An epigenetic candidate-gene association study of parental styles in suicide attempters with substance use disorders.

Suicide attempts (SA) are prevalent in substance use disorders (SUD). Epigenetic mechanisms may play a pivotal role in the molecular mechanisms of environmental effects eliciting suicidal behaviour in this population. Hypothalamic-pituitary-adrenal axis (HPA), oxytocin and neurotrophin pathways have been consistently involved in SA, yet , their interplay with childhood adversity remains unclear, particularly in SUD. In 24 outpatients with SUDs, we examined the relation between three parental dysfunctional styles and history of SA with methylation of 32 genes from these pathways, eventually analysing 823 methylation sites. Extensive phenotypic characterization was obtained using a semi-structured interview. Parental style was patient-reported using the Measure of Parental Style (MOPS) questionnaire, analysed with and without imputation of missing items. Linear regressions were performed to adjust for possible confounders, followed by multiple testing correction. We describe both differentially methylated probes (DMPs) and regions (DMRs) for each set of analyses (with and without imputation of MOPS items). Without imputation, five DMRs in OXTR, CRH and NTF3 significantly interacted with MOPS father abuse to increase the risk for lifetime SA, thus covering the three pathways. After imputation of missing MOPS items, two other DMPs from FKBP5 and SOCS3 significantly interacted with each of the three father styles to increase the risk for SA. Although our findings must be interpreted with caution due to small sample size, they suggest implications of stress reactivity genes in the suicidal risk of SUD patients and highlight the significance of father dysfunction as a potential marker of childhood adversity in SUD patients.

Predictors of abstinence maintenance after cocaine inpatient detoxification: A prospective study.

BACKGROUND AND OBJECTIVES: Cocaine is a highly addictive substance, and with no approved medication for cocaine use disorder (CUD), leading to a heavy burden. Despite validated psychosocial treatments, relapse rates after detoxification are very high in CUD. Few consistent factors can predict abstinence after detoxification. Our study, therefore, aimed at identifying factors predicting abstinence among CUD patients after inpatient detoxification. METHODS: Eighty-one CUD inpatients were included during detoxification and characterized for clinical and sociodemographic data at baseline and at a follow-up of 3 months after discharge, including a standard measure of their abstinence duration from cocaine. We performed Cox univariate analyzes to determine the factors associated with abstinence maintenance, followed by a multivariate Cox regression to identify independent predictors. RESULTS: Abstinence maintenance was shorter in patients injecting cocaine (hazard ratio [HR] = 5.16, 95% confidence interval [CI]: 2.01-13.27, p < .001) and using cocaine heavily in the month before inclusion (HR = 1.03, 95% CI: 1.00-1.06, p = .046). Conversely, abstinence maintenance was longer in patients with longer inpatient detoxification stays (HR = 0.96, 95% CI: 0.94-0.99, p = .015) and prescribed with selective serotonin reuptake inhibitors (SSRIs) (HR = 0.30, 95% CI: 0.16-0.56, p < .001). DISCUSSION AND CONCLUSIONS: Patients with severe CUD may require longer inpatient stays to achieve abstinence. Regarding SSRI prescription, more specific studies are needed to provide stronger recommendations about their use in clinical practice. SCIENTIFIC SIGNIFICANCE: Our findings suggest several modifiable factors to improve inpatient treatment response in CUD. As there are no specific recommendations about the optimal duration of inpatient stay, our results could pave the way for evidence-based guidelines.

The clinical course of comorbid substance use disorder and attention deficit/hyperactivity disorder: protocol and clinical characteristics of the INCAS study.

