Norms for Usual and Fast Walking Speed in Adults 45-69 Years Old From the French General Population: Constances Study.

OBJECTIVES: Walking speed (WS) represents an objective measure of motor function and health. We aimed to develop usual (UWS) and fast WS (FWS) norms for the general population using a regression-based approach, while considering age, sex, height, and education. DESIGN: Cross-sectional analysis of a population-based study. SETTING AND PARTICIPANTS: French Constances study (45-69 years). METHODS: UWS/FWS were measured over 3 m (dynamic start) using photoelectric cells. We addressed selection effects (related to survey sampling and nonresponse) and missing data using a combination of inverse probability weighting (IPW) and multiple imputation (MI). Norms by sex, age, height, and education (

Combined influence of immigration status and income on cervical cancer screening uptake.

The regular performance of Pap tests for cervical cancer screening reduces this disease's incidence and mortality. Income inequalities have been reported for this screening, partly because in some countries women must advance or even pay out-of-pocket costs. Because immigrant status is also associated with low Pap test uptake, we aimed to analyze the combined impact of immigrant status and low income on cervical cancer underscreening. This study, based on the French CONSTANCES cohort, uses data from the cohort questionnaires and linked health insurance fund data about Pap test reimbursement. To measure income inequalities in screening, we calculated a Slope Index of Inequality (SII) by linear regression, taking into account the migration status of participants. The majority of the 70,614 women included in the analysis were not immigrants (80.2%), while 12.9% were second-generation immigrants, and 6.9% first-generation immigrants. The proportion of underscreening increased with immigrant status, from 19.5% among nonimmigrants to 23.6% among the second generation, and 26.5% among the first (P < 0.01). The proportion of underscreening also increased as income level decreased. The income gradient rose significantly from 14% among nonimmigrants to 21% in second-generation immigrants and 19% in the first generation (P < 0.01). Among first-generation migrants, the shorter the duration of residence, the higher the SII. Women who are first- or second-generation immigrants are simultaneously underscreened and subject to a more unfavorable economic gradient than native French women born to native French parents. The accumulation of several negative factors could be particularly unfavorable to screening uptake.

Women with type 2 diabetes have LDL cholesterol levels higher than those of men, regardless of their treatment and their cardiovascular risk level.

BACKGROUND AND AIMS: Several works have shown that control of the principal cardiovascular risk factors, especially LDL-C, is poorer among women with type 2 diabetes than men with this disease. Our objectives were to compare the statin treatments and LDL-C levels between men and women with type 2 diabetes, according to the potency of the statin they take, while taking their cardiovascular risk level into account. METHOD AND RESULTS: This is a descriptive cross-sectional study within the French CONSTANCES cohort. At inclusion, each individual completed several self-administered questionnaires. Data were then matched to their health insurance fund reimbursement data. The study population comprises cohort members with pharmacologically treated type 2 diabetes. We identified 2541 individuals with type 2 diabetes; 2214 had an available LDL-C value. In the total sample, treatment by statins did not differ between men and women, while the women had a higher mean LCL-C level than men. The analyses stratified by cardiovascular risk showed that women at very high cardiovascular risk received significantly less frequent statin delivery than men (OR = 0.72 [0.56-0.92]; p = 0.01). At the same time, women received the same rate of high-potency statins as men. Women taking equivalently potent statins had significantly higher LDL-C levels than men did. CONCLUSION: For the same cardiovascular risk level and the same statin treatment, women had an LDL-C level higher than that of men. They thus present a residual cardiovascular risk that justifies intensification of their statin treatment if tolerance allows.

Characteristics of reproductive history, use of exogenous hormones and walking speed among women: Data from the CONSTANCES French Cohort Study.

