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Background: Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol-dependent patients in a series of small randomized controlled trials (RCTs). These results needed to be confirmed by a large trial investigating the treatment effect and its sustainability after medication discontinuation. Aims: To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients. Methods: Large double-blind, randomized, placebo-controlled trial in detoxified adult alcohol-dependent outpatients (80% men) from 11 sites in four European countries. Patients were randomized to 6 months SMO (3.3–3.9 g/day) or placebo followed by a 6-month medication-free period. Primary outcome was the cumulative abstinence duration (CAD) during the 6-month treatment period defined as the number of days with no alcohol use. Secondary outcomes included CAD during the 12-month study period. Results: Of the 314 alcohol-dependent patients randomized, 154 received SMO and 160 received placebo. Based on the pre-specified fixed-effect two-way analysis of variance including the treatment-by-site interaction, SMO showed efficacy in CAD during the 6-month treatment period: mean difference +43.1 days, 95% confidence interval (17.6–68.5; p = 0.001). Since significant heterogeneity of effect across sites and unequal sample sizes among sites ( n = 3–66) were identified, a site-level random meta-analysis was performed with results supporting the pre-specified analysis: mean difference +32.4 days, p = 0.014. The SMO effect was sustained during the medication-free follow-up period. SMO was well-tolerated. Conclusions: Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD. Trial registration: ClinicalTrials.gov Identifier: NCT04648423

AimsThe estimated effect of sodium oxybate (SMO) in the treatment of alcohol dependence is heterogeneous. Population severity and treatment duration have been identified as potential effect modifiers. Population severity distinguishes heavy drinking patients with MethodsNetwork meta-regression allows for testing potential effect modifiers. It was selected to investigate the effect of the above factors on SMO efficacy defined as continuous abstinence (abstinence rate) and the percentage of days abstinent (PDA). Randomized controlled trials for alcohol dependence with at least one SMO group conducted in high-severity and mild-severity populations were assigned to a high-severity and mild-severity group of studies, respectively.ResultsEight studies (1082 patients) were retained: four in the high-severity group and four in the mild-severity group. The high-severity group was associated with larger SMO effect sizes than the mild-severity group: abstinence rate risk ratio (RR) 3.16, P = 0.004; PDA +26.9%, P ConclusionsIn the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes.

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.

IntroductionDevelopment of fully internet-based programs could provide a new avenue to improve access to healthcare for problem gamblers. In this project, we aim to assess the efficacy of a web-based cognitive intervention targeting inhibitory control among problem gamblers, using a randomised controlled design. As impaired inhibitory control is involved in self-regulation difficulties in behavioural addictions, it represents a particularly relevant cognitive process to target for an online psychological intervention.Methods and analysisThis will be a single-blinded, randomised, comparative therapeutic web-based, controlled trial. Up to 200 non-treatment seeking adult problem gamblers with a Problem Gambling Severity Index-recent (PGSI-recent) score ≥5 will be included. The intervention will be a computerised cognitive training program targeting inhibitory skills. The comparator, an active control, will be a computerised neutral sensorial program. Both programs will be carried out under similar conditions: biweekly online training for 6 weeks and optional telephone support will be offered to patients for debriefing. The main objective of the study is to assess the clinical efficacy of the online cognitive training program at 6 weeks, measured with the PGSI-recent. The secondary objectives are to assess the efficacy on the gambling behaviour assessed by the account-based gambling data, on the self-reported gambling practice, and on the inhibition performance at the neuropsychological level at 6, 14 and 52 weeks. We will also assess the acceptability of this program and the preferred level of guidance. Data analysis will be in intention-to-treat.Ethics and disseminationThis randomized controlled trial will be executed in compliance with the Helsinki Declaration, and was approved by the local ethics boards (Comité de Protection des Personnes) in October 2017. The findings will be published in peer-reviewed journals.Trial registration numberNCT03673800.

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: There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no "spontaneous improvement" prior to treatment initiation (high-severity population) than in a mild-severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD.Methods: We conducted a systematic literature review on placebo-controlled RCTs for AD.We assigned retained RCTs to high- or mild-severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta-regression analysis.Results: Among the 19 retained RCTs (comprising 1996 placebo-treated patients), 11 trials were high-severity and 8 were mild-severity RCTs. The between-study variability in AR was lower in the high-severity than in the mild-severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (p = 0.004) and treatment duration (p = 0.017) and was lower in the high-severity studies (16.8% at 3 months) than the mild-severity studies (36.7% at 3 months).Conclusions: Pharmacological RCTs for AD should select high-severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD.

International audience; This dataset complement a previously published dataset [1] and corresponds to the physico-chemical parameters data series produced during the MESOLAC experimental project [2]. The presented dataset is composed of: 1. In situ profiles (0–3m) of temperature, conductivity, pH, dissolved oxygen (concentration and saturation). 2. In situ measurements of light spectral UV/VIS/IR irradiance (300–950 nm wavelength range) taken at 0, 0.25, 0.5, 1, 1.5, 2 and 2.5m. 3. Laboratory chemical analysis of samples collected at 0 and 2 m (conductivity, pH, total alkalinity, NH4, NO2, NO3, total and particulate nitrogen (Ntot, Npart), PO4, total and particulate phosphorus (Ptot, Ppart), total, organic particulate and total particulate carbon (Ctot, Cpart-org, Cpart-tot), Cl, SO4, SiO2. 4. Laboratory analysis of pigments extracted from samples collected at 0 and 2 m (Chla, Chlc, carotenoids, phaeopigments).The experimental design is the same as in Tran-Khac et al [1]. Briefly, it consisted of nine pelagic mesocosms (about 3000 L, 3m depth) deployed in July 2019 in Lake Geneva near the shore of Thonon les Bains (France) aiming to simulate predicted climate scenarios (i.e. extreme events) and assess the response of planktonic communities, ecosystem functioning and resilience.During the experiment, physical parameters were measured twice a week. At the same time, samples were collected at 0 and 2m of depth for subsequent chemical laboratory analyses. These data are presented in the dataset file, ordered by sampling event (numbered from S1 to S8), treatment (Control-C, High-H and Medium-M) and replicates (1 to 3). For each sampling point the measured parameters are listed in columns, missing data and values below the detection limit are marked as NA (not available).This data set aims to contribute to the understanding of the effect of environmental forcing on lake physico-chemical characteristics (such as temperature, oxygen and nutrient concentration) under simulated intense weather events. To a broader extent, the presented data can be used for a wide variety of applications, including monitoring of a large peri-alpine lake functioning under environmental stress and being included in further meta-analysis to generalise the effect of climate change on large lakes. The two complementary dataset differ in the acquired data and methods, temporal and spatial resolution. They complete each other in terms of physico-chemical characterization of the experimental treatments and together can allow comparison of the two different monitoring strategies (continuous vs punctual) during in situ experimental manipulations.

