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International audience; PURPOSE: After a huge campaign of information on the teratogenic risk of sodium valproate (VPA) having taken place in France we aimed to evaluate the trend of its prescriptions in young epileptic girls.METHOD: Using the French National Health Insurance Database we searched for patients aged 0-14 years being supplied an antiepileptic drug (AED) between 2010 and 2016.RESULTS: 113,362 children received at least one AED, 61,259 boys and 52,103 girls. Compared to 2010-2014 years, VPA was less prescribed in 2016 as first AED (29% vs 37.3% respectively). The difference between the two periods was greater for girls (-41%) than for boys (-12%).CONCLUSION: The changing trend of VPA as first AED prescribed, particularly in girls, reflects published evidence in terms of safety.

Immune checkpoint inhibitors and targeted therapies have profoundly altered the management of several cancers over the past decade. Metastatic melanoma has been at the forefront of these changes. We provide here a nationwide overview and an assessment of changes in survival in France. We included 10,936 patients receiving a systemic treatment for metastatic cutaneous melanoma between 2010 and 2017 using the French National Health Insurance database (Système National des Données de Santé). Over the study period, there was a doubling of the number of new patients receiving a systemic treatment. Cytotoxic chemotherapy was progressively replaced by targeted therapy and immune checkpoint inhibitors. Patients having initiated a first-line treatment since June 2015 gained 46% overall survival compared with those initiating treatment before 2012. Overall survival at 24 months rose from 21% to 44%. We provide real-world evidence for the improvement of overall survival in the past decade among patients with metastatic melanoma. Although the characteristics of the patients treated can vary across periods, this type of exhaustive real-world data provides evidence from broader populations than those included in clinical trials.

Background Isotretinoin is the only effective treatment for severe acne. An isotretinoin-related suicide risk is still debated and under scrutiny by regulatory agencies. Our objectives were: to assess the risk of suicide attempt before, during and after isotretinoin treatment; to detect any potential triggering effect of isotretinoin initiation on suicide attempt. Methods We implemented a cohort and nested case-time-control study of subjects treated with oral isotretinoin (course or initiation) aged 10–50 years, using the Nationwide French Health Insurance data (2009–2016). The main outcome was hospitalized suicide attempt. Standardized incidence ratios for hospitalized suicide attempts were calculated before, during and after isotretinoin treatment. The number of isotretinoin initiations was compared in risk and control periods of 2 months using a case-time-control analysis. Results In all, 443 814 patients (median age 20.0 years; interquartile range 17.0–27.0 years) were exposed to isotretinoin, amounting to 244 154 person-years, with a marked seasonality for treatment initiation. Compared with the French general population, the occurrence of suicide attempts under isotretinoin treatment was markedly lower, with a standardized incidence ratio of 0.6 [95% confidence interval (CI) = 0.53–0.67]; the same applied, to a lesser extent, before and after isotretinoin treatment. In the case-time-control analysis, among cases of suicide attempt, 108 and 127 isotretinoin initiations were observed in the risk and control periods respectively (i.e. 0–2 months and 2–4 months before the date of suicide attempt). The comparison with the 1199 and 1253 initiations observed among matched controls in the same two periods yielded a case-time-control odds ratio of 0.89 (95% CI = 0.68–1.16). A sensitivity analysis using three-month periods and a complementary analysis adding completed suicides for case definition showed consistent results. Conclusion Compared with the general population, a lower risk of suicide attempt was observed among patients exposed to isotretinoin and there was no evidence for a triggering effect of isotretinoin initiation on suicide attempt. A selection of patients at lower risk for suicidal behaviour and appropriate treatment management could explain these findings. Risk management plans should therefore be maintained.

OBJECTIVES: The safety of oral propranolol for infantile hemangioma has not yet been studied at population level since the pediatric use marketing authorization was obtained in Europe. METHODS: A survey of a nationwide, claim-based observational cohort of children RESULTS: In all, 1753 patients CONCLUSIONS: In this study on a large continuous nationwide claims database, we confirm the safety profile of oral propranolol in healthy children to be good.

Introduction L’isotretinoine orale a ete accusee d’induire un risque suicidaire, en particulier dans la phase initiale du traitement. Nous avons analyse le risque de tentative de suicide (TS) sous isotretinoine a partir des donnees nationales exhaustives de l’assurance maladie (SNIIRAM 2009–2016) qui couvrent 98 % de la population francaise. Materiel et methodes Tous les sujets ayant eu au moins une delivrance d’isotretinoine entre 10 et 50 ans sur la periode 2009–2016 ont ete selectionnes. Le risque de TS (defini par une hospitalisation codee TS) a ete analyse, par periodes de 2 mois : avant, pendant, et apres l’initiation de l’isotretinoine, en etablissant des ratios standardises d’incidence (SIR) par rapport a la population francaise, en tenant compte du sexe, de l’âge, de l’annee et du mois. Une seconde analyse a recherche un sur-risque de TS dans les 2 mois qui suivent l’initiation d’isotretinoine par une analyse case-time-control qui compare la frequence d’initiation d’isotretinoine dans la periode « a risque » des 2 mois precedant la TS, a celle, chez le meme sujet, de la periode temoin qui precede la periode a risque, et qui tient compte de l’eventuelle evolution naturelle des initiations entre les deux periodes, mesuree par l’observation faite chez des temoins n’ayant pas fait de TS (10 temoins apparies par cas). Le risque pour une periode de 3 mois post-initiation a ete etudie en analyse secondaire. Resultats Au total, 4533 TS chez 3561 sujets ont ete observees dans notre « population isotretinoine » de 447 396 sujets. Les ratios standardises d’incidence de TS etaient inferieurs a 1, avant mais aussi apres l’initiation du traitement ( Fig. 1 ). Parmi les 3954 TS de la seconde analyse, et leurs 39 540 temoins, le risque de TS dans les 2 mois apres l’initiation etait de OR = 0,87 (IC95 % : 0,66–1,14 ; p = 0,30), et dans les 3 mois de OR = 0,87 (IC95 % : 0,64–0,99 ; p = 0,042). Discussion Cette etude depasse de beaucoup en nombre d’evenements et donc en puissance statistique toutes les etudes prealablement menees sur cette question. Nous mettons en evidence un risque abaisse de TS chez les patients recevant de l’isotretinoine, notamment dans les 2 a 3 mois qui suivent l’initiation. Pour en rendre completement compte, nous proposons la conjonction de 2 effets : (1) un processus de selection des patients par les dermatologues consistant a ecarter de la prescription d’isotretinoine les sujets les plus a risque de faire une TS ; (2) une diminution de la part du risque de TS lie a l’acne elle-meme, dans les 2 a 3 premiers mois de traitement consequence de l’efficacite therapeutique rapide de l’isotreninoine. Conclusion Les prescripteurs semblent avoir adapte les decisions d’indication de l’isotretinoine selon un rapport benefice–risque particulierement pertinent pour la sante publique.