OBJECTIVE: To investigate the cross-sectional associations of reproductive history and use of exogenous hormones with fast walking speed (WS) in women. STUDY DESIGN: Between 2012 and 2020, 33,892 French women aged 45 years or more, recruited at health centers, underwent physical function tests and self-reported information on reproductive history and use of exogenous hormones. Linear mixed models with the center as random intercept were used to estimate the association of exposures with WS. MAIN OUTCOME MEASURES: Fast WS. RESULTS: Mean WS was 172.2 cm/s. WS increased with age at menarche (ß+1y = 0.23, 95 % confidence interval = 0.05 to 0.40), age at first birth (ß+1y = 0.20, 95 % CI = 0.13 to 0.27) and duration of breastfeeding (ßfor ≥10 vs ≤5months = 1.38; 95 % CI = 0.39 to 2.36). In addition, parity was quadratically associated with WS, with women with 3 children having the highest WS (p for U-shaped relationship < 0.01). Menopausal status had no impact on WS but age at menopause was positively associated with WS (ß+5y = 0.52, 95 % CI = 0.17 to 0.87) and partly explained the deleterious impact of artificial menopause on WS. WS increased with reproductive lifetime duration (ß+5y = 0.49, 95 % CI = 0.16 to 0.83) and decreased with time since onset of menopause (ß+5y = -0.65, 95 % CI = -0.99 to -0.31). By contrast, there was no association of WS with oral contraception and postmenopausal hormone therapy. CONCLUSION: Our findings suggest that reproductive life characteristics may be associated with WS and timing of exposure could play a role.

Comparison of manual and automated measures of walking speed: Distance and pace matter.

BACKGROUND: Walking speed (WS) represents a global marker of individual health and provides a simple and objective measure of motor performances for use in clinical and research settings. WS is most often measured over relatively short distances at usual (UWS) or fast (FWS) pace, using manual (e.g., stopwatch) or automated methods (e.g., photoelectric cells). As the time needed to walk over these distances is very short, we hypothesized that measurement error related to manual compared to automated WS measures is more pronounced for shorter distances and FWS and investigated the reliability and agreement of WS in a subsample of the Constances cohort at two paces and over two distances. METHODS: We recruited 100 community-dwelling participants (50 % women) aged 45-70y (mean = 56.1y). WS was measured manually (stopwatches) and using photoelectric cells, at two paces (UWS/FWS) and over two distances (3 m/5 m). Agreement was examined using Bland and Altman plots and intraclass correlation coefficients (ICC). RESULTS: Participants were on average 169.8 cm tall, and their mean body mass index was 25.4 kg/m2. Agreement between manual stopwatches and photoelectric cells was excellent (ICCs between 0.92 and 0.97), but it was lower for smaller distances, with significantly lower ICCs over 3 m compared to 5 m both for UWS (differenceICC = -0.04) and FWS (differenceICC = -0.05). Bias of manual measures was constant for UWS and increased with increasing FWS. There were inter-rater effects, with better agreement for UWS and 5 m compared to FWS and 3 m. CONCLUSIONS: Both distance and pace have an influence on the reliability of WS measures using manual timing methods. Our findings also suggest the presence of rater effects and better agreement for 5 m and UWS. These findings are helpful for the design of studies that include manual measures of WS, especially FWS, in order to reduce measurement error and suggest that longer distances are preferable.

Prevalence of Hearing Loss and Hearing Aid Use Among Adults in France in the CONSTANCES Study.

Importance: Although hearing loss is common in the population worldwide, the prevalence of hearing loss and hearing aid use is not known. Objective: To estimate the prevalence of hearing loss and hearing aid use in the adult French population. Design, Setting, and Participants: This cohort study used data from the CONSTANCES cohort, a representative sample of the French population. Volunteers aged 18 to 75 years were recruited at 21 preventive health centers between January 1, 2012, and December 31, 2019. The present study included participants with audiometric data. Main Outcomes and Measures: The main outcomes were prevalence of hearing loss and disabling hearing loss overall and by sex and age group and prevalence of self-reported hearing aid use among those with disabling hearing loss. Hearing loss was defined as a pure-tone average (PTA) in the better ear of 20 dB or higher, and disabling hearing loss was defined as a PTA in the better ear of 35 dB or higher. Results: Of 200 870 participants in the CONSTANCES study, 186 460 had full audiometric data and were included in this study (mean [SD] age, 47.1 [13.5] years); 100 330 (53.8%) were female, and 86 130 (46.2%) were male. Of these participants, 24.8% (95% CI, 24.6%-25.0%) had hearing loss and 4.3% (95% CI, 4.2%-4.4%) had disabling hearing loss. The prevalence rates of hearing loss increased from 3.4% (95% CI, 2.8%-3.9%) at age 18 to 25 years to 73.3% (95% CI, 69.5%-77.2%) at age 71 to 75 years among men and from 4.4% (95% CI, 3.9%-5.0%) at age 18 to 25 years to 64.1% (95% CI, 59.7%-68.4%) at age 71 to 75 years among women. The prevalence of disabling hearing loss increased from 0.3% (95% CI, 0.2%-0.4%) among participants aged 18 to 25 years to 23.3% (95% CI, 20.7%-26.0%) among participants aged 71 to 75 years. Among the 8050 participants with disabling hearing loss, 36.8% (95% CI, 35.8%-37.9%) reported using hearing aids, including 56.7% (95% CI, 38.9%-74.4%) aged 18 to 25 years and 32.9% (95% CI, 26.8%-39.2%) aged 71 to 75 years. Conclusions and Relevance: In this cohort study, hearing loss was prevalent in France, and the prevalence of hearing loss increased with age among both men and women. Hearing aids were underused, particularly among older individuals. These findings suggest that hearing loss prevention and screening in the French population are needed.