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.

Background. Impairment or distress caused by gambling disorder can be subjectively assessed via quality of life. The aim of this study was to develop a new patient-reported outcome instrument to explore the health-related quality of life (HRQoL) in gambling disorders, the Gambling quality-of-life scale (GQoLS), and to document its psychometric properties. Methods. A previous qualitative study had been conducted using focus groups of problem gamblers to identify areas of HRQoL impacted by gambling. The seven domains identified served as the basis for the hypothetical structure of GQoLS. Draft items were generated from the patient’s speeches to illustrate each of these domains. Cognitive debriefing interviews were realized to obtain a final hypothetical GQoLS. A validation study was then carried out to determine the final version of GQoLS and its psychometric properties (structural validity, construct validity, internal consistency). Results. The final GQoLS was composed of 21 items, with a total mean score of 38.3 (±13.6). Structural validity found a major dimension and four other minor dimensions. The five dimensions were: “emotion”, “lifestyle”, “loneliness”, “taboo” and “preoccupation”. GQoLS was moderately to strongly correlated with PGSI and EQ-5D visual analogic scale. Cronbach’s alpha coefficient was 0.92. Conclusion. GQoLS is the first HRQoL instrument specific to patients with a gambling disorder and developed from the patient’s perspective. GQoLS presents good psychometric properties. GQoLS can be used in clinical research to demonstrate the effectiveness of an intervention on outcomes that are relevant from the patient’s perspective.

International audience; Sodium oxybate (SMO) has been approved in Italy and Austria for the maintenance of abstinence in alcohol dependent (AD) patients. Although SMO is well tolerated in AD patients, cases of abuse and misuse have been reported outside the therapeutic setting. Here we report on a phase IIb double-blind, randomized, placebo-controlled trial for the maintenance of abstinence in AD patients with a new abuse and misuse deterrent formulation of SMO. A total of 509 AD patients were randomized to 12 weeks of placebo or one of four SMO doses (0.75, 1.25, 1.75 or 2.25 g t.i.d.) followed by a one-week medication-free period. The primary endpoint was the percentage of days abstinent (PDA) at end of treatment. An unexpectedly high placebo response (mean 73%, median 92%) was observed. This probably compromised the demonstration of efficacy in the PDA, but several secondary endpoints showed statistically significant improvements. A post-hoc subgroup analysis based on baseline severity showed no improvements in the mild group, but statistically significant improvements in the severe group: PDA: mean difference +15%, Cohen's d = 0.42; abstinence: risk difference +18%, risk ratio = 2.22. No safety concerns were reported. Although the primary endpoint was not significant in the overall population, several secondary endpoints were significant in the intent-to-treat population and post-hoc results showed that treatment with SMO was associated with a significant improvement in severe AD patients which is consistent with previous findings. New trials are warranted that take baseline severity into consideration.

Sugar has been shown to be a powerful substitute for drugs in preclinical studies on addiction. However, the link between sugar intake and alcohol use disorder (AUD) is poorly understood. We assessed the influence of sucrose on ethanol drinking in both nondependent (ND) and dependent (D) Long-Evans rats during acute withdrawal using the postdependent state model. Ethanol (10%-40%) and sucrose (1%-4%) solutions were offered in an operant paradigm either independently or concurrently under ratio schedules of reinforcement. We showed that D rats displayed an enhanced motivation for both 10% ethanol solution (10E) and 4% sucrose solution (4S) as compared with ND rats, and a clear preference for 4S was observed in both groups. During acute withdrawal, D rats showed a strong motivation for 30% ethanol (30E), even when adulterated with quinine, but still preferred 4S despite the fact that a high level of negative reinforcement could be expected. However, when a premix solution (30E4S) was offered concurrently with 4S, the preference for 4S was lost in D animals, which consumed as much premix as 4S, whereas ND animals displayed preference for 4S. Altogether, those results suggest that reinforcing properties of sucrose surpass those of ethanol in D rats under acute withdrawal, which indicates that sugar is a powerful substitute for ethanol. Our results suggest that craving for sugar may be increased in AUD patients during withdrawal and raise the issue of dependence transfer from alcohol to sugar.

Background Models based on the uniqueness of addiction processes between behavioral addictions are highly contentious, and the inclusion of gaming disorder in the addiction nosography remains controversial. An exploratory approach could clarify a hypothesized common and subjectively identifiable process in addictive behaviors and the necessarily different expressions of the disorder due to behavior specificities, in particular the sociocultural characteristics and profiles of users. Objective The aim of this study was to describe the nature of contacts to a help service by exploring commonality and specificities of burden and help-seeking for problem gambling or gaming. Methods This was an observational quantitative-qualitative study. We included all contacts (ie, online questions and contacts by phone or chat when the helper completed a summary) to a helpline for gamers, gamblers, and relatives over a 7-year period. We constituted a text corpus with online questions and summaries of contacts by phone or chat. We collected basic sociodemographic data, including the device used to contact the service (phone or internet), contacting the service for oneself (“user”) or being a relative of a user and type of relative, gambling (yes/no), gaming (yes/no), and age and sex of the gambler/gamer. We describe the corpus descriptively and report the computerized qualitative analysis of online questions, chat, and summary of phone calls. We performed a descendant hierarchical analysis on the data. Results A total of 14,564 contacts were made to the helpline, including 10,017 users and 4547 relatives. The corpus was composed of six classes: (1) gaming specificities, (2) shared psychological distress and negative emotions, (3) the procedure for being banned from gambling, (4) the provided help, (5) gambling specificities, and (6) financial problems. Conclusions Negative emotions and shared distress linked to gambling and gaming support current scientific consensus that these behaviors can produce psychological distress in se; however, meaningful differences were observed in core symptoms of addiction between gamers and gamblers, beyond specificities related to the behavior itself: loss of control was elicited in the class corresponding to gambling specificities and not by gamers and their relatives.