BACKGROUND: Substance use disorders (SUD) often co-occur with attention deficit hyperactivity disorder (ADHD). Although the short-term effects of some specific interventions have been investigated in randomized clinical trials, little is known about the long-term clinical course of treatment-seeking SUD patients with comorbid ADHD. AIMS: This paper presents the protocol and baseline clinical characteristics of the International Naturalistic Cohort Study of ADHD and SUD (INCAS) designed and conducted by the International Collaboration on ADHD and Substance Abuse (ICASA) foundation. The overall aim of INCAS is to investigate the treatment modalities provided to treatment-seeking SUD patients with comorbid ADHD, and to describe the clinical course and identify predictors for treatment outcomes. This ongoing study employs a multicentre observational prospective cohort design. Treatment-seeking adult SUD patients with comorbid ADHD are recruited, at 12 study sites in nine different countries. During the follow-up period of nine months, data is collected through patient files, interviews, and self-rating scales, targeting a broad range of cognitive and clinical symptom domains, at baseline, four weeks, three months and nine months. RESULTS: A clinically representative sample of 578 patients (137 females, 441 males) was enrolled during the recruitment period (June 2017-May 2021). At baseline, the sample had a mean age (SD) of 36.7 years (11.0); 47.5% were inpatients and 52.5% outpatients; The most prevalent SUDs were with alcohol 54.2%, stimulants 43.6%, cannabis 33.1%, and opioids 14.5%. Patients reported previous treatments for SUD in 71.1% and for ADHD in 56.9%. Other comorbid mental disorders were present in 61.4% of the sample: major depression 31.5%, post-traumatic stress disorder 12.1%, borderline personality disorder 10.2%. CONCLUSIONS: The first baseline results of this international cohort study speak to its feasibility. Data show that many SUD patients with comorbid ADHD had never received treatment for their ADHD prior to enrolment in the study. Future reports on this study will identify the course and potential predictors for successful pharmaceutical and psychological treatment outcomes. TRIAL REGISTRATION: ISRCTN15998989 20/12/2019.

Plasma tau, NfL, GFAP and UCHL1 as candidate biomarkers of alcohol withdrawal-associated brain damage: A pilot study.

In this translational study, we investigated the plasma tau protein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), which are established biomarkers of neurological injury, as predictive biomarkers of alcohol withdrawal-associated brain toxicity. In the clinical study, patients with severe alcohol use disorder (AUD) on D1 of hospitalization for alcohol cessation (AC) (N = 36) were compared to severe AUD patients with at least 3 months of abstinence (N = 16). Overall, patients were 40 men (76.9%), aged 49.8 years [SD ±9.9]. Tau, NfL, GFAP and UCHL1 levels were measured using SIMOA and analysed with a quasipoisson regression model adjusted for age and sex. The NfL level was higher in the AC group (p = 0.013). In the AC group, the tau (p = 0.021) and UCHL1 (p = 0.021) levels were positively associated with the dose of diazepam per weight, and the tau (p = 0.045), NfL (p = 4.9 × 10-3 ) and UCHL1 (p = 0.036) levels were higher in the presence of signs of Wernicke's encephalopathy (n = 9). In the preclinical study, NfL and GFAP levels were assessed in the alcohol deprivation effect (ADE) procedure (N = 17) and control Wistar rats (N = 15). Furthermore, ADE rats were prospectively assessed: after 24 h (T1) and 3 weeks of AC (T2) (paired-samples Wilcoxon and Mann-Whitney tests). The NfL level was higher in the ADE model than in the control rats at both T1 and T2 (p = 0.033 and p = 1.3 × 10-3 ) and higher at T2 than at T1 (p = 0.040). Plasma tau, NfL and UCHL1 are potential biomarkers of brain suffering during alcohol withdrawal.

Childhood trauma and the severity of past suicide attempts in outpatients with cocaine use disorders.

Introduction: Suicide attempts have been associated with both cocaine use disorder (CocUD) and childhood trauma. We investigated how childhood trauma is an independent risk factor for serious and recurrent suicide attempts in CocUD. Method: 298 outpatients (23% women) with CocUD underwent standardized assessments of substance dependence (Diagnostic and Statistical Manual-mental disorders, fourth edition, text revised), impulsiveness, resilience, and childhood trauma, using validated tools. Suicide attempts history was categorized as single vs. recurrent or non-serious vs. serious depending on the lifetime number of suicide attempts and the potential or actual lethality of the worst attempt reported, respectively. Bivariate and multinomial regression analyses were used to characterize which childhood trauma patterns were associated with the suicide attempts groups. Results: 58% of CocUD patients reported childhood trauma. Recurrent and serious suicide attempts clustered together and were thus combined into "severe SA." Severe suicide attempt risk increased proportionally to the number of childhood traumas (test for trend, p = 9 × 10-7). Non-severe suicide attempt risk increased with impulsiveness and decreased with resilience. In multinomial regression models, a higher number of traumas and emotional abuse were independently and only associated with severe vs. non-severe suicide attempts (effect size = 0.82, AUC = 0.7). The study was limited by its cross-sectional design. Conclusion: These preferential associations between childhood trauma and severe suicide attempts warrant specific monitoring of suicide attempts risk in CocUD, regardless of the severity of addiction profiles.

