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.

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.

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.

Risk factors for uncontrolled blood pressure among individuals with hypertension on treatment: the CONSTANCES population-based study.

BACKGROUND: We aimed to assess factors associated with uncontrolled blood pressure (BP) among individuals with hypertension on treatment, by sex. METHODS: We conducted a nested cross-sectional analysis using data from the population-based cohort study CONSTANCES, designed as a randomly selected sample of French adults aged 18-69 years at study inception. We included 11 760 participants previously diagnosed with hypertension and taking antihypertensive medications. Uncontrolled BP was defined as mean systolic BP ≥140 mmHg and/or mean diastolic BP ≥90 mmHg. Sex-specific age-adjusted multivariable analyses were performed using logistic regression models stratified by stages of uncontrolled hypertension. RESULTS: The mean age of participants was 59.4 years. The prevalence of uncontrolled BP was 51.4%, and it was higher in men than in women [adjusted odds ratio (aOR), 1.80; 95% CI, 1.67-1.94]. In both sexes, the lower the age, the lower the prevalence of uncontrolled hypertension. Low level of education and history of cardiovascular events had, respectively, higher and lower odds of uncontrolled BP. In men, additional risk factors included overweight and obesity (aOR, 1.15; 95% CI, 1.00-1.32; and aOR, 1.45; 95% CI, 1.23-1.70, respectively), lack of physical activity (aOR, 1.20; 95% CI, 1.04-1.40), low adherence to a Dietary Approach to Stop Hypertension diet (aOR, 1.21; 95% CI, 1.05-1.40) and heavy alcohol consumption (aOR, 1.33; 95% CI, 1.08-1.63), with the last two factors persisting across different stages of uncontrolled BP. CONCLUSIONS: From a population-based perspective, socio-economic and behavioural characteristics were risk factors for uncontrolled hypertension, but they differed by sex and by stage of uncontrolled hypertension. Modifiable risk factors, such as weight, diet, physical activity and alcohol consumption, have an important role in the control of hypertension.

Lifetime exposure to unemployment and prior working conditions are associated with retiree's health: A retrospective study in a large population-based French cohort.

It is unclear whether unemployment exposure, as well as working conditions, can have sustained effects on the health of retirees who are no longer exposed. The aim of the present study is to investigate this issue in 29,281 French retirees from the CONSTANCES cohort in whom the prevalence of suboptimal self-rated health, disability for routine tasks, cardiovascular diseases and cancers is assessed according to lifetime exposure to unemployment and prior working conditions. The analyses are performed retrospectively using multivariable logistic regression models with adjustment for potential confounders such as sex, birth year, parental histories of cardiovascular disease and cancer, social position, retirement age and duration. High lifetime exposure to unemployment is associated with an increased prevalence of suboptimal self-rated health (adjusted odds ratio (95% CI), 1.39 (1.23-1.57)), disability for routine tasks (1.41 (1.26-1.57)) and several cardiovascular diseases including stroke (1.66 (1.19-2.31)), myocardial infarction (1.65 (1.18-2.31)) and peripheral arterial disease (2.38 (1.46-3.90)). Bad prior working conditions are associated with an increased prevalence of disability for routine tasks (1.17 (1.04-1.33)) and cancers (1.27 (1.04-1.54)), notably prostate cancer (1.60 (1.01-2.64)). These findings suggest that unemployment and working conditions have long-term health effects that may cumulate over lifetime, emphasizing that risk evaluation and preventive strategies in retirees, as in workers, should take into account the life-course of individuals in addition to traditional risk factors.

Development of a crosswalk to convert French PCS2003 into international ISCO88 occupational classifications. Application to the Occupational Asthma-specific Job-Exposure Matrix (OAsJEM).

INTRODUCTION: The problem of transcoding is recurrent when researchers wish to link occupational data from cohorts to Job-Exposure Matrices (JEMs) which were not set up in the same classifications. The Occupational Asthma-specific JEM (OAsJEM) is a JEM developed for assessing exposure to agents known at risk for asthma for jobs coded with ISCO88 occupation classification. To apply the OAsJEM in the CONSTANCES cohort, in which jobs and industries were coded with French PCS2003 and NAF2008 classifications respectively, we developed a crosswalk to convert jobs from PCS2003 into ISCO88 classification. METHODS: This work was carried out by 2 skilled coders and 1 novice coder who have worked independently by using different tools and transcoding strategies defined a priori. Consensus meetings were organized with skilled coders to define the final crosswalk. This work was elaborated in 2 steps: (i) for 38 ISCO88 codes classified as potentially exposed to cleaning and disinfection products by the OAsJEM, and (ii) for all jobs from the ISCO88 classification. A comparison between the 3 initial coder's crosswalk proposals and the final crosswalk was made for the 38 ISCO codes in step (i). RESULTS: The final crosswalk provided 998 matches between the 482 4-digit PCS2003 codes, 308 4-digit ISCO88 codes, and 31 3-digit ISCO88 codes. Information regarding the NAF2008 industry classification was also used in some cases to improve the final crosswalk. For the selected 38 ISCO88 codes, the final crosswalk provided 110 combinations, but the number of proposed ISCO88-PCS2003 couples by each of the 3 coders varied greatly from 68 to 153. In addition, an important variability between the 3 coders were observed among the number of common combinations between the initial coder's proposals and the final crosswalk (from 47% to 78%). DISCUSSION: We have developed a crosswalk specifically for an application of the OAsJEM in population-based surveys using the PCS2003 occupation classification. The development of this crosswalk is of great interest for the use of OAsJEM on the data of the CONSTANCES cohort and on any other survey with occupational data coded according to the French classifications. This OAsJEM crosswalk could be used by other teams to evaluate occupational exposures known to be at risk of asthma from occupational calendars coded with French classifications.