Outdoor air pollution exposure and cognitive performance: findings from the enrolment phase of the CONSTANCES cohort.

BACKGROUND: Air pollution exposure is one of the modifiable risk factors of cognitive decline. We aimed to test the association between exposure to several outdoor air pollutants and domain-specific cognitive performance. METHODS: In this cross-sectional study, we used data from the enrolment phase of the French CONSTANCES cohort. From the 220 000 people (aged 18-69 years) randomly recruited in the French CONSTANCES cohort, participants aged 45 years old or older (104 733 people) underwent a comprehensive cognitive assessment (verbal episodic memory, language skills, and executive functions). After exclusion of those who were not suitable for our analysis, 61 462 participants with available data were included in the analyses. We used annual mean concentrations at residential addresses, derived from land-use regression models, to assign exposure to particulate matter with aerodynamic diameters less than 2·5 µm (PM2·5), nitrogen dioxide (NO2), and black carbon. We used multiple linear regression models with different covariate adjustments to test the associations between each pollutant and cognitive outcomes. We did several sensitivity analyses, including multilevel modelling, meta-analysis by centre of recruitment, and exclusion of specific population groups. FINDINGS: We found significantly poorer cognitive function, especially on semantic fluency and domains of executive functions, with an increase in exposure to black carbon and NO2. Exposure to PM2·5 was mainly significant for the semantic fluency test. We found that decrease in cognitive performance with an increase of one interquartile range of exposure ranged from 1% to nearly 5%. The largest effect size (percentage decrease) for both PM2.5 and NO2 was found for the semantic fluency test (PM2.5 4·6%, 95% CI 2·1-6·9 and NO2 3·8%, 1·9-5·7), whereas for black carbon, the largest effect size was found for the digit symbol substitution test of the domains of executive functions (4·5%, 2·7-6·3). Monotonic and linear exposure-response associations were found between air pollution exposure and cognitive performance, starting from a low level of exposures. INTERPRETATION: Significantly poorer cognitive performance was associated with exposure to outdoor air pollution even at low levels of exposure. This highlights the importance of further efforts to reduce exposure to air pollution. FUNDING: The Caisse Nationale d'Assurance Maladie, and partly funded by Merck Sharp & Dohme and L'Oréal, the French National Research Agency, and Fondation de France. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Association Between Occupational Exposure to Formaldehyde and Cognitive Impairment.

