Prevalence and direct costs of potentially inappropriate prescriptions in France: a population-based study.

BACKGROUND: Potentially inappropriate prescriptions (PIPs) in the older population remain a growing public health concern due to the many associated adverse events increasing healthcare service use and health costs. This study aimed to assess the prevalence and direct costs of PIPs in older adults aged ≥65 years in France. METHODS: A population-based cross-sectional study was conducted in 2017 using a representative sample of the French national healthcare reimbursement system database. PIPs were defined using the French REMEDI[e]S tool. Overall reimbursed direct costs and by PIP category were extrapolated to the French older population. RESULTS: The overall PIP prevalence was estimated at 56.7% (95% CI: 56.4-57.0). Medications with an unfavorable benefit/risk ratio had the highest prevalence (34.0%, 95% CI: 33.7-34.3). Direct costs associated with PIPs represented 6.3% of the total reimbursed medication costs in 2017 (€507 million). Drug duplications were the main contributors to these costs (39.2% of the total reimbursed PIP costs, €199 million) and among all PIPs, proton pump inhibitors (>8 weeks) were the most expensive PIPs (€152 million). CONCLUSIONS: PIP prevalence is still high among French older adults, with substantial direct costs. Large-scale interventions targeting the most prevalent and/or costly PIPs are needed to reduce their clinical and economic impacts.

A safety signal of somnambulism with the use of antipsychotics and lithium: A pharmacovigilance disproportionality analysis.

AIMS: Antipsychotics and lithium are widely used in psychiatry, particularly in schizophrenia and bipolar disorders. Recently, some cases of somnambulism or sleep-related eating disorder (SRED) have been reported in patients treated with these drugs. This study investigated the risk of reporting somnambulism or SRED associated with the use of antipsychotics and lithium. METHODS: The World Health Organization pharmacovigilance database (VigiBase), comprising >18 million adverse events, was queried. All somnambulism or SRED reports related to antipsychotics or lithium were identified. The association between antipsychotics or lithium and somnambulism or SRED was computed using the proportional reporting ratio (PRR) and information component. RESULTS: Among the 5784 cases reporting somnambulism or SRED, 508 suspected at least 1 antipsychotic or lithium. Most patients were aged 18-64 years (62.0%), and 37.0% were men. In most cases (77.6%), antipsychotic or lithium were the only drug class involved, and 53.3% of cases suspected quetiapine. Somnambulism was reported in 88.6% of cases and SRED in 18.1%. A significant association was found for second-generation antipsychotics (PRR 3.44, 95% confidence interval 3.13) and lithium (PRR 2.03, [1.22; 3.37]), but not for first-generation antipsychotics (PRR 0.99, [0.68; 1.44]). CONCLUSIONS: We found a significant signal of somnambulism or SRED related to second-generation antipsychotics and lithium. While case reports mentioned mostly quetiapine and olanzapine, almost all second-generation antipsychotics were associated with somnambulism or SRED.

Targeted vaccination campaigns of teenagers after two clusters of B invasive meningococcal disease in Brittany, France, 2017.

BACKGROUND: In December 2016, three cases of serogroup B invasive meningococcal disease, including two children from the same middle school (11 to 15 years old pupils), occurred in the department (administrative district) Côtes-d'Armor (Brittany, France). They were infected by a rare strain (B:P1.7-2,4:F5-9:cc162), covered by the 4CMenB vaccine (Bexsero®). Four months later, two cases due to the same strain occurred in a high school in the same area (15 to 19 years old students). In accordance with French recommendations, vaccination was proposed to students of both schools and to all individuals aged 11-19 years living or studying in the hyperendemic area. We describe these vaccination campaigns, from the alert to the impact evaluation. METHODS: The target population included 8884 people: 579 in the middle school, 2007 in the high school and 6298 in the community. In both schools, vaccination sessions were organized directly on site. In the community, teenagers were vaccinated by general practitioners. The vaccination campaign took place from May to October 2017. An active pharmacovigilance follow-up was set up to document adverse effects of the vaccine. RESULTS: Considering the whole target population, the vaccination coverage was estimated at 43% for 1 dose and 34% for 2 doses. Higher vaccination coverage was observed in the schools (79% in the middle school and 42% in the high school for 2 doses) than in the community (27% for 2 doses). The reported adverse effects were consistent with the safety profile of the vaccine and no severe adverse effect was reported. CONCLUSIONS: This vaccination campaign was the third one implemented with Bexsero® in France and constitutes a reproducible approach for future targeted vaccination campaigns. No additional cases of the same strain have occurred since the end of the campaigns in the area.

