[The psychosocial rehabilitation in addiction medicine]. / La réhabilitation psychosociale en addictologie.

OBJECTIVES: Addictive behaviors constitute complex behaviors that are usually related to social habits, such as substance use, gambling or gaming activities, or sexual or physical activity. They progressively overrun and stifle the routine habits of the concerned individuals, for example within their occupational or family spheres of life, as well as in their hobbies or in their main physiological functions, such as sleep or eating cycles. The rehabilitation approach of care integrates the objective of restoring the altered habits and functional rhythms, to optimize the clinical outcomes and improve quality of life of the concerned persons. METHODS: Using a focused and narrative literature review, we aimed to explain what psychosocial rehabilitation consists in, and why this approach is particularly relevant for the addiction care, although to date it has remained insufficiently developed in the routine practice of many facilities. RESULTS: The "rehab" approach, is first based on a structured and comprehensive assessment of the clinical and functional aspects of the patient, which secondarily allows to frame an individualized project of care that is closely built together with the patient. This project of care can integrate classical pharmacotherapeutic and psychotherapeutic tools, but it also emphasizes wider approaches for restoring some basic social and physiological functions of the concerned person, such as sleep, eating, social functioning, physical activity, or spiritual needs. Priorities among these different dimensions have to be defined by the concerned person. CONCLUSIONS: The "rehab" approach is particularly relevant in addiction medicine. It represents a more global conception of care that conceives the recovery of social and physiological functioning as a core treatment objective for the concerned persons. The consequences for care organization are that many additional professionals should be integrated into the treatment schemes for addiction, including peer counselors, occupational therapists, physical activity coaches, or dieticians.

Should the French approval of baclofen for alcohol dependence be extended to abstinence maintenance?

Ever since 2018 France has been the only country to approve the gamma aminobutyric acid type B (GABA-B) receptor agonist baclofen for alcohol dependence. This authorization follows a ten-year period of intensive off-label use during which baclofen was used in doses of up to 300 and even 400mg per day to support the gradual reduction of alcohol consumption in patients suffering from alcohol dependence. However, in international clinical trials, baclofen has mainly been studied to support the maintenance of abstinence. The French use of baclofen was therefore somewhat atypical as it paved the way for drug-supported approaches to reducing alcohol consumption, even before nalmefene was marketed. In line with this specific use of baclofen, approval was granted only for alcohol reduction support. However, a recent Cochrane systematic review and meta-analysis by Agabio et al. found significant efficacy only for abstinence maintenance, while no significant effect was found on alcohol reduction outcomes and no dose-response relationship was identified in the analyses. The safety of baclofen was judged to be good. Based on these substantial new results, the Société française d'alcoologie (SFA) now considers that baclofen should also be approved for the maintenance of abstinence. The extension of approval should not lead to the removal of the initial indication or the possibility of using high doses, as some patients have found this therapeutic regimen particularly useful for them. France, which has been a open skies national laboratory on the use of baclofen in alcohol dependence for over ten years, should let this original therapeutic option available to patients. However, it should update the regulatory framework defining the main conditions of access to treatment for patients based on the latest and highest scientific evidence.

Opinions of French psychiatrists on the regulatory status of cannabis: Results from the "PsyCan - Encéphale" national online survey.

