Etat et ressenti des vaccinations professionnelles contre rougeole, coqueluche, varicelle et grippe saisonnière, chez les professionnels au contact des nourrissons (enquête auprès de 1400 professionnels libéraux et hospitaliers de Maine-et-Loire)

Contexte: l'application des recommandations vaccinales professionnelles chez les professionnels de santé (PDS) est peu évaluée en France sauf pour la grippe. Objectif: Evaluer la connaissance des recommandations, les couvertures vaccinales, les raisons de vaccination et non vaccination, chez les PDS au contact des nourrissons dans le département du Maine et Loire, en milieu hospitalier et extra-hospitalier. Méthode: Enquête descriptive, par questionnaire. 432 PDS hospitaliers en pédiatrie (pédiatrie médicale, néonatalogie, réanimation, chirurgie, urgences) et de maternité. 610 médecins généralistes, 20 pédiatres libéraux, 180 médecins remplaçants, 92 PDS de Protection Maternelle et Infantile, 39 sage-femmes libérales. Résultats: 574 réponses. Recommandations annoncées connues: rougeole 64,6%, coqueluche 83,4%, varicelle 51,6%, grippe 89,7%. Evaluation de l'immunité naturelle et vaccinale rougeole 87,4%, varicelle 92,5%, vaccination adulte coqueluche 74,3%, couverture grippe 2008-2009 44,4% avec 60 à 89% pour les médecins libéraux. Raisons de vaccination: la protection personnelle pour la grippe, suivre les recommandations générales ou professionnelles pour les autres. Obstacles à la vaccination: manque d'informations sur les recommandations et négligence pour la rougeole; confusions dans les recommandations, sur la gravité de la maladie, la négligence pour coqueluche,varicelle,grippe. Conclusion: Les couvertures vaccinales restent insuffisantes. Les obstacles à la vaccination des professionnels de santé pourraient diminuer par un enseignement sur leur rôle de vecteurs, la gravité potentielle de ces pathologies chez le nourrisson, l'efficacité et la sûreté vaccinale.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Minéralisation osseuse de l'enfant diabétique (étude par absorptiométrie biphotonique à rayons X)

ANGERS-BU Médecine-Pharmacie (490072105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Pharmacie clinique et pharmacovigilance à l’hôpital : bilan et perspectives après 9 ans d’expérience

Introduction. La sous-notification reste un obstacle important à l’évaluation en pharmacovigilance et les pharmaciens déclarent peu d’effets indésirables en France. Objectifs. Rapporter comment l’intégration du pharmacien dans les unités de soins peut contribuer à la détection et au signalement des effets indésirables médicamenteux et étudier la validité des déclarations produites. Matériel et méthode. De 2002 à 2010, nous avons recueilli et analysé de manière prospective toutes les déclarations de pharmacovigilance faites par les pharmaciens dans un établissement hospitalo-universitaire et transmises au centre régional de pharmacovigilance (CRPV). La validité a été évaluée sur la base du nombre de cas retenus par le CRPV. Résultats. Deux mille dix-sept déclarations ont été envoyées. Au cours des quatre dernières années, le nombre annuel de dossiers envoyés a varié entre 250 et 350. Il a été multiplié par 10 par rapport à l’année 2001. Seulement 8,6 % des dossiers transmis n’ont pas été validés comme effet indésirable par le CRPV pour différents motifs : pas de lien de causalité entre l’effet indésirable et la prise de médicament, problème de chronologie, manque de données... Conclusion. L’intégration de la déclaration des effets indésirables dans les activités quotidiennes du pharmacien constitue un moyen d’augmenter de manière très significative (augmentation d’un facteur 9,6 à 13,4) le nombre de dossiers transmis au système de pharmacovigilance

Relevance of CYP2B6 and CYP2D6 Genotypes to Methadone Pharmacokinetics and Response in the OPAL Study

International audienceAIMS: Our study aimed to evaluate the impacts of the cytochrome P450 (CYP) 2B6-G516T and CYP2D6 genetic polymorphisms on pharmacokinetic and clinical parameters in patients receiving methadone maintenance treatment. METHODS: Opioid PhArmacoLogy (OPAL) was a clinical survey of the sociodemographic characteristics, history and consequences of pathology associated with methadone maintenance treatment response and current addictive comorbidities. A subgroup of 72 methadone patients was genotyped. RESULTS: When comparing the three CYP2B6 genotype groups, the methadone (R)- and (S)-methadone enantiomer concentrations/doses (concentrations relative to doses) were different (P = .029, P = .0019). The CYP2D6 phenotypes did not seem to be relevant with regard to methadone levels. On multivariate analysis, neither the CYP2B6 genotype nor the CYP2D6 phenotype explained the (R)-methadone concentration/dose values (P~= .92; P = .86); the (S)-methadone concentration/dose values (P = .052; P = .95 [although there was a difference between the TT group and GT and GG groups \P = .019\]); or opiate cessation (P = .12; P = .90). CONCLUSION: The genotyping of CYP2B6 G516T could be an interesting tool to explore methadone intervariability

Excessive self-grooming of Shank3 mutant mice is associated with gene dysregulation and imbalance between the striosome and matrix compartments in the striatum

