Preuves de bénéfice et décision thérapeutique : enquête auprès de médecins généralistes sur la prescription d’hydroxychloroquine pour traiter la Covid-19

National audienceIntroduction. Dans l’attente des résultats des premiers grands essais thérapeutiques sur les traitements de la Covid-19, les médecins étaient partagés sur la question de l’utilisation immédiate de l’hydroxychloroquine (HCQ).Objectifs. L’objectif principal de cette étude était d’évaluer l’intention de prescription d’HCQ par les médecins généralistes à des patients atteints de la Covid-19 en ambulatoire. Les objectifs secondaires étaient d’évaluer les variations de ce taux de prescription après la publication des résultats de l’essai Discovery, en fonction de paramètres liés à la maladie, à la situation de prescription, ou au prescripteur.Méthodes. L’enquête de pratiques a été réalisée par une étude observationnelle transversale, par auto-questionnaire en ligne, du 7 au 21 avril 2020, auprès des médecins généralistes libéraux, maîtres de stage des universités (MSU) rattachés à l’Université Claude-Bernard de Lyon 1.Résultats. 483 médecins ont été interrogés et 185 questionnaires (38,3 %) ont été reçus. 23 % des médecins généralistes ayant répondu à l’enquête ont déclaré qu’ils prescriraient de l’HCQ, 15 % en ambulatoire. 9,4 % ont déclaré qu’ils en prescriraient uniquement si le patient le demandait avec insistance, et après information éclairée. Le taux de prescription a augmenté selon la gravité de la situation clinique, la gravité intrinsèque de la maladie, et la nature du bénéficiaire de la prescription, avec une augmentation lors d’une prescription au médecin lui-même ou à l’un de ses proches. Les prescripteurs étaient significativement plus âgés que les non-prescripteurs (54 vs 46 ans [p = 0,002]).Conclusion. L’attitude dominante des médecins interrogés est celle d’une décision thérapeutique fondée sur la nécessité d’une preuve de bénéfice validée de haute qualité, et d’une abstention thérapeutique en son absence

Risks and benefits of Nalmefene in the treatment of adult alcohol dependence: a systematic literature review and meta-analysis of published and unpublished double-blind randomized controlled trials.

Nalmefene is a recent option in alcohol dependence treatment. Its approval was controversial. We conducted a systematic review and meta-analysis of the aggregated data (registered as PROSPERO 2014:CRD42014014853) to compare the harm/benefit of nalmefene versus placebo or active comparator in this indication.Three reviewers searched for published and unpublished studies in Medline, the Cochrane Library, Embase, ClinicalTrials.gov, Current Controlled Trials, and bibliographies and by mailing pharmaceutical companies, the European Medicines Agency (EMA), and the US Food and Drug Administration. Double-blind randomized clinical trials evaluating nalmefene to treat adult alcohol dependence, irrespective of the comparator, were included if they reported (1) health outcomes (mortality, accidents/injuries, quality of life, somatic complications), (2) alcohol consumption outcomes, (3) biological outcomes, or (4) treatment safety outcomes, at 6 mo and/or 1 y. Three authors independently screened the titles and abstracts of the trials identified. Relevant trials were evaluated in full text. The reviewers independently assessed the included trials for methodological quality using the Cochrane Collaboration tool for assessing risk of bias. On the basis of the I2 index or the Cochrane's Q test, fixed or random effect models were used to estimate risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% CIs. In sensitivity analyses, outcomes for participants who were lost to follow-up were included using baseline observation carried forward (BOCF); for binary measures, patients lost to follow-up were considered equal to failures (i.e., non-assessed patients were recorded as not having responded in both groups). Five randomized controlled trials (RCTs) versus placebo, with a total of 2,567 randomized participants, were included in the main analysis. None of these studies was performed in the specific population defined by the EMA approval of nalmefene, i.e., adults with alcohol dependence who consume more than 60 g of alcohol per day (for men) or more than 40 g per day (for women). No RCT compared nalmefene with another medication. Mortality at 6 mo (RR = 0.39, 95% CI [0.08; 2.01]) and 1 y (RR = 0.98, 95% CI [0.04; 23.95]) and quality of life at 6 mo (SF-36 physical component summary score: MD = 0.85, 95% CI [-0.32; 2.01]; SF-36 mental component summary score: MD = 1.01, 95% CI [-1.33; 3.34]) were not different across groups. Other health outcomes were not reported. Differences were encountered for alcohol consumption outcomes such as monthly number of heavy drinking days at 6 mo (MD = -1.65, 95% CI [-2.41; -0.89]) and at 1 y (MD = -1.60, 95% CI [-2.85; -0.35]) and total alcohol consumption at 6 mo (SMD = -0.20, 95% CI [-0.30; -0.10]). An attrition bias could not be excluded, with more withdrawals for nalmefene than for placebo, including more withdrawals for safety reasons at both 6 mo (RR = 3.65, 95% CI [2.02; 6.63]) and 1 y (RR = 7.01, 95% CI [1.72; 28.63]). Sensitivity analyses showed no differences for alcohol consumption outcomes between nalmefene and placebo, but the weight of these results should not be overestimated, as the BOCF approach to managing withdrawals was used.The value of nalmefene for treatment of alcohol addiction is not established. At best, nalmefene has limited efficacy in reducing alcohol consumption

Development of a patient decision aid for COVID-19 vaccination with the Comirnaty vaccine

Background: SARS-CoV-2 has been responsible for a pandemic since the beginning of 2020. Vaccine arrival brings a concrete solution to fight the virus. However, vaccine hesitancy is high. In France, the first available vaccine was Comirnaty from Pfizer-BioNTech. Shared decision-making, based on tools such as patient decision aids (PtDAs), can help patients make an informed choice about vaccination with Comirnaty. Objective: The French College of Teachers in General Practice (CNGE) aimed to create a PtDA for people who have to decide whether they will receive the Comirnaty vaccine. Methods: Development of the PtDA was performed according to the International Patient Decision Aids Standards (IPDAS). The initial design was based on a literature review and semistructured interviews with 17 patients to explore and clarify patients' expectations. A first draft of the PtDA was then alpha tested by a patient expert group and a physician expert group. The PtDA was finally beta tested in 14 prevaccine consultations. A steering group was consulted throughout the work. Patient support, community groups and the French National Authority for Health (HAS) were involved in the development process. Results: A literature review identified one randomized trial on Comirnaty efficacy and safety. The first part of the PtDA allows patients to identify their own risk factors. The second part of the PtDA provides information on vaccination: benefits and risks, unknown data, and technical explanations about the mRNA vaccine. Conclusions: We developed a PtDA to be used in primary care settings for shared decision-making regarding vaccination with Comirnaty