OBJECTIVE: To explore the opinions of French psychiatrists toward the legalization of medical or recreational use of cannabis in France. METHODS: Psycan was an anonymous Internet survey conducted between September 28, 2021 and March 29, 2022, among subscribers of the Encéphale Online community, i.e., approximately 4000 French psychiatrists. Participants were asked to complete a structured questionnaire, collecting their socio-demographic features, clinical experience, opinions toward cannabis legalization, and perceived impact of cannabis derivatives for psychiatric disorders. Logistic regression models were used to identify factors associated with being for or against cannabis legalization. RESULTS: In total, 413 psychiatrists answered the survey, of whom 253 (61.3%) declared being in favour of recreational cannabis, and 349 (84.4%) of medical cannabis. Being in favour of legalization of recreational cannabis was negatively associated with being female (odd ratio [OR]=0.61; 95% confidence interval [CI]=0.41-0.93), and with the frequency of meeting patients with cannabis use disorder (OR=0.60; 95%CI=0.43-0.83). Most respondents were concerned about the development of psychotic disorders. The most frequent pro-legalization arguments were improved prevention, better control of product content, and better protection of youth, respectively. Arguments against legalization were increased societal damages, increased impact on health, including mental health. CONCLUSIONS: A majority of French psychiatrists were in favour of the marketing of medical cannabis, and, to a lesser extent, the legalization of recreational cannabis. For recreational cannabis, the proportion of pro-legalization psychiatrists was slightly more elevated than that found in the French general population.

[DARJELY, a multidisciplinary support system for young isolated migrants in Lyon]. / DARJELY, le dispositif lyonnais d'accompagnement multidisciplinaire des jeunes migrants en errance.

Young, isolated migrants (YIMs) represent some particularly vulnerable populations that have arrived unaccompanied on the national territory and are particularly exposed to mafia networks, delinquency, and prostitution. YIMs thus cumulate social (e.g., precarity, or isolation), psychiatric (e.g., post-traumatic stress disorder, mood, or anxiety disorders), and addiction (e.g., prescription drug dependence) disorders. This addition of vulnerabilities makes the social and medical support difficult to operationalize as it requires multidisciplinary and coordinated programs. In Lyon, the 2nd-largest urban agglomeration in France, the "Dispositif d'accompagnement en Réseau pour l'accès aux soins psychiatriques et addictologiques des jeunes migrants en errance à Lyon" (DARJELY), ("Network System for supporting psychiatric and addiction care to YIMs in Lyon") has been implemented since early 2023 and gathers the following components: (i) a coordinating pair of professionals (i.e., a street worker and an addiction nurse) who ensure a case management of individual situations and articulate the medical and social support with external partners, (ii) an addiction medicine team, (iii) a psychiatric team working at the same place as the addiction medicine team, and (iv) a socio-educational team that can meet YIMs "in situ" and refer them into care, in particular toward teams (ii) and (iii). Overall, DARJELY is thus an innovative system which offers multidisciplinary and coordinated missions toward YIMs including: (i) meeting YIMs on the ground and referring them to specialized care units through the coordination team; (ii) orchestrating the follow-up with other social or medical stakeholders on the local territory; (iii) collecting and synthetizing data for local decision-makers and partners; and (iv) producing research data for improving the understanding of these hard-to-reach populations. All these missions meet current needs of public health regarding these complex populations whose number has been constantly increasing over the recent years.

Screening problematic use of substances among young subjects attending an emergency department, and subsequent treatment seeking.

INTRODUCTION: Young individuals constitute a key population for the screening of problematic use of substances (PUS), but they are not likely to seek support and are hard to reach. Targeted screening programs should thus be developed in the places of care they may attend for other reasons, including emergency departments (EDs). We aimed to explore the factors associated with PUS in young people attending an ED; we measured the subsequent access to addiction care after ED screening. METHODS: This was a prospective interventional single-arm study which included any individual aged between 16 and 25 years who attended the main ED of Lyon, France. Baseline data were sociodemographic characteristics, PUS status using self-report questionnaires and biological measures, level of psychological health, and history of physical/sexual abuse. Quick medical feedback was provided to the individuals presenting a PUS; they were advised to consult an addiction unit, and contacted by phone at three months to ask whether they had sought treatment. Baseline data were used to compare PUS and non-PUS groups using multivariable logistic regressions, to provide adjusted odds ratios (aORs) and 95% confidence intervals (95% CI), with age, sex, employment status, and family environment as the adjustment variables. The characteristics of PUS subjects who subsequently sought treatment were also assessed using bivariable analyses. RESULTS: In total, 460 participants were included; 320 of whom (69.6%) were presenting current substance use, and 221 (48.0%) with PUS. Compared to non-PUS individuals, PUS ones were more likely to be males (aOR=2.06; 95% CI [1.39-3.07], P<0.001), to be older (per one-year increase: aOR=1.09; 95% CI [1.01-1.17], P<0.05), to have an impaired mental health status (aOR=0.87; 95% CI [0.81-0.94], P<0.001), and to have a history of sexual abuse (aOR=3.33; 95% CI [2.03-5.47], P<0.0001). Only 132 (59.7%) subjects with PUS could be reached by phone at 3 months, among whom only 15 (11.4%) reported having sought treatment. Factors associated with treatment seeking were social isolation (46.7% vs. 19.7%; P=0.019), previous consultation for psychological disorders (93.3% vs. 68.4%; P=0.044), lower mental health score (2.8±1.6 vs. 5.1±2.6; P<0.001), and post-ED hospitalization in a psychiatric unit (73.3% vs. 19.7%; P<0.0001). DISCUSSION/CONCLUSION: EDs are relevant places to screen PUS in youth, but the level of seeking further treatment needs to be substantially improved. Offering systematic screening during an emergency room visit could allow for more appropriate identification and management of youth with PUS.

