Prazosin and cyproheptadine in combination in the treatment of alcohol use disorder: A randomized, double-blind, placebo-controlled trial.

BACKGROUND AND AIMS: Pre-clinical studies suggest that the simultaneous blockade of the α1b and 5HT2A receptors may be effective in reducing alcohol consumption. This study aimed to assess the efficacy and safety of prazosin (α1b blocker) and cyproheptadine (5HT2A blocker) combination in decreasing total alcohol consumption (TAC) in alcohol use disorder (AUD). DESIGN, SETTING AND PARTICIPANTS: This was a double-blind, parallel group, placebo-controlled, Phase 2, randomized clinical trial conducted in 32 addiction treatment centres in France. A total of 108 men and 46 women with severe AUD took part. INTERVENTION: Participants were randomly assigned to one of the following 3-month treatments: (1) low-dose group (LDG) receiving 8 mg cyproheptadine and 5 mg prazosin extended-release (ER) formulation daily; (2) high-dose group (HDG) receiving 12 mg cyproheptadine and 10 mg prazosin ER daily; and (3) placebo group (PG) receiving placebo of cyproheptadine and prazosin ER. A total of 154 patients were randomized: 54 in the PG, 54 in the LDG and 46 in the HDG. MEASUREMENTS: The primary outcome was TAC change from baseline to month 3. FINDINGS: A significant main treatment effect in the change in TAC was found in the intent-to-treat population (P = 0.039). The HDG and LDG showed a benefit in the change in TAC from baseline to month 3 compared with PG: -23.6 g/day, P = 0.016, Cohen's d = -0.44; -18.4 g/day, P = 0.048 (Bonferroni correction P < 0.025), Cohen's d = -0.36. In a subgroup of very high-risk drinking-level participants (> 100 g/day of pure alcohol for men and > 60 g/day for women), the difference between the HDG and the PG in the primary outcome was -29.8 g/day (P = 0.031, Cohen's d = -0.51). The high and low doses were well-tolerated with a similar safety profile. CONCLUSIONS: A randomized controlled trial of treatment of severe alcohol use disorder with a cyproheptadine-prazosin combination for 3 months reduced drinking by more than 23 g per day compared with placebo. A higher dose combination was associated with a larger magnitude of drinking reduction than a lower dose combination while showing similar safety profile.

World addiction medicine reports: formation of the International Society of Addiction Medicine Global Expert Network (ISAM-GEN) and its global surveys.

Addiction medicine is a dynamic field that encompasses clinical practice and research in the context of societal, economic, and cultural factors at the local, national, regional, and global levels. This field has evolved profoundly during the past decades in terms of scopes and activities with the contribution of addiction medicine scientists and professionals globally. The dynamic nature of drug addiction at the global level has resulted in a crucial need for developing an international collaborative network of addiction societies, treatment programs and experts to monitor emerging national, regional, and global concerns. This protocol paper presents methodological details of running longitudinal surveys at national, regional, and global levels through the Global Expert Network of the International Society of Addiction Medicine (ISAM-GEN). The initial formation of the network with a recruitment phase and a round of snowball sampling provided 354 experts from 78 countries across the globe. In addition, 43 national/regional addiction societies/associations are also included in the database. The surveys will be developed by global experts in addiction medicine on treatment services, service coverage, co-occurring disorders, treatment standards and barriers, emerging addictions and/or dynamic changes in treatment needs worldwide. Survey participants in categories of (1) addiction societies/associations, (2) addiction treatment programs, (3) addiction experts/clinicians and (4) related stakeholders will respond to these global longitudinal surveys. The results will be analyzed and cross-examined with available data and peer-reviewed for publication.

Association between alcohol use and retinal dysfunctions in patients with alcohol use disorder: A window on GABA, glutamate, and dopamine modulations.

BACKGROUND: Alcohol is the most widely consumed addictive substance around the world and have deleterious effect on the central nervous system. Alcohol consumption affect the balance of certain neurotransmitters like GABA, glutamate and dopamine. The retina provides an easy means of investigating dysfunctions of synaptic transmission in the brain. The purpose of this study is to assess the impact of alcohol consumption on retinal function using pattern electroretinogram (PERG) and flash electroretinogram (fERG). METHODS: We recorded PERG and fERG under scotopic and photopic condition in 20 patients with alcohol use disorder and 20 controls. Implicit time and amplitude of numerous parameters were evaluated: a- and b-waves for fERG, OP3 and OP4 for dark-adapted 3.0 oscillatory potentials fERG, P50 and N95 for PERG. RESULTS: Patients with alcohol use disorder showed a significant increase in N95 implicit time without a significant change in the amplitudes of oscillatory potentials. CONCLUSION: The results of our study reflect the impact of alcohol use on ganglion cell function and could highlight alterations in glutamatergic neurotransmission inside the retina. We believe that ERG could be used as an early marker of alcohol consumption.

