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.

Pictograms to aid laypeople in identifying the addictiveness of gambling products (PictoGRRed study).

The structural addictive characteristics of gambling products are important targets for prevention, but can be unintuitive to laypeople. In the PictoGRRed (Pictograms for Gambling Risk Reduction) study, we aimed to develop pictograms that illustrate the main addictive characteristics of gambling products and to assess their impact on identifying the addictiveness of gambling products by laypeople. We conducted a three-step study: (1) use of a Delphi consensus method among 56 experts from 13 countries to reach a consensus on the 10 structural addictive characteristics of gambling products to be illustrated by pictograms and their associated definitions, (2) development of 10 pictograms and their definitions, and (3) study in the general population to assess the impact of exposure to the pictograms and their definitions (n = 900). French-speaking experts from the panel assessed the addictiveness of gambling products (n = 25), in which the mean of expert's ratings was considered as the true value. Participants were randomly provided with the pictograms and their definitions, or with a standard slogan, or with neither (control group). We considered the control group as representing the baseline ability of laypeople to assess the addictiveness of gambling products. Each group and the French-speaking experts rated the addictiveness of 14 gambling products. The judgment criterion was the intraclass coefficients (ICCs) between the mean ratings of each group and the experts, reflecting the level of agreement between each group and the experts. Exposure to the pictograms and their definition doubled the ability of laypeople to assess the addictiveness of gambling products compared with that of the group that read a slogan or the control group (ICC = 0.28 vs. 0.14 (Slogan) and 0.14 (Control)). Laypeople have limited awareness of the addictive characteristics of gambling products. The pictograms developed herein represent an innovative tool for universally empowering prevention and for selective prevention.

Improvement of participation rate in colorectal cancer (CRC) screening by training general practitioners in motivational interviewing (AmDepCCR).

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer death in France (17,712 annual deaths). However, this cancer is preventable in the majority of cases by the early detection of adenomas. In France, the organized screening for CRC relies on general practitioners (GPs). The tests delivered by the GPs are carried out in 89% of cases. However, GPs do not systematically offer the test, because of time management and communication. METHODS: AmDepCCR is a cluster randomized trial. Patients are prospectively included by their GPs. The study is designed in 2 phases for the GPs: first, GPs who have never participated in motivational interviewing (MI) training will be recruited then randomly split in 2 groups. Secondly, a 6-day motivational interviewing training will be carried out for the intervention group. Then, patients will be included in both groups during a period of 1 year. The primary outcome will be the number of CRC screenings achieved in each group and its difference. The secondary outcome will be the reluctance to screening and the patient's self-estimated life expectancy at 0, 6, 12, and 24 months using the Health Belief Model (HBM). DISCUSSION: This study will help to know if GPs motivational interviewing is useful to improve organized CRC screening. In addition, it may help to improve communication between patients and GPs. GPs will be able to improve their practice in other fields of application through motivational interviewing (other screenings, addictions…). TRIAL REGISTRATION: 2019-A01776-51 NCT04492215 .

Screening for cardiovascular risk in the general population: The SPICES implementation survey.

Background: In 2019, cardiovascular diseases (CVD) caused 32% of deaths worldwide. The SPICES survey involved five countries in an international primary CVD prevention implementation study in the general population. The French SPICES survey was implemented in the Centre Ouest Bretagne area (COB), which is a rural, economically deprived, medically underserved territory with high cardiovascular mortality. A CVD screening in the general population was needed to select the implementation population without overburdening family practitioner (FP) workforces. The efficacy and the replicability of such a screening were unknown. The aims of this study were to identify the characteristics of the individuals undergoing CVD risk assessment with the Non-Laboratory Interheart risk score (NL-IHRS), and to identify barriers and explore facilitators when screening the general population. Methods: An implementation study combining a cross-sectional descriptive study with qualitative interviews was undertaken. The NL-IHRS was completed by trained screeners selected from health students, pharmacists, nurses, and physiotherapists in the area with a dedicated e-tool in sport and cultural events and public places. After the screening, all screener groups were interviewed until theoretical saturation for each group. Thematic analysis was performed using double-blind coding. Results: In 5 months, 3,384 assessments were undertaken in 60 different places, mostly by health students. A total of 1,587, 1,309, and 488 individuals were at low, moderate, and high CVD risk. Stressed or depressed individuals were remarkably numerous (40.1 and 24.5% of the population, respectively). Forty-seven interviews were conducted. The main facilitators were willingness of the population, trust between screeners and the research team, and media publicity. The main barriers were lack of motivation of some screeners, some individuals at risk, some stakeholders and difficulties in handling the e-tool. Conclusion: The efficacy of CVD risk screening while using mostly health students was excellent and preserved the FP workforce. Replicability was highly feasible if research teams took great care to establish and maintain trust between screeners and researchers. The e-tools should be more user-friendly.