Profile of patients with a positive HCV viral load in a large French psychiatric hospital (2019-2021): A case-control study.

Hepatitis C virus (HCV) is highly prevalent in people with mental disorders (PWMDs). However, in the international context of HCV elimination, no previous study has explored the features of seropositive PWMDs with vs. without a positive viral load (VL). We retrospectively retrieved all HCV serology results of patients hospitalized in 2019, 2020 and 2021 in the second-largest psychiatric hospital of France. Using the medical records of all patients found seropositive for HCV, the following data were collected: sex (male, female), age (in years), previous history of illicit drug use except cannabis (yes or no) and previous history of incarceration (yes or no). We conducted a case-control comparison of these variables between the PWMDs who had and did not have a positive VL, thus providing odds ratios and 95% confidence intervals (ORs [95% CI]). In a total of 13,276 inpatients, 2540 (19.1%) underwent at least one HCV serology; 55 of them (2.16%) were found positive. A VL count was performed for 48 of them, finding 15 (31.3%) individuals with active HCV. Compared with those with a negative VL, these 15 individuals were less likely to have previous documented illicit drug use (OR = 0.18; 95% CI [0.05-0.68]) and to have been previously incarcerated (OR = 0.23; 95% CI [0.06-0.99]); age and sex did not statistically differ. In the context of HCV elimination, PWMDs yet to be treated for HCV are more likely to be those with no identified risk factor for HCV, which supports a strategy of systematic screening for HCV among PWMDs.

Five Challenges in Implementing Cognitive Remediation for Patients with Substance Use Disorders in Clinical Settings.

Many patients with substance use disorders (SUDs) present cognitive deficits, which are associated with clinical outcomes. Neuropsychological remediation might help rehabilitate cognitive functions in these populations, hence improving treatment effectiveness. Nardo and colleagues (Neuropsychology Review, 32, 161-191, 2022) reviewed 32 studies applying cognitive remediation for patients with SUDs. They underlined the heterogeneity and lack of quality of studies in this research field but concluded that cognitive remediation remains a promising tool for addictive disorders. We capitalize on the insights of this review to identify the key barriers that currently hinder the practical implementation of cognitive remediation in clinical settings. We outline five issues to be addressed, namely, (1) the integration of cognitive remediation in clinical practices; (2) the selection criteria and individual factors to consider; (3) the timing to be followed; (4) the priority across trained cognitive functions; and (5) the generalization of the improvements obtained. We finally propose that cognitive remediation should not be limited to classical cognitive functions but should also be extended toward substance-related biases and social cognition, two categories of processes that are also involved in the emergence and persistence of SUDs.

Clinical features and outcomes of COVID-19 patients hospitalized for psychiatric disorders: a French multi-centered prospective observational study.

