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The assessment of mood disorders and addiction linked to the practice of chemsex is of interest given the psychoactive substances used. The aim of this study was to assess risky sexual and addictive behavior to chemsex and related anxiety/depression symptoms in individuals receiving HIV pre-exposure prophylaxis (PrEP). In this cross-sectional study, all adults presenting for PrEP renewal at French sexual health centers were enrolled from January 2018 to March 2019. Participants completed a questionnaire on chemsex (i.e., the use of psychoactive substances before/during sex), including adapted Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) to chemsex addiction (questions of ASSIST were modified to focus on chemsex). Anxiety/depression was assessed with the Hospital Anxiety and Depression Scale. In the last 3 months before enrollment, 39.8% (94/236) of participants reported chemsex. The main psychoactive substances consumed during chemsex were cathinones (74.6%), gamma-hydroxybutyrate (66.3%), and other psychostimulants (60%). The median score of the chemsex-focused ASSIST was 8 [IQR

International audience; Introduction - Sustained high alcohol intake is necessary but not sufficient to produce alcohol-related cirrhosis. Identification of risk factors, apart from lifetime alcohol exposure, would assist in discovery of mechanisms and prediction of risk. Methods - We conducted a multicenter case-control study (GenomALC) comparing 1,293 cases (with alcohol-related cirrhosis, 75.6% male) and 754 controls (with equivalent alcohol exposure but no evidence of liver disease, 73.6% male). Information confirming or excluding cirrhosis, and on alcohol intake and other potential risk factors, was obtained from clinical records and by interview. Case-control differences in risk factors discovered in the GenomALC participants were validated using similar data from 407 cases and 6,573 controls from UK Biobank. Results - The GenomALC case and control groups reported similar lifetime alcohol intake (1,374 vs 1,412 kg). Cases had a higher prevalence of diabetes (20.5% (262/1,288) vs 6.5% (48/734), P = 2.27 × 10) and higher premorbid body mass index (26.37 ± 0.16 kg/m) than controls (24.44 ± 0.18 kg/m, P = 5.77 × 10). Controls were significantly more likely to have been wine drinkers, coffee drinkers, smokers, and cannabis users than cases. Cases reported a higher proportion of parents who died of liver disease than controls (odds ratio 2.25 95% confidence interval 1.55-3.26). Data from UK Biobank confirmed these findings for diabetes, body mass index, proportion of alcohol as wine, and coffee consumption. Discussion - If these relationships are causal, measures such as weight loss, intensive treatment of diabetes or prediabetic states, and coffee consumption should reduce the risk of alcohol-related cirrhosis.

International audience; BACKGROUND and AIMS: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. METHODS: Three cohorts (GenomALC-1: n=1690, GenomALC-2: n=3037, UK Biobank: relevant n=6898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to eight genetic loci identified previously as associated with alcohol-related cirrhosis and three clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC). RESULTS: A combination of three single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated for cirrhosis risk. The odds ratio (OR) and 95% confidence intervals (CI) for the extreme score quintiles (Q1-Q5) of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18;8.60) (GenomALC-1); 2.81 (2.03;3.89) (GenomALC-2); and 3.10 (2.32;4.14) (UK Biobank). Patients with diabetes and high-risk score, compared to those without diabetes and a low-risk score, had ORs increased to 14.7 (7.69;28.1) (GenomALC-1) and 17.1 (11.3;25.7) (UK Biobank). Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76±0.06 versus 0.61±0.02, p=0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption. CONCLUSIONS: A risk score based on three genetic risk variants and diabetes status can provide meaningful risk stratification for cirrhosis in excess drinkers, allowing earlier prevention planning including intensive intervention. LAY SUMMARY: Excessive chronic drinking leads to liver cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. Our study has developed a genetic risk score (GRS) test that can identify patients at high risk and shows that the risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and high GRS. Risk assessment using this test has potential for early and personalised management of this disease in high-risk patients.

