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Levamisole was initially prescribed for the treatment of intestinal worms. Because of immunomodulatory properties, levamisole has been used in inflammatory pathologies and in cancers in association with 5-fluorouracil. Levamisole is misused as a cocaine adulterant. Post-marketing reports have implicated levamisole in the occurrence of adverse drug reactions (ADRs) and its use is now limited in Europe and North America. In contrast, all other parts of the World continue to use single-dose levamisole as an anthelmintic. The aim of this study was to identify ADRs reported after levamisole exposure in VigiBase, the World Health Organisation's pharmacovigilance database, and analyse their frequency compared to other drugs and according to levamisole type of use.All levamisole-related ADRs were extracted from VigiBase. Disproportionality analyses were conducted to investigate psychiatric, hepatobiliary, renal, vascular, nervous, blood, skin, cardiac, musculoskeletal and general ADRs associated with levamisole and other drugs exposure. In secondary analyses, we compared the frequency of ADRs between levamisole and mebendazole and between levamisole type of use.Among the 1763 levamisole-related ADRs identified, psychiatric disorders (reporting odds ratio with 95% confidence intervals: 1.4 [1.2-2.6]), hepatobiliary disorders (2.4 [1.9-4.3]), vasculitis (6.5 [4.1-10.6]), encephalopathy (22.5 [17.4-39.9]), neuropathy (4.3 [2.9-7.1]), haematological disorders, mild rashes and musculoskeletal disorders were more frequently reported with levamisole than with other drug. The majority of levamisole-related ADRs occurred when the drug was administrated for a non-anti-infectious indication.The great majority of the levamisole-related ADRs concerned its immunomodulatory indication and multiple-dose regimen. Our results suggest that single-dose treatments for anthelmintic action have a good safety profile.

International audience; Background: Stuttering is a speech disorder characterized by poor fluency of speech despite the speech production organs being normal. Numerous factors contribute to stuttering, and it may also be an iatrogenic effect of certain drugs. The aim of this study was to investigate the association between stuttering and drug exposure.Research design and methods: We investigated the association between drugs and stuttering. We analyzed reports in the World Health Organization global individual case safety reports database (Vigibase) up to 31 May 2020 with the MedDRA lower level terms 'stutter' and 'stuttering.' The association between a drug and the occurrence of the adverse drug reaction was estimated by disproportionality analysis. Reporting odds ratios (ROR) were calculated with 95% confidence intervals.Results: In total, 724 notifications were identified using the MedDRA terms selected. The main drugs implicated were methylphenidate (ROR = 19.58; 95% CI: 13.3-28.8), topiramate (ROR = 12.5; 95% CI: 7.1-22.1), olanzapine (ROR = 12; 95% CI: 8-17.9) and golimumab (ROR = 10.2; 95% CI: 5.5-19.1).Conclusions: When stuttering occurs in a patient treated by drugs affecting neurotransmission, a drug-induced origin of the stutter should be considered.

International audience; Chimeric-antigen-receptor T cells directed against CD19 (CAR-T) are emerging hematological therapeutics with scarce data on its overall safety profile spectrum. To determine the clinical features and incidence of adverse-drug reactions (ADR) associated with CAR-T. This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase and meta-analysis of data from CAR-T trials and cohorts in the literature was also performed through March, 2020. The primary objective was to identify ADR associated with approved CAR-T (axicabtagene-ciloleucel; tisagenlecleucel). We conducted a Bayesian disproportionate analysis with the 95% lower credibility-interval of information component (IC025 , significance > 0). We also performed a systematic-review and meta-analysis of CAR-T trials and cohorts in the literature to evaluate ADR incidence. Nine ADR classes were associated with CAR-T: Cytokine release syndrome (CRS, n = 1378, IC025 = 4.24), neurological disorders (n = 963, IC025 = 2.42), hematological disorders (n = 532, IC025 = 3.32), infections (n = 287, IC025 = 2.38), cardiovascular disorders (n = 256, IC025 = 2.81), pulmonary disorders (n = 186, IC025 = 3.80), reno-metabolic disorders (n = 123, IC025 = 1.89), hemophagocytic-lymphohistiocytosis (n = 36, IC025 = 5.01) and hepatic disorders (n = 32, IC025 = 2.49). ADR-related fatalities accounted for 99/1783 (5.5%) of the reports and 262/1783 (14.7%) for all-cause mortality. These ADR-related fatalities were associated with hemophagocytic-lymphohistiocytosis, cerebral vascular disorder, infections, and respiratory failure. In meta-analyses, the most frequent any-grade ADRs were CRS, hematological disorders, and neurological disorders. Fatal ADR were most found with neurological disorders, CRS, and infections. Note, CAR-T infusion may be associated with severe ADR mainly following the week of administration, though rarely fatal. Infections, hemophagocytic-lymphohistiocytosis and end organ failures including neurological or lung involvements require scrutiny.