Cerebrospinal Fluid Biomarkers in Patients With Alcohol Use Disorder and Persistent Cognitive Impairment.

BACKGROUND: The prevalence of cognitive impairment is high among alcohol-dependent patients. Although the clinical presentation of alcohol-related cognitive disorder (ARCD) may resemble that of Alzheimer's disease (AD), the prognosis and treatment of the 2 diseases are different. Cerebrospinal fluid (CSF) biomarkers (tau, phosphorylated tau, and amyloid ß) have high diagnostic accuracy in AD and are currently being used to discriminate between psychiatric disorders and AD, but are not used to diagnose ARCD. The aim of this study was to characterize CSF biomarkers in a homogeneous, cognitively impaired alcohol-dependent population. METHODS: This single-center study was conducted in an addiction medicine department of a Parisian Hospital. We selected patients with documented persistent cognitive impairment whose MoCA (Montreal Cognitive Assessment) score was below 24/30 after at least 1 month of documented inpatient abstinence from alcohol. We measured the CSF biomarkers (tau, phosphorylated tau, and amyloid ß 1-42 and 1-40) in 73 highly impaired alcohol-dependent patients (Alcohol Use Disorders Identification Test score over 11 for women and 12 for men) with. RESULTS: Patients' average age was 60 ± 9.1 years and 45 (61.6%) had a normal CSF profile, 8 (11.0%) had a typical CSF AD profile, and 20 (27.4%) had an intermediate CSF profile. CONCLUSIONS: This study revealed a high prevalence of AD in alcohol-dependent patients with persistent cognitive deficits and several anomalies in their CSF profiles. Thus, it is important to consider AD in the differential diagnosis of persistent cognitive deficits in patients with alcohol dependence and to use CSF biomarkers in addition to imaging and neuropsychological testing to evaluate alcohol-related cognitive impairment.

Is R(+)-Baclofen the best option for the future of Baclofen in alcohol dependence pharmacotherapy? Insights from the preclinical side.

For several decades, studies conducted to evaluate the efficacy of RS(±)-Baclofen in the treatment of alcohol dependence yielded contrasting results. Human and animal studies recently questioned the use of the racemic drug in patients since a potential important role of the different enantiomers has been revealed with an efficacy thought to reside with the active R(+)-enantiomer. Here we conducted experiments in the postdependent rat model of alcohol dependence to compare the efficacy of R(+)-Baclofen or S(-)-Baclofen to that of RS(±)-Baclofen on ethanol intake, seeking, and relapse. R(+)-Baclofen was more effective than RS(±)-Baclofen in reducing ethanol intake and seeking during acute withdrawal and during relapse after abstinence. We also used an original population approach in order to identify drug responders. We found a significant proportion of responders to S(-)-Baclofen and RS(±)-Baclofen, displaying an increase in ethanol intake, and this increasing effect on alcohol intake was not seen in the R(+)-Baclofen group. At an intermediate dose of R(+)-Baclofen, devoid of any motor side effects, we identified a very large proportion of responders (75%) with a large decrease in ethanol intake (90% decrease). Finally, the response to RS(±)-Baclofen on ethanol intake was correlated to plasma level of Baclofen. R(+)-Baclofen and RS(±)-Baclofen were effective in reducing sucrose intake. Our study has important clinical implication since it suggests that the wide variability in the therapeutic responses of patients to RS(±)-Baclofen may come from the sensitivity to the R(+)-Baclofen but also to the one of the S(-)-Baclofen that can promote an increase in ethanol intake.

A governmental program to encourage medical students to deliver primary prevention: experiment and evaluation in a French faculty of medicine.

