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Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20–1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01–1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59–0.67) to 0.65 (95% CI, 0.62–0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=−4.82×10 −3 per year [95% CI, −6.49×10 −3 to −3.14×10 −3 ]; P =1.82×10 −8 ), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86–0.98]; P =0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.

International audience; The healthcare burden of cardiovascular diseases remains a major issue worldwide. Understanding the underlying mechanisms and improving identification of people with a higher risk profile of systemic vascular disease through noninvasive examinations is crucial. In ophthalmology, retinal vascular network imaging is simple and noninvasive and can provide in vivo information of the microstructure and vascular health. For more than 10 years, different research teams have been working on developing software to enable automatic analysis of the retinal vascular network from different imaging techniques (retinal fundus photographs, OCT angiography, adaptive optics, etc.) and to provide a description of the geometric characteristics of its arterial and venous components. Thus, the structure of retinal vessels could be considered a witness of the systemic vascular status. A new approach called "oculomics" using retinal image datasets and artificial intelligence algorithms recently increased the interest in retinal microvascular biomarkers. Despite the large volume of associated research, the role of retinal biomarkers in the screening, monitoring, or prediction of systemic vascular disease remains uncertain. A PubMed search was conducted until August 2022 and yielded relevant peer-reviewed articles based on a set of inclusion criteria. This literature review is intended to summarize the state of the art in oculomics and cardiovascular disease research.

International audience; AIM: Drug shortage is a growing global health issue. The aim of the study was to evaluate the consequences of drug shortages on patient safety based on data recorded in the French Pharmacovigilance Database. METHODS: All cases involving drug shortages reported from 1985 to the end of 2019 were extracted from the database. RESULTS: Following the selection process, 462 cases were included. The number of cases increased significantly from 2004 to 2019. Cases mainly involved drugs from the nervous system (22.1%, CI95[17.5;27.0]), the cardiovascular system (16.4%, CI95[11.9;21.4]), and anti-infectives for systemic use (14.3%, CI95[9.7;19.2]) ATC classes. Most of the cases reported an adverse drug reaction (ADR) belonging to the SOC nervous system (21%, CI95[18;24]), skin and subcutaneous (14%, CI95[11;17]), general (13%, CI95[10;17]), and gastrointestinal (8%, CI95[5;11]) disorders. Disease worsening was observed in 15.9% of the cases, mostly related to a lack of efficacy of the replacement drug. Half of the cases were considered as serious. Evolution was favourable in 79.4% of the cases. Death and/or life-threatening situations were reported in 5.8% of the cases. Medication errors (ME) were identified in 51 cases (11%), mostly occurring at the administration step and involving a human factor. CONCLUSION: This study emphasises the clinical impact of drug shortage in terms of ADRs, ME and inefficiency. These observations underline the importance of a global health policy programme to limit the occurrence of drug shortages and to reinforce the information provided to patients and health care professionals in this context to limit risk.

International audience; We present the phenotypes of seven previously unreported patients with Marbach-Schaaf neurodevelopmental syndrome, all carrying the same recurrent heterozygous missense variant c.1003C>T (p.Arg335Trp) in PRKAR1B. Clinical features of this cohort include global developmental delay and reduced sensitivity to pain, as well as behavioral anomalies. Only one of the seven patients reported here was formally diagnosed with autism spectrum disorder (ASD), while ASD-like features were described in others, overall indicating a lower prevalence of ASD in Marbach-Schaaf neurodevelopmental syndrome than previously assumed. The clinical spectrum of the current cohort is similar to that reported in the initial publication, delineating a complex developmental disorder with behavioral and neurologic features. PRKAR1B encodes the regulatory subunit R1beta of the protein kinase A complex (PKA), and is expressed in the adult and embryonal central nervous system in humans. PKA is crucial to a plethora of cellular signaling pathways, and its composition of different regulatory and catalytic subunits is cell-type specific. We discuss potential molecular disease mechanisms underlying the patients' phenotypes with respect to the different known functions of PKA in neurons, and the phenotypes of existing R1beta-deficient animal models.

International audience; In health cohort studies, repeated measures of markers are often used to describe the natural history of a disease. Joint models allow to study their evolution by taking into account the possible informative dropout usually due to clinical events. However, joint modeling developments mostly focused on continuous Gaussian markers while, in an increasing number of studies, the actual quantity of interest is non-directly measurable; it constitutes a latent variable evaluated by a set of observed indicators from questionnaires or measurement scales. Classical examples include anxiety, fatigue, cognition. In this work, we explain how joint models can be extended to the framework of a latent quantity measured over time by indicators of different nature (e.g. continuous, binary, ordinal). The longitudinal submodel describes the evolution over time of the quantity of interest defined as a latent process in a structural mixed model, and links the latent process to each observation of the indicators through appropriate measurement models. Simultaneously, the risk of multi-cause event is modelled via a proportional cause-specific hazard model that includes a function of the mixed model elements as linear predictor to take into account the association between the latent process and the risk of event. Estimation, carried out in the maximum likelihood framework and implemented in the R-package JLPM, has been validated by simulations. The methodology is illustrated in the French cohort on Multiple-System Atrophy (MSA), a rare and fatal neurodegenerative disease, with the study of dysphagia progression over time stopped by the occurrence of death.

International audience; OBJECTIVE: To identify and critically appraise risk prediction models for living donor solid organ transplant counselling.STUDY DESIGN AND SETTING: We systematically reviewed articles describing the development or validation of prognostic risk prediction models about living donor solid organ (kidney and liver) transplantation indexed in Medline until April 4(th) 2021. Models were eligible if intended to predict, at transplant counselling, any outcome occurring after transplantation or donation in recipients or donors. Duplicate study selection, data extraction, assessment for risk of bias and quality of reporting was done using the CHARMS checklist, PRISMA recommendations, PROBAST tool, and TRIPOD Statement.RESULTS: We screened 4691 titles and included 49 studies describing 68 models (35 kidney, 33 liver transplantation). We identified 49 new risk prediction models and 19 external validations of existing models. Most models predicted recipients outcomes (n=38, 75%), e.g., kidney graft loss (29%), or mortality of liver transplant recipients (55%). Many new models (n= 46, 94%) and external validations (n=17, 89%) had a high risk of bias because of methodological weaknesses. The quality of reporting was generally poor.CONCLUSION: We advise against applying poorly developed, reported or validated prediction models. Future studies could validate or update the few identified methodologically appropriate models.

International audience; OBJECTIVES: To describe the investigation, follow-up, management and outcomes in a cohort of chronic kidney disease and kidney transplant recipients exposed to a case of pulmonary tuberculosis. METHODS: Contacts were investigated following a concentric circles approach and followed-up according to their level of priority. In those with an evidence of latent tuberculous infection, treatment decision was based on the level of exposure, individual vulnerability, as well as the results of an interferon-gamma release assay. RESULTS: 130 patients with chronic kidney disease and 180 kidney transplant recipients were identified as contacts and followed-up over a two-year period.Only few vulnerable high-priority contacts received an anti-tuberculosis treatment, including the 2 (100%)highly exposed patients in circle 1, 11/78(14.1%)chronic kidney disease patients and 4/142 (2.8%) kidney transplant recipients in circle 2, and10/52 (19.2%) chronic kidney disease patients and 2/36 (5.6%) kidney transplant recipients in circle 3;all having a positive interferon-gamma release assay result. No incident case of tuberculosis disease occurred. CONCLUSIONS: These findings suggest that latent tuberculosis treatment, as recommended in European guidelines, might be reasonably avoided in vulnerable high-priority contacts of circle 2 with a negative interferon-gamma release assay in countries with low prevalence of tuberculosis.

