Association Between education and walking speed: counterfactual mediation analysis in favor of a motor reserve hypothesis.

We quantified the extent to which the association between education and fast walking speed (FWS) is explained by 17 mediators (cardiovascular risk factors/diseases, comorbidities, health behaviours, socio-professional characteristics, cognition), and examined whether mediators interact with education, in favor of a reserve hypothesis. Cross-sectional analyses are based on Constances (population-based study of French adults 45-69y). 3m-FWS was measured using photoelectric cells. Education was categorized as lower/higher. After multiple imputation of missing values, we used counterfactual mediation models for multiple mediators allowing for education×mediator interactions, to estimate the total effect (TE), total indirect effect (TIE), and mediated interaction (IMD) of lower education on FWS. Analyses are based on 71,222 participants (52.6% women; mean age=57.2y; 27.2% higher education; mean FWS=180.2cm/s). In joint mediation analyses, the TE of lower education was -8.19cm/s (95% confidence interval [CI]=-8.87;-7.51), with a TIE of -5.76cm/s (95%CI=-6.10;-5.41; proportion mediated=70.3%, 95%CI=65.6;75.0). The IMD was negative (-2.52, 95%CI=-3.31;-1.72); 30.8% of the TE and 43.8% of the TIE were attributable to the IMD. Several mediators explain a large part of the association between lower education and slower FWS. The detrimental effect of mediators was more pronounced in participants with lower than in those with higher education, in agreement with a reserve hypothesis.

Primary hypocholesterolemia is associated with an increased risk of hepatic complications in the general population.

BACKGROUND & AIMS: Beyond cardiovascular disease protection, the health consequences of very low concentrations of low-density lipoprotein-cholesterol (LDL-C) remain a matter of debate. In primary hypobetalipoproteinemia (HBL), liver steatosis and cirrhosis have occasionally been reported. Here, we aimed to investigate the association between HBL and the risk of hepatic complications (cirrhosis complications and/or primary liver cancer) in the general population. METHODS: A cohort study was conducted in the French population-based cohort CONSTANCES. Participants with primary HBL (LDL-C <5th percentile for age and sex, [HBL]) were compared with those with normal LDL-C concentrations (40th-60th percentile, [Control]). Participants on lipid-lowering therapies were excluded. For hepatic complications, follow-up events were compared by calculating the incidence density ratio (IDR). The same analyses were replicated in the UK Biobank (UKBB) cohort. RESULTS: In the CONSTANCES and UKBB cohorts, 34,653 and 94,666 patients were analyzed, with median ages of 45 and 56 years, mean LDL-C concentrations (HBL vs. control) of 71 vs. 128 mg/dl and 86 vs. 142 mg/dl, and mean follow-up durations of 5.0 and 11.5 years, respectively. The HBL group presented a higher incidence of hepatic complications than the control group: 0.32/ vs. 0.07/1,000 person-years (IDR = 4.50, 95% CI 1.91-10.6) in CONSTANCES, and 0.69/ vs. 0.21/1,000 person-years (IDR = 3.27, 95% CI 2.63-4.06) in the UKBB. This risk proved to be independent of classic risk factors for liver disease (obesity, alcohol consumption, diabetes, viral hepatitis), including in a 5-year landmark analysis excluding early events. Sensitivity analyses based on apoliprotein-B levels (instead of LDL-C levels) or genetically defined HBL showed similar results. CONCLUSIONS: HBL is associated with a markedly increased risk of hepatic complications. HBL must be considered as a substantial independent risk factor for liver diseases which justifies specific prevention and screening. IMPACT AND IMPLICATIONS: Hypobetalipoproteinemia (HBL) is a lipid disorder characterized by permanent, inherited low levels (below the 5th percentile) of low-density lipoprotein-cholesterol. While HBL is associated with a lower risk of cardiovascular events, some studies suggest that it may be associated with a potential risk of hepatic steatosis and hepatic complications. Here, we studied the association between HBL and hepatic complications (defined as cirrhosis complications and/or primary liver cancer) in two populations of several hundred thousand people, both in France (CONSTANCES cohort) and the United Kingdom (UKBB). The results show that HBL is associated with a significant and independent excess risk of hepatic complications, including primary liver cancer. Thus, in people with HBL, the value of regular liver monitoring must be studied.