Prevalence of chronic kidney disease in France: methodological considerations and pitfalls with the use of Health claims databases.

Background: Health policy-making require careful assessment of chronic kidney disease (CKD) epidemiology to develop efficient and cost-effective care strategies. The aim of the present study was to use the RENALGO-EXPERT algorithm to estimate the global prevalence of CKD in France. Methods: An expert group developed the RENALGO-EXPERT algorithm based on healthcare consumption. This algorithm has been applied to the French National Health claims database (SNDS), where no biological test findings are available to estimate a national CKD prevalence for the years 2018-2021. The CONSTANCES cohort (+219 000 adults aged 18-69 with one CKD-EPI eGFR) was used to discuss the limit of using health claims data. Results: Between 2018 and 2021, the estimated prevalence in the SNDS increased from 8.1% to 10.5%. The RENALGO-EXPERT algorithm identified 4.5% of the volunteers in the CONSTANCES as CKD. The RENALGO-EXPERT algorithm had a positive predictive value of 6.2% and negative predictive value of 99.1% to detect an eGFR<60 ml/min/1.73 m². Half of 252 false positive cases (ALGO+, eGFR > 90) had been diagnosed with kidney disease during hospitalization, and the other half based on healthcare consumption suggestive of a 'high-risk' profile; 95% of the 1661 false negatives (ALGO-, eGFR < 60) had an eGFR between 45 and 60 ml/min, half had medication and two-thirds had biological exams possibly linked to CKD. Half of them had a hospital stay during the period but none had a diagnosis of kidney disease. Conclusions: Our result is in accordance with other estimations of CKD prevalence in the general population. Analysis of diverging cases (FP and FN) suggests using health claims data have inherent limitations. Such an algorithm can identify patients whose care pathway is close to the usual and specific CKD pathways. It does not identify patients who have not been diagnosed or whose care is inappropriate or at early stage with stable GFR.

Gonadotropic status in adult women with pituitary stalk interruption syndrome.

OBJECTIVE: Pituitary stalk interruption syndrome (PSIS) is a rare cause of congenital hypopituitarism. Limited data exist on the gonadotropic status and fertility of adult women with PSIS. Our study aims to describe pubertal development and the evolution of gonadotropic function and fertility in adult women with PSIS. DESIGN: A retrospective multicentric French study. METHODS: We described gonadotropic function in 56 adult women with PSIS from puberty onward. We compared live birth rates per woman with PSIS with age-matched controls from the large French epidemiological cohort (CONSTANCES). Additionally, we assessed height, body mass index (BMI), blood pressure, other metabolic parameters, and socioeconomic status. RESULTS AND CONCLUSIONS: Among 56 women with PSIS, 36 did not experience spontaneous puberty. Of these, 13 underwent ovarian stimulation, resulting in 7 women having a total of 11 children. In the subgroup with spontaneous puberty (n = 20), 4 had a total of 8 pregnancies, while 6 developed secondary gonadotropic deficiency. Women with PSIS had fewer children than controls (0.33 vs 0.63, P = .04). Median height was also lower (160.5 vs 165.0 cm, P < .0001). Although mean blood pressure was lower in women with PSIS compared with controls (111.3/65.9 ± 11.2/8.1 vs 118.7/72.1 ± 10.1/7.7 mmHg, P < .001), there were no significant differences in other metabolic parameters, notably BMI and lipid profile. Employment/academic status was not different in the 2 groups, but fewer women with PSIS were in relationships (42% vs 57.6% in controls, P = .02). The fertility prognosis in patients with PSIS needs optimization. Patients should be informed about the likelihood of declining gonadotropic function over time.

Psychological burden associated with incident persistent symptoms and their evolution during the COVID-19 pandemic: a prospective population-based study.

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.

Human genetic structure in Northwest France provides new insights into West European historical demography.

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.