BACKGROUND Models based on the uniqueness of addiction processes between behavioral addictions are highly contentious, and the inclusion of gaming disorder in the addiction nosography remains controversial. An exploratory approach could clarify a hypothesized common and subjectively identifiable process in addictive behaviors and the necessarily different expressions of the disorder due to behavior specificities, in particular the sociocultural characteristics and profiles of users. OBJECTIVE The aim of this study was to describe the nature of contacts to a help service by exploring commonality and specificities of burden and help-seeking for problem gambling or gaming. METHODS This was an observational quantitative-qualitative study. We included all contacts (ie, online questions and contacts by phone or chat when the helper completed a summary) to a helpline for gamers, gamblers, and relatives over a 7-year period. We constituted a text corpus with online questions and summaries of contacts by phone or chat. We collected basic sociodemographic data, including the device used to contact the service (phone or internet), contacting the service for oneself (“user”) or being a relative of a user and type of relative, gambling (yes/no), gaming (yes/no), and age and sex of the gambler/gamer. We describe the corpus descriptively and report the computerized qualitative analysis of online questions, chat, and summary of phone calls. We performed a descendant hierarchical analysis on the data. RESULTS A total of 14,564 contacts were made to the helpline, including 10,017 users and 4547 relatives. The corpus was composed of six classes: (1) gaming specificities, (2) shared psychological distress and negative emotions, (3) the procedure for being banned from gambling, (4) the provided help, (5) gambling specificities, and (6) financial problems. CONCLUSIONS Negative emotions and shared distress linked to gambling and gaming support current scientific consensus that these behaviors can produce psychological distress in se; however, meaningful differences were observed in core symptoms of addiction between gamers and gamblers, beyond specificities related to the behavior itself: loss of control was elicited in the class corresponding to gambling specificities and not by gamers and their relatives.

International audience; Researchers have claimed that craving and Attentional Bias (AB) towards alcohol-related cues can be explained by a common incentive-salience mechanism. However, the exact relationship between AB and craving is a matter of debate. The aim of this study was to show that metacognitions moderate the effect of AB on craving. A sample of 38 alcohol abusers undergoing post-withdrawal treating in a hospital setting completed the visual Dot Probe Detection Task (DPDT), while both pre- and post-task measures of craving were recorded. Our results confirmed significant effects of both exposure to pictures of alcohol, and metacognitions, on craving; in particular, the interaction Metacognition * DPDT was significant. Although we initially confirmed a significant main effect of AB on craving, it became non-significant when adjusted for inter-subject variance, and metacognitions. The effect of the interaction AB * Metacognition on craving was not significant. Our findings support the hypothesis that craving and AB share variance, but the relationship appears to be spurious, and caused by confounding factors. We discuss these results with reference to the metacognitive model of addiction.

Background and Aim The main aim of this study was to evaluate if the binge eating disorders (BEDs) related to obesity were associated with the severity of non‐alcoholic fatty liver disease (NAFLD). Methods Severely obese patients who had been referred for bariatric surgery were included in this study at the Nice University Hospital. All patients underwent a liver biopsy at the time of surgery. Between 2008 and 2015, 388 patients had an assessable Bulimia Test (BULIT) self‐questionnaire at the time of surgery. A subgroup (n = 183), between 2011 and 2015, also responded to a Beck Depression Inventory, Hospital Anxiety and Depression Scale, and a Fatigue Impact Scale autoquestionnaire. A control group of 29 healthy people matched by age and gender was included. Results Among the 388 obese patients (median age 40 years, body mass index 41.7 kg/m2, 81% women), 14 patients had a “probable diagnosis” of BED, and 47 patients had a “high risk” of developing a BED according to the BULIT. Obese patients had significantly more severe BED, depression, anxiety, and fatigue compared to controls. Steatosis, non‐alcoholic steatohepatitis, or fibrosis was not associated with BED. Similarly, the severity of NAFLD was not associated with depression, anxiety, or fatigue. Conclusions Severely obese patients had more severe BED, depression, anxiety, and fatigue than lean subjects independent of the severity of NAFLD., Non‐alcoholic fatty liver disease, the emerging liver disease of the 21st century, is related to obesity. However, binge eating disorders, and also frequently associated psychiatric disorders (depression, anxiety, and fatigue), are not associated with the severity of liver pathology in severely obese patients.

Medication development for alcohol relapse prevention or reduction of consumption is highly challenging due to methodological issues of pharmacotherapy trials. Existing approved medications are only modestly effective with many patients failing to benefit from these therapies. Therefore, there is a pressing need for other effective treatments with a different mechanism of action, especially for patients with very high (VH) drinking risk levels (DRL) because this is the most severely affected population of alcohol use disorder patients. Life expectancy of alcohol-dependent patients with a VH DRL is reduced by 22 years compared with the general population and approximately 90 000 alcohol-dependent subjects with a VH DRL die prematurely each year in the EU (Rehm et al. ). A promising new medication for this population is sodium oxybate, a compound that acts on GABAB receptors and extrasynaptic GABAA receptors resulting in alcohol-mimetic effects. In this article, a European expert group of alcohol researchers and clinicians summarizes data (a) from published trials, (b) from two new-as yet unpublished-large clinical trials (GATE 2 (n = 314) and SMO032 (n = 496), (c) from post hoc subgroup analyses of patients with different WHO-defined DRLs and (d) from multiple meta-analyses. These data provide convergent evidence that sodium oxybate is effective especially in a subgroup of alcohol-dependent patients with VH DRLs. Depending on the study, abstinence rates are increased up to 34 percent compared with placebo with risk ratios up to 6.8 in favor of sodium oxybate treatment. These convergent data are supported by the clinical use of sodium oxybate in Austria and Italy for more than 25 years. Sodium oxybate is the sodium salt of γ-hydroxybutyric acid that is also used as a recreational (street) drug suggestive of abuse potential. However, a pharmacovigilance database of more than 260 000 alcohol-dependent patients treated with sodium oxybate reported very few adverse side effects and only few cases of abuse. We therefore conclude that sodium oxybate is an effective, well-tolerated and safe treatment for withdrawal and relapse prevention treatment, especially in alcohol-dependent patients with VH DRL.