International audience; IntroductionSocioeconomic status (SES) is recognized as an important determinant of kidney health. We aimed to evaluate the association of social deprivation with different indicators at kidney replacement therapy (KRT) initiation in the French pediatric metropolitan population.MethodsAll patients with end-stage kidney disease (ESKD) who started KRT before 20 years old in France between 2002 and 2015 were included. We investigated different indicators at KRT initiation, which are as follows: KRT modality (dialysis vs. pre-emptive transplantation), late referral to a nephrologist, and dialysis modality (hemodialysis [HD] vs. peritoneal dialysis [PD], urgent vs. planned start of dialysis, use of catheter vs. use of fistula for HD vascular access). An ecological index (European Deprivation Index [EDI]) was used as a proxy for social deprivation.ResultsA total of 1115 patients were included (males 59%, median age at dialysis 14.4 years, glomerular/vascular diseases 36.8%). The most deprived group represented 38.7% of the patients, suggesting pediatric patients with ESKD come from a more socially deprived background. The most deprived group was more likely to initiate KRT with dialysis versus kidney transplantation. Among patients on HD, the odds of starting treatment in emergency with a catheter was >2-fold higher for the most deprived compared with the least deprived children (adjusted odds ratio [aOR] 2.35, 95% CI 1.16–4.78).ConclusionChildren from the most deprived area have lower access to pre-emptive transplantation, have lower access to PD, tend to be late referred to a nephrologist, and have more urgent initiation of HD with a catheter.

International audience; PURPOSE: This study aimed to investigate the genetic cause of food-dependent Cushing syndrome (FDCS) observed in patients with primary bilateral macronodular adrenal hyperplasia (PBMAH) and adrenal ectopic expression of the glucose-dependent insulinotropic polypeptide receptor. Germline ARMC5 alterations have been reported in about 25% of PBMAH index cases but are absent in patients with FDCS. METHODS: A multiomics analysis of PBMAH tissues from 36 patients treated by adrenalectomy was performed (RNA sequencing, single-nucleotide variant array, methylome, miRNome, exome sequencing). RESULTS: The integrative analysis revealed 3 molecular groups with different clinical features, namely G1, comprising 16 patients with ARMC5 inactivating variants; G2, comprising 6 patients with FDCS with glucose-dependent insulinotropic polypeptide receptor ectopic expression; and G3, comprising 14 patients with a less severe phenotype. Exome sequencing revealed germline truncating variants of KDM1A in 5 G2 patients, constantly associated with a somatic loss of the KDM1A wild-type allele on 1p, leading to a loss of KDM1A expression both at messenger RNA and protein levels (P = 1.2 × 10(-12) and P < .01, respectively). Subsequently, KDM1A pathogenic variants were identified in 4 of 4 additional index cases with FDCS. CONCLUSION: KDM1A inactivation explains about 90% of FDCS PBMAH. Genetic screening for ARMC5 and KDM1A can now be offered for most PBMAH operated patients and their families, opening the way to earlier diagnosis and improved management.

International audience; Numerous studies demonstrate parallels between CVD, type 2 diabetes mellitus (T2DM) and COVID-19 pathology, which accentuate pre-existing complications in patients infected with COVID-19 and potentially exacerbate the infection course. Antidiabetic drugs such as sodium-glucose transporter-2 (SGLT-2) inhibitors have garnered substantial attention recently due to their efficacy in reducing the severity of cardiorenal disease. The effect of SGLT-2 inhibitors in patients with COVID-19 remains unclear particularly since SGLT-2 inhibitors contribute to altering the RAAS cascade activity, which includes ACE-2, the major cell entry receptor for SARS-CoV2. A study, DARE-19, was carried out to unveil the effects of SGLT-2 inhibitor treatment on comorbid disease complications and concomitant COVID-19 outcomes and demonstrated no statistical significance. However, the need for further studies is essential to provide conclusive clinical findings.

International audience; α-synucleinopathies, encompassing Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are devastating neurodegenerative diseases for which available therapeutic options are scarce, mostly because of our limited understanding of their pathophysiology. Although these pathologies are attributed to an intracellular accumulation of the α-synuclein protein in the nervous system with subsequent neuronal loss, the trigger(s) of this accumulation is/are not clearly identified. Among the existing hypotheses, interest in the hypothesis advocating the involvement of infectious agents in the onset of these diseases is renewed. In this article, we aimed to review the ongoing relevant factors favoring and opposing this hypothesis, focusing on (1) the potential antimicrobial role of α-synuclein, (2) potential entry points of pathogens in regard to early symptoms of diverse α-synucleinopathies, (3) pre-existing literature reviews assessing potential associations between infectious agents and Parkinson's disease, (4) original studies assessing these associations for dementia with Lewy bodies and multiple system atrophy (identified through a systematic literature review), and finally (5) potential susceptibility factors modulating the effects of infectious agents on the nervous system. © 2022 International Parkinson and Movement Disorder Society.

International audience; Longitudinal observational cohort studies are being conducted worldwide to understand cognition, biomarkers, and the health of the aging population better. Cross-cohort comparisons and networks of registries in Alzheimer's disease (AD) foster scientific exchange, generate insights, and contribute to the evolving clinical science in AD. A scientific working group was convened with invited investigators from established cohort studies in AD, in order to form a research collaboration network as a resource to address important research questions. The Connecting Cohorts to Diminish Alzheimer's Disease (CONCORD-AD) collaboration network was created to bring together global resources and expertise, to generate insights and improve understanding of the natural history of AD, to inform design of clinical trials in all disease stages, and to plan for optimal patient access to disease-modifying therapies once they become available. The network brings together expertise and data insights from 7 cohorts across Australia, Europe, and North America. Notably, the network includes populations recruited through memory clinics as well as population-based cohorts, representing observations from individuals across the AD spectrum. This report aims to introduce the CONCORD-AD network, providing an overview of the cohorts involved, reporting the common assessments used, and describing the key characteristics of the cohort populations. Cohort study designs and baseline population characteristics are compared, and available cognitive, functional, and neuropsychiatric symptom data, as well as the frequency of biomarker assessments, are summarized. Finally, the challenges and opportunities of cross-cohort studies in AD are discussed.

SNPs associated with human stroke risk have been identified in the intergenic region between Forkhead family transcription factors FOXF2 and FOXQ1 , but we lack a mechanism for the association. FoxF2 is expressed in vascular mural pericytes and is important for maintaining pericyte number and stabilizing small vessels in zebrafish. The stroke-associated SNPs are located in a previously unknown transcriptional enhancer for FOXF2 , functional in human cells and zebrafish. We identify critical enhancer regions for FOXF2 gene expression, including binding sites occupied by transcription factors ETS1, RBPJ, and CTCF. rs74564934, a stroke-associated SNP adjacent to the ETS1 binding site, decreases enhancer function, as does mutation of RPBJ sites. rs74564934 is significantly associated with the increased risk of any stroke, ischemic stroke, small vessel stroke, and elevated white matter hyperintensity burden in humans. Foxf2 has a conserved function cross-species and is expressed in vascular mural pericytes of the vessel wall. Thus, stroke-associated SNPs modulate enhancer activity and expression of a regulator of vascular stabilization, FOXF2 , thereby modulating stroke risk.

International audience; BACKGROUND: The excess mortality observed in Acute Myeloblastic Leukaemia (AML) patients, partly attributed to unequal access to curative treatments, could be linked to care pathways. METHODS: We included 1039 AML incident cases diagnosed between 2012-2016 from the 3 French blood cancer registries (3,625,400 inhabitants). We describe patients according to age, the medical entry unit and access to the specialised haematology unit (SHU) during follow-up. Multivariate logistic regression model was done to determine the association between covariables and access to SHU. A total of 713 patients (69%) had access to SHU during care. RESULTS: The most common care pathway concerned referral from the general practitioner to SHU, n = 459(44%). The univariate analysis observed a downward trend for the most deprived patients. Patients who consulted in SHU were younger (66 years vs. 83, p

International audience; Objectives : The co-occurrence of multiple medical or psychosocial conditions (geriatric syndromes (GS) and age-related diseases) is a growing concern in older people. Given the diversity of these conditions and their complex interactions, our aim was to determine whether they could be structured into synthetic dimensions in order to facilitate the management of multimorbidity.Design : The underlying structure of 10 GSs and 8 age-related diseases was identified using a multiple correspondence analysis (MCA), and confronted to subjective and objective health outcomes.Setting : Community residents from Bordeaux City (France) older than 75 years in 2010Participants : 630 adults aged 75+ years who lived in Bordeaux and participated in the 10-year follow-up of the Three-City study.Measurements : GSs included physical frailty, cognitive impairment and dementia, dependency, depressive symptoms, polymedication, thinness, falls, sensory deficit, social isolation, incontinence. Age-related diseases were cancer, cardiac diseases, peripheral vascular diseases, diabetes, hypertension, pulmonary diseases, osteoporosis, other chronic diseases. Association of the MCA-derived independent dimensions was assessed with 10-year visit subjective health and well-being, and with incident death and entry into institution during the remaining cohort follow-up.Results : Most of the participants (82%) had at least two age-related syndromes or diseases. The MCA structured the 18 conditions into three major dimensions: Degradation (D) driven by GS, Vascular (V), and Psychosocial (P) representing 68.7%, 7.4%, and 5.7% of the total variance, respectively. Dimension D was a strong predictor of future death and institutionalization. Dimensions D and P were strongly associated with current well-being.Conclusions : This work confirmed that multimorbidity is very common among older adults, and demonstrated the essential role of GS as manifestations of aging, even more than age-related diseases.