International audience; L'infection pandémique par le coronavirus 2019 (COVID-19) qui se propage depuis la Chine génère un énorme flux d'informations et un point émergent est l'association fréquente de l'infection par le COVID-19 avec des anomalies hépatiques. Des études chinoises ont montré une augmentation des transaminases et d'autres enzymes hépatiques chez 14 à 53 % des patients infectés.

Background Ivermectin is known to cause severe encephalopathies in subjects infected with loiasis, an endemic parasite in Sub-Saharan Africa (SSA). In addition, case reports have described ivermectin-related serious adverse drug reactions (sADRs) such as toxidermias, hepatic and renal disorders. The aim of this study was to identify suspected sADRs reported after ivermectin administration in VigiBase, the World Health Organization’s global individual case safety reports database and analyze their frequency relative to the frequency of these events after other antinematodal drugs reported in SSA and other areas of the world (ROW). Methods All antinematodal-related sADRs were extracted from VigiBase. Disproportionality analyses were conducted to investigate nervous, cutaneous, psychiatric, respiratory, renal, hepatic and cardiac suspected sADRs reported after ivermectin and benzimidazole drug administration across the world, in SSA and RoW. Principal findings 2041 post-ivermectin or post-benzimidazole suspected sADRs were identified including 667 after ivermectin exposure (208 in SSA and 459 in the RoW). We found an increased reporting for toxidermias, encephalopathies, confusional disorders after ivermectin compared to benzimidazole drug administration. Encephalopathies were not only reported from SSA but also from the RoW (adjusted reporting odds ratios [aROR] 6.30, 95% confidence interval: 2.68–14.8), highlighting the fact these types of sADR occur outside loiasis endemic regions. Conclusion We described for the first time suspected sADRs associated with ivermectin exposure according to geographical origin. While our results do not put in question ivermectin’s excellent safety profile, they show that as for all drugs, appropriate pharmacovigilance for adverse reactions is indicated., Author summary Ivermectin is a drug used worldwide for various indications: onchocerciasis, lymphatic filariasis, strongyloidiasis, human sarcoptic scabies, acarodermatitis and rosacea. In the early 1990s, it was discovered that ivermectin could induce severe encephalopathies in some patients with high parasite loads of Loa loa, a filarial nematode. This objective of this pharmacovigilance study is to summarize serious neurological and non-neurological post-ivermectin adverse drug reactions reported in the World Health Organization database called VigiBase. This study shows that reported serious adverse drug reactions associated with ivermectin are fairly consistent with those mentioned in the official product information of ivermectin but also provides some new signals. Serious post-ivermectin encephalopathies can also occur outside of Loa loa endemic regions but the understanding of the mechanism by which it occurs requires further studies. A new signal concerning two serious toxidermias (DRESS syndrome and acute generalized exanthematous pustulosis) is also described. A lack of reporting of adverse drug reactions is noticeable in some Sub-Saharan African countries, and actions are needed to increase the reporting rates of these adverse effects in these countries.

International audience; La neurotoxicité du métronidazole, antibiotique et antiparasitaire, est rapportée chez l’humain et l’animal depuis les années 80. Chez le chien, il s’agit principalement de troubles de l’équilibre et/ou de tremblements. Alors que jusqu’à présent des doses de métronidazole élevées (supérieures à la dose habituellement utilisée qui peut aller jusqu’à 50 mg/kg/jour) étaient généralement incriminées, une étude récente fait état d’effets indésirables neurologiques dès 26 mg/kg/jour. L’analyse des données de la pharmacovigilance corrobore les résultats de cette étude, en identifiant un risque lié à une utilisation prolongée du médicament, même à dose réduite. Des précautions parti-culières d’emploi sont donc nécessaires pour limiter le risque d’apparition de ces effets indésirables.

L’ostéochimionécrose des mâchoires (OCNM) est un effet indésirable rare de certains médicaments inhibiteurs de la résorption osseuse. Elle a été découverte grâce à la veille sanitaire après commercialisation et non pendant les essais cliniques préalables. Le but de ce travail a été d’étudier les cas d’OCNM en France depuis leur apparition, et le degré de déclaration de ceux-ci. Matériel et méthodes : il s’agit d’une étude descriptive. Les données constituant l’état des lieux de l’OCNM sont issues de l’article du Dr De Boissieu « Bisphosphonate-related osteonecrosis of the jaw: data from the French national pharmacovigilance database » et des données de Vigibase (la base de données mondiale des notifications spontanées d'Effets Indésirables des Médicaments gérée par l'Organisation Mondiale de la Santé) ainsi que de la Base Nationale de Pharmacovigilance sur les cas d’OCNM des cinq dernières années. La déclaration de l’OCNM en France a été étudiée grâce à un questionnaire de pratique adressé aux praticiens sur les cas d’OCNM et les données déclarées. Résultats : sur la période 1985 – 2020 1299 cas d’OCNM ont été identifiés, 670 pour la période 2015 – 2020. Les OCNM surviennent principalement à la mandibule chez des patients de sexe féminin de plus de 65 ans traités pour des pathologies oncologiques. Après 2015 le principal médicament pourvoyeur d’OCNM est le Dénosumab, suivi par le Zolédronate et l’Alendronate qui étaient auparavant en tête. La pathologie est largement sous-déclarée car 70 % des praticiens voyant des OCNM dans leur pratique ne les déclarent pas. Conclusion : la surveillance dépend de la déclaration des cas, qui apparaît être insuffisante car les praticiens manquent d’information sur les processus de déclaration et sur leur rôle au sein de la pharmacovigilance. Il est nécessaire de réaliser d’autres travaux pour étudier l’impact précis de cette sous-déclaration sur l’étendue de l’importance de l’OCNM en santé publique et dans la balance bénéfice-risque des médicaments.