International audience; Addiction transfer from alcohol to sugar has been demonstrated in the alcohol postdependent state model in rats. To assess whether changes in sugar intake and craving can occur during alcohol withdrawal in humans we conducted a prospective, observational study in a university hospital addictions treatment center. Recruited patients had severe alcohol use disorder, were hospitalized for 7 days in the short-stay unit for alcohol withdrawal and then for 6 weeks in the rehabilitation unit. During the hospital stay, they had no access to alcohol but had full access to sweet products and beverages in a shop and vending machines located inside the hospital. Alcohol craving was assessed using a visual analogue scale on days 1, 15 and 45. Sugar craving, sweet products stored by patients in their rooms and weight were assessed on the same days. Thirty-five patients were included. Sugar craving increased in 14 patients during the hospital stay while no change was observed in the remaining 21. Significant increases in both the amounts of sweet products stored in the patients' rooms (p

International audience; Up to 50% of liver transplantation (LT) recipients with known or clandestine alcohol-use disorder (AUD) before surgery return to alcohol use after LT. However, only severe alcohol relapse, which varies in frequency from 11% to 26% of patients, has an impact on longterm survival and significantly decreases survival rates after 10 years. Therefore, it is crucial to identify patients with the highest risk of severe relapse in order to arrange specific, standardized monitoring by an addiction team before and after LT. The aims of this study were to describe the effects of combined management of AUD on the rate of severe alcohol relapse and to determine the risk factors before LT that predict severe relapse. Patients transplanted between January 2008 and December 2014 who had met with the LT team's addiction specialist were included in the study. Patients who exhibited alcohol-related relapse risk factors received specific addiction follow-up. A total of 235 patients were enrolled in the study. Most of them were men (79%), and the mean age at the time of the LT was 55.7 years. Severe relapse occurred in only 9% of the transplant recipients. Alcohol-related factors of severe relapse were a pretransplant abstinence of 6 months and family, legal, or professional consequences of alcohol consumption, whereas the nonalcohol-related factors were being single and being eligible for a disability pension. In conclusion, the integration of an addiction team in a LT center may be beneficial. The addiction specialist can identify patients at risk of severe relapse in the pretransplantation period and hence arrange for specific follow-up.

International audience; OBJECTIVE:The aim of this study was to evaluate the prevalence and the kind of psychoactive substances consumed by people with obesity.METHODS:Patients were included at their first visit for bariatric surgery. Socio-demographic characteristics, anxiety, depressive disorders and psychoactive substance consumption were assessed. The prevalence of psychoactive substance consumption was compared to that of the general population reported by the French National Institute of Prevention and Health Education.RESULTS:One hundred (100) patients were consecutively recruited: 60 women (mean age 41 ± 14 years) and 40 men (mean age 46 ± 13 years). Sixty-seven percent of subjects consumed alcohol. Consumption rates of cannabis (21% vs. 10%), cocaine (7.0% vs. 0.8%) and amphetamine (6.0% vs. 0.3%) were significantly (p < .0001) higher in people with obesity than in the general population.CONCLUSIONS:People with obesity have an excess risk of amphetamine, cocaine and cannabis consumption. This consumption may increase the risk of cardiovascular and psychiatric morbidity and should therefore be detected before surgery.

International audience; Background and aims: Completely substituting e-cigarettes (EC) for combustible tobacco cigarettes reduces exposure to toxicants and carcinogens. However, a large proportion of EC users (dual users) continue to smoke conventional cigarettes. This study aimed to compare estimated nicotine intake and e-cigarette use characteristics between exclusive EC users and dual users.Design: Web-based anonymous cross-sectional survey.Setting: France.Participants: A total of 3189 adults, current users of electronic cigarettes (EC). Data collection between 4 October 2014 and 11 November 2014.Measurements: Primary outcome: estimated nicotine intake per day (mg) from participants' reports.Secondary outcomes: duration, frequency of EC use and nicotine content of e-liquids used/day. Dual use was defined as using at least one cigarette per day while also using EC.Findings: A total of 2836 respondents reported exclusive EC use and 353 reported being dual users. Backward stepwise logistic regression showed that dual users had higher estimated combined daily nicotine intake from e-liquids and cigarettes [estimate: 2.14, standard error (SE) = 0.26, adjusted odds ratio (aOR) = 8.48, 95% confidence interval (CI) = 5.11-14.09, P < 0.001], but lower daily nicotine intake from EC (estimate: -2.14, SE = 0.26, aOR = 0.12, CI = 0.07-0.196, P < 0.001) and reported fewer months of EC use (estimate: -0.31, SE = 0.14, aOR = 0.73, CI = 0.56-0.95, P = 0.022) compared with exclusive EC users.Conclusion: Dual e-cigarette users in France may have higher nicotine intake overall than exclusive e-cigarette users, but they may take in less nicotine from their e-cigarettes.

International audience; Background: The objective was to explore the role of patient sex in cognitive recovery and to identify predictive factors for non-recovery in alcohol use disorder (AUD). Methods: All patients with AUD admitted to a residential addictions treatment center were systematically assessed at admission and after 6 weeks of abstinence in a controlled environment. The inclusion criteria were that patients were admitted for AUD with baseline alcohol-related cognitive impairment (baseline total Montreal Cognitive Assessment (MoCA) score \textless 26) and reassessed at 6 weeks (n = 395). A logistic regression model was built to determine the influence of sex on recovery status (MoCA \textless or >= 26) taking into account the interaction effect of sex with alcohol consumption on cognitive function. Results: The mean age was 50.10 years (SD = 9.79), and 27.41% were women. At baseline, the mean MoCA scores were 21.36 (SD = 3.04). Participants who did not achieve recovery (59.3% of women vs 53.8% of men) had lower total MoCA scores at baseline. The 2 factors that was significantly and independently associated with non-recovery and with a non-zero coefficient was being a woman and initial MoCA score (respective adjusted odds ratios (AOR) = 1.5 and 0.96, p-values \textless 0.05). Conclusions: These results could influence the time required in a controlled environment to maintain abstinence and the duration of in-care for women.