Abstract Autism spectrum disorders (ASD) are characterised by atypical social communication and stereotyped behaviours. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are detected in 1-2% of patients with ASD and intellectual disability (ID), but the mechanisms underpinning the symptoms remain largely unknown. Here, we characterized the behaviour of Shank3 mutant mice deleted for exon 11 ( Shank3 Δ11/Δ11 ) from three to twelve months of age. We observed decreased locomotor activity, increased stereotyped self-grooming and atypical socio-sexual interaction compared to wild-type littermates. We then used RNAseq on four brain regions of the same animals to identify differentially expressed genes (DEG). DEGs were identified mainly in the striatum and were associated with synaptic transmission (e.g. Grm2 , Dlgap1 ), G-protein-signalling pathways (e.g. Gnal , Prkcg1 , and Camk2g ), as well as excitation/inhibition balance (e.g. Gad2 ). Downregulated and upregulated genes were respectively enriched in the gene clusters of medium-sized spiny neurons expressing the dopamine 1 (D1-MSN) and the dopamine 2 receptor (D2-MSN). Moreover, expression of DEGs reported as striosome markers within the striatum ( Cnr1 , Gnal1 , Gad2 , and Drd4 ) were positively correlated with excessive self-grooming. Finally, we showed that the striosome compartment of Shank3 Δ11/Δ11 mice was enlarged and displayed higher expression of GAD65 compared to wild-type mice. Altogether, these results shed light on a possible role of the striosomes/matrix imbalance in excessive self-grooming in Shank3 Δ11/Δ11 mice. Such striatal alterations could be present in a subgroup of patients with ASD and ID and could open the way to new therapeutic approaches

How do people who use drugs receiving Opioid Medication Therapy perceive their treatment ? A multicentre study

International audienceAbstract Background The resurgence of heroin use and the misuse of pharmaceutical opioids are some of the reasons for a worldwide increase in opioid dependence. Opioid Medication Therapies (OMT) have amply demonstrated their efficacy. From a medical point of view, the main objectives of OMT concern medical and social outcomes, centred on risk reduction and the cessation of opioid use. But patient points of view can differ and few studies have explored opioid-dependent patient viewpoints on their OMT. This variable seems important to consider in a patient-centred approach. The aim of our study was to explore points of view of people who use drugs (PWUD) treated with OMT, in a large multicentre sample. Method A cross-sectional multicentre study explored the points of view of PWUD with Opioid Use Disorder following OMT. Data regarding the patients’ points of view were collected using a self-administered questionnaire developed by the scientific committee of the study. A descriptive analysis and an exploratory factor analysis were performed to explore the structure of items exploring patient viewpoints. Results 263 opioid dependent PWUD were included, a majority were men consuming heroin prior to being prescribed OMT. 68% were on methadone, 32% were on buprenorphine. Most PWUD identified a positive impact on their lives, with 92.8% agreeing or strongly agreeing that OMT had changed a lot of things in their lives. The exploratory factor analysis identified three factors: (F1) items related to points of views concerning the objectives and efficacy of OMT; (F2) items related to the legitimacy of OMT as a treatment compared to a drug, (F3) items related to experiences and relationships with OMT. Conclusion Patient viewpoints on efficacy were correlated with the pharmacological benefits of OMT and with the associated psychosocial measures. The implications of OMT in relationships, such as the feeling of being judged, concerned a majority. Points of view were ambivalent concerning the role of OMT as a treatment or as a drug. Involving patient points of view in therapeutic strategies decisions could help enhance positive views among PWUD on OMT and help PWUD towards their recovery. Trial registration: OPAL study was registered: (NCT01847729)

Excessive self-grooming, gene dysregulation and imbalance between the striosome and matrix compartments in the striatum of Shank3 mutant mice

International audienceAutism is characterized by atypical social communication and stereotyped behaviors. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are detected in 1–2% of patients with autism and intellectual disability, but the mechanisms underpinning the symptoms remain largely unknown. Here, we characterized the behavior of Shank3 Δ11/Δ11 mice from 3 to 12 months of age. We observed decreased locomotor activity, increased stereotyped self-grooming and modification of socio-sexual interaction compared to wild-type littermates. We then used RNAseq on four brain regions of the same animals to identify differentially expressed genes (DEGs). DEGs were identified mainly in the striatum and were associated with synaptic transmission (e.g., Grm2, Dlgap1 ), G-protein-signaling pathways (e.g., Gnal , Prkcg1 , and Camk2g ), as well as excitation/inhibition balance (e.g., Gad2 ). Downregulated and upregulated genes were enriched in the gene clusters of medium-sized spiny neurons expressing the dopamine 1 (D1-MSN) and the dopamine 2 receptor (D2-MSN), respectively. Several DEGs ( Cnr1 , Gnal , Gad2 , and Drd4 ) were reported as striosome markers. By studying the distribution of the glutamate decarboxylase GAD65, encoded by Gad2 , we showed that the striosome compartment of Shank3 Δ11/Δ11 mice was enlarged and displayed much higher expression of GAD65 compared to wild-type mice. Altogether, these results indicate altered gene expression in the striatum of Shank3 -deficient mice and strongly suggest, for the first time, that the excessive self-grooming of these mice is related to an imbalance in the striatal striosome and matrix compartments