BACKGROUND: Patients with psychiatric disorders are exposed to high risk of COVID-19 and increased mortality. In this study, we set out to assess the clinical features and outcomes of patients with current psychiatric disorders exposed to COVID-19. METHODS: This multi-center prospective study was conducted in 22 psychiatric wards dedicated to COVID-19 inpatients between 28 February and 30 May 2020. The main outcomes were the number of patients transferred to somatic care units, the number of deaths, and the number of patients developing a confusional state. The risk factors of confusional state and transfer to somatic care units were assessed by a multivariate logistic model. The risk of death was analyzed by a univariate analysis. RESULTS: In total, 350 patients were included in the study. Overall, 24 (7%) were transferred to medicine units, 7 (2%) died, and 51 (15%) patients presented a confusional state. Severe respiratory symptoms predicted the transfer to a medicine unit [odds ratio (OR) 17.1; confidence interval (CI) 4.9-59.3]. Older age, an organic mental disorder, a confusional state, and severe respiratory symptoms predicted mortality in univariate analysis. Age >55 (OR 4.9; CI 2.1-11.4), an affective disorder (OR 4.1; CI 1.6-10.9), and severe respiratory symptoms (OR 4.6; CI 2.2-9.7) predicted a higher risk, whereas smoking (OR 0.3; CI 0.1-0.9) predicted a lower risk of a confusional state. CONCLUSION: COVID-19 patients with severe psychiatric disorders have multiple somatic comorbidities and have a risk of developing a confusional state. These data underline the need for extreme caution given the risks of COVID-19 in patients hospitalized for psychiatric disorders.

Sodium Oxybate for Alcohol Dependence: A Network Meta-Regression Analysis Considering Population Severity at Baseline and Treatment Duration.

AIMS: The 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 <14 days of abstinence before treatment initiation (high-severity population) from other patients (mild-severity population). Treatment duration reflects the planned treatment duration. This study aimed to systematically investigate the effect of these potential effect moderators on SMO efficacy in alcohol-dependent patients. METHODS: Network 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. RESULTS: Eight 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 < 0.001. For PDA, longer treatment duration was associated with larger SMO effect size: +11.3% per extra month, P < 0.001. In the high-severity group, SMO showed benefit: abstinence rate RR 2.91, P = 0.03; PDA +16.9%, P < 0.001. In the mild-severity group, SMO showed benefit only in PDA for longer treatment duration: +23.9%, P < 0.001. CONCLUSIONS: In the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes.

Education and Training in Addiction Medicine and Psychology across Europe: A EUFAS Survey.

INTRODUCTION: Training in addiction medicine and addiction psychology is essential to ensure the quality of treatment for patients with substance use disorders. Some earlier research has shown varying training between countries, but no comprehensive study of addiction training across Europe has been performed. The present study by the European Federation for Addiction Societies (EUFAS) aimed to fill this gap. METHODS: A Delphi process was used to develop a questionnaire on specialist training in addiction treatment in 24 European countries. The final questionnaire consisted of 14 questions on either addiction medicine or addiction psychology, covering the nature and content of the training and institutional approval, the number of academic professorial positions, and the estimated number of specialists in each country. RESULTS: Information was not received from all countries, but six (Belgium, Denmark, Ireland, Italy, Poland, and Romania) reported no specialized addiction medicine training, while 17 countries did. Seven countries (Belgium, France, Ireland, Italy, Russia, Switzerland, and the Netherlands) reported no specialized addiction psychology training, while 14 countries did. Training content and evaluation methods varied. Approval was given either by governments, universities, or professional societies. Eighteen countries reported having professorships in addiction medicine and 12 in addiction psychology. The number of specialists in addiction medicine or psychology varied considerably across the countries. DISCUSSION: The survey revealed a large heterogeneity in training in addiction medicine and addiction psychology across Europe. Several countries lacked formal training, and where formal training was present, there was a large variation in the length of the training. Harmonization of training, as is currently the case for other medical and psychology specializations, is warranted to ensure optimal treatment for this under-served patient group.