Multimorbid outpatients: A high frequency of FP appointments and/or family difficulties, should alert FPs to the possibility of death or acute hospitalization occurring within six months; A primary care feasibility study.

BACKGROUND: The European General Practitioners Research Network (EGPRN) designed and validated a comprehensive definition of multimorbidity using a systematic literature review and qualitative research throughout Europe. This definition was tested as a model to assess death or acute hospitalization in multimorbid outpatients. OBJECTIVE: To assess which criteria in the EGPRN concept of multimorbidity could detect outpatients at risk of death or acute hospitalization in a primary care cohort at a 6-month follow-up and to assess whether a large scale cohort with FPs would be feasible. METHOD: Family Physicians included a random sample of multimorbid patients who attended appointments in their offices from July to December 2014. Inclusion criteria were those of the EGPRN definition of Multimorbidity. Exclusion criteria were patients under legal protection and those unable to complete the 2-year follow-up. Statistical analysis was undertaken with uni- and multivariate analysis at a 6-month follow-up using a combination of approaches including both automatic classification and expert decision making. A Multiple Correspondence Analysis (MCA) completed the process with a projection of illustrative variables. A logistic regression was finally performed in order to identify and quantify risk factors for decompensation. RESULTS: 19 FPs participated in the study. 96 patients were analyzed. 3 different clusters were identified. MCA showed the central function of psychosocial factors and peaceful versus conflictual relationships with relatives in all clusters. While taking into account the limit of a small cohort, age, frequency of family physician visits and extent of family difficulties were the factors which predicted death or acute hospitalization. CONCLUSION: A large scale cohort seems feasible in primary care. A sense of alarm should be triggered to prevent death or acute hospitalization in multimorbid older outpatients who have frequent family physician visits and who experience family difficulties.

Multicentre study for validation of the French addictovigilance network reports assessment tool.

AIMS: The French health authority (ANSM) is responsible for monitoring medicinal and other drug dependencies. To support these activities, the ANSM manages a network of 13 drug dependence evaluation and information centres (Centres d'Evaluation et d'Information sur la Pharmacodépendance - Addictovigilance - CEIP-A) throughout France. In 2006, the Nantes CEIP-A created a new tool called the EGAP (Echelle de GrAvité de la Pharmacodépendance- drug dependence severity scale) based on DSM IV criteria. This tool allows the creation of a substance use profile that enables the drug dependence severity to be homogeneously quantified by assigning a score to each substance indicated in the reports from health professionals. This article describes the validation and psychometric properties of the drug dependence severity score obtained from the scale ( Clinicaltrials.gov NCT01052675). METHOD: The validity of the EGAP construct, the concurrent validity and the discriminative ability of the EGAP score, the consistency of answers to EGAP items, the internal consistency and inter rater reliability of the EGAP score were assessed using statistical methods that are generally used for psychometric tests. RESULTS: The total EGAP score was a reliable and precise measure for evaluating drug dependence (Cronbach alpha = 0.84; ASI correlation = 0.70; global ICC = 0.92). In addition to its good psychometric properties, the EGAP is a simple and efficient tool that can be easily specified on the official ANSM notification form. CONCLUSION: The good psychometric properties of the total EGAP score justify its use for evaluating the severity of drug dependence.