Empathy of dental students and educators in French hospitals: A cross-sectional study.

Empathy is a key factor in the dentist-patient relationship. The aim of this study was to determine empathy in dental students and educators in French hospital dental services. A cross-sectional study was conducted among dental students and educators who practiced in 10 hospital dental services affiliated with the Faculty of Dentistry of the University of Lorraine in France. A questionnaire was self-administered online using the Jefferson Scale of Physician Empathy (JSPE). The study included 209 participants comprising 50 students in fourth year, 66 students in fifth year, 48 students in sixth year, and 45 educators. Participants were 63.6% females, aged 27 ± 8 years. The mean empathy score was 109.40 ± 11.65. The sub-scores of the three dimensions were 57.02 ± 6.64 for Perspective Taking, 42.56 ± 6.22 for Compassionate Care, and 9.78 ± 2.61 for Walking in the Patient's Shoes. Females showed significant higher empathy scores than males (111.36 vs. 105.84). The empathy score was correlated with age and insignificantly decreased during clinical training (from 110.06 in fourth year to 106.63 in sixth year). French dental students and educators showed high levels of empathy.

A Structural Validation of the Brief COPE Scale among Outpatients with Alcohol and Opioid Use Disorders.

Recovery from substance use disorder requires access to effective coping resources. The most widely self-reported questionnaire used to assess coping responses is the Brief COPE; however, different factorial structures were found in a variety of samples. This study aimed to examine across outpatients with substance use disorders the factor structure of the short dispositional French version of the Brief Coping Orientation to Problem Experienced (COPE) inventory. The French version of the Brief COPE was administered in a sample of 318 outpatients with alcohol or opioid substance use disorder. A clustering analysis on latent variables (CLV) followed by a confirmatory factorial analysis (CFA) was conducted to examine the factor structure of the scale. The internal consistency of the Brief COPE and its subscales were also studied. The analysis revealed a nine-factor structure with a revised 24-item version consisting of functional strategies (four items), problem-solving (four items), denial (two items), substance use (two items), social support seeking (four items), behavioral disengagement (two items), religion (two items), blame (two items), and humor (two items) that demonstrated a good fit to the data. This model explained 53% of the total variance with an overall McDonald's omega (ω) of 0.96 for the revised scale. The present work offers a robust and valid nine-factor structure for assessing coping strategies in French outpatients with opioid or alcohol substance use disorder. This structure tends to simplify its use and interpretation of results for both clinicians and researchers.

Online SPE UPLC-MS/MS method for the simultaneous determination of 33 psychoactive drugs from swab-collected human oral fluid samples.

Oral fluid is easy and safe to collect and allows the detection of drugs of abuse after local exposure by oral, smoked, and/or inhaled intake, or systemic exposure. A routine online solid-phase extraction UPLC-MS/MS method was developed for the simultaneous determination of 33 psychoactive drugs in oral fluid. The selected drugs were fourteen fentanyl analogs and nineteen other abused psychoactive compounds, including classical narcotics, which were analyzed in a run of 10 min. Limits of detection and of quantification ranged from 0.02 to 1 ng/mL and from 0.02 to 5 ng/mL depending on the analyte, respectively. Matrix effect was in the range - 17 to + 15.7% for all analytes having a deuterated analog. Accuracy ranged from 82.7 to 113.4% and precision CV was at worst of 18.6%. Carryover was below 0.8% for all analytes. Recovery from FLOQSwabs™ showed high variability between analytes with THC, D2FF, 4-ANPP, ocfentanil, and valerylfentanyl being recovered below 40%. A stability study performed over 2 weeks on collecting devices loaded with artificial oral fluid showed huge variation between analytes with morphine, BZE, and norfentanyl being the more stable. Storage at 4 °C allowed drug detection for 1 week except for THC and remifentanil. The method was successfully applied to the detection of abused psychoactive compounds in oral fluid samples from 6 patients admitted to an addiction department.

Health-related quality of life in outpatients with substance use disorder: evolution over time and associated factors.