Willingness to use a drug consumption room among people who use drugs in Lyon, France, a city with no open scene of drug use (the TRABOUL survey).

BACKGROUND: Drug consumption rooms (DCRs) have been developed in cities with open drug scenes, with the aim to reduce drug-related harm. In Lyon, France's second-largest city, there is no distinct drug use area, which raised doubts regarding the need for a DCR. METHODS: We conducted a face-to-face survey of 264 people who use drugs (PWUDs), recruited in harm reduction or addiction treatment centers, in the streets or in squats. We assess their willingness to use a DCR, and we collected sociodemographic and medical features. Bivariable comparisons and analyses adjusted for sociodemographic parameters explored the association between willing to use a DCR and other variables, thus providing crude (ORs) and adjusted odds ratios (aORs) and 95% confidence intervals (95% CI). RESULTS: In total, 193 (73.1%) PWUDs accepted to participate (mean age 38.5 ± 9.3 years; 80.3% men). Among them, 64.2% declared willing to use a DCR. Being treatment-seeker (aOR 0.20, 95% CI [0.08-0.51]; p < 0.001) and not living alone (aOR 0.29; 95% CI [0.10-0.86], p = 0.025) were negatively associated with willing to use a DCR. By contrast, receiving precarity social insurance (aOR 4.12; 95% CI [1.86-9.14], p < 0.001), being seropositive for hepatitis C (aOR 3.60; 95% CI [1.20-10.84], p = 0.022), being cannabis user (aOR 2.45; 95% CI [1.01-5.99], p = 0.049), and reporting previous problems with residents (aOR 5.99; 95% CI [2.16-16.58], p < 0.001) or with the police (aOR = 4.85; 95% CI [1.43-16.39], p = 0.011) were positively associated. CONCLUSIONS: PWUDs, especially the most precarious ones, largely supported the opening of a DCR in Lyon, a city with no open drug scene.

Management of alcohol-related liver disease: the French Association for the Study of the Liver and the French Alcohol Society clinical guidelines.

Excessive alcohol consumption is the leading cause of liver diseases in Western countries, especially in France. Alcohol-related liver disease (ARLD) is an extremely broad context and there remains much to accomplish in terms of identifying patients, improving prognosis and treatment, and standardising practices. The French Association for the Study of the Liver wished to organise guidelines together with the French Alcohol Society in order to summarise the best evidence available about several key clinical points in ARLD. These guidelines have been elaborated based on the level of evidence available in the literature and each recommendation has been analysed, discussed and voted by the panel of experts. They describe how patients with ARLD should be managed nowadays and discuss the main unsettled issues in the field.

Gender-related associations between psychiatric disorders and alcohol use disorder: Findings from the french "Mental health in the general population" survey.

Women with alcohol use disorder (AUD) might be particularly vulnerable to psychiatric comorbidities. However, population surveys have yielded disparate findings. We used data from the French Mental Health in the General Population survey to investigate gender-related risks of psychiatric comorbidities associated with AUD. A cross-sectional survey based on face-to-face interviews, including the Mini International Neuropsychiatric Interview, was conducted among 38,717 subjects. Logistic regression models were used to assess risks of psychiatric comorbidities associated with AUD. After adjustment for socio-demographics and other psychiatric disorders, both women and men with AUD were at higher risk of comorbid depressive disorder (odds ratio [OR] = 2.6, 95% confidence interval [CI]: 2.0-3.4 in women, and OR = 2.0, 95% CI: 1.7-2.4 in men), bipolar I disorder (2.5; 1.4-4.4 in women vs. 2.6; 1.9-3.4 in men), and psychotic disorder (1.6; 1.01-2.5 in women vs. 1.8; 1.4-2.3 in men). Women with AUD exhibited an increased risk of comorbid panic disorder (OR = 1.6, 95% CI: 1.1-2.2) while the increased risk of post-traumatic stress disorder (PTSD) was significant in men only (OR = 2.6, 95% CI: 1.6-4.2). The increased risk of comorbid substance use disorder (SUD) was more elevated in women, compared to men (12.9; 8.1-18.1 vs. 4.8; 4.0-5.8 in men). Most of psychiatric conditions were over-represented in both women and men with AUD, relative to controls. Gender-specific findings were that women with AUD had an increased risk of comorbid SUD or panic disorder, while men had a significantly higher risk of comorbid PTSD.