International audience; Aims: Amoxicillin (AMX)-induced crystal nephropathy (AICN) is a rarely reported adverse drug reaction (ADR) but its increase has been recently reported in the Paris area. Our aim was to investigate the incidence, characteristics and outcome of AICN in France.Methods: Retrospective analysis of all AICN cases reported to the French National Pharmacovigilance Database and the Marketing Authorization Holders Pharmacovigilance Database. AICN notification rate was compared to intravenous AMX and AMX-clavulanate sales.Results: In total, 101 AICN cases were included. Intravenous AMX/AMX-clavulanate was prescribed as surgical prophylaxis (32 surgical patients) or to treat infection (69 medical patients). AKI KDIGO stage 3 was observed in 70 patients and 24/70 patients required renal replacement therapy and/or intensive care unit admission. The annual notification rate of AICN was increased by a factor of 13 since 2010 (6 [0;7] and 77 [24;111] cases per 100 000 patient-years of exposure, before and after 2010 respectively; P < .001). In surgical patients, the increase in AICN has been reported since 2010 and was mainly related to inadequate AMX administration. In medical patients, the increase in AICN was observed since 2014. After 2014, medical patients were older (67 [42;77] vs 74 years [64;84] respectively; P < .05) and were treated more frequently for endocarditis (0/20 vs 15/49 respectively; P < .01). A contributing factor was observed or suspected in 62 patients.Conclusion: AICN is a severe ADR that dramatically increased in France since 2010. Assessment of AICN contributing factors and AMX drug monitoring in patients receiving high dose of AMX could reduce the risk of AICN.

Methylphenidate (MPH) is a piperidine similar to amphetamines, and is indicated for attention deficit hyperactivity disorder. Studies concerning stuttering occurring with MPH are contradictory. We investigated the association between MPH and stuttering. We analysed reports in the World Health Organization global individual case safety reports database, Vigibase, up to 31 December 2018, with the MedDRA preferred term “dysphemia” and the lower level terms “stutter” and “stuttering”. The association between exposure to MPH and occurrence of the adverse drug reaction was estimated by disproportionality analysis. Reporting odds ratios (RORs) were calculated with 95% confidence intervals (CIs). In total, 2975 cases of dysphemia were reported, of which 46 reports were associated with MPH. For the Preferred Term “dysphemia”, the ROR was 7.3 (95% CI: 5.4-9.8). With the Lower Level Term “stuttering”, 584 cases were registered in the database of which 17 involved MPH. The ROR was 13.9 (95% CI: 8.6-22.5). This study found a signal for stuttering with MPH.

International audience; Dihydropyrimidine dehydrogenase (DPD) deficiency is the main cause of early severe toxicities induced by fluoropyrimidines (FP). The French Group of Clinical Oncopharmacology (GPCO)-Unicancer and the French Pharmacogenetics Network (RNPGx) initiated two surveys, one addressed to oncologists, the other to biologists, in order to evaluate routine practices regarding DPD deficiency screening at national level, as well as compliance, motivations and obstacles for implementation of these tests. These anonymized online surveys were performed with the logistic assistance of the Francophone Federation of Digestive Oncology (FFCD) and the support of numerous medical and biological societies. The surveys were conducted in 2016-2017 before the creation of the French INCa/HAS expert panel, which contributed to the drafting of rules and recommendations for DPD deficiency screening published in December 2018. In all, 554 questionnaires from clinicians were analyzed (23% participation) and 35 from biologists. The main arguments raised by clinicians for justifying the limited practice of DPD deficiency screening were: the lack of recommendations from medical societies or Health Authorities, delays in obtaining results, and the lack of adequate reimbursement by the health insurance system. The goal of these surveys was to provide the French Health Authorities with an overview on nationwide DPD-deficiency screening practices and thus help to design recommendations for the standardization and improvement of the management and safety of cancer patients receiving FP-based chemotherapy.

La principale limite du système de pharmacovigilance français basé sur la notification spontanée des effets indésirables médicamenteux est la sous-notification. Depuis 2015, la déclaration des effets indésirables est ouverte aux patients mais la participation des professionnels de santé reste indispensable pour garantir l'efficacité du système. Le pharmacien d'officine est à l'interface entre les patients et l'ensemble des prescripteurs, il bénéficie d'une vue globale sur les traitements, qu'ils soient prescrits ou d'automédication. L'objectif de cette thèse est d'analyser, en Ille-et-Vilaine, la notification des effets indésirables à l'officine et de s'intéresser à la place du pharmacien d'officine au sein du système de pharmacovigilance français grâce à l'analyse des notifications réalisées par les pharmaciens d'officine ainsi que la diffusion d'un questionnaire à l'ensemble des pharmaciens d'officine du département.