International audience; Background and aims - Only a minority of heavy drinkers progress to alcohol-associated cirrhosis (ALC). The aim of this study was to identify common genetic variants that underlie risk for ALC. Approach and results - We analyzed data from 1,128 subjects of European ancestry with ALC and 614 heavy-drinking subjects without known liver disease from Australia, the United States, the United Kingdom, and three countries in Europe. A genome-wide association study (GWAS) was performed, adjusting for principal components and clinical covariates (alcohol use, age, sex, body mass index, and diabetes). We validated our GWAS findings using UK Biobank. We then performed a meta-analysis combining data from our study, the UK Biobank, and a previously published GWAS. Our GWAS found genome-wide significant risk association of rs738409 in patatin-like phospholipase domain containing 3 (PNPLA3) (odds ratio [OR] = 2.19 [G allele], P = 4.93 × 10 ) and rs4607179 near HSD17B13 (OR = 0.57 [C allele], P = 1.09 × 10 ) with ALC. Conditional analysis accounting for the PNPLA3 and HSD17B13 loci identified a protective association at rs374702773 in Fas-associated factor family member 2 (FAF2) (OR = 0.61 [del(T) allele], P = 2.56 × 10 ) for ALC. This association was replicated in the UK Biobank using conditional analysis (OR = 0.79, P = 0.001). Meta-analysis (without conditioning) confirmed genome-wide significance for the identified FAF2 locus as well as PNPLA3 and HSD17B13. Two other previously known loci (SERPINA1 and SUGP1/TM6SF2) were also genome-wide significant in the meta-analysis. GeneOntology pathway analysis identified lipid droplets as the target for several identified genes. In conclusion, our GWAS identified a locus at FAF2 associated with reduced risk of ALC among heavy drinkers. Like the PNPLA3 and HSD17B13 gene products, the FAF2 product has been localized to fat droplets in hepatocytes. Conclusions - Our genetic findings implicate lipid droplets in the biological pathway(s) underlying ALC.

OBJECTIVES To assess the alcohol consumption, tobacco addiction and psychoactive substance use (PSU) of people living with HIV (PLHIV). DESIGN Cross-sectional study in an HIV outpatient unit. METHODS Autoquestionnaire systematically proposed to all patients during their usual clinical care visit during a 6-months period, for alcohol (AUDIT test), tobacco (Short Fagerstrom Test) and PSU (ASSIST V3.0 test). RESULTS Of 1334 distributed questionnaires, 1018 PLHIV responded: 76.8% were men [528 patients were MSM), and the median age was 49 years (interquartile range: 42-46). A prevalence of excessive alcohol drinking was found in 22% [95% confidence interval (CI) 19.5-24.7%] and 44.6% (CI 41.5-47.7%) were current smokers, with high dependence in 29.1% (CI 24.9-33.7%). The prevalence of PSU was 37.8% (CI 34.8-41%) in the past 3 months: cannabis 27.7%, poppers 16.4%, cocaine 8.9%, psychotropic medications 7.1%, gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL) 4.7%, stimulants 3.1%, synthetic cathinones 2.7%, hallucinogens 1.5%. In the past 3 months, PSU was more prevalent in MSM than in non-MSM patients (46 versus 30%, P

TPE can improve the efficacy of addiction medicine, for the benefit of patients and staff. It can help the patient withdraw from addiction, or at least achieve a better quality of life with this chronic condition./ce:para.

Introduction L’objectif de l’enquete etait d’evaluer la prevalence de la consommation de substances psychoactives (SPA) ainsi que la relation entre celles-ci et la prise de risque sexuel des consultants de 11 CDAG-CIDDIST. Methodes Enquete transversale basee sur un questionnaire anonyme auto-administre entre janvier et avril 2014. Resultats Cinq mille trois cent soixante-quatre consultants ont participe (87 %), parmi lesquels 2 754 (51,3 %) ont rapporte l’usage d’une SPA au moins une fois dans leur vie. La consommation de SPA (> 1 fois dans l’annee) etait de 39,6 % (cannabis), 9,6 % (cocaine/ecstasy/amphetamines), 5,8 % (poppers/solvants), et 5,8 % (champignons/ketamine/LSD). Les deux groupes de sujets, consommateurs et non-consommateurs different sur l’âge median (23 ans [IQR25–75 : 19–28] versus 25 ans [IQR25–75 : 21–36], p 1 fois dans l’annee) differe en fonction de l’orientation sexuelle avec une predominance de consommation de cannabis (66 %), cocaine/amphetamine/ecstasy (32 %) et LSD/ketamine/champignons (19 %) pour les FSF et de poppers (28 %), GHB (5 %) et cathinones (3 %) pour les hommes homosexuels. Sur une echelle de 1 a 10, le risque VIH percu median etait de 3 (IQR25–75 : 1–5) pour les consommateurs et de 2 (IQR25–75 : 1–4) pour les non-consommateurs (p – chez les consommateurs reguliers de cocaine, de LSD/ketamine/champignons avec un OR a 2,89 [1,79–4,67] p – chez les consommateurs au moins une fois dans l’annee de cocaine, poppers, LSD/ketamine/champignons, avec un OR a 1,60 [1,21–2,12] p – chez les consommateurs mensuels de cocaine, et reguliers ou mensuels de poppers avec un OR a 2,09 [1,45–3,02] p Discussion Cette etude montre une forte prevalence de l’usage de SPA au sein de cette jeune population. L’association entre consommation de SPA et prise de risque sexuel constitue un comportement a risque d’IST. La prevention doit etre axee sur cette problematique. Investigateurs et centres participants P. Belalbre (CDAG-CIDDIST Carcassonne, France), M. Ferreyra, H. Aumaitre (CDAG-CIDDIST Perpignan, France), J. Verdier (CDAG Perpignan, France), I. Brosson (CDAG-CIDDIST Nimes, France), V. Tribout (CDAG-CIDDIST Montpellier, France), J.M. Jacquet (CDAG Sete, France), D. Bastide (CDAG-CIDDIST Ales, France), J. Crouzet, T. Fraisse, (CDAG Bagnols-sur-Ceze, France), N. Morla (CDAG-CIDDIST Narbonne, France), M. Favre (CDAG-CIDDIST Beziers, France), D. Ruiz (CDAG Mende, France).

