[Satisfaction of a pharmacovigilance declaration support network in general practice]. / Satisfaction des médecins généralistes d'un réseau d'aide à la déclaration de pharmacovigilance PharmacoMIP-MG.

OBJECTIVE: General practitioners (GPs) report little adverse drug reactions (ADR), although it is mandatory in France. The objective was to evaluate the satisfaction of the GPs who participated to a pharmacovigilance ADR declaration support network via a clinical research assistant (CRA) moving to their GP office in the French South-West region of Midi-Pyrénées. STUDY DESIGN: A satisfaction questionnaire was sent to the 59 active GPs of this network in November 2016. RESULTS: A total number of 44 GPs responded to the survey (mean age 44±11years; 48% of women). The overall satisfaction grade was rated 9/10 (SD±1). The personalized help from a CRA was highly appreciated (n=39; 89%), reduced time-loss (n=35; 90%), and facilitated communication with the local pharmacovigilance department (n=33; 85%). Most GP (95%; n=35) stated that they would keep reporting ADRs, 83% (n=35) stated to declare ADRs via the CRA, the others stated to declare ADRs directly to the Regional Pharmacovigilance Center, mainly via numerical or online tools. For 59% (n=26) their participation to the network had a positive impact on their relationship with patients through the improvement of their vigilance to ADR. DISCUSSION: Most of the active GP answered. They were very satisfied of the pharmacovigilance CRA network helping ADR reports. It may corroborate the increase of ADRs reporting in Midi-Pyrénées since this network was set up.

Effect of CYP3A4*22, POR*28, and PPARA rs4253728 on sirolimus in vitro metabolism and trough concentrations in kidney transplant recipients.

BACKGROUND: Recent studies have identified new candidate polymorphisms in the genes related to CYP3A activity or calcineurin inhibitor dose requirements in kidney transplant recipients. These genes and polymorphisms are CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4) (rs35599367-C>T; *22); POR [P450 (cytochrome) oxidoreductase] (rs1057868-C>T; *28); and PPARA (peroxisome proliferator-activated receptor alpha) (rs4253728-G>A). We investigated the impact of these polymorphisms on sirolimus (SRL) in vitro hepatic metabolism, SRL trough concentrations (C0), and SRL adverse events in kidney transplant recipients. METHODS: The clinical study included 113 stable kidney transplant patients switched from a calcineurin inhibitor to SRL (SRL C0 measured at 1, 3, and 6 months thereafter). We investigated SRL metabolism in vitro using human liver microsomes derived from individual donors (n = 31). Microsomes and patients were genotyped by use of Taqman® allelic discrimination assays. The effects of polymorphisms and covariates were studied using multilinear regression imbedded in linear mixed-effect models or logistic regressions. RESULTS: In vitro, the CYP3A4*22 allele resulted in approximately 20% lower metabolic rates of SRL (P = 0.0411). No significant association was found between CYP3A4, CYP3A5, or PPARA genotypes and SRL dose, C0, or C0/dose in kidney transplant patients. POR*28 was associated with a minor but significant decrease in SRL log-transformed C0 [CT/TT vs CC, ß = -0.15 (0.05); P = 0.0197] but this did not have any impact on the dose administered, which limited the relevance of the finding. After adjustment for nongenetic covariates and correction for false discovery finding, none of the single-nucleotide polymorphisms tested showed significant association with SRL adverse events. CONCLUSIONS: These recently described polymorphisms do not seem to substantially influence the pharmacokinetics of SRL or the occurrence of SRL adverse events in kidney transplant recipients.

Discussing alcohol use with the GP: a qualitative study.

BACKGROUND: Despite most GPs recognising their role in the early diagnosis of alcohol use disorder (AUD), only 23% of GPs routinely screen for alcohol use. One reason GPs report for not screening is their relationship with patients; questions regarding alcohol use are considered a disturbance of a relationship built on mutual trust. AIM: To analyse the feelings and experiences of patients with AUD concerning early screening for alcohol use by GPs. DESIGN & SETTING: A qualitative study of patients (n = 12) with AUD in remission or treatment, recruited from various medical settings. METHOD: Semi-structured interviews were conducted, audiorecorded, and transcribed verbatim. The authors conducted an inductive analysis based on grounded theory. The analysis was performed until theoretical data saturation was reached. RESULTS: The participants experienced AUD as a chronic, destructive, and shameful disease. The participants expected their GPs to play a primary role in addressing AUD by kind listening, and providing information and support. If the GPs expressed a non-judgmental attitude, the participants could confide in them; this moment was identified as a key milestone in their trajectory, allowing relief and a move toward treatment. The participants thought that any consultation could be an opportunity to discuss alcohol use and noted that such discussions required a psychological and benevolent approach. CONCLUSION: The participants felt fear or denial from the GPs, even though they felt that discussing alcohol use is part of the GP's job. The participants requested that GPs adopt non-judgmental attitudes and kindness when approaching the subject of alcohol use.