International audience; The effectiveness of environmental protection measures is based on the early identification and diagnosis of anthropogenic pressures. Similarly, restoration actions require precise monitoring of changes in the ecological quality of ecosystems, in order to highlight their effectiveness. Monitoring the ecological quality relies on bioindicators, which are organisms revealing the pressures exerted on the environment through the composition of their communities. Their implementation, based on the morphological identification of species, is expensive because it requires time and experts in taxonomy. Recent genomic tools should provide access to reliable and high-throughput environmental monitoring by directly inferring the composition of bioindicators' communities from their DNA (metabarcoding). The French-Swiss program SYNAQUA (INTERREG France-Switzerland 2017-2019) proposes to use and validate the tools of environmental genomic for biomonitoring and aims ultimately at their implementation in the regulatory bio-surveillance. SYNAQUA will test the metabarcoding approach focusing on two bioindicators, diatoms, and aquatic oligochaetes, which are used in freshwater biomonitoring in France and Switzerland. To go towards the renewal of current biomonitoring practices, SYNAQUA will (1) bring together different actors: scientists, environmental managers, consulting firms, and biotechnological companies, (2) apply this approach on a large scale to demonstrate its relevance, (3) propose robust and reliable tools, and (4) raise public awareness and train the various actors likely to use these new tools. Biomonitoring approaches based on such environmental genomic tools should address the European need for reliable, higher-throughput monitoring to improve the protection of aquatic environments under multiple pressures, guide their restoration , and follow their evolution.

Introduction Screening of cognitive impairment is a major challenge in alcoholics seeking treatment, since cognitive dysfunction may impair the overall efficacy of rehabilitation programs and consequently increase relapse rate. We compared the performance of two screening tools: the MoCA (Montreal Cognitive Assessment), which is widely used in patients with neurological diseases and already used in patients with alcohol use disorder (AUD), and the BEARNI (Brief Evaluation of Alcohol-Related Neuropsychological Impairments), a recent test specifically developed for the alcoholic population. Methods We compared the sensitivity and specificity of the MoCA and the BEARNI in a sample of AUD patients with and without cognitive impairment assessed by a battery of neuropsychological tests. Results Ninety patients were included. There were 67 men and 23 women aged 48.9 ± 9.6 years. According to the neuropsychological tests, 51.1% of patients had no cognitive impairment, while it was mild or moderate to severe in 31.1 and 17.8%, respectively. The BEARNI sensitivity was extremely high (1.0), since all patients with cognitive impairment were identified, but its specificity was very low (0.04). The MoCA had a lower sensitivity (0.79) than the BEARNI, but its specificity was significantly better (0.65). A detailed analysis of the BEARNI scores showed a discrepancy between the qualitative and quantitative interpretation of the test which could, at least in part, explain its low specificity. Conclusion Both the MoCA and the BEARNI are screening tools which identified alcoholic patients with cognitive impairment. However, in routine use, the MoCA appeared to be more appropriate given the low specificity of the BEARNI.

International audience; AIM: To determine the detection rates, clinical features, and risk factors for lack of registration of alcohol use in medical patients admitted in European hospitals.METHODS: A point-prevalence, cross-sectional, multicenter survey involving 2100 medical inpatients from 43 hospitals from 8 European countries. Patients were screened for current alcohol use, using standardized questionnaires. Alcohol use recording in medical records was assessed.RESULTS: Of the 2100, more than a half reported alcohol use. Significant differences were shown in the prevalence of drinking and the recording rates of alcohol use among the hospitals and countries involved. Overall, 346 patients (16%) fulfilled criteria for alcohol use disorder. Alcohol use was registered in 909 (43%) of medical records, with quantification in 143 (7%). Multivariate analysis showed that women (OR 1.49), older age patients (OR 1.23), patients from the Northern European countries (OR 4.79) and from hospitals with high local alcohol prevalence (OR 1.59) were more likely to have lack of alcohol use registration in their medical files.CONCLUSIONS: A considerable proportion of medical patients admitted in European hospitals fulfill criteria for alcohol use disorders. These patients are frequently overlooked during hospitalization and not appropriately registered in medical records. Women, older patients, and inpatients from European areas with high local alcohol use prevalence are at higher risk associated with a non-recording of alcohol use.

Liver transplantation is the gold standard treatment for terminal cirrhosis and liver cancer (if no surgical option is available). In France, the leading cause of liver transplantation is alcoholic cirrhosis. Severe alcohol relapse is often considered as a failure and concerns 11 to 26% of cases. The severe relapse causes a significant decrease in survival after 5 years of follow up, regardless of the origin of the transplantation. Predictors of relapse, like pretransplant abstinence duration, additional psychiatric co-morbidity, age, and level of social support have been assessed. However, alcohol addiction and liver transplantation are complex entities that cannot be reduced to a list of predictive factors. A multidisciplinary approach including an addiction specialist should identify and minimize the risk of severe relapse.

International audience; BACKGROUND : The Montreal Cognitive Assessment (MoCA) score is a convenient and promising tool for estimating alcoholic patients' global cognitive functioning, a major challenge for all specialized alcohol treatment centers. However, whether or not the score should be corrected for education level and whether the proposed cutoff is relevant in patients with alcohol use disorders (AUD) should be determined.METHODS : We compared the MoCA scores in patients hospitalized for AUD with and without cognitive impairment assessed by a battery of neuropsychological (NP) tests. Sensitivity, specificity, and cutoff of the MoCA score were analyzed using receiver operating characteristic curve analysis.RESULTS : Thirty-one patients with and 25 without cognitive impairment were included in the study. There were 40 men and 16 women, with a mean age of 49.5 years. The mean uncorrected MoCA score was 23.1 ± 3.3 in those with and 27.0 ± 1.9 in those without cognitive impairment. NP tests were significantly correlated with the MoCA score. Uncorrected MoCA scores identified more than 80% of the patients with a cutoff score equal to 26, to obtain similar accuracy with the corrected score required using a cutoff score equal to 27.CONCLUSIONS : Our results confirm that the MoCA test is a convenient and reliable screening tool to measure cognition defects in alcoholic patients. As using the 1-point education adjustment increases the cutoff score by 1 point, it is suggested to use the noncorrected score and the usual cutoff, that is, 26. Being easy to administer and only moderately time-consuming, the MoCA score should be used extensively in addiction treatment centers.