Substance Use, Substance Use Disorders, and Co-Occurring Psychiatric Disorders in Recently Incarcerated Men: A Comparison with the General Population.

INTRODUCTION: The rates of alcohol and illegal drug use and the prevalence of alcohol and illegal drug use disorders (AUDs and DUDs) are high in prison populations, particularly in men entering jail. However, these rates have never been exhaustively assessed and compared to those of the general population in France. METHODS: We based our research on two surveys, conducted in the same French region, which included a total of 630 men entering jail and 5,793 men recruited from the general population. We used the Mini-International Neuropsychiatric Interview to assess alcohol and drug use, AUD, DUD, as well as co-occurring psychiatric disorders, and we examined differences in prevalence rates between the two populations. Logistic regression models were performed to (i) identify the factors associated with AUD and DUD and (ii) test whether the interaction between admission to jail and the presence of AUD, DUD, or both is linked to the presence of at least one co-occurring psychiatric disorder. RESULTS: Compared to the general population sample, the prevalence of AUD (33.8% vs. 8.7%, p < 0.001) and DUD (at least one type of drug: 28.7% vs. 5.0%, p < 0.001; cannabis: 24.0% vs. 4.7%, p < 0.001; opioids: 6.8% vs. 0.4%, p < 0.001; stimulants: 5.2% vs. 0.8%, p < 0.001) was significantly higher in the jail population sample, as well as the rates of past-year use of various substances (alcohol: 62.1% vs. 56.4%, p = 0.007; at least one type of illegal drug: 50.0% vs. 14.4%, p < 0.001; cannabis: 45.6% vs. 13.9%, opioids: 9.4% vs. 0.7%; stimulants: 8.6% vs. 1.9%). Admission to jail was associated with a higher risk of AUD (aOR = 3.80, 95% CI: 2.89-5.01, p < 0.001) or DUD (aOR = 4.25, 95% CI: 3.10-5.84, p < 0.001). History of trauma was also associated with both AUD (aOR = 1.81, 95% CI: 1.53-2.14, p < 0.001) and DUD (aOR = 2.15, 95% CI: 1.74-2.65, p < 0.001), whereas history of migration was only associated with DUD (aOR = 1.38, 95% CI: 1.12-1.71, p = 0.003). AUDs and DUDs were more strongly associated with co-occurring psychiatric disorders in incarcerated men than in the general population. Among individuals with AUD, DUD, or both, co-occurring anxiety and mood disorders were particularly more frequent in jail than in the general population. DISCUSSION/CONCLUSION: As in most countries, AUD and DUD are highly prevalent among men entering jail in France. Our results also suggest that incarceration constitutes an independent vulnerability factor for a dual disorder, which supports a systematic assessment and treatment of psychiatric disorders in men entering jail and diagnosed with an AUD or DUD.

One-month alcohol abstinence national campaigns: a scoping review of the harm reduction benefits.

Over the last decade, one-month alcohol abstinence campaigns (OMACs) have been implemented within the general population in an increasing number of countries. We identified the published studies reporting data on OMACs to explore the following aspects: profile of participants, rates and factors associated with the completion of the abstinence challenge, and outcomes and harm reduction benefits in participating in the challenges. We screened 322 records, including those found in the grey literature, and reviewed 6 studies and 7 Dry July Annual Reports. Compared to non-participating alcohol users, participants were more likely to be female, have a higher income, and a higher level of education. They were heavier drinkers and were more concerned by the consequences of alcohol on health and by their health in general. Participants who achieved the one-month abstinence challenge were lower drinkers and more likely to have registered on the campaign-related Internet communities. Both successful and unsuccessful participants frequently reported health benefits, including sleep improvement and weight loss. Successful participants were more likely to durably change their alcohol drinking habits. Overall, OMACs provide short- or mid-term harm reduction benefits for both successful and unsuccessful participants. Findings were limited by the paucity of studies, their observational nature, and heterogeneity in the features of the different national campaigns, which would probably gain in enhanced internationalization.