International audience; A flagship recommendation of the citizen's steering committee on immunization, the mandatory immunization for infants extended to 11 vaccines, introduced in January 2018, is part of a set of recommendations that must be considered as a whole, each component being indispensable to the achievement of objectives: restore confidence in vaccination and increase immunization coverage. Roundtable # 6 participants identified a decade of concrete initiatives that could address, at least in part, the committee's recommendations, including: developing information systems and data generation; simplify the vaccination journey and increase vaccination opportunities; developing training of health professionals; learning vaccines at school; using motivational interviewing in educational intervention; undertaking local initiatives; improving supply and communicate on the value of vaccines. To carry out these actions, it has been proposed that a joint ministerial task-force bringing together the different stakeholders at the national level should be set up to promote their implementation and follow-up, and at regional level, the establishment of an Agences régionales de santé awareness plan making vaccination a priority.

International audience; In the information retrieval task, searching and choosing keywords to form the query is crucial. The present study analyzes and describes the keywords' search strategy into a thesaurus in the field of pharmacovigilance. Two ergonomics experts shadowed 22 pharmacovigilance specialists during their daily work. They focus on the strategies for searching and choosing MedDRA terms to build pharmacovigilance queries. Interviews of four pharmacovigilance specialists completed the observations. Results highlight that, for unusual or complex searches, pharmacovigilance specialists proceed iteratively in three main phases: (i) preparation of a list of terms and of evaluation criteria, (ii) exploration of the MedDRA hierarchy and choice of a term, and (iii) evaluation of the results against the criteria. Overall, the search and the choice of keywords within a thesaurus shares similarity with the information retrieval task and is closely interwoven with the query building process. Based on the results, the paper proposes design specifications for new interfaces supporting the identification of MedDRA terms so that pharmacovigilance reports searches achieve a good level of expressiveness.

Les statines sont des médicaments qui agissent en inhibant la biosynthèse du cholestérol. Ils sont indiqués dans la prévention des événements cardiovasculaires et de l’hypercholestérolémie et sont très largement prescrits en France et à travers le monde. Si les études cliniques permettent de détecter les principaux effets indésirables des médicaments, une surveillance post-commercialisation est indispensable pour garantir la sécurité d’emploi d’un médicament dans la population générale et détecter de nouveaux effets indésirables. Cette surveillance se traduit notamment par l’évaluation des rapports périodiques de sécurité déposés par les titulaires d’Autorisations de Mise sur le Marché (AMM), la mise en place d’études épidémiologiques, l’analyse de la littérature scientifique, la collecte et l’analyse de cas de pharmacovigilance. Ces cas sont regroupés dans des bases contenant l’ensemble des notifications spontanées d’évènements indésirables ou encore la détection de signaux de sécurité à l’aide. Récemment, un signal potentiel de dépressions a été identifié. Les connaissances concernant ce risque étant limitées et contradictoires, une investigation approfondie de ce signal par une analyse de disproportionnalité apparaît fondamentale. Cette thèse traite donc de l’évaluation des signaux de dépression liés à l’utilisation des statines après un état des lieux de leur utilisation ainsi qu’un point sur les dépressions en tant que pathologie et comme effet indésirable.

Angiotensin receptor blockers (ARBs) can induce or exacerbate psoriasis. Psoriasis is unlisted in the Summary of Product Characteristics (SmPC) of ARBs. We aimed to investigate the association between psoriasis and ARB exposure.We reviewed spontaneous reports recorded in the French national Pharmacovigilance Database (FPVD). The association between psoriasis and ARB exposure was assessed using the case/non-case method. We also analyzed literature reports.We identified 89 reports of psoriasis during ARB exposure in the FPVD. Time to onset was most often less than 1 year. Outcome was favorable in 67% of reports after ARB discontinuation. Almost all ARBs were concerned. The reporting odds ratio (ROR) for psoriasis with this therapeutic class was 4.86 (95%CI 3.92-6.03). In the literature, we found 14 published reports of psoriasis with ARB exposure. Time to onset ranged from 6 weeks to 9 months. Outcome was also favorable after ARB discontinuation in the literature.This underestimated adverse drug reaction is a class effect, time to onset is most often less than 1 year and outcome seems favorable after ARB discontinuation. The case/non-case approach highlights a potential safety signal. The SmPC of ARBs should be updated, increased awareness among healthcare professionals is warranted.