Background The human intestinal microbiota exerts beneficial or harmful effects in several disorders. Many factors, including alcohol consumption, may influence its composition and trigger bacterial translocation. Excessive alcohol consumption increases gut permeability and translocation of endotoxin into peripheral circulation. Although plasma endotoxin concentrations have been measured often, quantitative changes following alcohol withdrawal have never been described in subjects with alcohol use disorder (AUD). The aim of this study was to measure microbial translocation (MT) and gut permeability markers in patients with AUD, to compare these markers to healthy controls (HC) and to monitor markers during the first 6 weeks of abstinence. Methods Sixty-five patients with AUD and hospitalized for alcohol withdrawal were included. Epidemiological, clinical, biological, and addictological data were gathered. Blood samples were collected at baseline, then 3 and 6 weeks after alcohol withdrawal. A hundred healthy volunteers were used as controls. Three markers of MT were monitored in plasma samples: sCD14 and lipopolysaccharide-binding protein (LBP) were quantified using ELISA, and 16S rDNA was quantified using real-time polymerase chain reaction. Zonulin and intestinal fatty acid binding protein (I-FABP) blood levels were also monitored as indirect markers of gut permeability, using ELISA. Results At baseline, LBP, 16S rDNA, sCD14 and I-FABP markers were significantly higher in patients with AUD than in HC. Six weeks after alcohol withdrawal plasma levels of sCD14 and LBP decreased significantly. Cannabis consumption and body mass index (BMI) before alcohol withdrawal influenced baseline MT levels and the decrease in MT markers after 6 weeks. Finally, markers of MT and gut permeability did not correlate with each other before and after alcohol withdrawal. Conclusions Before alcohol withdrawal, MT markers were higher in patients with AUD than in HC. After 6 weeks of abstinence, an improvement in MT markers was observed. Our data suggest that there is a link between MT, its improvement, BMI, and cannabis consumption.

International audience; Aims:The prevalence of insomnia ranges from 36% to 91% in alcohol-dependent patients and may persist after alcohol withdrawal. Acamprosate has been shown to decrease insomnia in abstinent patients. Based on a large clinical trial database, the aim of the present study is to assess the efficacy of acamprosate in reducing insomnia, and if indeed it does reduce insomnia, to better understand its action mechanism.Short Summary:The aim of the study is to confirm the efficacy of acamprosate to reduce insomnia using an individual patient data meta-analysis. Twelve studies were found including 3508 patients. After a 6-month follow-up, the mean insomnia decrease over baseline was -26% and -45% for the placebo and acamprosate groups, respectively (P < 0.001).Methods:An individual patient data meta-analysis selected all the randomized trials of acamprosate in which insomnia was documented. Our main endpoint was insomnia change after a 6-month follow-up, measured by the validated Short Sleep Index (SSI) derived from the Hamilton Depression and Anxiety Scale. The meta-analysis was conducted using a two-level multilevel (patient/trial) mixed model with random treatment effect, random study effect and adjusting for baseline severity covariates.Results:Twelve studies were found including 3508 patients, 59.8% of whom were suffering from insomnia (95% CI 58.1-61.4). Psychiatric history, severe addiction, living alone and abnormal gamma-GT levels were found to be the risk factors of insomnia. After 6 months, the mean SSI decrease over baseline was -26% and -45% for placebo and acamprosate, respectively (treatment effect = 19%, 12.5-25.5; P < 0.001). By using a univariate mediation model, we found that the mediating effect of abstinence on insomnia accounted for 55.7% of the overall effect of acamprosate on insomnia reduction.Conclusions:Insomnia is prevalent among alcohol-dependent patients. It decreases spontaneously with abstinence but more frequently with acamprosate treatment.

International audience; Liver transplantation (LT) is the gold standard treatment for end-stage liver disease. Whatever the primary indication of LT, substance abuse after surgery may decrease survival rates and quality of life. Prevalence of severe alcohol relapse is between 11 and 26%, and reduces life expectancy regardless of the primary indication of LT. Many patients on waiting lists for LT are smokers and this is a major risk factor for both malignant tumors and cardiovascular events post-surgery. The aim of this review is to describe psychoactive substance consumption after LT, and to assess the impact on liver transplant recipients. This review describes data about alcohol and illicit drug use by transplant recipients and suggests guidelines for behavior management after surgery. The presence of an addiction specialist in a LT team seems to be very important.

Background: Continuing to smoke or to drink after the treatment of an upper aerodigestive tract (UADT) cancer is known to worsen the prognosis. We assessed the feasibility and efficacy of an addiction treatment program integrated into the cancer treatment. Method: In four units devoted to UADT tumors, we proposed an addiction treatment to all patients still drinking or smoking at the end of the cancer treatment; the abstinence rate was assessed 6 and 12 months later. Results: One hundred and sixteen patients were included. Among the 73 patients still drinking and/or smoking at the end of the cancer treatment, 46.6% accepted an addiction treatment. In the latter, abstinence rate was increased, 52.2% versus 31.03% ( p = .07) at M12. In patients both drinking and smoking, addiction treatment doubled the rate of abstinence of both products (31% vs. 14%). Conclusion: Offering addiction treatment to patients with UADT cancer improves abstinence rate and helps maintain long-term withdrawal.

International audience; BACKGROUND:Alcohol relapses after liver transplantation (LT) constitute a critical issue. Because there is no widely accepted definition of LT, its prevalence varies from 7 to 95% across studies. Only a severe relapse, the frequency of which is estimated to be 11 to 26%, decreases life expectancy after 5 years of LT and requires specific care. To improve the early identification of alcohol consumption among transplanted patients, liver transplant teams may be helped by input from an addiction team. Nevertheless, added benefit of involvement by addiction specialists in treating posttransplant patients has not been demonstrated. Thus, the aim of this study was to compare the evaluation of the alcohol consumption after LT performed routinely during the transplant consultation or obtained from a specific addiction consultation.METHODS:This was a prospective single-site study. Patients were seen consecutively by their hepatologist and by an addiction specialist, and they completed the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). Thus, the patient's alcohol status was assessed using 3 different sources of information: the hepatologist's interview, the AUDIT-C score, and the addiction specialist visit.RESULTS:One hundred forty-one patients were consecutively evaluated. Alcohol consumption was identified by the hepatologist in 31 patients (21.9%), in 52 (36.8%) using the AUDIT-C questionnaire, and in 58 (41.1%) by the addiction specialist. The 31 patients concerned reported an average of 6.5 alcohol units/wk to the transplant physician, a number which was significantly greater (p = 0.001) by 8.6 units/wk when they were interviewed by the addiction specialist.CONCLUSIONS:This study highlights the clinical utility of a systematic addiction consultation among liver transplant patients, irrespective of the reason for transplantation.

