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Highlights • Vitamin D may mitigate COVID-19 through its effects on gene expression. • Increased vitamin D concentration is associated with better prognosis in COVID-19 cases. • The benefits of vitamin D supplementation in COVID-19 patients remain to be determined. • The use of vitamin D supplements as an adjuvant treatment for COVID-19 needs to be examined urgently., Using Hill's methodology for exploring causality, we aimed to determine in early May 2020 whether evidence supports vitamin D as a biological determinant of COVID-19 outcomes. Vitamin D is a secosteroid hormone theoretically able to reduce COVID-19 risk through regulation of (i) the renin-angiotensin system, (ii) cellular innate and adaptive immunity, and (iii) physical barriers. Inverse associations were found between 25-hydroxyvitamin D concentrations and COVID-19 incidence and mortality. Randomized controlled trials testing vitamin D supplementation in the treatment of COVID-19 are in progress. Positive results in such studies would encourage the use of vitamin D supplements as an adjuvant treatment in COVID-19.

International audience; Objectives:Using registry data to compare fungaemia caused by uncommon yeast species (UYS; i.e. other than Candida albicans , Candida glabrata , Candida parapsilosis , Candida tropicalis and Candida krusei ) and C. albicans -related fungaemia can reveal specific predisposing factors of UYS with potential impact on treatment strategies.Methods:We analysed 338 episodes of UYS fungaemia prospectively collected from 27 hospitals (Paris, France; 1 October 2002-31 December 2014) and compared these with 1998 single episodes of C. albicans fungaemia using univariate and multivariate analyses.Results:The proportion of UYS fungaemia was stable over time. Thirty-five different species were identified (27 ascomycetes, 8 basidiomycetes), 11 had caspofungin MIC 50 >0.25 mg/L and 15 fluconazole MIC 50 >4 mg/L. Haematological malignancies [OR=2.39 (95% CI 1.79-3.18)] and prior exposure to antifungal drugs [OR=1.87 (1.30-2.69)] were independent predisposing factors for UYS infections upon multivariate analysis. However, when considering the genus/species complex level, only infections due to Candida kefyr -related species [OR=4.01 (2.42-6.64)] and to Trichosporon spp. [OR=5.38 (1.72-16.81)] remained associated with haematological malignancies, those due to the GEOTRICHUM group with acute leukaemia [OR=61.29 (19.23-195.36)], and infections with Trichosporon spp. or the GEOTRICHUM group with prior exposure to caspofungin [OR=15.67 (3.62-67.80) and OR=13.17 (3.33-52.03), respectively] but not to fluconazole. The global mortality at day 30 for UYS was similar to that for C. albicans (35.4%, and 39.9%, respectively), but very divergent results were observed according to the specific UYS.Conclusions:UYS encompass a high diversity of species, each with its own behaviour and predisposing factors for human infections. This variety makes it important to rapidly identify an isolate to the species level in order to optimize antifungal treatment.

Objective.This retrospective study evaluated the role of percutaneous cementoplasty in the treatment of avascular necrosis (AVN) of the hip in order to postpone or avoid total hip replacement.Methods.The study population comprised 40 patients (47 hips) with mean age of 46 ± 4.7 years and mean body mass index of 26.7 ± 4.6 kg/m2. AVN was classified according to the Ficat-Arlet classification as one stage I, 30 stage II, and 16 stage III. The minimum followup was 9 months.Results.It was found that 74.5% of hips were secondarily operated for total hip replacement a mean of 19.9 ± 15 months (median 14 mo) after cementoplasty. As well, 94% of patients with stage 3AVN and 68% with stage 2AVN underwent surgery. Twelve hips were not operated, with a mean followup of 39 ± 19.2 months. Pain decreased by more than 80% after cementoplasty in two-thirds of patients, but the mean pain-free interval was only 8.1 ± 6.6 months (median 5 mo). Nineteen of the 29 working patients were able to transiently return to work. The outcome was more unfavorable with radiological stage III AVN, joint effusion, and/or a double-line sign around the lesions on magnetic resonance images.Conclusion.Despite early relief of pain, the results of the cementoplasty technique were disappointing, with need for arthroplasty surgery in most cases within 2 years. Alternative percutaneous techniques using different filler materials with osteoinductive properties should be evaluated in further studies.