BACKGROUND: Health-related quality of life (HRQoL) is an important element of patient care and clinical research. The aim of this study was to describe HRQoL changes and identify associated factors during a 6-month follow-up of outpatients starting care for alcohol or opioid dependence. METHODS: HRQoL was measured at baseline and 3 and 6 months later using the SF-12. Data on the patients' sociodemographics, clinical characteristics and levels of anxiety and depression were collected using the Hospital Anxiety and Depression Scale (HADS). Repeated-measures analyses were performed to assess factors associated with global HRQoL differences and the evolution of HRQoL indicated by both physical and mental scores (PCS and MCS, respectively). RESULTS: The mean PCS and MCS scores were initially low at 45.4 (SD = 8.6) and 36.0 (SD = 10.9), respectively. The improvement in HRQoL was rapid in the first 3-month period and then slowed and remained stable over the subsequent 3-month period. Being employed (p = 0.012), having no comorbidities (p = 0.014) and having no depression (p = 0.004) were associated with significant differences in the average PCS scores at the 3 time points. Patients who had lower overall HRQoL MCS scores on average were those for whom a medication was initiated (p = 0.009), as was the case for patients with anxiety (p < 0.001) and depression (p < 0.001). Patients with depression at baseline were also those for whom a significantly greater increase in MCS score during the 6 months of follow-up was observed. CONCLUSION: Our findings highlight the importance of screening early psychological distress and considering other factors associated with HRQoL changes in outpatients after the first 3-month period of treatment for substance use disorder.

Factors associated with family involvement in a family-centered care program among incarcerated French adolescents with conduct disorder.

PURPOSE: This study aims to identify the patient characteristics that may influence family involvement in a family-centered care program during detention. DESIGN/METHODOLOGY/APPROACH: Little is known about the needs of incarcerated adolescents and their families. This exploratory study used a cross-sectional design to collect data from incarcerated adolescents with conduct disorder followed in a French outpatient psychiatric department. Logistic regression models were used to identify the sociodemographic, clinical and family characteristics of these incarcerated adolescents that could predict family involvement in their care. FINDINGS: Among 44 adolescents with conduct disorder, the probability of family involvement during the adolescent's detention was 9.6 times greater (95% CI 1.2-14.4, p = 0.03) for adolescents with no than for those with cannabis substance use disorder, and family involvement decreased with the age of the adolescent (OR = 0.22, 95% CI 0.1-0.9, p = 0.04). RESEARCH LIMITATIONS/IMPLICATIONS: Increased knowledge of the characteristics of these adolescents and their families is needed to develop programs that will increase family interventions by specialty treatment services during detention. ORIGINALITY/VALUE: No study has yet been published on French incarcerated adolescents with conduct disorder. As conduct disorder is one of the most important mental health disorders among delinquent adolescents, this study provides knowledge about these adolescents and the need to involve their parents in their care to prevent the further escalation of problem behaviors.

[Competency-based pedagogical approach: illustration applied to the care relationship]. / Approche pédagogique par compétences : illustration appliquée à la relation de soins.

The reform of health studies and the inclusion in the Bachelor-Master-Doctorate curriculum implies a new way of teaching, with an inverted pedagogical relationship between student and teacher. The competency-based approach contributes to the development of the student's professional and interpersonal skills, in the same way as the support provided by the nurse in the care relationship, particularly in therapeutic education, in order to promote patient autonomy.

Multiplex detection of 14 fentanyl analogues and U-47700 in biological samples: Application to a panel of French hospitalized patients.

Synthetic opioids (SO) associated with the recent alarming increase of deaths and intoxications in United States of America and Europe are not detected by the usual first-line opiates drug screening assays. We developed a liquid chromatography tandem mass spectrometry analytical method for the multiplex detection of 14 fentanyl analogues (2-furanylfentanyl, 4-ANPP, 4-methoxybutyrylfentanyl, acrylfentanyl, alfentanil, carfentanil, despropionyl-2-fluorofentanyl, fentanyl, methoxyacetylfentanyl, norfentanyl, ocfentanil, remifentanil, sufentanil and valerylfentanyl) and U-47700 in whole blood and urine samples. The method was validated according to the requirements of ISO 15189. A simple and fast liquid-liquid extraction (LLE) with De-Tox Tube-A was performed leading to better recovery of molecules in urine than in blood samples. Depending on the compound, the limits of detection (LODs) ranged from 0.01 to 0.10 ng/mL and from 0.02 to 0.05 ng/mL in whole blood and urine, respectively. Calibration curves were linear in the range 0.5-50.0 ng/mL and the limit of quantification (LOQ) ranged from 0.10 to 0.40 ng/mL in blood. Internal quality controls at 1 and 40 ng/mL showed intra-day and between-day precision and accuracy bias below 10% in urine and 15% in blood. The method was applied to the screening of 211 urine samples from patients admitted in emergency or addiction departments. The presence of legal fentanyl analogues in 5 urine samples was justified by their therapeutic use as analgesics. Only one patient was concerned by fentanyl misuse and addiction whereas no illegal SO was detected. This study is not in favor of a huge misuse of SO in the Lorraine region.