Healthy lifestyle change and all-cause and cancer mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

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.

Depression and anxiety before and at the beginning of the COVID-19 pandemic and incident persistent symptoms: a prospective population-based cohort study.

Many patients affected by COVID-19 suffer from debilitating persistent symptoms whose risk factors remained poorly understood. This prospective study examined the association of depression and anxiety symptoms measured before and at the beginning of the COVID-19 pandemic with the incidence of persistent symptoms. Among 25,114 participants [mean (SD) age, 48.72 years (12.82); 51.1% women] from the SAPRIS and SAPRIS-Sérologie surveys nested in the French CONSTANCES population-based cohort, depression and anxiety symptoms were measured with the Center for Epidemiologic Studies-Depression scale and the 12-item General Health Questionnaire before the pandemic, and with the 9-item Patient Health Questionnaire and the 7-Item Generalized Anxiety Disorder scale at the beginning of the pandemic (i.e., between April 6, 2020 and May 4, 2020). Incident persistent symptoms were self-reported between December 2020 and January 2021. The following variables were also considered: gender, age, educational level, household income, smoking status, BMI, hypertension, diabetes, self-rated health, and SARS-CoV-2 infection according to serology/PCR test results. After a follow-up of seven to ten months, 2329 participants (9.3%) had been infected with SARS-CoV-2 and 4262 (17.0%) reported at least one incident persistent symptom that emerged from March 2020, regardless of SARS-CoV-2 infection. In multi-adjusted logistic regression models, participants in the highest (versus the lowest) quartile of depressive or anxiety symptom levels before or at the beginning of the pandemic were more likely to have at least one incident persistent symptom (versus none) at follow-up [OR (95%CI) ranging from 2.10 (1.89-2.32) to 3.01 (2.68-3.37)], with dose-response relationships (p for linear trend <0.001). Overall, these associations were significantly stronger in non-infected versus infected participants, except for depressive symptoms at the beginning of the pandemic. Depressive symptoms at the beginning of the pandemic were the strongest predictor of incident persistent symptoms in both infected and non-infected participants [OR (95%CI): 2.88 (2.01-4.14) and 3.03 (2.69-3.42), respectively]. In exploratory analyses, similar associations were found for each symptom taken separately in different models. Depression and anxiety symptoms should be tested as a potential target for preventive interventions against persistent symptoms after an infection with SARS-CoV-2.

Chronic occupational exposures to irritants and asthma in the CONSTANCES cohort.

OBJECTIVES: The impact of chronic occupational exposures to irritants on asthma remains discussed. We studied the associations between occupational exposures and asthma, with specific interest for chronic exposure to irritants, including disinfectants and cleaning products (DCPs) and solvents. METHODS: Cross-sectional analyses included 115 540 adults (55% women, mean age 43 years, 10% current asthma) working at inclusion in the French population-based CONSTANCES cohort (2012-2020). Current asthma was defined by ever asthma with symptoms, medication or asthma attacks (past 12 months), and the asthma symptom score by the sum of 5 respiratory symptoms (past 12 months). Both lifetime and current occupational exposures were assessed by the Occupational Asthma-specific Job-Exposure Matrix. Associations were evaluated by gender using logistic and binomial negative regressions adjusted for age, smoking status and body mass index. RESULTS: In women, associations were observed between current asthma and lifetime exposure to irritants (OR 1.05, 95% CI 1.00 to 1.11), DCPs (1.06, 95% CI 1.00 to 1.12) and solvents (1.06, 95% CI 0.98 to 1.14). In men, only lifetime exposure to DCPs (1.10, 95% CI 1.01 to 1.20) was associated with current asthma. Lifetime exposure to irritants was associated with higher asthma symptom score both in women (mean score ratio: 1.08, 95% CI 1.05 to 1.11) and men (1.11, 95% CI 1.07 to 1.15), especially for DCPs (women: 1.09, 95% CI 1.06 to 1.13, men: 1.21, 95% CI 1.15 to 1.27) and solvents (women 1.14, 95% CI 1.10 to 1.19, men: 1.10, 95% CI 1.05 to 1.15). For current exposures, no consistent associations were observed with current asthma and asthma symptom score. CONCLUSIONS: Lifetime occupational exposures to irritants were associated with current asthma and higher asthma symptom score. These exposures should be carefully considered in asthma management.