BACKGROUND: A public health student service was set up by the French government in 2018 with the aim of increasing awareness of primary health promotion among the 47,000 students of medicine and other health professions. It is an annual program involving community-based actions on nutrition, physical activity, addiction or sexuality. Our objective was to evaluate its implementation at local level and the different experiences of the stakeholders. METHODS: A quasi-experimental study using process evaluation was performed in a Faculty of Medicine in Paris. Quantitative and qualitative data were collected from medical students who carried out preventive health actions, in the institutions in which the actions took place and from a subsample of beneficiaries. RESULTS: One hundred and eight actions were carried out by 341 students in 23 educational or social institutions, mostly high schools (n = 12, 52%). Two thirds of the students did not feel sufficiently prepared to deliver preventive health interventions (65.7%, 224/341); however the beneficiaries found that the interventions were good (278/280, 99,2%). Nineteen (83%) of the host institutions agreed to welcome health service students again, of which 9 required some modifications. For students, the reporting of a satisfactory health service experience was associated with the reporting of skills or knowledge acquisition (p < 0.01). Delivering actions in high schools and to a medium-sized number of beneficiaries per week was associated with students' satisfaction. No effect of gender or theme of prevention was observed. For 248/341 (72.7%) students, the public health service program prompts them to address prevention issues in the future. CONCLUSION: The public health service undertaken by medical students through the program is a feasible and acceptable means of delivering preventive actions. Reinforcement of training and closer interaction with the host institutions would improve results.

Biomarkers to predict staging and treatment response in opioid dependence: A narrative review.

Opioid use disorder is a devastating disorder with a high burden in terms of overdose mortality, with an urgent need for more personalized prevention or therapeutic interventions. For this purpose, the description and validation of biological measures of staging or treatment response is a highly active research field. We conducted a narrative review on the pathophysiology of opioid use disorder to propose staging of the disease and search for research studies proposing or demonstrating the predictive value of biomarkers. We propose a IV stage description of opioid use disorder, from (I) vulnerability stage to (II) disease progression, (III) constituted opioid dependence and were several type of treatments can be applied, to the reach a (IV) modified health state. We classified biomarkers studies according to the stage of the disorder they were intended to predict, and to the three categories of methods they used: anatomical and functional aspects of the brain, genetic/transcriptomic/epigenetic studies, and lastly biomarkers of systemic modifications associated with opioid use disorder, especially regarding the immune system. Most studies predicting Stage III that we reviewed collected data from small samples sizes and were cross-sectional association studies comparing opioid dependent patients and control groups. Pharmacogenetic biomarkers are proposed to predict treatment response. Future research should now emphasize prospective studies, replication in independent samples, and predictive value calculation of each biomarker. The most promising results are multimodal evaluations to be able to measure the state of the brain reward system in living individuals.

Brain 18FDG-PET pattern in patients with alcohol-related cognitive impairment.

PURPOSE: Brain positron emission tomography using 18F-fluorodeoxyglucose (18FDG-PET) provides a metabolic assessment of brain function that is useful for differential diagnosis among several neurodegenerative diseases manifested by cognitive impairment (CI). The purpose of the study is to describe the pattern of 18FDG-PET abnormalities in patients with CI related to alcohol use disorder. METHODS: Patients admitted to the addiction medicine department of a university hospital in Paris between January 2017 and October 2018 with a confirmed diagnosis of alcohol-related cognitive impairment (ARCI) or Wernicke encephalopathy (WE) were included. Brain 18FDG-PET uptake was measured after at least 1 month of monitored abstinence from alcohol. Standardized uptake values were obtained for 13 regions of interest (ROI) and normalized to the pons. Individual patients' ROI Z-scores were calculated from healthy sex- and age-matched controls provided by Cortex ID software. RESULTS: Twenty-five patients were included in the analysis (20 males and 5 females; mean age 57.6 years (45-76 years old)). The group consisted of 19 ARCI and 6 WE cases. The mean hypometabolism was most severe in the prefrontal medial cortex (PFM) (- 2.80 (± 1.30)), the prefrontal lateral cortex (- 2.20 (± 1.35)), and the anterior cingulate cortex (- 2.24 (± 1.19)). Hypometabolism (Z-score < - 2) was most frequent in the PFM (72.0% of the sample, N = 18). Other regions were also affected (with 5.32/13 hypometabolic ROIs on average (SD = 4.16, range 0-13)). The Z-scores in the 13 ROIs did not differ significantly between the ARCI and WE patients (p ≥ 0.05). CONCLUSIONS: Predominant prefrontal and cingulate cortex hypometabolism was the most frequent brain 18FDG-PET pattern in our sample of patients with ARCI and WE.