ObjectiveSince the beginning of COVID-19 pandemic, several studies have shown an increase of psychological distress in the general population. Previous research demonstrated that high levels of anxiety are associated with reporting more somatic symptoms. The ability to adaptively regulate emotions is essential to deal with stressful situations, and it is one of the main components of mindfulness practice. The aim of the present study was to document the effect of mindfulness practice on somatic symptoms and psychological distress in the context of COVID-19 pandemic.MethodsThe study has a descriptive cross-sectional design. During the second wave of COVID-19 pandemic, between November 2020 and January 2021 participants living in France responded to an online survey on the impact of COVID-19 on psychological distress and physical health. The questionnaire included the assessment of COVID-19-related anxiety, mindfulness practice and experience, dispositional mindfulness, somatization, depression, generalized anxiety, and emotion regulation.ResultsA total of 569 people (mean age = 39.8 years, 90% women) were included in the study. COVID-19 related anxiety was associated with higher levels of somatic symptoms, generalized anxiety, and depression. About half of the sample (n = 318, 56%) reported moderate to severe somatic symptoms that were associated with higher levels of depression and anxiety, lower levels of dispositional mindfulness and to the use of maladaptive emotion regulation strategies. Overall, 164 subjects (28.8%) reported practicing meditation. No differences were found in dispositional mindfulness (MAAS score) between beginners and advanced practitioners, regardless of the type, years, frequency, and length of practice. Participants with less experience in mindfulness practice reported a significant higher number of somatic symptoms than non-practitioners and a higher use of rumination. Moreover, mindfulness experience was associated with the use of more adaptive emotion regulation strategies.ConclusionMindfulness meditation has been promoted as a practice enhancing well-being and helping to cope with the psychological impact of stressful events. However, in a distressing situation as COVID-19 pandemic, a limited experience in mindfulness practices might result in the development or endurance of somatic symptoms. Adequate training and a focus on mindful acceptance, may contribute to enhance the effectiveness of mindfulness practice.

International audience; Background: In recent years, several blinded randomized controlled trials (RCT) have been conducted on cognitive rehabilitation (CR) in adults with multiple sclerosis (MS). Objective: To review all blinded RCTs on CR in MS published since 2013. Methods: The National Library of Medicine database (Medline) and PSYCINFO were searched using the keywords MS and CR or cognitive training or NP rehabilitation or memory rehabilitation or attention rehabilitation. Results: After the exclusion of some papers not specifically focused on CR, a final list of 26 studies was established. The papers belong to three main categories: individual specific rehabilitation (8studies), group rehabilitation (4 studies), and computerized training (CT) (14 studies), while one study combined group rehabilitation and CT. Among the individual rehabilitation studies, 5 were devoted to memory, and most of the 19 other selected studies were about several cognitive domains. Most of the studies mainly concerned RRMS patients, except for 2 studies that were carried out exclusively in progressive forms. Despite the methodological limitations of some studies and the great heterogeneity of the protocols, the results are generally in favor of the efficacy of CR in neuropsychological tests. Conclusion: Recent blinded RCTs about CR in MS show promising results. © 2021 by the author. Licensee MDPI, Basel, Switzerland.

International audience; Despite considerable improvements in terms of prevention, management, and regulation, air pollution remains a leading environmental health issue worldwide [...].

ObjectiveTo determine the predictive value of the large panel of occupational constraints (OC) on all-cause mortality with a 20-year follow-up, in general population of workers.MethodsIn VISAT prospective cohort study, 3,138 workers (1,605 men; 1,533 women) were recruited during the periodic work health visits conducted by occupational physicians. OC (physical, organizational, psychological and employment categories) were collected through self-questionnaires. Exposure durations of each OC were divided by tertile distribution. Cox-regression models were performed to analyze the associations between all-cause mortality and each OC first separately and simultaneously in a single model.ResultsThe mortality rates were higher among exposed participants to most of OC compared to those unexposed. Being exposed and longer exposure increased the risks of all-cause mortality for exposures to carrying heavy loads, loud noise, working more than 48 h/week, starting its first job before 18 years old although these risks became non-significant after adjustments for cardiovascular risk factors. Shift work and night work confirmed a high risk of mortality whatever the adjustments and notably when the other occupational exposures were taking into account, with, respectively: HR: 1.38 (1.01–1.91) and 1.44 (1.06–1.95). After adjustments being exposed more than 13 years to a work requiring getting-up before 5:00 a.m. and more than 16 years in rotating shift work significantly increased the risk of mortality by one and a half.ConclusionThe links between each OC and all-cause mortality and the role of individual factors were stressed. For night-shift workers, it is urgent to implement preventive strategies at the workplace.

The objective of this study was to determine the relationship between maternal pre-pregnancy body mass index (BMI) and child hyperactivity-inattention symptoms (HIS) at 5 years, including preterm and term-born children, and to determine whether this association varied with gestational age. Maternal pre-pregnancy BMI and offspring HIS were assessed in 10,898 participants born ≥ 33 weeks of gestation from the ELFE cohort and 2646 children born between 23 and 34 weeks from the EPIPAGE 2 cohort. Reported pre-pregnancy weight (kg) and measured height (m) were collected from mothers at inclusion and used to classify BMI (kg/m2). Child HIS were evaluated using the Strengths and Difficulties Questionnaire around 5 years of age. Logistic regression estimated odds ratios (OR) of a high HIS score (≥ 90th percentile) in the ELFE cohort and generalized estimated equations were used in EPIPAGE 2 to account for non-independence of multiple births. As a negative control, paternal BMI was also considered as an exposure of interest in sensitivity analyses. Maternal pre-pregnancy obesity and overweight were associated with child HIS at 5 years in ELFE (adjusted OR [aOR] for obesity 1.27 [1.06, 1.53]; overweight aOR 1.16 [1.00, 1.36]) and pre-pregnancy obesity was associated with high HIS scores in preterm infants of EPIPAGE 2 (aOR 1.48 [1.06, 2.08]). In ELFE, the magnitude of the association increased with decreasing gestational age (interaction p = 0.02). High maternal pre-pregnancy BMI is associated with greater likelihood of high HIS scores in both at-term and preterm children at 5 years of age.

International audience; High-concentration topical capsaicin is used as a second line treatment for neuropathic pain. Transient, mild burning sensation and erythema are expected adverse drug reactions. Here, we report the first case of second degree burn after the application of a high-concentration topical capsaicin patch with secondary mobility sequelae. Nine months after the application, neuropathic pain still remained and the patient described mobility difficulties in daily activities, preventing her from returning to work. This report aims to raise the question of the benefit/risk ratio of high concentration topical capsaicin.

https://theconversation.com/insuffisance-cardiaque-avancee-vers-de-nouvelles-solutions-191606

ObjectivesGiven mixed evidence for carcinogenicity of current-use herbicides, we studied the relationship between occupational herbicide use and risk of non-Hodgkin’s lymphoma (NHL) in a large, pooled study.MethodsWe pooled data from 10 case-control studies participating in the International Lymphoma Epidemiology Consortium, including 9229 cases and 9626 controls from North America, the European Union and Australia. Herbicide use was coded from self-report or by expert assessment in the individual studies, for herbicide groups (eg, phenoxy herbicides) and active ingredients (eg, 2,4-dichlorophenoxyacetic acid (2,4-D), glyphosate). The association between each herbicide and NHL risk was estimated using logistic regression to produce ORs and 95% CIs, with adjustment for sociodemographic factors, farming and other pesticides.ResultsWe found no substantial association of all NHL risk with ever-use of any herbicide (OR=1.10, 95% CI: 0.94 to 1.29), nor with herbicide groups or active ingredients. Elevations in risk were observed for NHL subtypes with longer duration of phenoxy herbicide use, such as for any phenoxy herbicide with multiple myeloma (>25.5 years, OR=1.78, 95% CI: 0.74 to 4.27), 2,4-D with diffuse large B-cell lymphoma (>25.5 years, OR=1.47, 95% CI: 0.67 to 3.21) and other (non-2,4-D) phenoxy herbicides with T-cell lymphoma (>6 years, lagged 10 years, OR=3.24, 95% CI: 1.03 to 10.2). An association between glyphosate and follicular lymphoma (lagged 10 years: OR=1.48, 95% CI: 0.98 to 2.25) was fairly consistent across analyses.ConclusionsMost of the herbicides examined were not associated with NHL risk. However, associations of phenoxy herbicides and glyphosate with particular NHL subtypes underscore the importance of estimating subtype-specific risks.