International audience; Since September 1st 2011, the National Bureau for Compensation of Medical Accidents represents a unique portal for out-of-court settlement of litigations concerning the harm caused by benfluorex. In December 2012, its official record is as follows: 7627 patients files have been received, 1378 have been studied, 797 led to a recommendation, and compensation by the drug company Servier has been recommended for 46 cases. The large number of rejections raises a problem which needs to be examined in the light of the available evidence on benfluorex associated heart valve disease. This evidence concerns both the morphological characteristics of the disease and the epidemiology of its association with benfluorex. More than 90% of emergent double valve disease (aortic and mitral regurgitation), of emergent aortic valve regurgitation, and of prevalent grade 2 aortic valve regurgitation are attributable to benfluorex. The proportion of benfluorex-attributable disease is larger than 75% for prevalent double valve disease, or for prevalent aortic valve regurgitation of any grade. This probabilistic information, derived from the available epidemiological studies, needs to be considered as part of the evidence to establish or refute a causal link between benfluorex and valvular disease for a given patient, particularly if the patient has a low grade valvular insufficiency or no morphological anomaly.

International audience; RATIONALE: Measuring the attributable mortality of ventilator-associated pneumonia (VAP) is challenging and prone to different forms of bias. Studies addressing this issue have produced variable and controversial results. OBJECTIVES: We estimate the attributable mortality of VAP in a large multicenter cohort using statistical methods from the field of causal inference. METHODS: Patients (n = 4,479) from the longitudinal prospective (1997-2008) French multicenter Outcomerea database were included if they stayed in the intensive care unit (ICU) for at least 2 days and received mechanical ventilation (MV) within 48 hours after ICU admission. A competing risk survival analysis, treating ICU discharge as a competing risk for ICU mortality, was conducted using a marginal structural modeling approach to adjust for time-varying confounding by disease severity. MEASUREMENTS AND MAIN RESULTS: Six hundred eighty-five (15.3%) patients acquired at least one episode of VAP. We estimated that 4.4% (95% confidence interval, 1.6-7.0%) of the deaths in the ICU on Day 30 and 5.9% (95% confidence interval, 2.5-9.1%) on Day 60 are attributable to VAP. With an observed ICU mortality of 23.3% on Day 30 and 25.6% on Day 60, this corresponds to an ICU mortality attributable to VAP of about 1% on Day 30 and 1.5% on Day 60. CONCLUSIONS: Our study on the attributable mortality of VAP is the first that simultaneously accounts for the time of acquiring VAP, informative loss to follow-up after ICU discharge, and the existence of complex feedback relations between VAP and the evolution of disease severity. In contrast to the majority of previous reports, we detected a relatively limited attributable ICU mortality of VAP.

International audience; The goal of dynamic causal modelling (DCM) of neuroimaging data is to study experimentally induced changes in functional integration among brain regions. This requires (i) biophysically plausible and physiologically interpretable models of neuronal network dynamics that can predict distributed brain responses to experimental stimuli and (ii) efficient statistical methods for parameter estimation and model comparison. These two key components of DCM have been the focus of more than thirty methodological articles since the seminal work of Friston and colleagues published in 2003. In this paper, we provide a critical review of the current state-of-the-art of DCM. We inspect the properties of DCM in relation to the most common neuroimaging modalities (fMRI and EEG/MEG) and the specificity of inference on neural systems that can be made from these data. We then discuss both the plausibility of the underlying biophysical models and the robustness of the statistical inversion techniques. Finally, we discuss potential extensions of the current DCM framework, such as stochastic DCMs, plastic DCMs and field DCMs.

International audience; Mood disorders and sleep disturbances are closely related. In elderly people, the prevalence of insomnia and depressive symptoms is increased. Moreover, somatic co-morbidities associated with aging are known to be risk factors for both insomnia and depression. Assessment of the origin of sleep complaints must consider primary and secondary insomnia, and the existence of associated depression. Causal treatment of insomnia is necessary keeping in consideration that depressive dimension can, afterward, evolve on its own. In presence of intense sleep complaints in inadequacy with somatic examination, and not documented by sleep recordings, depression must be evoked. In patients with a diagnosis of depression, treatment and monitoring of the evolution of insomnia is necessary, because persistent disturbances of sleep are associated with poor prognosis. Concerning the therapeutics, beyond antidepressant treatment and psychotherapy, chronotherapy is a promising, but still not yet evaluated, approach, which presents the advantage to limit the use of psychotropics drugs.