BACKGROUND AND OBJECTIVES: To our knowledge, no study has investigated the effect of exposure to formaldehyde on cognition in the general population. Our objective was to examine the association between occupational exposure to formaldehyde and cognitive impairment in middle-aged and young-old adults (≥45 years). METHODS: In the French CONSTANCES cohort, cognitive function was assessed with a standardized battery of 7 cognitive tests to evaluate global cognitive function, episodic verbal memory, language abilities, and executive functions (e.g., Digit Symbol Substitution Test [DSST]). A global cognitive score was created using principal component analysis. Cognitive impairment was assessed in reference to norms of neuropsychological battery according to age, sex, and education. Lifetime exposure to formaldehyde was assessed using a French Job Exposure Matrix created in the framework of the Matgéné project. After performing multiple imputation, separate modified Poisson regression models were used to evaluate the association between cognitive impairment (<25th percentile) and formaldehyde exposure (exposed/never exposed), exposure duration, cumulative exposure index (CEI), and combination of CEI and time of last exposure. RESULTS: Among 75,322 participants (median age 57.5 years, 53% women), 8% were exposed to formaldehyde during their professional life. These participants were at higher risk of global cognitive impairment (for global cognitive score: adjusted relative risk [aRR] 1.17; 95% confidence interval [CI] 1.11-1.23), after adjusting for confounders (age, sex, education, income, solvent exposure, Effort-Reward Imbalance, night shift, repetitive work, and noisy work). They were at higher risk of cognitive impairment for all cognitive domains explored. Longer exposure duration and high CEI were associated with cognitive impairment, with a dose-effect relationship for exposure duration. Recent exposure was associated with impairment in all cognitive domains. Time did not fully attenuate formaldehyde-associated cognitive deficits especially in highly exposed individuals (for DSST: high past exposure aRR 1.23; 95% CI 1.11-1.36; high recent exposure: aRR 1.24; 95% CI 1.13-1.35). DISCUSSION: Our findings highlight the long-term detrimental effect of formaldehyde exposure on cognitive health in a relatively young population.

Brief Report: Frailty in Aging People Living With HIV: A Matched Controlled Study.

BACKGROUND: We compared the prevalence of frailty among aging people living with HIV (PLHIV) with people without HIV from the ANS EP58 HAND 55-70 Study. METHODS: Cross-sectional multicentric study which consecutively included 200 PLHIV and 1000 people without HIV from the French national CONSTANCES cohort, matched on age, sex, and education level. PLHIV were aged 55-70 years, with a HIV viral load < 50 copies/mL and a lymphocyte T-CD4 level > 200 cells/µL for the last 24 and 12 months, respectively. We measured frailty (>2 items) and prefrailty (one or 2 items) using a proxy of the 5-item Fried score. Multivariate logistic regression was performed to assess the association between HIV and frailty/prefrailty, adjusting for demographic, social, behavioral, and comorbidity confounders. RESULTS: Outcome measures were available for 192 PLHIV and 822 people without HIV. The median age was 62 years, and 84.9% were men. Among PLHIV, the median CD4 cell count was 645.5 cells/µL. Prevalence of frailty/prefrailty was 5.73%/57.3% in PLHIV vs. 1.73%/52.2% in people without HIV, respectively. HIV was associated with prefrailty/frailty [odds ratio = 1.89; 95% confidence interval = 1.37 to 2.61), but after adjusting for social and behavioral factors and comorbidities, HIV was not significantly associated with prefrailty/frailty (odds ratio = 1.24; 95% confidence interval: = 0.84 to 1.81). In PLHIV only, frailty/prefrailty was associated with depressive symptomatology, kidney disease, and time since HIV infection. CONCLUSIONS: Prevalence of frailty is increased in aging PLHIV with well-controlled HIV disease, but other factors than HIV are predominant, particularly depression and comorbidities.

Evolution of the prevalence of obesity in the adult population in France, 2013-2016: the Constances study.

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.

Personal protective equipment and doffing procedures in out-of-hospital practice: assessment with a contamination simulation.

BACKGROUND: The use of personal protective equipment (PPE) by emergency medical services (EMS) providers requires specific attention, as it takes place in out-of-hospital unsecured settings. The aim of this study was to evaluate which PPE gown was less contaminating during doffing procedures in an EMS setting. Six well-trained healthcare worker (HCW) subjects tested 4 different gowns: (1) surgical gowns (SG), (2) full body coveralls (FBC), (3) self-made alternative PPEs (SMP), and (4) non-surgical isolation gowns (NSIG). An invisible tracer was sprayed on the gown after donning each subject. After doffing, each HCW was photographed under UV lights to show areas of fluorescent "contamination" on their clothes. The number, size, and intensity level of contaminated areas were noted, as well as observational deviation from the procedure and doffing time. In addition, the subjects were asked to take a questionnaire about their perception of the level of comfort, ease of doffing, and overall safety for each gown. RESULTS: Despite a well-trained team of HCW subjects, contamination while doffing was observed with every type of PPE gown, and with each HCW subject. All body areas were contaminated at least once, except the face. Contamination was more frequent while doffing FBCs. On the other hand, the removal of SG was found to be the least contaminating. The mean doffing time was significantly shorter with SG 1:29 and longer with FBC 2:26 (p=0.005). CONCLUSION: Results of this study converge towards the selection of surgical gowns over other types of PPE gowns, which met both contamination criteria as well as staff appreciation in this context. Specific attention should be paid to the legs and abdomino-pelvic areas. Additional protection such as protective trousers or aprons could be added.