Background The COVID-19 pandemic has harshly burdened the healthcare systems. Health care workers (HCWs) are at substantial risk of infection and confronted several stressors as well leading them to experience burnout. This study aimed to assess the prevalence of burnout among Lebanese health HCWs and to identify its associated factors. Methods A cross-sectional online survey was conducted between the first of November and the end of December 2020 among Lebanese HCWs working in all active hospitals operating across the country. Data were collected using an Arabic, anonymous, self-reported questionnaire comprising four sections: (a) basic sociodemographic characteristics, (b) exposure to COVID-19 covariates, (c) occupational factors, and (d) the measurements including the Copenhagen Burnout Inventory (CBI). CBI subscale cut-off score of 50 was used to assess the prevalence of burnout among HCWs. Multinomial logistic regression analyses were performed to examine the factors associated with the different aspects of burnout. Results Out of the 1751 respondents, personal burnout (PB) was detected in its moderate and high-level aspects among 86.3% of Lebanese HCWs. Moderate and high levels of work-related burnout (WB), and client-related burnout (CB) hit 79.2% and 83.3% of HCWs, respectively. HCWs who were females, married, physicians, having a poor health status and specific living conditions (dependent child, elderly at home, family member with comorbidities, and a low income) were more likely to exhibit a high level of PB compared to no/low burnout level. Moreover, frontline HCWs, those infected by COVID-19 or those having a colleague infected by COVID-19, and those exhibiting a high perception of threat were more prone to experience a high-level PB rather than a low/no burnout. Working in a public hospital, extensive working hours, and insufficient sleeping hours were also found positively associated with high PB. However, older age and altruism were negatively associated with high PB compared to no/low PB among HCWs. As for WB, similar factors were found either positively or negatively associated with a high level of WB except health status and living conditions factors (dependent child or family member). As for CB, older age of HCWs (> 30 years) and altruism were negatively associated with high CB compared to no/low burnout level. However, working in the frontline, high threat perception, extensive working hours, insufficient sleeping hours, and low income were positively associated with high CB among HCWs compared to no/low burnout. Conclusion The prevalence of burnout among Lebanese HCWs during the pandemic was significant and alarming. Enacting and implementing preventive policies and effective interventions are urgently needed to cultivate wellness among HCWs.

ObjectiveTo assess the impact of changes in use of care and implementation of hospital reorganisations spurred by the COVID-19 pandemic (first wave) on the acute management times of patients who had a stroke and ST-segment elevation myocardial infarction (STEMI).DesignTwo cohorts of patients who had an STEMI and stroke in the Aquitaine Cardio-Neuro-Vascular (CNV) registry.Setting6 emergency medical services, 30 emergency units (EUs), 14 hospitalisation units and 11 cathlabs in the Aquitaine region.ParticipantsThis study involved 9218 patients (6436 patients who had a stroke and 2782 patients who had an STEMI) in the CNV Registry from January 2019 to August 2020.MethodHospital reorganisations, retrieved in a scoping review, were collected from heads of hospital departments. Other data were from the CNV Registry. Associations between reorganisations, use of care and care management times were analysed using multivariate linear regression mixed models. Interaction terms between use-of-care variables and period (pre-wave, per-wave and post-wave) were introduced.Main outcome measuresSTEMI cohort, first medical contact-to-procedure time; stroke cohort, EU admission-to-imaging time.ResultsPer-wave period management times deteriorated for stroke but were maintained for STEMI. Per-wave changes in use of care did not affect STEMI management. No association was found between reorganisations and stroke management times. In the STEMI cohort, the implementation of systematic testing at admission was associated with a 41% increase in care management time (exp=1.409, 95% CI 1.075 to 1.848, p=0.013). Implementation of plan blanc, which concentrated resources in emergency activities, was associated with a 19% decrease in management time (exp=0.801, 95% CI 0.639 to 1.023, p=0.077).ConclusionsThe pandemic did not markedly alter the functioning of the emergency network. Although stroke patient management deteriorated, the resilience of the STEMI pathway was linked to its stronger structuring. Transversal reorganisations, aiming at concentrating resources on emergency care, contributed to maintenance of the quality of care.Trial registration numberNCT04979208.

(1) Background: Three antimicrobial absorbable sutures have different triclosan (TS) loads, triclosan release kinetics and hydrolysis times. This in vitro study aims to analyse and compare their antimicrobial pharmacodynamics. (2) Methods: Time-kill assays were performed with eight triclosan-susceptible microorganisms common in surgical site infections (SSIs) and a segment of each TS. Microbial concentrations were measured at T0, T4, T8 and T24 h. Similar non-triclosan sutures (NTS) were used as controls. Microbial concentrations were plotted and analysed with panel analysis. They were predicted over time with a double-exponential model and four parameters fitted to each TS × microorganism combination. (3) Results: The microbial concentration was associated with the triclosan presence, timeslot and microorganism. It was not associated with the suture material. All combinations shared a common pattern with an early steep concentration reduction from baseline to 4–8 h, followed by a concentration up to a 24-h plateau in most cases with a mild concentration increase. (4) Conclusions: Microorganisms seem to be predominantly killed by contact or near-contact killing with the suture rather than the triclosan concentration in the culture medium. No significant in vitro antimicrobial pharmacodynamic difference between the three TS is identified. Triclosan can reduce the suture microbial colonisation and SSI risk.

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) have been discouraged for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, fearing that they could increase the risk of infection or the severity of SARS-CoV-2. Methods Original studies providing information on exposure to NSAIDs and coronavirus disease 2019 (COVID-19) outcomes were retrieved and were included in a descriptive analysis and a meta-analysis with Cochrane Revue Manager (REVMAN 5.4), using inverse variance odds ratio (OR) with random- or fixed-effects models. Results Of 92,853 papers mentioning COVID-19, 266 mentioned NSAIDs and 61 mentioned ibuprofen; 19 papers had analysable data. Three papers described NSAID exposure and the risk of SARS-CoV-2 positivity, five papers described the risk of hospital admission in positive patients, 10 papers described death, and six papers described severe composite outcomes. Five papers studied exposure to ibuprofen and death. Using random-effects models, there was no excess risk of SARS-CoV-2 positivity (OR 0.86, 95% confidence interval [CI] 0.71–1.05). In SARS-CoV-2-positive patients, exposure to NSAIDs was not associated with excess risk of hospital admission (OR 0.90, 95% CI 0.80–1.17), death (OR 0.88, 95% CI 0.80–0.98), or severe outcomes (OR 1.14, 95% CI 0.90–1.44). With ibuprofen, there was no increased risk of death (OR 0.94, 95% CI 0.78–1.13). Using a fixed-effect model did not modify the results, nor did the sensitivity analyses. Conclusion The theoretical risks of NSAIDs or ibuprofen in SARS-CoV-2 infection are not confirmed by observational data. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-021-01089-5.

CRISPR-Cas9 is a promising technology for gene therapy. However, the ON-target genotoxicity of CRISPR-Cas9 nuclease due to DNA double-strand breaks has received little attention and is probably underestimated. Here we report that genome editing targeting globin genes induces megabase-scale losses of heterozygosity (LOH) from the globin CRISPR-Cas9 cut-site to the telomere (5.2 Mb). In established lines, CRISPR-Cas9 nuclease induces frequent terminal chromosome 11p truncations and rare copy-neutral LOH. In primary hematopoietic progenitor/stem cells, we detect 1.1% of clones (7/648) with acquired megabase LOH induced by CRISPR-Cas9. In-depth analysis by SNP-array reveals the presence of copy-neutral LOH. This leads to 11p15.5 partial uniparental disomy, comprising two Chr11p15.5 imprinting centers (H19/IGF2:IG-DMR/IC1 and KCNQ1OT1:TSS-DMR/IC2) and impacting H19 and IGF2 expression. While this genotoxicity is a safety concern for CRISPR clinical trials, it is also an opportunity to model copy-neutral-LOH for genetic diseases and cancers., CRISPR-Cas9 generates double-strand breaks, which pose a threat to genome integrity. Here the authors show loss of heterozygosity in edited hematopoietic progenitor cells.