International audience; Purpose A higher prevalence of cardiovascular risk factors (CRFs) in HIV-infected patients, together with chronic infection and treatments, has resulted in an increased risk of silent myocardial ischaemia (SMI). The objective of this study was to evaluate whether myocardial SPECT should be used for screening HIV-infected patients with no clinical symptoms of coronary artery disease. Methods The prevalence of SMI detected by myocardial SPECT was determined in 94 HIV-infected patients with a normal clinical cardiovascular examination in relation to anthropomorphic parameters, CRFs, inflammatory and HIV infection status, and treatment. Results Coronary artery disease was detected in nine patients (eight with ischaemia, one with myocardial infarction), corresponding to 9.6 % positivity. All but two of the scintigraphic diagnoses of ischaemia were confirmed by coronarography. Univariate analysis revealed that the overall number of CRFs and the combination of gender and age were associated with a diagnosis of SMI (p

The rate of HIV-1 gene expression is a key step that determines the kinetics of virus spread and AIDS progression. Viral entry and gene expression were described to be the key determinants for cell permissiveness to HIV. Recent reports highlighted the involvement of miRNA in regulating HIV-1 replication post-transcriptionally. In this study we explored the role of cellular factors required for miRNA-mediated mRNA translational inhibition in regulating HIV-1 gene expression. Here we show that HIV-1 mRNAs associate and co-localize with components of the RNA Induced Silencing Complex (RISC), and we characterize some of the proteins required for miRNA-mediated silencing (miRNA effectors). RCK/p54, GW182, LSm-1 and XRN1 negatively regulate HIV-1 gene expression by preventing viral mRNA association with polysomes. Interestingly, knockdown of RCK/p54 or DGCR8 resulted in virus reactivation in PBMCs isolated from HIV infected patients treated with suppressive HAART.

L'ibuprofene est un anti-inflammatoire non steroidien de la famille des acides arylcarboxyliques. Il est actuellement largement prescrit, seul ou en association, en particulier a visee antipyretique. Son hepatotoxicite est connue mais semble moins frequente que les autres specialites de cette classe. Deux cas de ductopenie d'evolution chronique secondaire a la prise d'ibuprofene ont deja ete publies [1, 2]. Nous rapportons un nouveau cas d'atteinte des petites voies biliaires intra-hepatiques liee a la prise de ce medicament, a type de cholangite aigue d'evolution favorable.

Les chiffres de la consommation de cannabis se maintiennent à des niveaux élevés en France. Malgré une demande d’accompagnement en essor, le repérage pratiqué en médecine générale parait insuffisant. L’objectif principal de notre travail était d’identifier des freins au dépistage de l’usage de cannabis dans le Languedoc Roussillon. Les objectifs secondaires étaient de proposer un état des lieux des pratiques ainsi que d’évaluer l’intérêt d’un questionnaire informatif sur le thème du cannabis. Nous avons donc réalisé une étude quantitative d’épidémiologie descriptive à l’aide d’un questionnaire informatisé et dans lequel nous avons inséré des notes d’information issues de la littérature.Au total, 162 médecins ont participé à cette étude. La majorité d’entre eux estime avoir un rôle majeur dans le dépistage et la prise en charge de l’usage de cannabis. Même si l’abord de la consommation de cannabis est rarement systématique dans notre population d’étude, les médecins restent toutefois attentifs à la présence de ces complications. Les questionnaires d’aide au repérage ainsi que le RPIB apparaissent sous utilisés car très souvent méconnus. Les médecins de notre échantillon ne sont pas isolés dans leur pratique et connaissent pour la plupart des structures spécialisées sur lesquelles s’appuyer en cas de besoin. La majorité des répondants estimant pouvoir améliorer leur pratique en terme de dépistage et de prise en charge de l’usage de cannabis, se disent favorables à une formation ponctuelle sur le sujet dans le cadre de la FMC. Enfin, l’aspect informatif du questionnaire a été très bien reçu par les médecins et représente la principale force de cette étude.