International audience; We reviewed the literature about the usefulness of screening for carotid artery lesions in patients with coronary artery disease (CAD). The use of duplex ultrasonography to detect carotid lesions has a two-fold interest in this situation. First, it enables the detection of severe carotid artery stenosis (CS), a potentially reversible cause of stroke. Stroke is frequent in patients with CAD, accounting for at least in one-fourth of all cardiovascular events during follow-up. The mean prevalence of CS > 60% in patients with CAD is 9%, too low to justify routine carotid screening. However, older age, history of a cerebrovascular event, and peripheral arterial disease are useful factors for focusing screening on a high-risk subset of patients with CAD. Trials assessing the interest of prophylactic carotid surgery in asymptomatic CS of 60% or more found similar benefits in the subset of patients with CAD. Screening for CS in patients undergoing coronary artery bypass grafting is also important because CS is a marker, and sometimes the source, of perioperative stroke. Unfortunately, randomized studies to determine the best strategy in this situation are lacking. Second, while measurement of the carotid intima-media thickness does not provide substantial prognostic information for patients with CAD, the presence of plaque, especially hypoechogenic or echolucent (lipid-rich) plaque, is associated with an unstable or high-risk cardiovascular status. In this situation, specific studies are warranted to compare carotid imaging with biomarkers such as C-reactive protein and stratify the cardiovascular risk.

There appears to be very good epidemiological evidence for a relationship between chlorination by-products, as measured by trihalomethanes (THMs), in drinking water and bladder cancer, but the evidence for other cancers, including colorectal cancer appears to be inconclusive and inconsistent. There appears to be some evidence for a relationship between chlorination by-products, as measured by THMs, and small for gestational age (SGA)/intrauterine growth retardation (IUGR) and preterm delivery, but evidence for other outcomes such as low birth weight (LBW), stillbirth, congenital anomalies and semen quality appears to be inconclusive and inconsistent. The overall aim of the HIWATE study is to investigate potential human health risks (e.g. bladder and colorectal cancer, premature births, SGA, semen quality, stillbirth, congenital anomalies) associated with long-term exposure to low levels of disinfectants (such as chlorine) and DBPs occurring in water for human consumption and use in the food industry. The study will comprise risk–benefit analyses including quantitative assessments of risk associated with microbial contamination of drinking water versus chemical risk and will compare alternative treatment options. The outcome will be improved risk assessment and better information for risk management. The work is divided into different topics (exposure assessment, epidemiology, risk assessment and management) and studies.

Background and Purpose— High blood pressure (BP) is present in ≈80% of patients with acute ischemic stroke and is independently associated with poor outcome. There are few data examining the relationship between admission BP and acute CT findings. Methods— TAIST was a randomized controlled trial assessing 10 days of treatment with tinzaparin versus aspirin in 1489 patients with acute ischemic stroke ( Results— Higher systolic BP (SBP) was associated with abnormal CT scans because of independent associations with chronic changes of leukoariosis (OR, 1.12; 95% CI, 1.05–1.17) and old infarction (OR, 1.12; 95% CI, 1.06–1.17) at baseline, and signs of visible infarction at day 10 (OR, 1.06; 95% CI, 1.00–1.13). A lower SBP was associated with signs of acute infarction (OR, 0.94; 95% CI, 0.89–0.99). Hemorrhagic transformation, dense middle cerebral artery sign, mass effect, and cerebral edema at day 10 were not independently associated with baseline BP. Conclusion— Although high baseline BP is independently associated with a poor outcome after stroke, this was not shown to be through an association with increased hemorrhagic transformation, cerebral edema, or mass effect; trial design may be suboptimal to detect this. Higher SBP is associated with visible infarction on day 10 scans. The influence of changing BP in acute stroke on CT findings is still to be ascertained.