Chronic exposure to drinking water nitrate and trihalomethanes in the French CONSTANCES cohort.

Trihalomethanes (THMs) and nitrate are widespread chemicals in drinking water. Chronic exposure has been associated with increased cancer risk despite inconclusive evidence, partly due to the challenges in long-term exposure assessment and potential exposure misclassification. We estimated concentrations of nitrate and THMs in drinking water using a public regulatory monitoring database (SISE-Eaux) for CONSTANCES, a French population-based prospective cohort. We obtained 26,322,366 measurements of drinking water parameters from 2000 to 2020. We excluded missing, implausible and duplicated measurements; we corrected or imputed missing geocodes of sampling locations; we calculated the annual median concentration of nitrate and THMs by surveillance area. To predict missing annual median concentrations, linear mixed models with random intercept using surveillance area as a clustering variable were developed for each region for nitrate and the four THM components (chloroform, chlorodibromomethane, bromodichloromethane and bromoform) separately. Concentrations in the nearest surveillance area from the household were merged per year among 75,462 participants with residential history geocoded for 2000-2020. Estimated concentrations resulting from this approach were compared with measured concentrations in 100 samples collected in Paris, Rennes and Saint-Brieuc in 2021. Median annual concentrations of total THMs and nitrate at study participants' homes for 2000-2020 were, respectively, 15.7 µg/l (IQR: 15.2) and 15.2 mg/l (IQR: 20.8). Among these, 35% were based on measurements for nitrate (16% for THMs), 44% (46%) were predicted using on linear mixed models, and 21% (38%) were based on distribution unit median values. Conditional R2 predictive models ranged from 0.71 to 0.91 (median: 0.85) for nitrate, and from 0.48 to 0.80 for THMs (median: 0.68). These concentrations will allow future association analyses with risk of breast and colorectal cancer. Our cleaning process introduced here could be adapted to other large drinking water monitoring data.

Prevalence of self-reported severe periodontitis: Data from the population-based CONSTANCES cohort.

AIM: To assess the prevalence of severe periodontitis based on the population-based CONSTANCES cohort using a validated self-reported questionnaire. MATERIALS AND METHODS: Individuals were selected from the adult population in France using a random sampling scheme. Analyses were restricted to those invited in 2013-2014 who completed the periodontal health questionnaire at the 2017 follow-up. The risk of severe periodontitis was assessed using the periodontal screening score (PESS) and weighting coefficients were applied to provide representative results in the general French population. RESULTS: The study included 19,859 participants (9204 men, mean age: 52.8 ± 12.6 years). Based on a PESS ≥ 5, 7106 participants were at risk of severe periodontitis, corresponding to a weighted prevalence of 31.6% (95% confidence interval: 30.6%-32.7%). This prevalence was higher among participants aged 55 and over, those with lower socio-economic status as well as current smokers, e-cigarette users and heavy drinkers. Among individuals at risk of severe periodontitis, only 18.8% (17.3%-20.4%) thought they had gum disease, although 50.5% (48.6%-52.5%) reported that their last dental visit was less than 6 months. CONCLUSIONS: The present survey indicates that (1) self-reported severe periodontitis is highly prevalent with marked disparities between groups in the general French adult population, and (2) periodontitis could frequently be under-diagnosed given the low awareness.

Relationship between night work and health-related quality of life: an analysis based on profiles and cumulative duration of exposure to night work among French workers in the CONSTANCES cohort.

