402 research outputs found
Pharyngeal related non-lexical vowels in Sephardic Modern Hebrew
No full textThis paper examines non-lexical vowels in Sephardic Modern Hebrew. It is argued that two kinds of vowel, which are triggered by the pharyngeal consonants, should be identified: (a) true epenthetic vowels that emerge on the surface to repair illicit (marked) syllable structures. (b) 'Echo-vowels' that are created by overlapping a vowel and a pharyngeal consonant. These vowels do not repair illicit syllable structures, but rather ease the perception of clusters containing a pharyngeal. These vowels are not syllabic and phonological processes ignore them.This paper was published in Linguistics in Amsterdam 3 (2010), and can be found at: http://www.linguisticsinamsterdam.nl/Pariente, Itsik. "Pharyngeal related non-lexical vowels in Sephardic Modern Hebrew." Linguistics in Amsterdam 3 (2010)Peer reviewe
sj-pdf-1-vmj-10.1177_1358863X231209263 – Supplemental material for Real-world effect of iloprost in patients with chronic limb-threatening ischemia (CLTI): A cohort study
No full textSupplemental material, sj-pdf-1-vmj-10.1177_1358863X231209263 for Real-world effect of iloprost in patients with chronic limb-threatening ischemia (CLTI): A cohort study by Dari Loubna, Joël Constans, Carine Boulon, Caroline Caradu, François-Xavier Lapébie, Alessandra Bura-Riviére, Lucie Chastaingt, Philippe Lacroix, Julien Bezin and Antoine Pariente in Vascular Medicine</p
Evolving Roles of Spontaneous Reporting Systems to Assess and Monitor Drug Safety
No full textThis chapter aims to describe current and emerging roles of spontaneous reporting systems (SRSs) for assessing and monitoring drug safety. Moreover, it offers a perspective on the near future, which entails the so-called era of Big Data, keeping in mind both regulator and researcher viewpoints. After a panorama on key data sources and analyses of post-marketing data of adverse drug reactions, a critical appraisal of methodological issues and debated future applications of SRSs will be presented, including the exploitation and challenges in evidence integration (i.e., merging and combining heterogeneous sources of data into a unique indicator of risk) and patient’s reporting via social media. Finally, a call for a responsible use of these studies is offered, with a proposal on a set of minimum requirements to assess the quality of disproportionality analysis in terms of study conception, performing and reporting
Liver injury with novel oral anticoagulants: assessing post-marketing reports in the US Food and Drug Administration adverse event reporting system
No full textAim
We assessed the hepatic safety of novel oral anticoagulants (NOACs) analyzing the publicly available US-FDA adverse event reporting system (FAERS).
Methods
We extracted reports of drug-induced liver injury (DILI) associated with NOACs, including acute liver failure (ALF) events. Based on US marketing authorizations, we performed disproportionality analyses, calculating reporting odds ratios (RORs) with 95% confidence interval (CI), also to test for event- and drug-related competition bias, and case-by-case evaluation for concomitant medications.
Results
DILI reports represented 3.7% (n = 146) and 1.7% (n = 222) of all reports for rivaroxaban and dabigatran, respectively. No statistically significant association was found for dabigatran, in primary and secondary analyses. Disproportionality signals emerged for rivaroxaban in primary analysis (ALF: n = 25, ROR = 2.08, 95% CI 1.34, 3.08). In a large proportion of DILI reports concomitant hepatotoxic and/or interacting drugs were recorded: 42% and 37% (rivaroxaban and dabigatran, respectively), especially statins, paracetamol and amiodarone. Among ALF reports, fatal outcome occurred in 49% of cases (44% and 51%, rivaroxaban and dabigatran, respectively), whereas rapid onset of the event (<1 week) was detected in 46% of patients (47% and 44%, respectively).
Conclusions
The disproportionality signal for rivaroxaban calls for further comparative population-based studies to characterize and quantify the actual DILI risk of NOACs, taking into account drug- and patient-related risk factors. As DILI is unpredictable, our findings strengthen the role of (a) timely pharmacovigilance to detect post-marketing signals of DILI through FAERS and other data sources, (b) clinicians to assess early, on a case-by-case basis, the potential responsibility of NOACs when they diagnose a liver injury
Addition of dipeptidyl peptidase-4 inhibitors to sulphonylureas and risk of hypoglycaemia: systematic review and meta-analysis
No full textOBJECTIVE:
To quantify the risk of hypoglycaemia associated with the concomitant use of dipeptidyl peptidase-4 (DPP-4) inhibitors and sulphonylureas compared with placebo and sulphonylureas.
DESIGN:
Systematic review and meta-analysis.
DATA SOURCES:
Medline, ISI Web of Science, SCOPUS, Cochrane Central Register of Controlled Trials, and clinicaltrial.gov were searched without any language restriction.
STUDY SELECTION:
Placebo controlled randomised trials comprising at least 50 participants with type 2 diabetes treated with DPP-4 inhibitors and sulphonylureas.
REVIEW METHODS:
Risk of bias in each trial was assessed using the Cochrane Collaboration tool. The risk ratio of hypoglycaemia with 95% confidence intervals was computed for each study and then pooled using fixed effect models (Mantel Haenszel method) or random effect models, when appropriate. Subgroup analyses were also performed (eg, dose of DPP-4 inhibitors). The number needed to harm (NNH) was estimated according to treatment duration.