Potential influence of socioeconomic status on genetic correlations between alcohol consumption measures and mental health.

BACKGROUND: Frequency and quantity of alcohol consumption are metrics commonly used to measure alcohol consumption behaviors. Epidemiological studies indicate that these alcohol consumption measures are differentially associated with (mental) health outcomes and socioeconomic status (SES). The current study aims to elucidate to what extent genetic risk factors are shared between frequency and quantity of alcohol consumption, and how these alcohol consumption measures are genetically associated with four broad phenotypic categories: (i) SES; (ii) substance use disorders; (iii) other psychiatric disorders; and (iv) psychological/personality traits. METHODS: Genome-Wide Association analyses were conducted to test genetic associations with alcohol consumption frequency (N = 438 308) and alcohol consumption quantity (N = 307 098 regular alcohol drinkers) within UK Biobank. For the other phenotypes, we used genome-wide association studies summary statistics. Genetic correlations (rg) between the alcohol measures and other phenotypes were estimated using LD score regression. RESULTS: We found a substantial genetic correlation between the frequency and quantity of alcohol consumption (rg = 0.52). Nevertheless, both measures consistently showed opposite genetic correlations with SES traits, and many substance use, psychiatric, and psychological/personality traits. High alcohol consumption frequency was genetically associated with high SES and low risk of substance use disorders and other psychiatric disorders, whereas the opposite applies for high alcohol consumption quantity. CONCLUSIONS: Although the frequency and quantity of alcohol consumption show substantial genetic overlap, they consistently show opposite patterns of genetic associations with SES-related phenotypes. Future studies should carefully consider the potential influence of SES on the shared genetic etiology between alcohol and adverse (mental) health outcomes.

COPD Positive Screening with Spirometry Increases Motivation to Quit Tobacco Smoking in an Addiction Treatment Center.

Providing an on-site immediate diagnosis of Chronic Obstructive Pulmonary Disease (COPD) and lung age in tobacco smokers could be a motivational tool for smoking cessation. Our aim was to investigate the effects of an abnormal spirometry results on motivational change and subsequent smoking cessation. We conducted a retrospective analysis of smoking status after 3 months of tobacco counseling. Patients were recruited in an addiction outpatient center. Spirometry results were obtained with a portable device during the first visit. The sample was thus divided in 3 groups: COPD, subthreshold-group (no COPD but abnormal lung age) and normal spirometry. Among the three groups, we compared the immediate motivation change, difference in Q-MAT motivation scale score after minus before spirometry (Kruskal-Wallis test) and the smoking status after 3 months (Fisher test). We included 48 patients (37 males, median age 44 years, median cigarette-per-day 20). Spirometry results divided the sample in COPD (N = 13), subthreshold (N = 11) and normal group (N = 24). Mean Q-MAT score change after spirometry was different between groups (p = 0.019), greater in COPD (4.62 ± 3.38) than normal group (1.46 ± 3.11), and lower in patient with a co-occuring hazardous alcohol use (p = 7.6 × 10-3). Three-months smoking status was different between spirometry results groups (p = 0.0021). COPD (5/13, 38.5%) and subthreshold patients (6/10, 60.0%) had stopped more frequently than patients from the normal-group (2/22, 9.1%). The effect of immediate spirometry results on motivation to quit varies according to the screened pulmonary damages and hazardous alcohol use. It could be a useful tool in addiction treatment centers.

High-Throughput Monitoring of Cocaine and Its Metabolites in Hair Using Microarrays for Mass Spectrometry and Matrix-Assisted Laser Desorption/Ionization-Tandem Mass Spectrometry.