Adherence to opioid agonist therapy predicts uptake of direct-acting antivirals in people who use drugs: results from the French national healthcare database (the ANRS FANTASIO study).

BACKGROUND: Opioid agonist therapy (OAT) is associated with reduced injection, reduced HCV transmission, and more opportunities to initiate hepatitis C virus (HCV) treatment in people who use drugs (PWUD). We aimed to study the extent to which adherence to OAT was predictive of increased uptake of direct-acting antivirals (DAA) in PWUD with chronic HCV infection. METHODS: Using the French national healthcare system database, we targeted PWUD (i.e. with a history of OAT) who had chronic HCV infection and were eligible for DAA during 2014-2016. Adherence to OAT was computed as a time-varying variable expressing the proportion of days covered by OAT receipt, over any six-month interval before DAA receipt. We used a Cox proportional hazards model to estimate the association between adherence to OAT and the rate of DAA uptake after adjustment for age, sex, alcohol use disorder, socioeconomic status, and liver disease severity. RESULTS: Among the 22,615 persons included in the ANRS FANTASIO study, 3438 (15.2%) initiated DAA during the study period. After multivariable adjustment, adherence to OAT was associated with a higher rate of DAA initiation. However, this association was not linear, and only individuals on OAT for 20% or more of the time in the previous six-month period had a higher rate of DAA initiation (adjusted hazard ratio [95% confidence interval]: 1.28 [1.18-1.38]). Other variables associated with DAA initiation were male sex, older age, cirrhosis or liver cancer, and higher socioeconomic status. CONCLUSIONS: Adherence to OAT is a major predictor of DAA initiation in PWUD living with chronic HCV infection in France. Our results also suggest that even moderate adherence to OAT can facilitate DAA uptake. Adequate HCV training for OAT prescribers together with interventions to ensure adherence to OAT will help improve DAA initiation rates and reach HCV elimination goals.

Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: A meta-regression analysis to develop an enrichment strategy.

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.

Efficacy and safety of topiramate in binge eating disorder: a systematic review and meta-analysis.

BACKGROUND: To assess the efficacy and safety of topiramate in treating binge eating disorder (BED), using a systematic review and meta-analysis of the available randomized clinical trials (RCTs). METHODS: The RCTs assessing topiramate vs placebo with or without adjunctive psychotherapy in BED were reviewed using a systematic search in the PubMed, Web of Science, PsycINFO, Cochrane Database of Systematic Review, and ClinicalTrials.gov search Websites, from inception to November 2019. Main outcomes were the changes in binge frequency, quality of life, and weight, respectively. Effect estimates were pooled using random-effect models and presented as risk ratios (RRs) or mean differences (MDs) and their 95% confidence interval (95% CI). Data extraction was performed by two independent reviewers. RESULTS: Three studies were eligible for inclusion, involving 528 BED patients. Topiramate was found to be significantly more efficacious than placebo in reducing: (a) the number of binge episodes per week (MD = -1.31; 95% CI = -2.58 to -0.03; I2 = 94%); (b) the number of binge days per week (MD = -0.98; 95% CI = -1.80 to -0.16; I2 = 94%); and (c) weight (MD = -4.91 kg; 95% CI = -6.42 to -3.41; I2 = 10%). However, participants in the topiramate groups withdrew significantly more frequently for safety reasons, relative to placebo participants (RR = 1.90; 95% CI = 1.13-3.18, I2 = 0%). CONCLUSIONS: Preliminary findings support a possible efficacy of topiramate for the treatment of BED, even if safety concerns could limit the practical use of this treatment in BED subjects.

Religiosity and prevalence of suicide, psychiatric disorders and psychotic symptoms in the French general population.