An increase in amoxicillin-induced crystal nephropathy (AICN) incidence has been recently suggested. The aims of this study were to investigate the trend of AICN incidence through Paris' regional centers of pharmacovigilance (Paris RCPVs) and better describe this rare adverse drug reaction. Forty-five AICN cases were identified between 1985 and 2016. All cases, except one, were reported since 2010. Amoxicillin (AMX) was administered intravenously (65 [interquartile range {IQR}, 43 to 110] mg/kg of body weight/day) in all patients, either for treating infection ( n = 15) or as surgical prophylaxis ( n = 30). Delay between AMX administration and AICN onset was 1 (IQR, 1 to 3) day; 30, 4, and 11 patients developed KDIGO stage 1, 2, and 3 acute kidney injury, respectively. Delay between AICN onset and kidney function recovery was 4 (IQR, 2 to 6) days. Precipitating factors were identified in only one-third of cases. Twelve patients required intensive care unit admission, and 8 needed renal replacement therapy. Neither chronic kidney disease nor death was observed. We confirmed the recent and dramatic increase of AICN in the Paris RCPVs since 2010. The absence of precipitating factors in the majority of cases and the onset of AICN in apparent routine indications, such as surgical prophylaxis, are alarming and justify a high vigilance from all AMX prescribers.

International audience; Suspected adverse drug reactions (ADR) reported by patients through social media can be a complementary source to current pharmacovigilance systems. However, the performance of text mining tools applied to social media text data to discover ADRs needs to be evaluated. In this paper, we introduce the approach developed to mine ADR from French social media. A protocol of evaluation is highlighted, which includes a detailed sample size determination and evaluation corpus constitution. Our text mining approach provided very encouraging preliminary results with F-measures of 0.94 and 0.81 for recognition of drugs and symptoms respectively, and with F-measure of 0.70 for ADR detection. Therefore, this approach is promising for downstream pharmacovigilance analysis.

Motivation: Spontaneous adverse event reports have a high potential for detecting adverse drug reactions. However, due to their dimension, exploring such databases requires statistical methods. In this context, disproportionality measures are used. However, by projecting the data onto contingency tables, these methods become sensitive to the problem of co-prescriptions and masking effects. Recently, logistic regressions have been used with a Lasso type penalty to perform the detection of associations between drugs and adverse events. However, the choice of the penalty value is open to criticism while it strongly influences the results. Results: In this paper, we propose to use a logistic regression whose sparsity is viewed as a model selection challenge. Since the model space is huge, a Metropolis-Hastings algorithm carries out the model selection by maximizing the BIC criterion. Thus, we avoid the calibration of penalty or threshold. During our application on the French pharmacovigilance database, the proposed method is compared to well established approaches on a reference data set, and obtains better rates of positive and negative controls. However, many signals are not detected by the proposed method. So, we conclude that this method should be used in parallel to existing measures in pharmacovigilance., Comment: 7 pages, 3 figures, submitted to Biometrical Journal

Background. Adverse drug reactions (ADR) are common, sometimes serious but underreported to regional pharmacovigilance (PV) centers by general practitioners (GP). Patients can declare on their own but their statements are less accurate and can result in a lake of precision. Involving statements from physicians and patients could improve the detection of the PV signal. Hence the idea of a joint declaration patient - physician (JDPP) of ADR. The objective is to evaluate the perception of Ille-et-Vilaine GP on JDPP. Methods. The inclusion criteria are private practice in general medicine in Ille-et-Vilaine. GPs are recruited by telephone. The number of subjects is determined by data saturation. The insight of GPs is collected through individual interviews including a quantitative questionnaire to characterize the population and 4 open questions. The interviews are coded - manually - to highlight the collection of GPs. Results. 12 GPs are included in the study. ADRs encountered were common, known and not serious. 50% of GPs surveyed have already told the regional PV center. No statement was made at the request of a patient. GPs adhere to the concept of JDPP because they see a benefit in terms of public health and security of the drug. For them, the main obstacles are the time factor and the bureaucracy, lack of PV training and abusive demands of patients. GPs think that the lack of information in PV, particularly for filling the declaration form was the main obstacle to patients. The expected improvements are simplification and time savings, better training and information for GPs and patients via national awareness campaigns on medication. Conclusion. The JDPP is welcomed by GPs surveyed although many improvements are to be considered. It would be needed to make a similar experience with patients before testing JDPP locally.; Contexte. Les effets indésirables médicamenteux (EIM) sont fréquents, parfois graves mais sont sous-notifiés aux centres régionaux de pharmacovigilance (CRPV) par les médecins généralistes (MG). Les patients peuvent déclarer seul mais leurs déclarations sont peu précises. Associer les déclarations des médecins à celles des patients pourrait améliorer le signal en PV. D’où l’idée d’une déclaration commune patient – MG (DCPM) des EIM. L’objectif est d’évaluer la perception des MG d’Ille-et-Vilaine sur une DCPM. Méthodes. Les critères d’inclusion sont l’exercice libéral, en médecine générale, en Ille-et-Vilaine. Les MG sont recrutés par téléphone. Le nombre de sujets est fixé par la saturation des données. Le regard des MG est recueilli via des entretiens individuels comprenant un questionnaire quantitatif pour caractériser la population et quatre questions ouvertes. Les entretiens sont codés – manuellement – afin de faire ressortir la perception des MG. Résultats. Douze MG sont inclus dans l’étude. Les EIM rencontrés étaient fréquents, connus et non graves et 50% des MG interrogés ont déjà déclaré au CRPV. Aucune déclaration n’a été faite à la demande d’un patient. Les MG adhèrent au concept de la DCPM car ils y voient un intérêt en termes de santé publique et de sécurisation du médicament. Pour eux, les principaux freins sont le facteur temps, la lourdeur administrative, le manque de formation en PV et les demandes abusives des patients. Les MG pensent que le manque d’information en PV – en particulier pour le remplissage de la fiche de déclaration - était le frein principal pour les patients. Les améliorations attendues étaient une simplification et un gain de temps, une meilleure formation et information des MG et des patients via des campagnes nationales de sensibilisation sur le médicament. Conclusion. La DCPM est bien accueillie par les MG interrogés même si plusieurs améliorations sont à envisager. Il faudrait effectuer une expérience similaire auprès des patients avant de tester la DCPM au niveau local.