Because of inhomogeneous matrix-assisted laser desorption/ionization (MALDI) matrix crystallization and laser shot-to-shot variability, quantitation is not generally performed by MALDI mass spectrometry. Here we introduce a high-throughput MALDI method using an innovative high-density microarray for mass spectrometry (MAMS) technology, which allows semiquantitative measurement of cocaine and its metabolites, benzoylecgonine, cocaethylene, and ecgonine methyl ester. A MAMS slide containing lanes of hydrophilic spots and an automated slider to drag a sample droplet over several small spots can accomplish automatic sample aliquoting and lead to homogeneous crystallization of the matrix-analyte mixture and, thus, to a reproducible signal (average RSD 6%). Four hair samples of self-reported drug users were analyzed in parallel by MALDI-MS/MS and by a validated LC-MS/MS method. The consumption profiles as well as the metabolite-parent drug ratios obtained correlated well, confirming the effectiveness of the MALDI-MS/MS method to establish a calendar of consumption in only 1 mg of hair. The analysis time for 10 hair samples is below 40 min, with 12 replicates per sample. Since only 3 µL of a 20 µL extract is analyzed, complementary assays are possible, such as the detection of additional drugs. The semiquantitative MALDI method worked well with only a small amount of hair and gave results in less than 4 min per sample, including replicates. This was made possible by the use of MAMS slides for sample preparation, which thus present significant advantages over traditional methods in cases where results are required urgently or if samples are scarce.

Nutritional Status During Inpatient Alcohol Detoxification.

AIMS: As low rates of thiamine are thought to be implicated in alcohol-related cognitive disorders, we wanted to assess patients with alcohol use disorders (AUD) during detoxification for their nutritional status and test if vitamins blood levels were associated with a surrogate of cognitive impairment. METHODS: We performed a retrospective chart review of medical records of 94 consecutive patients hospitalized for alcohol detoxification in a specialized addiction medicine department. Nutritional status was assessed with Body Mass Index (BMI). Vitamins blood levels were available for 80 patients, but thiamine only for 52 patients. The Montreal Cognitive Assessment (MoCA) score was used to screen for cognitive impairment at Day 10 of entry and was available in 59 patients. A binary logistic regression was performed to identify factors associated with MoCA scores below the threshold (26 points). RESULTS: The mean BMI was 23.28 ± 3.78 kg/m2 and 8.79% of weighted patients qualified for malnutrition. The mean MoCA score was 22.75 ± 4.88 points, and 66% of tested patients were below the threshold of suspected cognitive impairment. No low blood thiamine level was found. In multivariate analysis, BMI, but not vitamins blood rates, was significantly associated with a pathological MoCA screening test. CONCLUSION: Clinical examination is more sensitive than biomarkers to determine malnourished AUD patients who are at-risk for cognitive impairment. Malnourished patients with AUD should receive a full neuropsychological testing. SUMMARY: This retrospective chart review study screened for cognitive disorders during alcohol inpatient detoxification with the MoCA test. Body mass index, but not vitamins blood rates, was associated with a pathological MoCA. Clinical examination is more sensitive than biomarkers to determine malnourished AUD patients who are at-risk for cognitive impairment.

Opinion of health professionals and drug users before the forthcoming opening of the first drug consumption room in Paris: a quantitative cross-sectional study.