Collective Critical Care Ambulance: an innovative transportation of critical care patients by bus in COVID-19 pandemic response.

BACKGROUND: During the COVID-19 pandemic, as the number of available Intensive Care beds in France did not meet the needs, it appeared necessary to transfer a large number of patients from the most affected areas to the less ones. Mass transportation resources were deemed necessary. To achieve that goal, the concept of a Collective Critical Care Ambulance (CCCA) was proposed in the form of a long-distance bus re-designed and equipped to accommodate up to six intensive care patients and allow Advanced Life Support (ALS) techniques to be performed while en route. METHODS: The expected benefit of the CCCA, when compared to ALS ambulances accommodating a single patient, was to reduce the resources requirements, in particular by a lower personnel headcount for several patients being transferred to the same destination. A foreseen prospect, comparing to other collective transportation vectors such as airplanes, was the door-to-door capability, minimalizing patients' handovers for safety concerns and time efficiency. With the project of a short-distance transfer of several Intensive Care Unit (ICU) patients together, the opportunity came to test the CCCA under real-life conditions and evaluate safely its technical feasibility and impact in time and resources saving, before it could be proposed for longer distances. RESULTS: Four COVID-19 patients were transported over 37 km. All patients were intubated and under controlled ventilation. One of them was under Norepinephrine support. Mean loading time was 1 min 39 s. Transportation time was 29 min. At destination, the mean unloading time was 1 min 15 s. No serious adverse effect, in particular regarding hemodynamic instability or ventilation disorder, has been observed. No harmful incident has occurred. CONCLUSIONS: It was a very instructive test. Collective medical evacuation by bus for critically ill patients under controlled ventilation is suitable and easy to implement. Design, ALS equipment, power autonomy, safety and resources saving, open the way for carrying up to 6 ICU-patients over a long distance. The CCCA could bring a real added-value in an epidemic context and could also be helpful in many other events generating multiple victims such as an armed conflict, a terrorist attack or a natural disaster.

The pathophysiology of "happy" hypoglycemia.

BACKGROUND: Hypoglycemia usually includes various neurological symptoms, which are the consequence of neuroglycopenia. When it is severe, it is associated with altered mental status, even coma. CASE PRESENTATION: We report the case of a patient with severe hypoglycemia, completely asymptomatic, due to the increase of lactate production in response to tissue hypoperfusion following a hemorrhagic shock. This illustrates that lactate can substitute glucose as an energy substrate for the brain. It is also a reminder that this metabolite, despite its bad reputation maintained by its role as a marker of severity in critical care patients, has a fundamental role in our metabolism. CONCLUSIONS: Following the example of the "happy hypoxemia" recently reported in the literature describing asymptomatic hypoxemia in COVID-19 patients, we describe a case of "happy hypoglycemia."

Women with obesity in cervical cancer screening. The double penalty: Underscreening and income inequalities.

The regular performance of Pap tests reduces the mortality of cervical cancer. Obesity is associated with low Pap test rates. We analyze the combined role of obesity and low income. We calculated a Slope Index of Inequality. Among the 28,905 women included, 23.1% were underscreened. The rate of underscreening increased with BMI. The income gradient increased significantly from 0.17 among normal-weight women to 0.19 in overweight and 0.23 in obese women (p = 0.047). Women who are obese are subject to a double penalty in cervical cancer screening: they are underscreened and subject to a more unfavorable economic gradient than normalweight women.

Cumulative Exposure to Long Working Hours and Occurrence of Ischemic Heart Disease: Evidence From the CONSTANCES Cohort at Inception.