International audience; Despite the increasing attention to the relationship between asthma and work exposures, occupational asthma remains underrecognized and its population burden underestimated. This may be due, in part, to the fact that traditional approaches to studying asthma in populations cannot adequately take into account the healthy worker effect (HWE). The HWE is the potential bias caused by the phenomenon that sicker individuals may choose work environments in which exposures are low; they may be excluded from being hired; or once hired, they may seek transfer to less exposed jobs or leave work. This article demonstrates that population- and workplace-based asthma studies are particularly subject to HWE bias, which leads to underestimates of relative risks. Our objective is to describe the HWE as it relates to asthma research, and to discuss the significance of taking HWE bias into account in designing and interpreting asthma studies. We also discuss the importance of understanding HWE bias for public health practitioners and for clinicians. Finally, we emphasize the timeliness of this review in light of the many longitudinal "child to young adult" asthma cohort studies currently underway. These prospective studies will soon provide an ideal opportunity to examine the impact of early workplace environments on asthma in young adults. We urge occupational and childhood asthma epidemiologists collaborate to ensure that this opportunity is not lost.

International audience; The putative association between pesticide exposures and Parkinson's disease (PD) remains controversial. We identified all subjects who developed PD in Olmsted County, Minnesota, from 1976 through 1995, and matched them by age (+/- 1 year) and sex to general population controls. We assessed exposures to chemical products by means of telephone interview with cases, controls, or their proxies (149 cases; 129 controls). Exposure to pesticides related or unrelated to farming was associated with PD in men (odds ratio, 2.4; 95% confidence interval, 1.1-5.4; P = 0.04). The association remained significant after adjustment for education or smoking. Analyses for the other six categories of industrial and household chemicals were all nonsignificant. This population-based study suggests a link between pesticides use and PD that is restricted to men. Pesticides may interact with other genetic or nongenetic factors that are different in men and women.

International audience; OBJECTIVE: We sought to study the association between occupational sun exposure and mycosis fungoides (MF), a peripheral T-cell lymphoma. SUBJECTS AND METHODS: A European multicenter case-control study including seven rare cases (one being MF) was conducted between 1995 and 1997. From the 118 accepted cases, 104 were interviewed, of which 76 were definite cases. Population controls were selected randomly from the regions of case ascertainment. Information based on occupational experiences was coded according to industry types. A job exposure matrix was created according to the expected exposure to sunlight. RESULTS: Once exposures to aromatic halogenated hydrocarbons were eliminated (odds ratio = 2.3; 95% confidence interval = 0.9-6.2), a high MF risk was associated with exposures to solar radiation. CONCLUSION: It would appear that workers exposed to sunlight have a higher risk of MF. However, this factor is not the only one involved.

Epilepsy and onchocerciasis (river blindness) constitute serious public health problems in several tropical countries. There are four main mechanisms that might explain a relationship between these two diseases: (i) the presence of Onchocerca volvulus in the central nervous system; (ii) the pathogenicity of various O. volvulus strains; (iii) immunological mechanisms involving cross-reactive immunization or cytokine production during infection; and (iv) the triggering role of insomnia due to itching.

International audience; OBJECTIVE: To assess intermittent pneumatic compression (IPC) in the prevention of venous thromboembolism (VTE). METHODS: The authors randomly allocated patients with a documented intracerebral hemorrhage (ICH) to elastic stockings (ES) alone or combined with IPC. The primary outcome was a combined criteria assessed at day 10: a symptomatic and well-documented VTE, or a death arising before day 10 and related to pulmonary embolism (PE), or an asymptomatic deep vein thrombosis (DVT) of the lower limbs detected by compression ultrasonography (CUS). Outcome assessment was blinded. RESULTS: One hundred fifty-one patients were randomized; 133 (88%) patients were evaluated at day 10. No clinical suspicion of VTE arose before day 10. Fourteen patients died before having a CUS but no death was definitely related to PE. Fourteen asymptomatic DVT were detected by CUS: three (4.7%) in the ES + IPC group (all distal) and 11 (15.9%) in the ES group (three proximal and eight distal). ES combined with IPC is associated with a reduced risk of asymptomatic DVT compared to ES alone: relative risk, 0.29 (95% CI 0.08 to 1.00). CONCLUSIONS: Asymptomatic deep vein thrombosis (DVT) was detected at day 10 in 15.9% of patients wearing elastic stockings alone. Intermittent pneumatic compression significantly decreased the occurrence of asymptomatic DVT for patients with intracerebral hemorrhage.

