The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Characteristics of the musculoskeletal symptoms observed among survivors of Ebola virus disease in the Postebogui cohort in Guinea

Objective.: Previous studies show that arthralgia is the most common symptom experienced by Ebola virus disease (EVD) survivors. Nevertheless, specific analyses of rheumatological sequelea are still lacking. Methods.: The Postebogui study is a prospective, multicentre cohort aiming to evaluate the long-term outcomes of EVD survivors infected during the 2014-15 outbreak in Guinea. Of the 216 participants enrolled in the study in October 2015, 44 patients with arthralgia/myalgia underwent a physical examination by a rheumatologist (the Eborheum cohort). Data were collected using a standardized questionnaire. Results.: In the Eborheum cohort, 61% of patients were female, the median age was 31.1 years, and the median time from Ebola Treatment Centre discharge was 8.8 months. Pain manifestation started after Ebola infection in all but one patient. Patients had mainly both mechanical and inflammatory pain (45%) and low back pain (77%). All patients reported pain in at least one peripheral joint. Pain in large joints was more frequently reported than in small joints (73 vs 41%). Oligo- and polyarticular presentations were similar, with symmetrical pain distribution. Furthermore, 36 patients had at least one painful 18-tender point count, most of whom reported extensive pain (n = 19) and symmetrical distribution (91%). Diagnoses were mainly non-specific musculoskeletal disorders (59%) and mechanical back pain (52%). No polyarthritis was observed. We found a higher percentage of depressed patients compared with the remaining Postebogui group (42 vs 11%; P < 0.001). Conclusion.: Results from the study come from the first complete rheumatological examination of a cohort of EVD survivors, nearly 9 months after Ebola Treatment Centre discharge. Importantly, we found that patients with arthralgia/myalgia included in the Eborheum cohort were more likely to experience depression than survivors not reporting these symptoms, highlighting the impact of pain symptoms among survivors

Efficacy of abatacept in systemic lupus erythematosus: a retrospective analysis of 11 patients with refractory disease

International audienceObjective The objective of this study was to assess the safety and efficacy of abatacept in patients with SLE refractory to conventional treatment in routine clinical practice. Methods This retrospective study included 11 SLE patients treated with abatacept for an active and refractory disease. The primary endpoint was the change in SLE Disease Activity Index (SLEDAI) score at six months. Response was defined as a decrease of SLEDAI ≥4 in a patient continuing abatacept. Results Indications of abatacept treatment were articular ( n=8), renal ( n=1) and cutaneous ( n=1) involvement and autoimmune thrombocytopenia ( n=1). Abatacept was discontinued before six months in two patients, because of adverse event ( n=1) and/or lupus flare ( n=2). The median SLEDAI decreased from 6 (2-20) to 4 (0-20) ( p=0.031). Decrease of SLEDAI ≥4 was observed in 6/11 patients (55%) and response to treatment according to the physician's judgement in 8/11 (73%) patients. Improvement of articular involvement was observed in 7/8 (87.5%) patients. Four adverse events were observed in three patients, but no severe infection occurred. Conclusion This study suggests some efficacy of abatacept in patients with refractory disease in routine clinical practice, particularly in the case of articular manifestations, with an acceptable safety profile. These data support conducting new controlled trials of abatacept in SLE patients

Essential competencies in prescribing: A first european cross-sectional study among 895 final-year medical students

International audienceEuropean medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final-year medical students across Europe. In a cross-sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final-year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final-year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed

MACVIA-LR (Fighting Chronic Diseases for Active and Healthy Ageing in Languedoc-Roussillon) : a Success Story of the European Innovation Partnership on Active and Healthy Ageing

The R\ue9gion Languedoc Roussillon is the umbrella organisation for an interconnected and integrated project on active and healthy ageing (AHA). It covers the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA): (A) Prevention and health promotion, (B) Care and cure, (C) and (D) Active and independent living of elderly people. All sub-activities (poly-pharmacy, falls prevention initiative, prevention of frailty, chronic respiratory diseases, chronic diseases with multimorbidities, chronic infectious diseases, active and independent living and disability) have been included in MACVIA-LR which has a strong political commitment and involves all stakeholders (public, private, patients, policy makers) including CARSAT-LR and the Eurobiomed cluster. It is a Reference Site of the EIP on AHA. The framework of MACVIA-LR has the vision that the prevention and management of chronic diseases is essential for the promotion of AHA and for the reduction of handicap. The main objectives of MACVIA-LR are: (i) to develop innovative solutions for a network of Living labs in order to reduce avoidable hospitalisations and loss of autonomy while improving quality of life, (ii) to disseminate the innovation. The three years of MACVIA-LR activities are reported in this paper