BACKGROUND: On the brink of the opening of the first French drug consumption room in Paris, the general opinion of the local involved health care professionals and drug users was not known. The objective of this study was to determine their expectations and to search for influencing factors. METHOD: We carried out a quantitative cross-sectional study. A multiple choice questionnaire was proposed to the surrounding willing general practitioners (GPs) and pharmacists, to the emergency doctors of Lariboisière hospital, and to the professionals of the harm reduction facilities and their drug users (PWUD). For each question, there was a choice between seven answers, from "- 3" (very negative impact) to "+ 3" (very positive impact). The influence of the characteristics of each group on its mean answers was explored by Mann-Whitney, Kruskal-Wallis, and Spearman's tests. RESULTS: The median expectations among the groups of responding GPs (N = 62), other health care professionals (N = 82), and PWUD (N = 57) were mainly positive. They thought that the drug consumption room (DCR) would improve the health of PWUD, reduce their at-risk behaviors, would not increase drug use or drug dealing in the neighborhood, and would reduce nuisance in the public space. Only the group of GPs expressed that the DCR could decrease the quietness of the neighborhood, and only the group of PWUD had higher expectations that the DCR would decrease the number of arrests and the number of violent behavior. GPs' expectations were significantly better in terms of health improvement of PWUD and reducing their precariousness if they had a previous experience in addiction medicine (Mann-Whitney, p = 0.004 and p = 0.019), with a longer practice (Spearman's rho, p = 0.021 and p = 0.009), and if they were currently prescribing opioid substitution treatments (Mann-Whitney, p = 0.030 and p = 0.002). Among non-GPs, those who were working in addiction medicine centers had significantly better expectations than pharmacists, and the professionals of the local emergency department had intermediate expectations. CONCLUSIONS: Health care professionals and drug users had a positive opinion of the to-be-created Parisian drug consumption room. Experience in addiction medicine influenced positively health professionals' expectations.

[Temporary approval for intranasal naloxone: Setting up in a French addiction center]. / Pratique de l'ATU de cohorte de la naloxone intranasale (Nalscue®) : mise en place dans un CSAPA parisien.

Intranasal naloxone aims at preventing opioid overdose related deaths in active drug users. In France, it has been available since July 2016 through a temporary approval which requires a hospital-based pharmacy and a nominative registration of each patient. We present the characteristics of the first patients who could receive this prescription in our hospital-based addiction center and how they used naloxone during follow-up. Results favor a larger dispensing of naloxone. Patients' as well as peers' and families' education is needed.

Use and knowledge of contraceptive methods by patients in two substance use disorders treatment centers in Paris.

BACKGROUND: Studies on contraceptive use by patients with substance use disorders (SUD) show a concerning low use of contraception. Mainly conducted in USA, they could be irrelevant to patients attending European SUD treatment centers, especially since these studies mostly investigate women suffering from social exclusion, severe material deprivation andopiates use with frequent high-risk drug use and sexual behaviors including sex trade, frequently not currently attending treatment centers. The purpose of this study is to describe contraceptive use by patients, both male and female, since contraception can not only be considered as a female problem, with severe SUD in two free clinics in Paris, France. METHODS: An anonymous self-report questionnaire was distributed to literate patients followed in two generalist substance use disorders treatment centers in hospitals of Paris, France: Espace Murger and Centre Cassini, during 5 weeks between February and March 2016. RESULTS: Out of the 78 respondents (with an age mean 40.7 years, in which women are represented as 48.1%, and 29.7% of them have children), 53 have had at least one sexual partner in the last 6 months. Contraception was "always" used by 55.3% of sexually active patients, "sometimes" by 19.1%, and "not" used by 25.5%. Male condoms were the main contraceptive method. The use of intrauterine devices was low, contrarily to what is observed in the French general population. However, the knowledge of contraceptive methods was common. CONCLUSIONS: In this population, with a high prevalence of at risk sexual behavior, the use of contraceptive methods is lower than in French general population. During standard care for SUD, contraception and desire to be a parent should be discussed and patients empowered to make their own choices. Lack of knowledge does not seem to be a hindrance to the use of contraception, but other sociological, psychological, or medical factors may limit contraceptive access and long-term use, especially for the long-acting reversible contraception methods. It is necessary to further develop this reflection by discussing the individual contraceptive choices with the patients themselves to clarify the nature of these constraints and maybe provide several contraceptive methods within the SUD care settings.

Hospital Stay and Engagement in Outpatient Follow-Up After Alcohol Emergency Detox: A 1-Year Comparison Study.