Excessive alcohol consumption has a modulating effect on immune functions that may contribute to decreased immunity and host defense. It is associated with increased intestinal permeability to endotoxins that is normalized after 14 d of abstinence. Whether and how blood monocyte subsets are impaired in patients with an AUD and what their evolution is after alcohol withdrawal are the paper’s objectives. With the use of flow cytometry, blood monocyte subsets were quantified in AUDs before (n = 40) and 2 wk after (n = 33) alcohol withdrawal and compared with HC donors (n = 20). Expression of TLR2 and TLR4 on monocyte subsets was also quantified. Cytokine response of monocytes was monitored following PGN and LPS stimulation. The CD14+CD16− subset was decreased, whereas the CD14dimCD16+ subset was expanded (P < 0.001) in AUD compared with HC. The frequencies of TLR2- and TLR4-expressing monocytes were reduced in AUD compared with HC. Although the basal production of IL-1, IL-6, and TNF by monocytes in AUD was compared with HC, the PGN- and LPS-mediated IL-6 and TNF production was increased in AUD. Frequencies of IL-6-expressing monocytes were higher in AUD than HC. Alcohol withdrawal partially restored the distribution of monocyte subsets and the frequency of IL-6-producing monocytes and increased the frequency of TNF-producing cells in response to LPS and PGN stimulation to levels compared with those in HC. Our findings indicate that chronic alcohol use alters the distribution as well as the phenotypic and functional characteristics of blood monocyte subsets, which are partially restored following 2 wk of alcohol withdrawal.

Resume Propos L’alcoolodependance a une prevalence stable au cours du temps d’environ 5–7 % chez les hommes et 2–3 % chez les femmes, ce qui correspond en France a au moins 1,5 millions de malades. Une mise au point sur ce sujet est justifiee en raison donc de sa prevalence, mais aussi en raison des progres significatifs qui ont ete faits pour la prise en charge de ces malades. Actualites et points forts Le sevrage alcoolique est bien codifie et repose principalement sur la prescription de benzodiazepines, plutot a demi-vie longue, de vitamine B1 et d’une hydratation suffisante. L’objectif est d’eviter le syndrome de sevrage qui peut aller jusqu’au delirium tremens et aux crises convulsives generalisees. Differentes therapies et medicaments ont une efficacite validee dans l’aide au maintien de l’abstinence. Les therapies cognitivocomportementales evaluent les differents processus qui favorisent la consommation d’alcool et utilisent des techniques comportementales afin de promouvoir un changement. Les entretiens motivationnels valorisent l’efficacite propre du patient et sa capacite a maintenir l’abstinence. Trois molecules ayant l’AMM ont demontre leur efficacite dans de nombreux travaux : l’acamprosate qui interagit avec le tonus GABAergique et glutamatergique ; la naltrexone, antagoniste des recepteurs opiaces ; le disulfirame qui inhibe l’acetaldehyde deshydrogenase ce qui provoque son effet antabuse. Perspectives Il existe deux voies de recherches importantes actuellement : la prise en charge des polyconsommations de produits psychoactifs ; la comprehension de la neurobiologie de la dependance qui pourrait ouvrir de nouvelles pistes therapeutiques.

Background. Cognitive dysfunction is a common feature in alcohol use disorders. Its persistence following alcohol detoxification may impair quality of life and increase the risk of relapse. We analyzed cognitive impairment changes using the Montreal Cognitive Assessment (MoCA) score in a large sample of alcohol-dependent inpatients hospitalized for at least 4 weeks. Method. This was an observational longitudinal survey. Inclusion criteria were alcohol dependence (DSM-IV) and alcohol abstinence for at least one week. The MoCA test was administered on admission and at discharge. Results. 236 patients were included. The mean MoCA score significantly increased from 22.1±3.7 on admission to 25.11±3.12 at discharge. The corresponding effect-size of improvement was high, 1.1 [95% CI 1.0–1.2]. The degree of improvement was inversely correlated with the baseline MoCA score. The rate of high and normal, that is, >26, MoCA values increased from 15.8% on admission to 53.8% at discharge. MoCA score improvement was not correlated with the total length of abstinence prior to admission. Conclusion. The MoCA score seems to be a useful tool for measuring changes in cognitive performance in alcohol-dependent patients. A significant improvement in cognitive function was observed whatever the degree of impairment on admission and even after a long abstinence period.

International audience; BACKGROUND:Alcoholism is known to be associated with cognitive deficits mainly concerning visuospatial capacity, executive function, memory, and attention. These impairments may affect treatment efficacy which should therefore be adapted. We evaluated the potential utility of the Montreal Cognitive Assessment (MoCA) to evaluate cognitive impairment in a large series of alcoholic patients hospitalized for withdrawal and rehabilitation.METHODS:Consecutive recruitment during a time period of patients admitted to an addiction treatment unit of a teaching hospital. Administration of the MoCA test on admission by trained staff members.RESULTS:A total of 166 patients aged 49.9 ± 9.2 years were included. Mean duration of administration was 20 minutes. The mean MoCA score was 23.5 ± 3.5 and 68.1% had an impaired value (12 years) significantly increased the likelihood of having a high MoCA score.CONCLUSIONS:Owing to their severity and frequency, screening for cognitive deficits is necessary in alcoholics during rehabilitation. MoCA is an appropriate tool for this purpose.

Predictive factors for alcoholic relapse after liver transplantation (LT) performed for alcoholic liver disease (ALD) have been assessed in numerous studies, often with contradictory results. The aim of the study was to assess pretransplantation alcohol consumption characteristics on alcoholic relapse after LT. Patients transplanted for ALD for at least 6 months were included. An anonymous questionnaire assessed socio-demographic characteristics, medical history, and alcohol consumption before and after LT. Relapse was defined as any alcohol use after LT. Severe relapse was defined by heavy drinking: more than 21 units/week for males and 14 units/week for females. A total of 61 patients were studied. The mean follow up after LT was 49 +/- 34 months. Alcoholic relapse occurred in 32 of 61 patients (52%) and severe relapse in eight of 61 patients (13%). Risk factors for severe relapse were: length of abstinence before LT (P = 0.0001), more than one alcohol withdrawal before LT (P = 0.001), alcohol dependence (P = 0.05), alcohol abuse in first relatives (P = 0.05), and younger age (P = 0.05). Information on previous alcohol consumption (dependence, number of withdrawals, family history) helps to predict severe relapse after LT in patients with ALD, allowing early awareness and specific postoperative care.

