled individual-level data on body-mass index (BMI) and non-communicable diseases from men and women with no initial evidence of these diseases in European cohort studies from the Individual-Participant-Data Meta-Analysis in Working Populations consortium. BMI was assessed at baseline (1991–2008) and non-communicable diseases (incident type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease) were ascertained via linkage to records from national health registries, repeated medical examinations, or self-report. Disease-free years from age 40 years to 75 years associated with underweight (BMI

Obese patients are raising specific questions in emergency care such as equipment issues or urgent procedures. Even though obesity prevalence and subsequent health expenditure are increasing worldwide, there is scarce literature about their specific resource utilization of Emergency Departments (ED). These few studies do not take into account both socio-economic situation and comorbidities which are well-known factors influencing healthcare use. Our objective was to assess the emergency care resource utilization of obese individuals (Body Mass Index (BMI) ≥ 30kg.m-2) compared to normal-weight individuals taking into account comorbidities and social-economic situations.The French CONSTANCES epidemiologic cohort is a randomly selected sample of French adults. Participants data are linked to the National Health Insurance Database collecting all medical acts. The rate of ED visits of obese (and each obesity class) and normal-weight participants were compared considering confounding factors (comorbidities, various socio-economic data). The primary endpoint was to have visited the ED between 2010 and 2013. Sex-separated analysis and multivariate logistic regression models were performed and adjusted odds-ratios [OR] (95% Confidence Intervals [CI]) were calculated.We included 21,035 normal-weight and 5,003 obese participants. Obese participants visited the ED more often than normal-weight participants (men: 30.5% vs. 26.7%; women: 30.3% vs. 24.4%, P

To examine the associations between job exposure to the public (e.g., customers, guests, users of a public service, patients) and alcohol, tobacco and cannabis use.From the French population-based CONSTANCES cohort, 16,566 men and 17,426 women currently working were included between 2012 and 2016. They reported their exposure to the public (daily versus no daily), and among the daily exposed participants (10,323 men and 13,318 women), the frequency of stressful exposure (often versus rarely). Dependent variables were: chronic alcohol consumption (42(28) drinks per week in men(women)), heavy episodic drinking (never, at most once a month, more than once a month), alcohol use risk with Alcohol Use Disorders Identification Test (mild, dangerous, problematic or dependence), tobacco use (non-smoker, former smoker, 1-9, 10-19, >19 cigarettes per day) and cannabis use (never, not in past year, less than once a month, once a month or more). Logistic regressions provided odds ratios of substance use, stratifying for gender and adjusting for sociodemographic confounders, depression, effort-reward imbalance and perceived health status.Exposed men had higher risks of alcohol (chronic alcohol consumption, heavy episodic drinking and alcohol use risk), tobacco and cannabis use. Exposed women had higher risks of tobacco and cannabis use. In men, stressful exposure was associated with increased risks of heavy episodic drinking, tobacco and cannabis use. In women, stressful exposure was associated with increased risks of chronic alcohol consumption, alcohol use risk, tobacco and cannabis use. All these findings remained significant in multivariable analyses, taking into account sociodemographic variables, depressive symptoms, perceived health status and effort-reward imbalance.Interventions to reduce emotional job demand should systematically integrate assessment and prevention measures of addictive behaviors. Vulnerable workers may be offered more specific interventions to reduce the impact of exposure to the public on their substance use.

Summary: 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 (

The health correlates of the metabolically healthy obese (MHO) phenotype, particularly in relation to depressive symptoms remains unclear. Accordingly, we examined the risk of depressive symptoms in this phenotype using a 16-year follow-up prospective study.A sample of 14 475 participants (75% men), aged 44-59 years in 1996, was drawn from the Gazel cohort. Obesity was defined as body mass index (BMI) ≥ 30 kg/m2 and metabolic health as having none of the self-reported following cardiovascular risk factors: hypertension, type 2 diabetes and dyslipidemia. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression (CES-D) scale in 1996, 1999, 2002, 2005, 2008 and 2012. Generalized Estimating Equations (GEE) were used to estimate the risk of depressive symptoms during a follow-up of 16 years.In multivariate analyses, metabolically unhealthy normal weight [Odds Ratio (OR) = 1.37; 95% Confidence Interval (CI): 1.25-1.51], overweight [1.44 (1.31-1.59)] and obese [1.30 (1.10-1.54)] but not MHO participants [1.04 (0.81-1.32)] had higher risk of depressive symptoms at the start of follow-up compared to metabolically healthy normal weight individuals. Depressive symptoms decreased over time in metabolically healthy normal weight individuals [0.52 (0.50-0.55)], this decrease was less marked only in metabolically unhealthy obese participants [1.22 (1.07-1.40)]. Compared to MHO participants, metabolically unhealthy obese individuals were at increased risk of depression at the start of follow-up, but with a similar reduction of this risk over time.Poor metabolic health, irrespective of BMI was associated with greater depressive symptoms at the start of follow-up, whereas a poorer course of depressive symptoms over time was observed only in those with both obesity and poor metabolic health.

BACKGROUND:Several social indicators have been used in epidemiological research to describe socioeconomic position (SEP) of people in societies. Among SEP indicators, those more frequently used are education, occupational class and income. Differences in the incidence of several health outcomes have been reported consistently, independently from the indicator employed. Main objectives of the study were to present the socioeconomic classifications of the social indicators which will be employed throughout the LIFEPATH project and to compare social gradients in all-cause mortality observed in the participating adult cohorts using the different SEP indicators. METHODS:Information on the available social indicators (education, own and father's occupational class, income) from eleven adult cohorts participating in LIFEPATH was collected and harmonized. Mortality by SEP for each indicator was estimated by Poisson regression on each cohort and then evaluated using a meta-analytical approach. RESULTS:In the meta-analysis, among men mortality was significantly inversely associated with both occupational class and education, but not with father's occupational class; among women, the increase in mortality in lower social strata was smaller than among men and, except for a slight increase in the lowest education category, no significant differences were found. CONCLUSIONS:Among men, the proposed three-level classifications of occupational class and education were found to predict differences in mortality which is consistent with previous research. Results on women suggest that classifying them through their sole SEP, without considering that of their partners, may imply a misclassification of their social position leading to attenuation of mortality differences.

OBJECTIVES: This study aims to estimate the association between repeated measures of occupational risk factors and the incidence of lateral epicondylitis in a large working population. METHODS: A total of 3710 workers in a French region were included in 2002–2005, and among them 1046 had a complete follow-up in 2007–2010. At both stages, occupational health physicians assessed the presence of lateral epicondylitis and workers self-reported their occupational exposures. Poisson models were performed to assess the incidence rate ratios (IRR) separately by sex using multiple imputed data. RESULTS: The annual incidence rate of lateral epicondylitis was estimated as 1.0 [95% confidence interval (95% CI) 0.7–1.3] per 100 workers among men and 0.9 (95% CI 0.6–1.3) among women. Workers aged >45 years had higher incidence than those aged 2 hours/day) was a risk factor, with an age-adjusted IRR of 3.2 (95% CI 1.5–6.4) for workers exposed at both questionnaires [3.3 (95% CI 1.4–7.6) among women]. CONCLUSIONS: This study highlights the importance of temporal dimensions for occupational risk factors on the incidence of lateral epicondylitis. Further research should evaluate the risk associated with the duration and repetition of occupational exposure on the incidence of lateral epicondylitis.