BACKGROUND: Inpatient alcohol detoxifications are only proposed after motivational outpatient encounters because detoxification directly from the emergency department (ED) is believed to be associated with early dropout and poor adherence to outpatient follow-up. The aim of this prospective follow-up study was to test the feasibility of unscheduled (UP) alcohol detoxification directly from the ED and to compare the 1-year follow-up of these patients to that of scheduled (SP) patients. METHODS: A quasi-naturalistic prospective follow-up study of 120 patients: 60 consecutively admitted patients referred directly by the ED for alcohol detoxification (UP) were compared to 60 consecutively admitted patients who had undergone the usual preparation for an inpatient detoxification program (SP). The length of hospitalization (in days) and attendance to postdischarge outpatient visits during the first year was compared. RESULTS: UP patients were older, less frequently employed, and had more somatic comorbidities compared with SP patients. The UP length of stay was significantly longer (20 ± 16 vs. 14 ± 6, p = 0.04). No difference in their postdischarge attendance was observed; the number of patients attending 1 session (57% UP vs. 65% SP, p = 0.227) and 5 sessions (22% UP vs. 32% SP, p = 0.151) and the mean number of postdischarge visits attended were comparable between the UP and SP groups (2.7 ± 6 vs. 4.5 ± 6; Mann-Whitney U = 1,517, p = 0.124). CONCLUSIONS: We did not find that UP patients who had been admitted for alcohol detoxification had a significantly higher dropout rate or lower postdischarge addiction treatment attendance. Because they may have several advantages, detoxification programs directly linked with EDs should be further evaluated.

Methadone dose in heroin-dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity.

AIMS: Methadone is characterized by wide intersubject variability regarding the dose needed to obtain full therapeutic response. We assessed the influence of sociodemographic, ethnic, clinical, metabolic and genotypic variables on methadone maintenance dose requirement in opioid-dependent responder patients. METHODS: Eighty-one stable patients (60 men and 21 women, 43.7 ± 8.1 years old, 63.1 ± 50.9 mg day(-1) methadone), divided into quartiles with respect to the median daily dose, were enrolled and underwent clinical examination, treatment history and determination of liver/intestinal cytochrome P450 (CYP) 3A4 activity measured by the midazolam test, R,S-methadone trough concentration and clinically significant polymorphisms of the OPRM1, DRD2, COMT, ABCB1, CYP2B6, CYP3A5, CYP2C19 and CYP2D6 genes. RESULTS: Methadone maintenance dose was correlated to the highest dose ever used (r(2) = 0.57, P < 0.0001). Fractioned methadone intake (odds ratio 4.87, 95% confidence interval 1.27-18.6, P = 0.02), bodyweight (odds ratio 1.57, 95% confidence interval 1.01-2.44, P = 0.04), history of cocaine dependence (80 vs. 44 mg day(-1) in never-addict patients, P = 0.005) and ethnicity (Asian > Caucasian > African, P = 0.04) were independently associated with high-dose methadone in multiple regression analysis. A modest correlation was observed between liver/intestinal CYP3A4 activity and methadone dose at steady state (Spearman rank correlation coefficient [rs ] = 0.21, P = 0.06) but not with highest dose ever used (rs = 0.15, P = 0.18) or dose-normalized R,S-methadone trough concentrations (rs = -0.05, P = 0.64). Concomitant CYP3A4 inhibitors only affected the relationship between methadone dose and R,S-methadone trough concentration. None of the genetic polymorphisms explored was predictive of the methadone maintenance dose. CONCLUSIONS: Methadone maintenance dose was predicted by sociodemographic and clinical variables rather than genetic polymorphisms or liver/intestinal CYP3A4 activity in stable patients.

Anxiety and substance use disorders: co-occurrence and clinical issues.

The co-occurrence of substance use disorders (SUDs) and anxiety disorders has been now well established. This association is frequent and can be explained by three models: the shared vulnerability factors model, the self-medication model, and the substance-induced model. General population epidemiological studies provide strong evidence of the frequency of the association for the most used substances: tobacco, alcohol, cannabis, and to a lesser extent sedatives, opiates, and cocaine. For substances that are less commonly used in the general population, the frequency of the co-occurrence can more precisely be studied in clinical samples. We provide the most recent literature results on the association of SUDs and anxiety, and evidence for one explicative model or the other when available. For substances with sedative properties (alcohol, benzodiazepines, cannabis, opioids), both evidence for a self-medication and for a toxic effect exist. For substances with psychostimulant properties (tobacco, cocaine, and amphetamines), the literature favors the toxic hypothesis to explain the association with anxiety disorders. We give practical steps for the recognition of these dual diagnoses and present therapeutic issues, although the strategies are rarely evidence based.