OBJECTIVE: The aim of this study is to estimate the association between night work and health-related quality of life (HRQoL) among French workers. The association between cumulative duration of night work and HRQoL was also investigated. METHODS: Three career-long night work exposure groups were defined at inclusion in the CONSTANCES cohort: permanent night workers, rotating night workers and former night workers. Day workers with no experience of night work were the reference group. HRQoL was assessed using the Short Form Health Survey (SF-12), in particular the physical component summary (PCS) and mental component summary (MCS) scores, with a higher score indicating better HRQoL. Several linear regression models were built to test the association between night work exposure and HRQoL. The relationship between cumulative duration of night work and HRQoL scores was analyzed using generalised additive models. RESULTS: The sample consisted of 10,372 participants. Former night workers had a significantly lower PCS score than day workers (ß [95% CI]: - 1.09 [- 1.73; - 0.45], p = 0.001), whereas permanent night workers had a significantly higher MCS score (ß [95% CI]: 1.19 [0.009; 2.36], p = 0.048). A significant decrease in PCS score from 5 to 20 years of cumulative night work was observed among former night workers. CONCLUSIONS: Former night workers had poorer physical HRQoL in contrast to permanent and rotating night workers who had similar or even better HRQoL than day workers, suggesting the well-known healthy worker survivor effect. Consequently, both current and former night workers require regular and specific follow-up focused on the physical components of their health.

Tobacco use and employment status: A cross-sectional analysis of the CONSTANCES cohort / Liens entre le statut tabagique et la situation vis-à-vis de l'emploi : analyse transversale de la cohorte CONSTANCES

This study aims to estimate the prevalence of tobacco use in 2017 and 2019 in the French population covered by the Régime Général d'Assurance Maladie according to employment status. From the French national CONSTANCES cohort, 18,008 randomly recruited volunteers aged between 18 and 69 years, affiliated to the Régime Général d'Assurance Maladie and enrolled in 2017, were included in the analysis. The prevalence of tobacco use according to employment status was estimated. Estimates of these prevalence data were calculated in 2017 and 2019 after correction for selection bias at inclusion and non-response at follow-up. In 2019, smoking prevalence was higher among unemployed people (29.2% among men and 20.7% among women) than among employed people (16.5% among men and 13.8% among women). Smoking prevalence was highest among those not in work for health reasons (38.5% among men and 35.8% among women). Smokers were more likely to be unemployed than non-smokers (OR 2.63 [95% confidence interval (CI): 1.79; 3.85] in men and OR 1.55 [95% CI: 1.08; 2.22] in women). Among men, the prevalence of employed people among light smokers (<10 cigarettes/day) significantly decreased between 2017 (87.1%) and 2019 (74.8%). These results underline the importance of reinforcing smoking prevention campaigns among the unemployed, particularly for health reasons.

Estimer les prévalences d'usage de tabac en 2017 et en 2019 en population française couverte par le Régime Général d'Assurance Maladie en fonction du statut vis-à-vis de l'emploi. À partir d'un échantillon de 18 008 volontaires inclus en 2017 dans CONSTANCES, une cohorte nationale en population générale française ayant recruté de manière aléatoire des volontaires de 18-69 ans affiliés au Régime Général d'Assurance Maladie, les prévalences d'usage du tabac en fonction de du statut vis-à-vis de l'emploi ont été estimées en 2017 et en 2019 après correction pour les biais de sélection à l'inclusion et de non-réponse au suivi. En 2019, la prévalence du tabagisme était plus élevée chez les actifs inoccupés (29,2 % chez les hommes et 20,7 % chez les femmes) par rapport aux actifs occupés (16,5 % chez les hommes et 13,8 % chez les femmes). La prévalence du tabagisme la plus élevée concernait les personnes sans activité professionnelle pour raisons de santé (38,5 % chez les hommes et 35,8 % chez les femmes). Les fumeurs étaient plus à risque d'être actifs inoccupés comparativement aux non-fumeurs (OR 2,63 [95 % Intervalle de confiance [IC] : 1,79 ; 3,85] chez les hommes et OR 1,55 [95 % IC : 1,08 ; 2,22] chez les femmes). Chez les hommes, la prévalence d'actifs occupés parmi les petits fumeurs (<10 cigarettes/jour) a baissé entre 2017 (87,1 %) et 2019 (74,8 %). Ces analyses soulignent l'importance d'intensifier les campagnes de prévention sur le tabagisme parmi les actifs inoccupés et les inactifs, en particulier pour raisons de santé.