International audience; Access to vaccination against a health threat such as that presented by the COVID-19 pandemic is an imperative driven, in principle, by at least three compelling factors: (1) the right to health of all people, irrespective of their status; (2) humanitarian need of undocumented migrants, as well as of others including documented migrants, refugees and displaced people who are sometimes vulnerable and living in precarious situations; and (3) the need to ensure heath security globally and nationally, which in the case of a global pandemic requires operating on the basis that, for vaccination strategies to succeed in fighting a pandemic, the highest possible levels of vaccine uptake are required. Yet some population segments have had limited access to mainstream health systems, both prior to as well as during the COVID-19 pandemic. People with irregular resident status are among those who face extremely high barriers in accessing both preventative and curative health care. This is due to a range of factors that drive exclusion, both on the supply side (e.g., systemic and practical restrictions in service delivery) and the demand side (e.g., in uptake, including due to fears that personal data would be transmitted to immigration authorities). Moreover, undocumented people have often been at increased risk of infection due to their role as "essential workers", including those experiencing higher exposure to the SARS-CoV-2 virus due to frontline occupations while lacking protective equipment. Often, they have also been largely left out of social protection measures granted by governments to their populations during successive lockdowns. This article reviews the factors that serve as supply-side and demand-side barriers to vaccination for undocumented migrants and considers what steps need to be taken to ensure that inclusive approaches operate in practice.

ContextThe COVID-19 pandemic has placed a tremendous stress on healthcare systems and caused reorganization. As the pandemic intensifies, identifying the profile of patients with COVID-19 was primordial in order to predict negative outcomes and organize healthcare resources. Age is associated with COVID-19’s mortality, but for obvious ethical reasons, chronological age cannot be the sole criterion for predicting negative outcomes.ObjectiveThe objective of this study was to determine the relationship between frailty index (FI) and length of hospital stay, and death in a non-COVID population of patients aged 75 years old and above.Methods and designA retrospective, analytical, single-centered observational study was performed in the geriatric short-stay accommodation unit at Guadeloupe University Hospital. For this study, 158 patients who were at least 75 years old were recruited from November 2020 to May 2021. FI was calculated as the number of deficits in a participant divided by the total number of deficits considered (the cut-off of FI is.25 in outpatient). Multivariate logistics regression analyses were conducted to assess the association between frailty and death, and length of stay.ResultsThe average age of the participants was 85.7 ± 6.74 with a range of 75–104. Twenty-four of the patients died during hospitalization. FI was only significantly associated with mortality even after adjustment for age and gender (HR 26.3, 95% CI 1.7–413.4, P = 0.021). The association was stronger in the highest tertile of the FI (age- and gender-adjusted HR 4.6, 95% CI 1.39–15.11, P = 0.01). There was no significant interaction between FI and length of stay.ConclusionOur study shows an association between FI (in terms of age-related deficit accumulation) and mortality in a non-COVID geriatric short-stay unit in Guadeloupe. The FI seems to have a lower capacity to catch events such as length of stay in this very complex population. Further research studies have to be conducted for better understanding and investigation of our findings.

IntroductionAddiction is considered a chronic disease associated with a high rate of relapse as a consequence of the addictive condition. Most of the current therapeutic work focuses on the notion of relapse prevention or avoidance and the control of its determinants. Since only a small portion of patients can access alcohol addiction treatment, it is crucial to find a way to offer new support towards safe consumptions, reductions or cessations. The harm reduction (HR) approach and mental health recovery perspective offers another way to support the patient with alcohol addiction. Vitae is a realist evaluation of the impact, viability and transferability of the IACA! programme, an HR programme based on the principle of psychosocial recovery for people with alcohol use disorders.Methods and analysisThe Vitae study adheres to the theory-driven evaluation framework where the realist evaluation method and contribution analysis are used to explore the effects, mechanisms and influence of context on the outcomes and to develop and adjust an intervention theory. This study is a 12-month, multi-case, longitudinal descriptive pilot study using mixed methods. It is multi-centred, and carried out in 10 addiction treatment or prevention centres. In this study, outcomes are related to the evolution of alcohol use and the beneficiaries trajectory in terms of psychosocial recovery during these 12 months after the start of IACA!. The target number of participants are 100 beneficiaries and 23 professionals.Ethics and disseminationThis research was approved by the Committee for the Protection of Persons Ouest V n°: 21/008-3HPS and was reported to the French National Agency for the Safety of Health Products. All participants will provide consent prior to participation. The results will be reported in international peer-reviewed journals and presented at scientific and public conferences.Trial registration numbersNCT04927455; ID-RCB2020-A03371-38.

International audience; Medication-related osteonecrosis of the jaw (MRONJ) is a complication caused by anti-resorptive agents and anti-angiogenesis drugs. Since we wanted to write a protocol for a randomized clinical trial (RCT), we reviewed the literature for the essential information needed to estimate the size of the active patient population and measure the effects of therapeutics. At the same time, we designed a questionnaire intended for clinicians to collect detailed information about their practices. Twelve essential criteria and seven additional items were identified and compiled from 43 selected articles. Some of these criteria were incorporated in the questionnaire coupled with data on clinical practices. Our review found extensive missing data and a lack of consensus. For example, the success rate often combined MRONJ stages, diseases, and drug treatments. The occurrence date and evaluation methods were not harmonized or quantitative enough. The primary and secondary endpoints, failure definition, and date coupled to bone measurements were not well established. This information is critical for writing a RCT protocol. With this review article, we aim to encourage authors to contribute all their findings in the field to bridge the current knowledge gap and provide a stronger database for the coming years.

Background Patients and caregivers express a desire for accurate prognostic information about time to institutionalization and mortality. Previous studies predicting institutionalization and mortality focused on the dementia stage. However, Alzheimer’s disease (AD) is characterized by a long pre-dementia stage. Therefore, we developed prediction models to predict institutionalization and mortality along the AD continuum of cognitively normal to dementia. Methods This study included SCD/MCI patients (subjective cognitive decline (SCD) or mild cognitive impairment (MCI)) and patients with AD dementia from the Amsterdam Dementia Cohort. We developed internally and externally validated prediction models with biomarkers and without biomarkers, stratified by dementia status. Determinants were selected using backward selection (p Results We included n=1418 SCD/MCI patients (n=123 died, n=74 were institutionalized) and n=1179 patients with AD dementia (n=413 died, n=453 were institutionalized). For both SCD/MCI and dementia stages, the models for institutionalization and mortality included after backward selection clinical characteristics, imaging, and cerebrospinal fluid (CSF) biomarkers. In SCD/MCI, the Harrell’s C-statistics of the models were 0.81 (model without biomarkers: 0.76) for institutionalization and 0.79 (model without biomarker: 0.76) for mortality. In AD-dementia, the Harrell’s C-statistics of the models were 0.68 (model without biomarkers: 0.67) for institutionalization and 0.65 (model without biomarker: 0.65) for mortality. Models based on data from amyloid-positive patients only had similar discrimination. Conclusions We constructed prediction models to predict institutionalization and mortality with good accuracy for SCD/MCI patients and moderate accuracy for patients with AD dementia. The developed prediction models can be used to provide patients and their caregivers with prognostic information on time to institutionalization and mortality along the cognitive continuum of AD.