Background: The association between chronic alcohol consumption and an increasing risk of infectious and neoplastic disease is related to an impairment of cellular immunity. However, studies of the number and activity of lymphocyte subsets show highly variable results. The aim of this study was to assess the expression of perforin, one of the main molecular agents of T and natural killer (NK) cell–mediated cytotoxicity, in alcoholic patients without cirrhosis. Methods: Eighteen patients with chronic alcoholism were prospectively included and compared with 18 age- and sex-matched healthy volunteers. Signs of hepatic insufficiency or portal hypertension, viral co-infection, other serious medical illness, and immune-related medications were exclusion criteria. Lymphocyte phenotype was assessed, and perforin expression was analyzed by flow cytometry in CD3+CD56+ T cells and NK cells. Granzyme synthesis was also evaluated in 11 of the 18 patients and compared with that of 11 age- and sex-matched controls. Results: The mean number of white blood cells and lymphocytes was not different between the controls and alcoholic patients, whereas the mean number of NK cells was significantly decreased in alcoholic patients (110 ± 79/mm3 versus 271 ± 192/mm3; p < 0.03). Perforin expression in T CD3+/CD56+ and in NK cells was significantly decreased in alcoholic patients compared with controls: 16 ± 3% vs. 36 ± 4% (p < 0.03) and 65 ± 15% vs. 78 ± 9% (p= 0.04), respectively. The percentage of cells expressing granzyme was similar in both groups. Conclusions: A decrease in perforin expression by cytotoxic cells could be a major factor in explaining the physiopathologic mechanisms of several alcohol-associated diseases.

Background/Aims : The aim of this study was to distinguish the types of alcohol consumption after liver transplantation (LT) for alcoholic cirrhosis and to assess the consequences of heavy drinking. Methods : Patients transplanted for alcoholic cirrhosis were studied. Alcoholic relapse diagnosis was based upon patient's and family members' reports, liver enzyme tests, graft biopsy, and use of urine alcohol test. Results : One hundred twenty-eight patients were studied, with a mean follow-up of 53.8 months. After LT, 69% of patients were abstinent, 10% were occasional drinkers, and 21% were heavy drinkers. Actuarial survival rates were not different, but three of the seven deaths observed among heavy drinkers were directly related to alcohol relapse. Although there was no difference between the three groups concerning the rejection rates, all rejection episodes observed in the group of heavy drinkers were related to poor compliance with immunosuppressive drugs. One heavy drinker developed alcoholic cirrhosis. Conclusions : The present study indicates that patients can resume heavy alcohol consumption after LT for alcoholic liver disease (ALD) and their grafts can be injured because of poor compliance with immunosuppressive drugs and alcohol-related liver injury. Although patient survival was not influenced by alcohol relapse, heavy alcohol consumption can be responsible for patients' death.

OBJECTIVES: Sleep disturbance constitutes a major risk factor for drinking relapse after alcohol withdrawal and necessitates regular follow-up. We reported previously that the sum-score of the 4 sleep items of the Hamilton Anxiety and Depression Scales (the Short Sleep Index [SSI]) constitutes a valid and simple sleep measurement tool. The objective of this study was to evaluate the psychometric features of the SSI relative to the lengthier Pittsburgh Sleep Quality Index (PSQI), which is widely used for measuring sleep disturbance in patients with alcohol use disorders during and after alcohol withdrawal. METHODS: In this French, multicenter, cross-sectional survey, alcoholic patients were recruited in 2 academic hospitals and 1 community treatment center. Demographic data, alcohol history, and current consumption of alcohol and other abused substances were documented. The SSI and the PSQI questionnaires were completed in face-to-face interviews by a trained clinical research associate. RESULTS: A total of 257 patients were studied (88 females), with a mean age of 49 years (range: 24-80 years). The prevalence of sleep disturbance as measured by the PSQI and the SSI was 73.5% and 74.3%, respectively. The correlation between the 2 indices was strong (r = 0.764; 95% CI: 0.709-0.811), with negative and positive predictive values for the SSI (score > 1) of 71.2% and 89%, respectively, and an area under the receiver operating characteristic curve of 0.91 (95% CI: 0.85-0.92). The discriminant and convergent validity of the SSI was found to be noninferior to the PSQI. CONCLUSIONS: Compared to the PSQI, the SSI represents a quick, quantifiable, and reliable method that could help clinicians assess and manage sleep disturbance in alcoholic patients. Language: en

International audience; The author would like to update "Conflicts of Interest" section of their previous publication [1] as follows: Conflicts of Interest Georges Brousse has received sponsorship to attend scientific meetings, speaker honoraria, and consultancy fees from Lundbeck and Merck-Lipha. Patrick Bendimerad received honoraria and travel reimbursements for conferences and consultancy by Lundbeck Laboratory and participated as a coinvestigator.in the multicenter investigational drug studies of Lundbeck. [...].During many years in France, risk reduction strategies for substance abuse concerned prevention strategies in the general population or interventions near users of illicit substances. In this spirit, the reduction of consumption only concerned opiate addicts. With regard to alcohol, the prevention messages relative to controlled consumption were difficult to transmit because of the importance of this product in the culture of the country. In addition, methods of treatment of alcoholism rested on the dogma of abstinence. Several factors have recently led to an evolution in the treatment of alcohol use disorders integrating the reduction of consumption in strategies. Strategies for reducing consumption should aim for consumption below recommended thresholds (two drinks per day for women, three for the men) or, at least, in that direction. It must also be supported by pharmacotherapy and psychotherapy, which offer possibilities. Failure to manage reduction will allow the goals to be revisited and to reconsider abstinence. Finally this evolution or revolution is a new paradigm carried in particular by a pragmatic approach of the disease andnew treatments. The aims of this article are to give elements of comprehension relating to the evolution of the practices in France in prevention and treatment of alcohol use disorders and in particular with regard to the reduction of consumption.

Merkel cell carcinoma (MCC) is an aggressive tumor, the incidence of which is seemingly increased in immunocompromised patients. We report on a new case of MCC occurring in a 69-year-old male liver transplant recipient 6.5 years after transplantation. The outcome was marked by early skin and lymph node relapses treated by radiotherapy alone, and the patient ultimately died 30 months after first diagnosis. Together with data from the literature, this case emphasizes the importance of early diagnosis and adequate management of this aggressive disease for which wide initial surgical excision, accurate staging, and close follow-up are of critical importance to outcome, especially in this setting of immunosuppressive treatment, which is usually associated with a higher rate of recurrence.