Long-term exposure to ambient air pollution and asthma symptom score in the CONSTANCES cohort.

BACKGROUND: The asthma symptom score allows to consider asthma as a continuum and to investigate its risk factors. One previous study has investigated the association between asthma score and air pollution and only for nitrogen dioxide (NO2). We aimed to study the associations between particulate matter with an aerodynamic diameter lower than 2.5 µm (PM2.5), black carbon (BC) and NO2 and the asthma symptom score in adults from CONSTANCES, a French population-based cohort. METHODS: Asthma symptom score (range: 0-5) was based on the number of five self-reported symptoms of asthma in the last 12 months. Annual individual exposure to PM2.5, BC and NO2 was estimated at participants' residential address using hybrid land-use regression models. Cross-sectional associations of each pollutant with asthma symptom score were estimated using negative binomial regressions adjusted for age, sex, smoking status and socioeconomic position. Associations with each symptom were estimated using logistic regression. The effect of BC independent of total PM2.5 was investigated with a residual model. RESULTS: Analyses were conducted on 135 165 participants (mean age: 47.2 years, 53.3% women, 19.0% smokers, 13.5% ever asthma). The ratio of mean score was 1.12 (95% CI 1.10 to 1.14), 1.14 (95% CI 1.12 to 1.16) and 1.12 (95% CI 1.10 to 1.14) per one IQR increase of PM2.5 (4.86 µg/m3), BC (0.88 10-5 m-1) and NO2 (17.3 µg/m3). Positive and significant associations were also found for each asthma symptom separately. BC effect persisted independently of total PM2.5. CONCLUSION: Exposure to each pollutant was associated with increased asthma symptom score in adults. This study highlights that BC could be one of the most harmful particulate matter components.

Changes in Lifestyle and Risk of Colorectal Cancer in the European Prospective Investigation Into Cancer and Nutrition.

INTRODUCTION: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multicountry European cohort. METHODS: We used baseline and follow-up questionnaire data from the European Prospective Investigation into Cancer cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index, and physical activity collected at the 2 time points. HLI ranged from 0 (most unfavorable) to 16 (most favorable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. The median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI > 11), those in the bottom tertile at follow-up (HLI ≤ 9) had a higher CRC risk (HR 1.34; 95% CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95% CI 0.59-1.00) than those remaining in the bottom tertile. DISCUSSION: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.

Rhinitis phenotypes and multimorbidities in the general population: the CONSTANCES cohort.

BACKGROUND: Scarce epidemiological studies have characterised allergic rhinitis (AR) and non-allergic rhinitis (NAR) in adults. In a population-based cohort, our aims were to 1) describe rhinitis, AR and NAR, and 2) explore how asthma and conjunctivitis may lead to the identification of novel rhinitis phenotypes. METHODS: In this cross-sectional analysis, current rhinitis was defined as present in the last 12 months using a questionnaire from the French CONSTANCES cohort. Participants with current rhinitis reporting nasal allergies were considered as AR, otherwise as NAR. We described AR and NAR phenotypes, and their phenotypes including co-occurrence with ever-asthma and ever-conjunctivitis. RESULTS: Among the 20 772 participants included in this analysis (mean±sd age 52.6±12.6 years; 55.2% female), crude prevalences of AR and NAR were 28.0% and 10.9%. AR participants more frequently reported persistent rhinitis (31.6% versus 25.1%) and moderate-to-severe rhinitis (40.1% versus 24.2%) than NAR participants. Among AR or NAR participants, those with ever-asthma reported more moderate-to-severe rhinitis. Participants with AR, ever-asthma and ever-conjunctivitis had an earlier age of rhinitis onset, more severe rhinitis and higher eosinophil counts than participants in other groups. Results were replicated in another cohort. CONCLUSIONS: In this large population-based cohort, 40% reported current rhinitis, with a lower prevalence of moderate-to-severe rhinitis than in clinical practice. For the first time in a general adult population, we showed that AR and NAR alone or in combination with asthma or in combination with asthma and conjunctivitis are different phenotypes. These results provide new insights on how best to manage rhinitis and its multimorbidities.