Companion of the pharmacy since the introduction of the system SESAM-vitale in 1998, management softwares (aka Logiciels de gestion d'Officine) of pharmacy are becoming over the years, a key element of the French informatics tool. This work proposes an exhaustive list of softwares commercialized in France in 2014 and a list of their functionalities classified by order needs: obligatory, essential and optional functions and services given by editors. After that, this work deals with a development of the different doers and institutions that interact with those softwares, especially by describing organization where the pharmacists had an active participation. A brief table comparing editors is proposed. A generalist explanation of free software is given because they are used inside some of this professionalssoftwares. Then, analyses of teletransmission data are undertaken, before a series of tables ranking the various LGO softwares of the market by the functionalities, the operating system, the software of database used. Finally, a discussion concludes this work, Compagnon de l'Officine depuis la mise en place du système SESAM-Vitale en 1998, les logiciels de gestion d'officine (LGO) sont devenus au fil des années, un élément clé de l'outil informatique du pharmacien officinal. Cet ouvrage propose une liste exhaustive des logiciels de gestion d'officine (LGO) présents sur le marché français en 2014, un catalogue des fonctionnalités et services proposés par les éditeurs en les classant par ordre de nécessité: les fonctionnalités obligatoires d'un LGO, celles jugées indispensables, les fonctionnalités optionnelles et les services que proposent les éditeurs de LGO.Il poursuit avec un développement sur les différents acteurs et institutions qui interagissent avec ces logiciels, notamment en décrivant les structures où les pharmaciens ont eu une participation active. Un tableau succinct comparant les éditeurs est proposé.Une explication généraliste sur les logiciels libres est abordée, car ils sont utilisés au sein de certains de ces logiciels métiers. Une analyse des chiffres de la télétransmission est entreprise par la suite, avant une succession de tableaux classant les différents LGO du marché en fonction des fonctionnalités qu'ils proposent, les systèmes d'exploitations sur lesquels ils tournent, les moteurs de bases de données qu'ils utilisent.Enfin une discussion conclue ce travail.

Companion of the pharmacy since the introduction of the system SESAM-vitale in 1998, management softwares (aka Logiciels de gestion d'Officine) of pharmacy are becoming over the years, a key element of the French informatics tool. This work proposes an exhaustive list of softwares commercialized in France in 2014 and a list of their functionalities classified by order needs: obligatory, essential and optional functions and services given by editors. After that, this work deals with a development of the different doers and institutions that interact with those softwares, especially by describing organization where the pharmacists had an active participation. A brief table comparing editors is proposed. A generalist explanation of free software is given because they are used inside some of this professionalssoftwares. Then, analyses of teletransmission data are undertaken, before a series of tables ranking the various LGO softwares of the market by the functionalities, the operating system, the software of database used. Finally, a discussion concludes this work; Compagnon de l'Officine depuis la mise en place du système SESAM-Vitale en 1998, les logiciels de gestion d'officine (LGO) sont devenus au fil des années, un élément clé de l'outil informatique du pharmacien officinal. Cet ouvrage propose une liste exhaustive des logiciels de gestion d'officine (LGO) présents sur le marché français en 2014, un catalogue des fonctionnalités et services proposés par les éditeurs en les classant par ordre de nécessité: les fonctionnalités obligatoires d'un LGO, celles jugées indispensables, les fonctionnalités optionnelles et les services que proposent les éditeurs de LGO.Il poursuit avec un développement sur les différents acteurs et institutions qui interagissent avec ces logiciels, notamment en décrivant les structures où les pharmaciens ont eu une participation active. Un tableau succinct comparant les éditeurs est proposé.Une explication généraliste sur les logiciels libres est abordée, car ils sont utilisés au sein de certains de ces logiciels métiers. Une analyse des chiffres de la télétransmission est entreprise par la suite, avant une succession de tableaux classant les différents LGO du marché en fonction des fonctionnalités qu'ils proposent, les systèmes d'exploitations sur lesquels ils tournent, les moteurs de bases de données qu'ils utilisent.Enfin une discussion conclue ce travail.