Background Long-working hours (LWH) are a probable risk factor for ischemic heart diseases (IHD); however, no previous study has considered duration of exposure to LWH when addressing this topic. We aimed to determine the association between cumulative exposure to LWH and IHD while accounting for relevant confounders. Methods and Results In this retrospective study, we included all baseline participants from the French population-based cohort CONSTANCES. Part-time employees and those who reported a cardiac event in the 5 years before LWH exposure were excluded. From self-administered questionnaires and clinical examinations, we obtained participants' age, sex, body mass index, occupational status, smoking habits, high blood pressure, diabetes mellitus, familial history of cardiovascular disease, dyslipidemia, exposure to LWH, and its duration. We defined LWH as working for >10 hours daily for at least 50 days per year. The main outcome was reported history of IHD, ie, myocardial infarction or angina pectoris, during a clinical examination. Of 137 854 included participants, 69 774 were men. There were 1875 cases (1.36%) of IHD, and exposure to LWH was reported by 42 462 subjects (30.8%) among whom 14 474 (10.50%) reported exposure for at least 10 years. Overall, exposure to LWH for ≥10 years was associated with an increased risk of IHD, adjusted odds ratio (aOR) 1.24 (1.08-1.43), P=0.0021. In stratified analyses, this effect was not observed in women, but was significant amongst men, aOR 1.28 (1.11-1.48), P=0.0008. Conclusions This large population-based study supports an association between cumulative exposure to LWH and IHD in men. Future research should consider relevant strategies for reducing LWH exposure and duration.

The effect of exposure to long working hours on stroke: A systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of individual experts. Evidence from mechanistic data and prior studies suggests that exposure to long working hours may cause stroke. In this paper, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from stroke that are attributable to exposure to long working hours, for the development of the WHO/ILO Joint Estimates. OBJECTIVES: We aimed to systematically review and meta-analyse estimates of the effect of exposure to long working hours (three categories: 41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on stroke (three outcomes: prevalence, incidence, and mortality). DATA SOURCES: A protocol was developed and published, applying the Navigation Guide to systematic reviews as an organizing framework where feasible. We searched electronic databases for potentially relevant records from published and unpublished studies, including Ovid MEDLINE, PubMed, EMBASE, Scopus, Web of Science, CISDOC, PsycINFO, and WHO ICTRP. We also searched grey literature databases, Internet search engines, and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts. STUDY ELIGIBILITY AND CRITERIA: We included working-age (≥15 years) individuals in the formal and informal economy in any WHO and/or ILO Member State but excluded children (aged < 15 years) and unpaid domestic workers. We included randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the effect of exposure to long working hours (41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on stroke (prevalence, incidence or mortality). STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first review stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. Missing data were requested from principal study authors. We combined relative risks using random-effects meta-analysis. Two or more review authors assessed the risk of bias, quality of evidence and strength of evidence, using the Navigation Guide and GRADE tools and approaches adapted to this project. RESULTS: Twenty-two studies (20 cohort studies, 2 case-control studies) met the inclusion criteria, comprising a total of 839,680 participants (364,616 females) in eight countries from three WHO regions (Americas, Europe, and Western Pacific). The exposure was measured using self-reports in all studies, and the outcome was assessed with administrative health records (13 studies), self-reported physician diagnosis (7 studies), direct diagnosis by a physician (1 study) or during a medical interview (1 study). The outcome was defined as an incident non-fatal stroke event in nine studies (7 cohort studies, 2 case-control studies), incident fatal stroke event in one cohort study and incident non-fatal or fatal ("mixed") event in 12 studies (all cohort studies). Cohort studies were judged to have a relatively low risk of bias; therefore, we prioritized evidence from these studies, but synthesised evidence from case-control studies as supporting evidence. For the bodies of evidence for both outcomes with any eligible studies (i.e. stroke incidence and mortality), we did not have serious concerns for risk of bias (at least for the cohort studies). Eligible studies were found on the effects of long working hours on stroke incidence and mortality, but not prevalence. Compared with working 35-40 h/week, we were uncertain about the effect on incidence of stroke due to working 41-48 h/week (relative risk (RR) 1.04, 95% confidence interval (CI) 0.94-1.14, 18 studies, 277,202 participants, I2 0%, low quality of evidence). There may have been an increased risk for acquiring stroke when working 49-54 h/week compared with 35-40 h/week (RR 1.13, 95% CI 1.00-1.28, 17 studies, 275,181participants, I2 0%, p 0.04, moderate quality of evidence). Compared with working 35-40 h/week, working ≥55 h/week may have led to a moderate, clinically meaningful increase in the risk of acquiring stroke, when followed up between one year and 20 years (RR 1.35, 95% CI 1.13 to 1.61, 7 studies, 162,644 participants, I2 3%, moderate quality of evidence). Compared with working 35-40 h/week, we were very uncertain about the effect on dying (mortality) of stroke due to working 41-48 h/week (RR 1.01, 95% CI 0.91-1.12, 12 studies, 265,937 participants, I2 0%, low quality of evidence), 49-54 h/week (RR 1.13, 95% CI 0.99-1.29, 11 studies, 256,129 participants, I2 0%, low quality of evidence) and 55 h/week (RR 1.08, 95% CI 0.89-1.31, 10 studies, 664,647 participants, I2 20%, low quality of evidence). Subgroup analyses found no evidence for differences by WHO region, age, sex, socioeconomic status and type of stroke. Sensitivity analyses found no differences by outcome definition (exclusively non-fatal or fatal versus "mixed") except for the comparison working ≥55 h/week versus 35-40 h/week for stroke incidence (p for subgroup differences: 0.05), risk of bias ("high"/"probably high" ratings in any domain versus "low"/"probably low" in all domains), effect estimate measures (risk versus hazard versus odds ratios) and comparator (exact versus approximate definition). CONCLUSIONS: We judged the existing bodies of evidence for human evidence as "inadequate evidence for harmfulness" for all exposure categories for stroke prevalence and mortality and for exposure to 41-48 h/week for stroke incidence. Evidence on exposure to 48-54 h/week and ≥55 h/week was judged as "limited evidence for harmfulness" and "sufficient evidence for harmfulness" for stroke incidence, respectively. Producing estimates for the burden of stroke attributable to exposures to working 48-54 and ≥55 h/week appears evidence-based, and the pooled effect estimates presented in this systematic review could be used as input data for the WHO/ILO Joint Estimates. PROTOCOL IDENTIFIER: https://doi.org/10.1016/j.envint.2018.06.016. PROSPERO REGISTRATION NUMBER: CRD42017060124.