Social inequalities, stressful work and non-fatal cardiovascular disease: follow-up findings from the CONSTANCES Study.

BACKGROUND: Studies show that a disadvantaged socioeconomic position (SEP) and psychosocial stress at work are both independently associated with an increased risk of cardiovascular disease (CVD). But it is not clear if the effect of stress at work on CVD varies by SEP. METHODS: We used baseline and follow-up data from the French population-based cohort study CONSTANCES, including 48 383 employed women and men aged 30-70 years. Three SEP indicators (education, income, occupation), stressful psychosocial work as measured by effort-reward imbalance, pre-existing CVD and confounders were assessed at baseline, and incident non-fatal CVD events reported during annual follow-up (up to five follow-ups) were used as outcomes. The effect modification hypothesis was both investigated on an additive and multiplicative scale. RESULTS: SEP was inversely associated with CVD risk (eg, for low vs high income, OR 1.28 (95% CI 1.12 to 1.46)), and for all three components of stressful work CVD risks were significantly increased (eg, for effort-reward ratio OR 1.26 (95% CI 1.17 to 1.36)). Employees with a disadvantaged SEP showed moderately increased effect sizes of stressful work on CVD. However, no clear evidence of an effect modification was found. CONCLUSIONS: Disadvantaged SEP and stressful work contribute to higher CVD risk in this cohort. Despite moderately increased effect sizes for disadvantaged SEP groups, no evidence was found to support an effect modification hypothesis.

Impact of asthma on working life: an analysis of the French CONSTANCES cohort.

OBJECTIVES: Asthma has significant occupational consequences. The objective of our study was to investigate the links between asthma and the career path, taking into account gender and age at asthma onset. METHODS: Using cross-sectional data collected at inclusion in the French CONSTANCES cohort in 2013-2014, we studied the links between each career path indicator (number of job periods, total duration of employment, numbers of part-time jobs and work interruptions due to unemployment or health issues, employment status at inclusion) on the one hand, and current asthma and asthma symptom score in the last 12 months on the other hand, as reported by the participants. Multivariate analyses were performed separately for men and women using logistic and negative binomial regression models adjusted for age, smoking status, body mass index and educational level. RESULTS: When the asthma symptom score was used, significant associations were observed with all of the career path indicators studied: a high symptom score was associated with a shorter total duration of employment as well as a greater number of job periods, part-time jobs and work interruptions due to unemployment or health issues. These associations were of similar magnitude in men and women. When current asthma was used, the associations were more pronounced in women for some career path indicators. CONCLUSION: The career path of asthmatic adults is more often unfavourable than that of those without asthma. Efforts should be made to support people with asthma in the workplace, in order to maintain employment and facilitate the return to work.

Liens entre le statut tabagique et la situation vis-à-vis de l'emploi : analyse transversale de la cohorte CONSTANCES.

This study aims to estimate the prevalence of tobacco use in 2017 and 2019 in the French population covered by the Régime Général d'Assurance Maladie according to employment status. From the French national CONSTANCES cohort, 18,008 randomly recruited volunteers aged between 18 and 69 years, affiliated to the Régime Général d'Assurance Maladie and enrolled in 2017, were included in the analysis. The prevalence of tobacco use according to employment status was estimated. Estimates of these prevalence data were calculated in 2017 and 2019 after correction for selection bias at inclusion and non-response at follow-up. In 2019, smoking prevalence was higher among unemployed people (29.2% among men and 20.7% among women) than among employed people (16.5% among men and 13.8% among women). Smoking prevalence was highest among those not in work for health reasons (38.5% among men and 35.8% among women). Smokers were more likely to be unemployed than non-smokers (OR 2.63 [95% confidence interval (CI): 1.79; 3.85] in men and OR 1.55 [95% CI: 1.08; 2.22] in women). Among men, the prevalence of employed people among light smokers (<10 cigarettes/day) significantly decreased between 2017 (87.1%) and 2019 (74.8%). These results underline the importance of reinforcing smoking prevention campaigns among the unemployed, particularly for health reasons.