[Thiamin and alcohol use disorder: A national survey of practice]. / Thiamine et trouble de l'usage d'alcool : une enquête de pratique nationale.

OBJECTIVE: The survey aimed to estimate, in the presence of alcohol use disorder, the frequency of systematic prescription of thiamine, the factors associated with it, and those related to the administration (oral, intravenous, intramuscular) when Wernicke's encephalopathy is suspected. METHODS: A self-questionnaire available on Internet was sent by e-mail to doctors and nurses taking care patients with alcohol use disorder. RESULTS: In all, 565 professionals responded. The systematic prescription frequency of thiamine was 84.8 %, addiction care centers and medical-psychological centers prescribed it 5 times less than in psychiatric hospitals (OR=0.2 IC [0.1-0.5] P<0.0001), and medicine/surgery/obstetrics (MSO) services 10 times more than psychiatric hospitals (OR=10.7 IC [2.5-45.3] P<0.0001). The prescription decreased with the exercise period, the interns prescribing it 10 times more systematically (OR=10.9 IC [3.6-32.9] P<0.0001). In the presence of symptoms related to Wernicke's encephalopathy, thiamine administration was mainly oral (67.1 %). Intravenous administration was used more by the MSO services (OR=18.3 IC [10.2-32.7] P<0.0001), while the intramuscular injection was used more in psychiatric hospitals (OR=4.6 IC [1.7-11.9] P=0.0353). CONCLUSION: The prescription of thiamine is rather systematic. In contrast, intravenous administration is underused, in the presence of symptoms related to Wernicke's encephalopathy, in favor of oral administration, and the more specific use of the intramuscular injection in psychiatry.

Empathy and Burnout - A Cross-Sectional Study Among Mental Healthcare Providers in France.

Previous studies have established a correlation between empathy and burnout among healthcare providers. The aim of this study is to explore whether empathy - the ability to understand what another person is experiencing, was related to mental healthcare staffs' burnout. We performed a descriptive, cross-sectional, observational study among medical and nursing mental healthcare staff working in the district of Moselle, France. Participants completed a survey including The French versions of the Jefferson Scale of Empathy (JSPE) and The Maslach Burnout Inventory-Human Services Survey (MBI-HSS). The sample included 241 (n=241) participants (N=420, response rate=51.7%). 187 (77.6%) respondents had low burnout, 43 (17.8%) had intermediate burnout and 11 (4.6%) had high burnout. 41 (17%) had low empathy, 156 (64.7) had moderate empathy and 44 (18.3%) scored high. Empathy scores were positively correlated with scores of personal accomplishment of the MBI-HSS (r=0.2; p<0.001), but negatively correlated with scores of depersonalization (r=-0.2; p<0.003). Highest means of depersonalization (DP) (M=8.7; SD=6.8; p<0.009) and lowest means of compassionate care (M=40.05; SD=7.9; p=0.0001) were found among forensic psychiatric security units staff. Participation in the Omega educational program was associated with lower scores of EE on the MBI-HSS survey (mean score 14.7 versus a mean score of 19.7 for nonparticipants). Empathic mental healthcare providers have lower levels of burnout. Forensic psychiatric staff showed low means of compassionate care and high depersonalization. Interventions designed to foster attributes and skills such as empathy, resilience, and perception of security may be an essential step in reducing and preventing burnout.

[Co-occurrent cannabis and tobacco uses: Clinical knowledge and therapeutic prospects]. / Consommations conjointes de cannabis et de tabac : connaissances cliniques et perspectives thérapeutiques.

Cannabis and tobacco are two of the most prevalent addictive drugs used worldwide. Concurrent use of cannabis and tobacco is common, whether simultaneous in joints or not. In France, cannabis is mainly used in joints also containing tobacco. According to the current literature, combined use of cannabis and tobacco exacerbates on additive or multiplicative mode the somatic, psychological and social consequences of each drug. In addition, concurrent use of cannabis and tobacco potentiates tobacco and cannabis dependence, which maintains the use of both drugs, increases the risk of relapse and reduces motivation to care. Combined use thus leads to a reduced likelihood of therapeutic success. We discuss the usefulness of simultaneous cessation treatment together with the use of currently available pharmacological and psychological help as valuable therapeutic tools.