International audience; OBJECTIVE: To examine the association of plasma cholesterol levels, lipid-lowering agent (LLA) intake, and APOE genotype with dementia prevalence. METHODS: The Three-City Study is a population-based cohort of 9,294 subjects selected from the electoral rolls of three French cities (Bordeaux, Dijon, Montpellier). Baseline examination included extensive assessment of exposure to vascular risk factors (including cholesterol levels and LLA use [statin or fibrate]) and clinical diagnosis of dementia. RESULTS: Two percent of participants were demented at baseline. Overall 32.4% of participants had hyperlipidemia, and 15.6% were prescribed statins and 13.7% fibrates. After adjusting for age, gender, education level, and study center, the odds ratio (OR) for dementia was observed to be lower among LLA users (OR = 0.61, 95% CI = 0.41 to 0.91) compared with subjects taking no LLAs. There was no differential effect between statin and fibrate users. The odds for dementia were increased in subjects with hyperlipidemia (OR = 1.43, 95% CI = 1.03 to 1.99). Further adjustment for potential confounders did not modify these associations. In addition, the association between LLA intake and dementia was not modified by APOE genotype, whereas hyperlipidemia was significantly associated with increased dementia prevalence only in non-epsilon4 carriers and non-Alzheimer disease cases. Finally, in participants taking LLAs, the odds for dementia were decreased only in those having normal lipid levels. CONCLUSIONS: This observational study provides further evidence that lipid-lowering agents are associated with decreased risk of dementia, whereas hyperlipidemia is associated with increased odds for non-Alzheimer-disease-type dementia. These effects appear to be independent of all major potential confounders.

Item does not contain fulltext Work in the asphalt industry has been associated with nonmalignant respiratory morbidity and mortality, but the evidence is not consistent. A historical cohort of asphalt workers included 58,862 men (911,209 person-years) first employed between 1913 and 1999 in companies applying and mixing asphalt in Denmark, Finland, France, Germany, Israel, the Netherlands, and Norway. The relations between mortality from nonmalignant respiratory diseases (including the obstructive lung diseases: chronic bronchitis, emphysema, and asthma) and specific chemical agents and mixtures were evaluated using a study-specific exposure matrix. Mortality from obstructive lung diseases was associated with the estimated cumulative and average exposures to polycyclic aromatic hydrocarbons and coal tar (p values of the test for linear trend = 0.06 and 0.01, respectively). The positive association between bitumen fume exposure and mortality from obstructive lung diseases was weak and not statistically significant; confounding by simultaneous exposure to coal tar could not be excluded. The authors lacked data on smoking and full occupational histories. In conclusion, exposures to polycyclic aromatic hydrocarbons, originating from coal tar and possibly from bitumen fume, may have contributed to mortality from obstructive lung diseases among asphalt workers, but confounding and bias cannot be ruled out as an explanation for the observed associations.

International audience; no abstract

International audience; In this study, the health-related selection hypothesis (that health predicts social mobility) and the social causation hypothesis (that socioeconomic status influences health) were tested in relation to cardiometabolic factors. The authors screened 8,312 United Kingdom men and women 3 times over 10 years between 1991 and 2004 for waist circumference, body mass index, systolic and diastolic blood pressure, fasting glucose, fasting insulin, serum lipids, C-reactive protein, and interleukin-6; identified participants with the metabolic syndrome; and measured childhood health retrospectively. Health-related selection was examined in 2 ways: 1) childhood health problems as predictors of adult occupational position and 2) adult cardiometabolic factors as predictors of subsequent promotion at work. Social causation was assessed using adult occupational position as a predictor of subsequent change in cardiometabolic factors. Hospitalization during childhood and lower birth weight were associated with lower occupational position (both P's ≤ 0.002). Cardiometabolic factors in adulthood did not consistently predict promotion. In contrast, lower adult occupational position predicted adverse changes in several cardiometabolic factors (waist circumference, body mass index, fasting glucose, and fasting insulin) and an increased risk of new-onset metabolic syndrome (all P's ≤ 0.008). These findings suggest that health-related selection operates at younger ages and that social causation contributes to socioeconomic differences in cardiometabolic health in midlife.