Evaluation of saliva as a source of accurate whole-genome and microbiome sequencing data.

This study sets out to establish the suitability of saliva-based whole-genome sequencing (WGS) through a comparison against blood-based WGS. To fully appraise the observed differences, we developed a novel technique of pseudo-replication. We also investigated the potential of characterizing individual salivary microbiomes from non-human DNA fragments found in saliva. We observed that the majority of discordant genotype calls between blood and saliva fell into known regions of the human genome that are typically sequenced with low confidence; and could be identified by quality control measures. Pseudo-replication demonstrated that the levels of discordance between blood- and saliva-derived WGS data were entirely similar to what one would expect between technical replicates if an individual's blood or saliva had been sequenced twice. Finally, we successfully sequenced salivary microbiomes in parallel to human genomes as demonstrated by a comparison against the Human Microbiome Project.

The burden of NAFLD in type 2 diabetic subjects from the general population: A Nationwide population-based follow-up study (NASHCO).

BACKGROUND: The epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD) in diabetes have been mainly investigated in the hospital setting. The goal of this study was to evaluate the characteristics of NAFLD and its impact on morbidity and mortality in type 2 diabetic subjects in a community setting. METHOD: This study included 199 341 participants in the nationwide Constances cohort. After patients with excessive alcohol consumption, viral hepatitis or other causes of liver disease were excluded, 164 285 were analysed and 8386 (5.3%) were considered to have type 2 diabetes. The non-invasive diagnosis of NAFLD and advanced fibrosis was made using a combination of the fatty liver index and Forns index. Median follow-up was 2.5 years. RESULTS: Diabetes increased the risk of NAFLD by sixfold (adjusted OR 6.05, 95% CI 5.68-6.45) and the risk of advanced fibrosis by 3.76-fold (aOR 3.76, 95% CI 2.87-4.91) in NAFLD subjects. After controlling for confounders, the presence of NAFLD in diabetic subjects was associated with an increased risk of severe liver-related events (aHR 2.53, 95% CI 1.36-4.69), cardiovascular disease (CVD, aHR 2.71, 95% CI 1.72-4.26) and overall mortality (aHR 2.91, 95% CI 1.53-5.53). The risk of hepatic and extrahepatic complications in diabetic subjects with NAFLD significantly increased with the severity of fibrosis (P < .05). CONCLUSION: This prospective, longitudinal study in a large community-based cohort provides real-world evidence of the risk for NAFLD and advanced fibrosis in diabetes, and its impact on liver disease progression, diabetes-related complications such as CVD, and overall mortality. These data could be used to estimate real clinical and economic burden of NAFLD in diabetic subjects.

The association of substance use with attaining employment among unemployed job seeking adults: Prospective findings from the French CONSTANCES cohort.

This study aimed to examine the prospective association between tobacco, alcohol and cannabis use with attaining employment among unemployed job seekers. Data from the French population-based CONSTANCES cohort on 5114 unemployed job seeking adults enrolled from 2012 to 2018 were analyzed. Binary logistic regressions were computed. Odds ratio (OR) and 95%CI of remaining unemployed at one-year of follow-up (versus attaining employment) according to substance use at baseline were obtained. The following independent variables were introduced into separate models: tobacco use (non-smoker, former smoker, light (<10cig/day), moderate (10-19cig/day) and heavy smoker (>19cig/day)), alcohol use according to the Alcohol Use Disorder Identification Test (non-users (0), low (<7), moderate (7-15) and high or very high-risk (>15)) and cannabis use (never used, no use in the previous 12 months, less than once a month, at least once a month but less than once per week, once per week or more). Analyses were adjusted for age, gender and education. At follow-up, 2490 participants (49.7%) were still unemployed. Compared to non-smokers, moderate and heavy smokers were more likely to remain unemployed, with ORs (95%CI) of 1.33 (1.08-1.64) and 1.42 (1.04-1.93), respectively. Compared to low-risk alcohol users, no alcohol users and high or very high-risk alcohol users were more likely to remain unemployed, with ORs (95% CI) of 1.40 (1.03-1.83) and 2.10 (1.53-2.87), respectively. Compared to participants who never used cannabis, participants who use cannabis once a week or more were more likely to remain unemployed, OR (95%CI) of 1.63 (1.33-2.01). Substance use may play an important role in difficulty attaining employment.