An Automated Detection System of Drug-Drug Interactions from Electronic Patient Records Using Big Data Analytics.

The aim of the study was to build a proof-of-concept demonstratrating that big data technology could improve drug safety monitoring in a hospital and could help pharmacovigilance professionals to make data-driven targeted hypotheses on adverse drug events (ADEs) due to drug-drug interactions (DDI). We developed a DDI automatic detection system based on treatment data and laboratory tests from the electronic health records stored in the clinical data warehouse of Rennes academic hospital. We also used OrientDb, a graph database to store informations from five drug knowledge databases and Spark to perform analysis of potential interactions betweens drugs taken by hospitalized patients. Then, we developed a machine learning model to identify the patients in whom an ADE might have occurred because of a DDI. The DDI detection system worked efficiently and computation time was manageable. The system could be routinely employed for monitoring.

Outcome-dependent geographic and individual variations in the access to renal transplantation in incident dialysed patients: a French nationwide cohort study.

This study investigated geographical variations of access to renal transplantation using three outcomes (access to the transplant waiting list, access to renal transplantation after waitlisting and access to renal transplantation after dialysis start). Associations of patient-related and regional variables with the studied outcomes were assessed using a Cox shared frailty model and a Fine and Gray model. At the study endpoint (December 31, 2015), 26.3% of all 18-90-year-old patients who started dialysis in the 22 mainland and four overseas French regions in 2012 (n = 9312) were waitlisted and 15.1% received a kidney transplant. The geographical disparities of access to renal transplantation varied according to the studied outcome. Patients from the Ile-de-France region had the highest probability of being waitlisted, but were less likely to receive a kidney transplant. Two regional factors were associated with the access to the waiting list and to renal transplantation from dialysis start: the incidence of preemptive kidney transplantation and of ESRD. The use of different outcomes to evaluate access to kidney transplantation could help healthcare policy-makers to select the most appropriate interventions for each region in order to reduce treatment disparities.

Prevalence and nature of statin drug-drug interactions in a university hospital by electronic health record mining.

AIM: Our aim was to describe prevalence, nature, and level of severity of potential statin drug-drug interactions in a university hospital. METHODS: In a cross-sectional study, statin drug-drug interactions were screened from medical record of 10,506 in-patients treated stored in the clinical data warehouse "eHOP." We screened drug-drug interactions using Theriaque and Micromedex drug databases. RESULTS: A total of 22.5% of patients were exposed to at least one statin drug-drug interaction. Given their lipophilicity and CYP3A4 metabolic pathway, atorvastatin and simvastatin presented a higher prevalence of drug-drug interactions while fluvastatin presented the lowest prevalence. Up to 1% of the patients was exposed to a contraindicated drug-drug interaction, the most frequent drug-drug interaction involving influx-transporter (i.e., OATP1B1) interactions between simvastatin or rosuvastatin with cyclosporin. The second most frequent contraindicated drug-drug interaction involved CYP3A4 interaction between atorvastatin or simvastatin with either posaconazole or erythromycin. Furthermore, our analysis showed some discrepancies between Theriaque and Micromedex in the prevalence and the nature of drug-drug interactions. CONCLUSIONS: Different drug-drug interaction profiles were observed between statins with a higher prevalence of CYP3A4-based interactions for lipophilic statins. Analyzing the three most frequent DDIs, the more significant DDIs (level 1: contraindication) were reported for transporter-based DDI involving OATP1B1 influx transporter. These points are of concern to improve prescriptions of statins.

Clinical pharmacokinetics of oral drugs in the treatment of multiple myeloma.

Treatment of myeloma is a long-term treatment mainly based on all-oral combinations of drugs. Because oral drugs have a more complex pharmacokinetics compared with IV treatments, an appropriate knowledge of the factors that may alter their systemic exposure is of particular clinical relevance. Both drug-drug interactions, food-effect, and dose-adaptation in renal and hepatic impairment may influence the systemic drug levels with a potential impact on drug efficacy or safety. Moreover, a better control of drug exposure may improve the side effect profiles of these treatments with a favourable impact on patient compliance. Furthermore, as long-term treatments, these drugs may also alter the systemic exposure of coadministered medications in these rather old patients. The aim of this review was to identify the factors modifying the systemic exposure of oral drugs used in myeloma by focusing on the pharmacokinetic drug-drug interactions and the effects of renal and hepatic impairment and of food impact.