In light of the recent emergence of a growing incidence and of an increasing number of notices to the pharmacovigilance of anaphylaxis shocks to succinylcholine in different French hospitals, this study provides an update on current knowledge about allergic shock to curare. It also provides an example of pharmacovigilance in France. This work makes a comparative analysis of the literature and research hypotheses that could explain this significant outbreak. Material and methods: this is a retrospective study of 19 cases of anaphylaxis to succinylcholine which occurred between 2010 and 2013 in two French university hospitals. Data from diagnostics, immediate biological and allergy tests were collected. Hemodynamic changes, ventilation, and the therapeutic management of these shocks were extracted from the consultations and anesthesia sheets. Results: 18 cases were validated. One case was withdrawn further to negative skin tests. Skin tests were not performed in two cases but these cases were kept on the basis of clinico-biological concordance and the absence of alternative diagnosis. A large proportion of severe shocks has been registered with 78% grade III and 22% grade IV. 39% patient’s had an allergic tendency. The injections were performed for 61% in the framework of scheduled surgery; for 28% in order to anticipate a difficult intubation; and for 61% because of inhalation risk or suspicion of full stomach. Bronchospasm and rash are often absent in favor of hemodynamic signs. Four hypotheses have been advanced to explain this outbreak.; Devant l’apparition récente d’une augmentation d’incidence et de déclarations à la pharmacovigilance de chocs anaphylactiques à la succinylcholine dans différents hôpitaux français, cette étude fait le point sur les connaissances actuelles concernant les chocs allergiques à ce curare. Elle donne un exemple de pharmacovigilance en France. Ce travail fait l’analyse comparative de la littérature et recherche les hypothèses pouvant expliquer cette recrudescence significative. Matériel et méthode : il s’agit d’une étude rétrospective de 19 cas de chocs anaphylactiques à la succinylcholine survenus entre 2010 et 2013 dans 2 centres hospitalo universitaires français. Les données des bilans diagnostics, biologiques immédiats et des bilans allergologiques ont été colligés. L’évolution hémodynamique, ventilatoire, ainsi que la prise en charge thérapeutique de ces chocs ont été extraits des consultations et des feuilles d’anesthésies. Résultats : 18 cas ont été validés. Un cas a été retiré sur la négativité des tests cutanés. Deux cas n’ont pas effectué leurs tests cutanés et ont été conservés sur la concordance clinico-biologique et l’absence de diagnostic différentiel. Il apparaît une forte proportion de chocs graves avec 78% de grade III et 22% de grade IV. Parmi les patients, 39% avaient un terrain allergique. Les injections se font pour 61% dans le cadre de chirurgies programmées avec 28% en prévision d’une intubation difficile et 61% pour risque d’inhalation ou suspicion d’estomac plein. Le bronchospasme et le rash cutané sont souvent absents au profit des signes hémodynamiques. Quatre hypothèses sont avancées pour expliquer cette recrudescence de cas.

International audience; AIM: To evaluate the performance of a query on international classification of diseases 10(th) version (ICD10) codes in the database of the programme for the medicalisation of information systems (programme de médicalisation des systèmes d'information, PMSI) to identify serious adverse drug reactions (ADR). METHODS: The query concerned hospital stays of patients discharged from the French University Hospital of Rennes in 2009. All the hospitalization summaries including a selected ICD10 code were analysed to validate ADR. RESULTS: Out of 383 cases, 142 cases were validated (37.1%). Performance of some ICD10 codes was particularly interesting, above 40% (T88.6, L27.0, J70.4, G62.0 and N14.1) and 79.5% of the ADR were detected by these five codes. During the study period, 98 ADR of the same type were spontaneously reported by physicians, 22 of which were common with the ICD10 query. CONCLUSIONS: The use of PMSI can be a tool for signal detection of serious ADR, in addition to spontaneous reporting.

BackgroundThere is no functional pharmacovigilance system in Cambodia to our knowledge. Mobile phone–based tools, such as short message service (SMS) text messages, are increasingly used for surveillance purposes. ObjectiveTo pilot-test the FrontlineSMS mobile phone–based tool for notification of adverse events, using Cambodia’s only International Vaccination Center at the Institut Pasteur du Cambodge as a field site. MethodsPeople receiving vaccinations, aged over 18 years, and who owned a cell phone were recruited in the study following informed consent. The names and mobile phone numbers of the participants interviewed were entered each day into the FrontlineSMS software. Two days after being vaccinated, participants received an automatically generated SMS text message asking whether any adverse events had occurred. Their SMS reply was number-coded and exported from the software daily to an Excel spreadsheet and examined before being saved. If the participant replied with a code for a severe adverse event (8 or 9), they were automatically advised to consult the nearest doctor. ResultsThe active surveillance study was conducted over 72 days in the spring of 2012. Patients agreed to be asked by SMS text message whether unwanted events had occurred after vaccination. Of 1331 persons aged over 18 years referred to the vaccination unit, 184 (13.8%) were asked and agreed to participate. When texted for clinical status 48 hours after vaccination, 52 (28.3%) participants did not reply, 101 (54.9%) sent an immediate SMS reply, and 31 (16.8%) sent an SMS reply after additional prompting. Of the initial 184 participants, 132 (71.7%) replied. These 132 participants received 135 vaccine doses and 109 (82.6%) reported no adverse events, whereas 23 (17.4%) reported adverse events, all benign. ConclusionsNotification using an SMS-based text message system is already used in Cambodia for syndromic surveillance in health centers and reporting by health care workers. Our results show that such tools can also be useful for notification by patients or health users in Cambodia, especially in an urban setting.