Association between COVID-19 infection and work exposure assessed by the Mat-O-Covid job exposure matrix in the CONSTANCES cohort.

OBJECTIVES: The COVID-19 pandemic has brought to light a new occupational health threat. We aimed to evaluate the association between COVID-19 infection and work exposure to SARS-CoV-2 assessed by a job-exposure matrix (JEM), in a large population cohort. We also estimated the population-attributable fraction among exposed subjects. METHODS: We used the SAPRIS-SERO sample of the CONSTANCES cohort, limited to subjects actively working, and with a job code available and a questionnaire on extra work activities. The following outcomes were assessed: COVID-19 diagnosis was made by a physician; a seropositivity to the ELISA-S test ('serology strict') and ELISA-S test intermediate with positive ELISA-NP or a positive neutralising antibodies SN ('serology large'). Job exposure was assessed using Mat-O-Covid, an expert-based JEM with an Index used as a continuous variable and a threshold at 13/1000. RESULTS: The sample included 18 999 subjects with 389 different jobs, 47.7% were men with a mean age of 46.2 years (±9.2 years). The Mat-O-Covid index taken as a continuous variable or with a threshold greater than 13/1000 was associated with all the outcomes in bivariable and multivariable logistic models. ORs were between 1.30 and 1.58, and proportion of COVID-19 attributable to work among exposed participants was between 20% and 40%. DISCUSSION: Using the Mat-O-Covid JEM applied to a large population, we found a significant association between work exposure to SARS-CoV-2 and COVID-19 infection, though the estimation of attributable fraction among exposed people remained low to moderate. Further studies during other exposed periods and with other methods are necessary.

Comorbidities Are Associated with Fibrosis in NAFLD Subjects: A Nationwide Study (NASH-CO Study).

BACKGROUND: The relationship between the severity of NAFLD and extra-hepatic events such as cardiovascular disease (CVD), extra-hepatic cancer (EHC) or chronic kidney diseases (CKD) has not been clearly investigated in the general population. AIMS: The aim of this study was to assess whether the severity of fibrosis in NAFLD subjects was associated with extra-hepatic diseases based on noninvasive markers in a large population-based cohort. METHODS: The study population included a cohort of 118,664 participants from the nationwide CONSTANCES cohort. After excluding individuals with excessive alcohol consumption and other causes of liver disease, 102,344 were included. The noninvasive diagnosis of NAFLD and fibrosis was performed using a combination of the Fatty Liver Index (FLI) and the Forns Index. The history of CVD or EHC was recorded by a physician, and CKD was defined by a glomerular filtration rate < 60 ml/mn. RESULTS: The prevalence of NAFLD (FLI > 60) was 18.2%, 10% with mild fibrosis (Forns Index < 4.2), 7.7% with intermediate fibrosis (Forns Index 4.2-6.9), and 0.4% with advanced fibrosis (Forns Index > 6.9). The prevalence of CVD, EHC, or CKD increased significantly with the severity of fibrosis (p < 0.0001). When adjusted for demographic, metabolic risk factors, and smoking, NAFLD with intermediate or advanced fibrosis remained associated with CVD (OR 1.36, p < 0.0001 and OR 3.07, p < 0.0001, respectively), EHC (OR 1.24, p = 0.001 and OR 1.64, p = 0.004, respectively), and CKD (OR 1.18, p = 0.03 and OR 2.09, p < 0.0001, respectively). CONCLUSIONS: In a large adult population-based cohort, there is a dose-dependent relationship between the severity of fibrosis and CVD, EHC, or CKD in NAFLD subjects.