BackgroundThe success of pharmacotherapies for smoking cessation in real-life remains limited, with a significant number of long-term relapses. Despite first promising results, the duration of the effectiveness of electronic cigarettes is still unknown. Our objective was to assess the duration of the effectiveness of electronic cigarettes on smoking cessation and reduction in daily smokers.MethodsThe databases EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov and PUBMED were consulted until March 23, 2022. We selected only randomized controlled trials with daily adult smokers. The intervention was the nicotinic electronic cigarette vs. non-nicotine electronic cigarette or other validated pharmacotherapies (varenicline, bupropion and nicotine replacement therapy). The minimum duration of the intervention was 3 months, with a follow-up of at least 6 months. Two independent reviewers used the PRISMA guidelines. The primary endpoint was smoking cessation at the end of the intervention and follow-up periods confirmed by a reduction in expired CO < 10 ppm. The reduction was defined as at least 50% of the initial consumption or by a decrease of daily mean cigarette consumption at the end of the intervention and follow-up periods.ResultsAbstinence at the end of the intervention and follow-up periods was significantly higher in the nicotine electronic cigarette group, compared to nicotine replacement therapy (NRT) [respectively: RR: 1.37 (CI 95%: 1.32–2.93) and RR: 1.49 (CI 95%: 1.14–1.95)] and to the non-nicotine electronic cigarette condition [respectively: RR: 1.97 (CI 95%: 1.18–2.68) and RR: 1.66 (CI 95%: 1.01–2.73)]. With regard to smoking reduction, the electronic cigarette with nicotine is significantly more effective than NRT at the end of the intervention and follow-up periods [respectively RR: 1.48 (CI 95%: 1.04–2.10) and RR: 1.47 (CI 95%: 1.18–1.82)] and non-nicotine electronic cigarette in the long term [RR: 1.31 (CI 95%: 1.02–1.68)].ConclusionsThis meta-analysis shows the duration of the effectiveness of the nicotine electronic cigarette vs. non-nicotine electronic cigarette and NRT on smoking cessation and reduction. There are still uncertainties about the risks of its long-term use and its potential role as a gateway into smoking, particularly among young people.

BackgroundThis study aims to test the effectiveness of an awareness-raising model designed based on the theory of planned behaviour regarding helmet use for motorcycle taxi drivers.MethodsThis quasi-experimental study took place in the cities of Parakou (intervention group) and Porto Novo (control group). Over a three-month period, a package of awareness-raising activities, based on the theory of planned behaviour, have been implemented in the intervention area. Data relate to knowledge, attitudes and practices regarding helmet use was collected prospectively before the intervention, at the end, and 6 months later. Stata 15 was used for data analysis. Chi-square or Fisher, Student’s or Kruskal-Wallis tests was carried out. The difference-in-difference method was used to determine the specific effect of the awareness activities.ResultsAfter the intervention, there was an improvement in the total score in both groups compared to baseline. The total score increased by 0.2 (0.06–0.3) in the experimental group when the number of sessions attended increased by one (p = 0.005). The difference-in-difference estimator measured among subjects who attended at least one awareness session, controlling for socio-demographic variables, showed a significantly higher difference in the total score of subjects in the experimental group compared to those in the control group both at the end of the interactive sessions and 6 months later.ConclusionThis model improves the helmet-wearing behaviour of motorbike taxi drivers in the experimental area. It could be adapted and applied to other socio-professional groups and other types of users.

Background In Benin, access to water, sanitation and hygiene (WASH) remains an issue. This study aims to provide an overview of household access to basic WASH services based on nationally representative data. Method Secondary analyses were run using the ‘HOUSEHOLD’ dataset of the fifth Demographic and Health Survey 2017–2018. The dependent variables were household access to individual and combined basic WASH services. The characteristics of the household head and those related to the composition, wealth and environment of the household were independent variables. After a descriptive analysis of all study variables, multivariate logistic regression was performed to identify predictors of outcome variables. Results The study included 14,156 households. Of these, 63.98% (95% CI = 61.63–66.26), 13.28% (95% CI = 12.10–14.57) and 10.11% (95% CI = 9.19–11.11) had access to individual basic water, sanitation and hygiene facilities, respectively. Also, 3% (95% CI = 2.53–3.56) of households had access to combined basic WASH services. Overall, the richest households and few, and those headed by people aged 30 and over, female and with higher levels of education, were the most likely to have access to individual and combined basic WASH services. In addition, disparities based on the department of residence were observed. Conclusion The authors suggest a multifactorial approach that addresses the identified determinants.

(1) Background: Insomnia is the most prevalent sleep disorder worldwide and cognitive behavioral therapy is the front-line treatment. Digital health technologies have a role to play in screening and delivering interventions remotely and without the need for human intervention. The KANOPEE app, which provides a screening and behavioral intervention for insomnia symptoms through an interaction with a virtual agent, showed encouraging results in previous studies during and after the COVID-19 lockdown, but has not yet been evaluated in a controlled study. This study aims at comparing the benefits of KANOPEE, a smartphone application dealing with insomnia complaints, with another application proposing an electronic sleep diary named “My Sleep Diary”. The acceptance and potential benefits of these digital solutions are tested in real-life settings (i.e., without soliciting human medical resources) and in the general population. (2) Methods: Subjects were included if they downloaded one of the apps between December 2020 and October 2021, and were of legal age. Both apps were available on downloading platforms in France. Primary outcome was Insomnia Severity Index (ISI), and secondary outcomes were total sleep time (TST), sleep efficiency (SE) and wake time after sleep onset (WASO). (3) Results: A total of 535 users completed the intervention with KANOPEE and 489 users completed My Sleep Diary, both for 17 days. KANOPEE users improved their ISI score significantly more than sleep diary users (interaction Time*Group: F(2,2002) = 17.3, p < 0.001). Similar results were found for nocturnal sleep parameters (TST) (KANOPEE users gained 48 min of sleep after intervention, while My Sleep Diary users gained only 16 min of sleep), and particularly in the population with moderate to severe initial sleep complaints (F(4,1980) = 8.9, p < 0.001). Other sleep markers (SE and WASO) were significantly improved in the KANOPEE users compared to the sleep diary ones (p < 0.001). (4) Conclusions: KANOPEE provides significantly greater benefits than an electronic sleep diary regarding reduction of insomnia complaints and estimated nocturnal sleep characteristics in a self-selected sample of the general population. Population with the most severe initial ISI score (≥15) benefited the most from the KANOPEE App compared to filling up a simple sleep diary.

International audience; Mobile technology is widely used in healthcare. However, designers and developers in many cases have focused on developing solutions that are often tailored to highly literate people. While the advent of the pandemic has called for people to seek and use Covid-19 related information to adapt their behaviors, it is relatively difficult for low literate to get easily access to health information through digital technologies. In this study, we present a Mobile based Interactive Voice Response service designed particularly for low-literate people which provides validated Covid-19 related health information in local African languages. We conducted a field study, among high school students, through a usability study to assess users' perception. The service received an excellent numerical usability score of 78.75.

BackgroundPathological anxiety is responsible for major functional impairments and resistance to conventional treatments in anxiety disorders (ADs), posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Focal neuromodulation therapies such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) are being developed to treat those disorders.MethodsWe performed a dimensional systematic review and meta-analysis to assess the evidence of the efficacy of TMS, tDCS and DBS in reducing anxiety symptoms across ADs, PTSD and MDD. Reports were identified through systematic searches in PubMed/Medline, Scopus and Cochrane library (inception to November 2020), followed by review according to the PRISMA guidelines. Controlled clinical trials examining the effectiveness of brain stimulation techniques on generic anxiety symptoms in patients with ADs, PTSD or MDD were selected.ResultsNineteen studies (RCTs) met inclusion criteria, which included 589 participants. Overall, focal brain activity modulation interventions were associated with greater reduction of anxiety levels than controls [SMD: −0.56 (95% CI, −0.93 to−0.20, I2 = 77%]. Subgroup analyses revealed positive effects for TMS across disorders, and of focal neuromodulation in generalized anxiety disorder and PTSD. Rates of clinical responses and remission were higher in the active conditions. However, the risk of bias was high in most studies.ConclusionsThere is moderate quality evidence for the efficacy of neuromodulation in treating pathological anxiety.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=233084, identifier: PROSPERO CRD42021233084. It was submitted on January 29th, 2021, and registered on March 1st, 2021. No amendment was made to the recorded protocol. A change was applied for the subgroup analyses based on target brain regions, we added the putative nature (excitatory/inhibitory) of brain activity modulation.