International audience; PURPOSE: Fluindione is an oral vitamin K antagonist (indanedione derivative) exclusively marketed in France and Luxembourg, known to have immuno-allergic adverse effects such as hepatitis, fever or interstitial nephritis. A few cases of drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with fluindione. The aim of the present study was to investigate fluindione-induced DRESS cases reported in France and to describe their characteristics. METHODS: We searched for potential cases of DRESS with fluindione reported in the French pharmacovigilance database since 2000. RESULTS: Thirty-six cases of DRESS were included and concerned 17 women and 19 men. The mean age was 65 years (median: 68 years, range: 28-95 years). Kidneys and liver were the most frequent organs involved. Thirty-five cases were serious. In 5 cases, the effect was life-threatening. Most of the patients recovered. Fluindione was the only medicine suspected in 26 cases. Skin patch tests, performed in 10 cases, were positive with fluindione in 9 cases. CONCLUSIONS: Fluindione is not known to be a frequent cause of DRESS. However, the number of reports found is probably underestimated. The seriousness of DRESS, as all immuno-allergic adverse effects, contraindicates fluindione reintroduction. Coumarinic derivatives are the alternatives in patients who need oral anticoagulant treatment.

International audience; Introduction and objectives: Works available on the spreading of a subject become increasingly concentrated on the core of the most productive journals, and dispersed between different sources that sometimes offer additional relevant item. To retrieve all the articles is practically impossible, this is why the availability of instruments to determine the fundamental core of sources is important to provide as much items as possible without losing relevant information. Material and methods: The method used applies bibliometric procedures developed by Bradford, Leimkühler and, Groos. The literature on the secondary effects of the drug Captopril is used as an example. Results: A core of 21 journals assures the retrieval of the core publications on captopril adverse effects; although, only 10 ensure the information in need to complete a clear strategic analysis. The most important components of this information can be retrieved by limiting the search to the titles. Most of the journals have a high circulation.Conclusions: The combined application of some bibliometric models connected wiith the fact that science growth obeys an exponential law, may simplify the definition of the core relevant information on a specific question.; Introducción y objetivo: La bibliografía sobre un tema suele concentrarse en un núcleo de revistas más productivas y el resto se dispersa en múltiples fuentes que, ocasionalmente, proporcionan algún trabajo relevante. Recuperar todos los trabajos resulta prácticamente imposible, por lo que resulta útil disponer de instrumentos que permitan determinar el núcleo básico de fuentes que obtengan el mayor número de trabajos sin perdercantidades importantes de información relevante.Material y métodos: El método aplicado emplea los procesos bibliométricos desarrollados por Bradford, Leimkuhler y Groos. Se utiliza como material la literatura técnica sobre los efectos secundarios del fármaco Captopril.Resultados: Un núcleo de 21 revistas asegura un seguimiento de las publicaciones sobre farmacovigilancia de los efectos secundarios del fármaco, si bien con tan sólo 10 se puede disponer de la información estratégica. La mayor parte de la información se puede recuperar limitando la búsqueda de títulos. La mayoría de las revistas tiene una circulación alta.Conclusiones: La aplicación combinada de algunos modelos bibliométricos junto a la consideración del carácter exponencial del crecimiento de la ciencia puede permitir definir el núcleo básico de información relevante sobre un tema determinado.; Introduction et objetifs: La bibliographie sur un sujet est souvent concentrée dans un noyau des journaux plus productifs et le reste se dispersée entre differentes sources qu'il arrive parfois d'offrir quelque travail rélévant. Récupérer tous les travaux devient impossible dans la pratique, ce qui rend utile de disposer d'instruments permettant de déterminer le noyau fondamental des sources fournissant le plus grand nombre de travaux sans perdre des quantités importantes de renseignements rélévants.Matériel et méthodes: La méthode appliquée fait emploi des procédés bibliométriques dévéloppés par Bradford, Leimkuhler et Groos. On fait usage en tant que matériel de la litérature téchnique sur les effets sécondaires du médicament Captopril.Résultats: Un noyeau de 21 registres assure un pilotage des publications sur la pharmacovigilance des effets sécondaires du médicament, bien qu'avec seulement 10 il est possible de disposer de l'information stratégique. La plus part de l'information peut être récupérée en limitant la recherche aux titres. La plus part des journaux présente une haute circulation.Conclusions: L'application combinée de quelques modèles bibliométriques accompagnée du caractère exponentiel de la croissance de la science peut permettre la définition du noyau fondamental de l'information rélévante sur un sujet déterminé.