We aimed to examine the association between religious beliefs and observance and the prevalence of psychiatric disorders, psychotic symptoms and history of suicide attempts in the French general population. The cross-sectional survey interviewed 38,694 subjects between 1999 and 2003, using the MINI. Current religious beliefs and observance were identified by means of two questions: "are you a believer?" and "are you religiously observant?". We studied the association between religiosity and psychiatric outcomes using a multivariable logistic regression model adjusted for sociodemographic characteristics, including migrant status. Religious beliefs were positively associated with psychotic symptoms and disorders [OR = 1.37, 95% CI (1.30-1.45) and OR = 1.38, 95% CI (1.20-1.58)], unipolar depressive disorder [OR = 1.15, 95% CI (1.06-1.23)] and generalized anxiety disorder [OR = 1.13, 95% CI (1.06-1.21)], but negatively associated with bipolar disorder [OR = 0.83, 95% CI (0.69-0.98)], alcohol use disorders [OR = 0.69, 95% CI (0.62-0.77)], substance use disorders [OR = 0.60, 95% CI (0.52-0.69)] and suicide attempts [OR = 0.90, 95% CI (0.82-0.99)]. Religious observance was positively associated with psychotic symptoms and disorders [OR = 1.38, 95% CI (1.20-1.58) and OR = 1.25, 95% CI (1.07-1.45)], but negatively associated with social anxiety disorder [OR = 0.87, 95% CI (0.76-0.99)], alcohol use disorders [OR = 0.60, 95% CI (0.51-0.70)], substance use disorders [OR = 0.48, 95% CI (0.38-0.60)] and suicide attempts [OR = 0.80, 95% CI (0.70-0.90)]. Among believers, religious observance was not associated with psychotic outcomes. Religiosity appears to be a complex and bidirectional determinant of psychiatric symptoms and disorders. In this respect, religiosity should be more thoroughly assessed in epidemiological psychiatric studies, as well as in clinical practice.

Validation of the Opioid Overdose Knowledge (OOKS) and Attitudes (OOAS) Scales in French, Spanish, and German Languages, among a Sample of Opioid Users.

INTRODUCTION: Improving the knowledge and attitudes of people facing an opioid overdose is one of the key prevention measures for reducing overdose occurrence and severity. In this respect, the Opioid Overdose Knowledge Scale (OOKS) and Opioid Overdose Attitudes Scale (OOAS) have been developed and validated in English to assess and improve knowledge and attitudes of opioid users and their families and care providers, in case of an overdose. Here, the OOKS and OOAS scales have been translated into French, Spanish, and German, and the different versions of the 2 scales have been assessed regarding their psychometric properties. METHODS: The translation procedure of the scales was based on the international recommendations, including a back translation by a native English speaker. Subsequently, 80 (Spain: 29, France: 27, Germany: 24) former or current heroin users, aged from 20 to 61 years (M = 39.4 ± 9.23), completed the OOKS and OOAS versions of their native language, in test-retest, without specific between-assessment training. Internal consistency was assessed using Cronbach's α, while test-retest reliability was assessed using intraclass correlation coefficient (ICC). The correlation between the OOKS and OOAS scores of a same language was assessed using Spearman's (ρ) coefficient. RESULTS: Internal consistency of the OOKS was found to be good to very good, with Cronbach's α ranging from 0.62 to 0.87. Test-retest reliability was also very good, with ICCs ranging from 0.71 to 0.82. However, results were less reliable for the OOAS, as internal consistency was questionable to acceptable, with Cronbach's α ranging from 0.12 to 0.63, while test-retest ICCs were very good for the French (0.91) and Spanish (0.99) versions and barely acceptable for the German version (0.41). No significant correlation was found between the OOKS and OOAS scores, irrespective of the version concerned. CONCLUSION: While satisfactory results were found for the 3 versions of the OOKS, results on the OOAS were relatively inconsistent, suggesting a possible gap between knowledge and attitudes on overdose among opioid users.