Background: Mental health literacy is a determinant of mental health, which can facilitate early detection of psychological problems and endorse timely access to care. Instruments to measure mental health literacy exist, but not in French. Assessment of mental health literacy in young adults is essential to tailor appropriate educational interventions promoting psychological wellbeing and preventing mental health problems in this vulnerable population. The aim of this study was to validate the French version of the Mental Health Literacy Scale (MHLS-FR) in university students. Methods: A total of 482 students from the University of Bordeaux, France, completed the translated version of the scale. Collected data were used to validate the MHLS-FR through psychometric analyses: descriptive statistics, item distribution, test-retest reliability, exploratory structural equation model, confirmatory factor analysis, Cronbach’s alpha and McDonald’s omega coefficients, and hypothesis testing. Results: The final scale included 26 items covering 6 dimensions. Cronbach’s alpha and McDonald’s omega coefficients were 0.744 and 0.961, respectively. With test-retest, about 50% of items had intraclass correlation coefficients superior to 0.5. Conclusions: The MHLS-FR can be considered as a valid and reliable instrument for measuring mental health literacy in French students.

The risk profiles of post-acute sequelae of COVID-19 (PASC) have not been well characterized in multi-national settings with appropriate controls. We leveraged electronic health record (EHR) data from 277 international hospitals representing 414,602 patients with COVID-19, 2.3 million control patients without COVID-19 in the inpatient and outpatient settings, and over 221 million diagnosis codes to systematically identify new-onset conditions enriched among patients with COVID-19 during the post-acute period. Compared to inpatient controls, inpatient COVID-19 cases were at significant risk for angina pectoris (RR 1.30, 95% CI 1.09–1.55), heart failure (RR 1.22, 95% CI 1.10–1.35), cognitive dysfunctions (RR 1.18, 95% CI 1.07–1.31), and fatigue (RR 1.18, 95% CI 1.07–1.30). Relative to outpatient controls, outpatient COVID-19 cases were at risk for pulmonary embolism (RR 2.10, 95% CI 1.58–2.76), venous embolism (RR 1.34, 95% CI 1.17–1.54), atrial fibrillation (RR 1.30, 95% CI 1.13–1.50), type 2 diabetes (RR 1.26, 95% CI 1.16–1.36) and vitamin D deficiency (RR 1.19, 95% CI 1.09–1.30). Outpatient COVID-19 cases were also at risk for loss of smell and taste (RR 2.42, 95% CI 1.90–3.06), inflammatory neuropathy (RR 1.66, 95% CI 1.21–2.27), and cognitive dysfunction (RR 1.18, 95% CI 1.04–1.33). The incidence of post-acute cardiovascular and pulmonary conditions decreased across time among inpatient cases while the incidence of cardiovascular, digestive, and metabolic conditions increased among outpatient cases. Our study, based on a federated international network, systematically identified robust conditions associated with PASC compared to control groups, underscoring the multifaceted cardiovascular and neurological phenotype profiles of PASC.

International audience; Driven by an increase in the availability of cheap low-cost mobile phones and a jump in the number of telecom subscribers, the African gaming world is booming. Most importantly, it has opened an opportunity for rural communities to have an almost identical mobile phone experience than people living in urban areas. It has also opened an opportunity to leverage this high penetration of mobile devices to design mobile-based applications such as mobile serious games. The latter assists individuals living in these communities to modify, change or shape their behaviors and attitudes desirably. This paper reviews mobile serious games in healthcare education, especially those intended to improve health literacy in rural Africa. The challenges and issues encountered in the design and use of persuasive mobile games as a tool can promote behavior change among people living in the rural African communities.

International audience; OBJECTIVE: Measuring access and preferences to Men who have Sex with Men focused community-based HIV testing sites (MSM-CBTS) in Côte d'Ivoire. DESIGN: A respondent-driven sampling telephone survey. SETTING: National survey conducted in 2018 in Côte d'Ivoire. PARTICIPANTS: 518 MSM aged over 18 years old. PRIMARY AND SECONDARY OUTCOME MEASURES: Knowledge, practices, satisfaction and preferences regarding MSM-CBTS. Factors associated with MSM-CTBS access or knowledge and with HIV testing venue preferences were examined. RESULTS: Only half of the respondents (47%) reported knowing of an MSM-CBTS. Of these, 79% had already attended one. Both knowing of and ever visiting an MSM-CBTS were significantly associated with a higher number of HIV tests performed in the past 12 months and having disclosed sexual orientation to one family member.In terms of preferences, 37% of respondents said they preferred undifferentiated HIV testing sites (ie, 'all patients' HIV testing sites), 34% preferred MSM-CBTS and 29% had no preference.Those who reported being sexually attracted to women, being bisexual and those who did not know an MSM non-governmental organisation were less likely to prefer MSM-CBTS. MSM who preferred undifferentiated HIV testing sites mentioned the lack of discretion and anonymity of community-based sites and the desire to avoid the gaze of others. CONCLUSION: Community-based HIV testing is well suited for MSM who identify as homosexual and those close to the MSM community, while maintaining undifferentiated HIV testing is essential for others. Both types of activities need to be maintained and developed. Healthcare professionals in undifferentiated HIV testing sites need to be properly trained in the non-judgemental reception of MSM.

International audience; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections initiate in the bronchi of the upper respiratory tract and are able to disseminate to the lower respiratory tract, where infections can cause an acute respiratory distress syndrome with a high degree of mortality in elderly patients. We used reconstituted primary bronchial epithelia from adult and child donors to follow the SARS-CoV-2 infection dynamics. We show that, in epithelia from adult donors, infections initiate in multiciliated cells and spread within 24 to 48 h throughout the whole epithelia. Syncytia formed of ciliated and basal cells appeared at the apical side of the epithelia within 3 to 4 d and were released into the apical lumen, where they contributed to the transmittable virus dose. A small number of reconstituted epithelia were intrinsically more resistant to virus infection, limiting virus spread to different degrees. This phenotype was more frequent in epithelia derived from children versus adults and correlated with an accelerated release of type III interferon. Treatment of permissive adult epithelia with exogenous type III interferon restricted infection, while type III interferon gene knockout promoted infection. Furthermore, a transcript analysis revealed that the inflammatory response was specifically attenuated in children. Taken together, our findings suggest that apical syncytia formation is an underappreciated source of virus propagation for tissue or environmental dissemination, whereas a robust type III interferon response such as commonly seen in young donors restricted SARS-CoV-2 infection. Thus, the combination of interferon restriction and attenuated inflammatory response in children might explain the epidemiological observation of age-related susceptibility to COVID-19.

International audience; Although central venous catheter (CVC)-related thrombosis (CRT) is a severe complication of home parenteral nutrition (HPN), the amount and quality of data in the diagnosis and management of CRT remain low. We aimed to describe current practices regarding CVC management in French adult and pediatric HPN centers, with a focus on CVC obstruction and CRT. Current practices regarding CVC management in patients on HPN were collected by an online-based cross-sectional survey sent to expert physicians of French HPN centers. We compared these practices to published guidelines and searched for differences between pediatric and adult HPN centers' practices. Finally, we examined the heterogeneity of practices in both pediatric and adult HPN centers. The survey was completed by 34 centers, including 21 pediatric and 13 adult centers. We found a considerable heterogeneity, especially in the responses of pediatric centers. On some points, the centers' responses differed from the current guidelines. We also found significant differences between practices in adult and pediatric centers. We conclude that the management of CVC and CRT in patients on HPN is a serious and complex situation for which there is significant heterogeneity between HPN centers. These findings highlight the need for more well-designed clinical trials in this field.

Background: Characterizing self- and informant-reported cognitive complaints, as well as awareness of cognitive decline (ACD), is useful for an early diagnosis of Alzheimer’s disease (AD). However, complaints and ACD related to cognitive functions other than memory are poorly studied. Furthermore, it remains unclear which source of information is the most useful to distinguish various groups on the AD spectrum.Methods: Self- and informant-reported complaints were measured with the Everyday Cognition questionnaire (ECog-Subject and ECog-StudyPartner) in four domains (memory, language, visuospatial, and executive). ACD was measured as the subject-informant discrepancy in the four ECog scores. We compared the ECog and ACD scores across cognitive domains between four groups: 71 amyloid-positive individuals with amnestic AD, 191 amnestic mild cognitive impairment (MCI), or 118 cognitively normal (CN), and 211 amyloid-negative CN controls, selected from the ADNI database. Receiver operating characteristic curves analysis was performed to evaluate the accuracy of the ECog and ACD scores in discriminating clinical groups.Results: Self- and informant-reported complaints were generally distributed as follows: memory, language, executive, and visuospatial (from the most severe to the least severe). Both groups of CN participants presented on average more memory and language complaints than their informant. MCI participants showed good agreement with their informants. AD participants presented anosognosia in all domains, but especially for the executive domain. The four ECog-StudyPartner sub-scores allowed excellent discrimination between groups in almost all classifications and performed significantly better than the other two classifiers considered. The ACD was excellent in distinguishing the participants with AD from the two groups of CN participants. The ECog-Subject was the least accurate in discriminating groups in four of the six classifications performed.Conclusion: In research, the study of complaint and anosognosia should not be reduced solely to the memory domain. In clinical practice, non-amnestic complaints could also be linked to Alzheimer’s disease. The presence of an informant also seems necessary given its accuracy as a source of information.