Increased Prevalence of Neurocognitive Impairment in Aging People Living With Human Immunodeficiency Virus: The ANRS EP58 HAND 55-70 Study.

BACKGROUND: There are limited data on the comparative prevalence of neurocognitive impairment (NCI) in aging people living with human immunodeficiency virus (PLHIV) and people not living with HIV. METHODS: This was a cross-sectional study of PLHIV randomly matched by age (±4 years), gender, and education with 5 HIV-uninfected individuals from the CONSTANCES cohort. PLHIV were fluent in French and sequentially included during routine outpatient visits if aged 55-70 years, with HIV viral load <50 copies/mL, and lymphocyte T-CD4 level ≥200 cells/µL in the past 24 and 12 months, respectively. The primary outcome was NCI as defined by the Frascati criteria. Multivariate normative comparison (MNC) and -1.5 standard deviations in ≥2 neurocognitive domains were secondary outcomes of NCI. RESULTS: Two hundred PLHIV were matched with 1000 controls. Median age was 62 years, and 85% were men. In PLHIV, the median T-CD4 lymphocyte level was 650 cells/µL, and median nadir T-CD4 lymphocyte level was 176 cells/µL. NCI was found in 71 (35.5%) PLHIV and in 242 (24.2%) controls (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.25, 2.41). After adjusting for confounders, HIV remained significantly associated with NCI (OR, 1.50; 95% CI, 1.04, 2.16). Adjusted results were similar with NCI defined by MNC (ORMNC, 2.95; 95% CI, 1.13, 3.50) or -1.5 SD (OR-1.5, 2.24; 95% CI, 1.39, 3.62). CONCLUSIONS: In this matched study of aging individuals, HIV was significantly associated with an increased risk of NCI after adjusting for major confounders. Results were confirmed with more stringent NCI classifications. CLINICAL TRIALS REGISTRATION: NCT02592174.