International audience; OBJECTIVE: To determine whether use of glucagon-like peptide 1 (GLP-1) receptor agonists (RA) is associated with increased risk of thyroid cancer. RESEARCH DESIGN AND METHODS: A nested case-control analysis was performed with use of the French national health care insurance system (SNDS) database. Individuals with type 2 diabetes treated with second-line antidiabetes drugs between 2006 and 2018 were included in the cohort. All thyroid cancers were identified through hospital discharge diagnoses and medical procedures between 2014 and 2018. Exposure to GLP-1 RA was measured within the 6 years preceding a 6-month lag-time period and considered as current use and cumulative duration of use based on defined daily dose (≤1, 1 to 3, >3 years). Case subjects were matched with up to 20 control subjects on age, sex, and length of diabetes with the risk-set sampling procedure. Risk of thyroid cancer related to use of GLP-1 RA was estimated with a conditional logistic regression with adjustment for goiter, hypothyroidism, hyperthyroidism, other antidiabetes drugs, and social deprivation index. RESULTS: A total of 2,562 case subjects with thyroid cancers were included in the study and matched with 45,184 control subjects. Use of GLP-1 RA for 1-3 years was associated with increased risk of all thyroid cancer (adjusted hazard ratio [HR] 1.58, 95% CI 1.27-1.95) and medullary thyroid cancer (adjusted HR 1.78, 95% CI 1.04-3.05). CONCLUSIONS: In the current study we found increased risk of all thyroid cancer and medullary thyroid cancer with use of GLP-1 RA, in particular after 1-3 years of treatment. ARTICLE HIGHLIGHTS: Preclinical studies suggest that GLP-1 receptor agonists have specific effects on the thyroid gland, potentially involving the development of thyroid cancer. Studies on this subject produced conflicting results, potentially due to a lack of statistical power. The results of this nationwide population-based study suggest that use of GLP-1 receptor agonists is associated with increased risk of thyroid cancer. The increased risk was higher in the case of 1-3 years of GLP-1 receptor agonist use. Clinicians should be aware of this potential risk in initiating a GLP-1 receptor agonist and carefully monitor exposed patients.

Objectives This work aimed to describe the nutritional status of French older adults (age ≥ 90 years) and studied the association between oral health and nutritional status. Methods A cross-sectional study was carried out in 2014 among the participants of a cohort on cerebral and functional aging in France at their 25-year follow up (the PAQUID cohort). Nutritional status (Mini Nutritional Assessment [MNA]) and oral health status (number of decayed, missing, and filled teeth [DMFT], number of posterior occluding pairs, xerostomia [Xerostomia Inventory], and prosthetic rehabilitation) were recorded at the participants’ living places by two dentists. Univariate and multivariate logistic regressions were used to explore the association between oral health and nutritional status, with adjustments for potential confounders. Odds ratios (OR) were estimated with their 95% confidence interval (CI). Results 87 participants were included in the analyses: 74.7% were females and the mean age was 94.1 years (± 3.0). Malnutrition or risk of malnutrition (MNA p = 0.002) was found to be associated with malnutrition or risk of malnutrition. Conclusion Being at risk of malnutrition was common among people ≥ 90 years old and was associated with xerostomia. NCT04065828.

Objectives During periods such as the COVID-19 crisis, there is a need for responsive public health surveillance indicators in order to monitor both the epidemic growth and potential public health consequences of preventative measures such as lockdown. We assessed whether the automatic classification of the content of calls to emergency medical communication centers could provide relevant and responsive indicators. Methods We retrieved all 796,209 free-text call reports from the emergency medical communication center of the Gironde department, France, between 2018 and 2020. We trained a natural language processing neural network model with a mixed unsupervised/supervised method to classify all reasons for calls in 2020. Validation and parameter adjustment were performed using a sample of 39,907 manually-coded free-text reports. Results The number of daily calls for flu-like symptoms began to increase from February 21, 2020 and reached an unprecedented level by February 28, 2020 and peaked on March 14, 2020, 3 days before lockdown. It was strongly correlated with daily emergency room admissions, with a delay of 14 days. Calls for chest pain and stress and anxiety, peaked 12 days later. Calls for malaises with loss of consciousness, non-voluntary injuries and alcohol intoxications sharply decreased, starting one month before lockdown. No noticeable trends in relation to lockdown was found for other groups of reasons including gastroenteritis and abdominal pain, stroke, suicide and self-harm, pregnancy and delivery problems. Discussion The first wave of the COVID-19 crisis came along with increased levels of stress and anxiety but no increase in alcohol intoxication and violence. As expected, call related to road traffic crashes sharply decreased. The sharp decrease in the number of calls for malaise was more surprising. Conclusion The content of calls to emergency medical communication centers is an efficient epidemiological surveillance data source that provides insights into the societal upheavals induced by a health crisis. The use of an automatic classification system using artificial intelligence makes it possible to free itself from the context that could influence a human coder, especially in a crisis situation. The COVID-19 crisis and/or lockdown induced deep modifications in the population health profile. Supplementary Information The online version contains supplementary material available at 10.1186/s13049-021-00862-w.

Background and Purpose The enzyme α/β‐hydrolase domain containing 6 (ABHD6), a new member of the endocannabinoid system, is a promising therapeutic target against neuronal‐related diseases. However, how ABHD6 activity is regulated is not known. ABHD6 coexists in protein complexes with the brain‐specific carnitine palmitoyltransferase 1C (CPT1C). CPT1C is involved in neuro‐metabolic functions, depending on brain malonyl–CoA levels. Our aim was to study CPT1C–ABHD6 interaction and determine whether CPT1C is a key regulator of ABHD6 activity depending on nutritional status. Experimental Approach Co‐immunoprecipitation and FRET assays were used to explore ABHD6 interaction with CPT1C or modified malonyl–CoA‐insensitive or C‐terminal truncated CPT1C forms. Cannabinoid CB1 receptor‐mediated signalling was investigated by determining cAMP levels. A novel highly sensitive fluorescent method was optimized to measure ABHD6 activity in non‐neuronal and neuronal cells and in brain tissues from wild‐type (WT) and CPT1C–KO mice. Key Results CPT1C interacted with ABHD6 and negatively regulated its hydrolase activity, thereby regulating 2‐AG downstream signalling. Accordingly, brain tissues of CPT1C–KO mice showed increased ABHD6 activity. CPT1C malonyl–CoA sensing was key to the regulatory role on ABHD6 activity and CB1 receptor signalling. Fasting, which attenuates brain malonyl–CoA, significantly increased ABHD6 activity in hypothalamus from WT, but not CPT1C–KO, mice. Conclusions and Implications Our finding that negative regulation of ABHD6 activity, particularly in the hypothalamus, is sensitive to nutritional status throws new light on the characterization and the importance of the proteins involved as potential targets against diseases affecting the CNS., We thank Dr. Gemma Fabriàs and Alexandre García from the Research Unit of BioActive Molecules (Institut de Química Avançada de Catalunya, IQAC) for technical assistance in the analysis of endocannabinoid levels. We also thank Prof. Kenneth Mackie from the Department of Psychological and Brain Sciences, Indiana University Bloomington (USA), for providing ABHD6 antibody for western blotting assays in brain tissue. This work was supported by the Ministerio de Economía, Industria y Competitividad (MINECO), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) (SAF2017‐83813‐C3‐3‐R to N.C. and R.R.‐R.), Joint Bilateral Project Japan‐Spain/AEI (PCI2018‐092997/AEI to R.R.‐R.) and Fundació La Marató de TV3 (Grant 87/C/2016 to N.C.). A.F. and C.R. are recipients of a fellowship from the Agència de Gestió d'Ajuts Universitaris i de la Recerca (AGAUR) in Catalonia.