RESULTS:
10 studies were included, representing a total of 6546 participants (4020 received DPP-4 inhibitors plus sulphonylureas, 2526 placebo plus sulphonylureas). The risk ratio of hypoglycaemia was 1.52 (95% confidence interval 1.29 to 1.80). The NNH was 17 (95% confidence interval 11 to 30) for a treatment duration of six months or less, 15 (9 to 26) for 6.1 to 12 months, and 8 (5 to 15) for more than one year. In subgroup analysis, no difference was found between full and low doses of DPP-4 inhibitors: the risk ratio related to full dose DPP-4 inhibitors was 1.66 (1.34 to 2.06), whereas the increased risk ratio related to low dose DPP-4 inhibitors did not reach statistical significance (1.33, 0.92 to 1.94).
CONCLUSIONS:
Addition of DPP-4 inhibitors to sulphonylurea to treat people with type 2 diabetes is associated with a 50% increased risk of hypoglycaemia and to one excess case of hypoglycaemia for every 17 patients in the first six months of treatment. This highlights the need to respect recommendations for a decrease in sulphonylureas dose when initiating DPP-4 inhibitors and to assess the effectiveness of this risk minimisation strategy
Therapie
No full textPsychotropics are widely used drugs, especially in the elderly, especially in France. This, and the risks associated to their use, logically led to concerns that resulted in numerous studies, reports, and regulatory actions intending to limit this use. This review objective was to provide an overview of psychotropic use in elderly subjects in France for antipsychotics, antidepressants, and benzodiazepines and related drugs. The narrative review performed is structured in two parts. The first reminds the initial steps of psychotropic use monitoring in the general French population. The second provides information on psychotropic use in elderly in France using the latest open data released by the French Health Insurance system and processed using the dedicated DrugSurv tool developed within the DRUGS-SAFE® and DRUGS-SAFE® programs. This was completed examining the most recent studies regarding psychotropic use in elderly in France, whether they consisted in publications or reports. At least before the COVID-19 epidemic, decreases in psychotropic prevalence of use among the elderly in France could be observed, mostly for antipsychotics or benzodiazepines (e.g. antipsychotics, 2006-2013: 10.3% decrease and benzodiazepines 2012-2020: decrease from 30.6% to 24.7% in subjects aged ≥65). Psychotropic prevalence of use remained however very high overall (e.g. antidepressants, 2013: 13% in subjects aged 65-74 and 18% in aged ≥65), exceeding that of most other countries, with a significant proportion of inappropriate use (e.g. in 30% of benzodiazepine users, all ages) carrying a clearly identified risks for uncertain benefit. Initiatives have been multiplied at the national level to reduce psychotropic overuse in the elderly. The reported prevalences demonstrate their effectiveness is obviously insufficient. This limited effectiveness is not specific to psychotropics and might reside in a failure to create strong adherence to messages and recommendations. Other levels should be considered, especially regional, for interventions coupled with pharmacoepidemiologic monitoring allowing impact assessment
Pharmacoepidemiological study of the COVID-19 epidemic's impact on cardiovascular treatments
No full textDepuis janvier 2020, la pandémie de COVID-19 a entraîné dans le monde entier la mise en place de mesures de contrôle épidémiques inédites et d’importantes modifications du mode de vie dictées par la nécessité de faire face aux vagues successives de la pandémie. Le suivi quotidien de l'expansion de la pandémie et de l'efficacité de son contrôle a permis d'évaluer ses conséquences directes sur la santé en termes d'infections, d'hospitalisations, de décès, et à plus long terme d’impact sur l’espérance de vie. Des interrogations ont émergé concernant d’autres impacts de l’épidémie. Ainsi rapidement, une baisse importante du nombre d’hospitalisations pour accidents cardiovasculaires a été constatée pendant les périodes les plus strictes de restriction de la mobilité. Elle a fait craindre une diminution de l’accès aux soins liée à ces restrictions ou à l’embolisation du système de santé par l’épidémie elle-même. Des études publiées ont ensuite démontré que les conséquences sanitaires de la pandémie dépassaient largement les cas décomptés quotidiennement. S’agissant des maladies cardiovasculaires, une des principales craintes concernant l’impact de la pandémie porte sur un retard de prise en charge ou sur une perte de la continuité des soins pour les patients déjà traités. Dans ces maladies pour lesquelles les traitements jouent un rôle préventif essentiel, l'optimisation et la permanence du traitement sont déterminantes en termes de risque de survenue d’événements. Dans ce contexte, nous avons souhaité évaluer l'impact de la pandémie sur les traitements médicamenteux de prévention cardiovasculaire en France et avons cherché à en estimer les conséquences sanitaires. Nous avons ainsi utilisé les données issues du Système National des Données de Santé (SNDS). Dans une première étude, nous avons étudié à l’aide d’analyses de séries chronologiques interrompues l’impact quantitatif potentiel de l’épidémie et des mesures associés sur les traitements cardiovasculaires. Nous avons ainsi mis en évidence un phénomène initial massif de stockage pour ces traitements précédant immédiatement le premier confinement. Par la suite, nous avons observé une diminution de l’utilisation de ces médicaments comparativement à l’attendu durant le premier confinement, avant un retour à un niveau habituel au cours des mois qui ont suivi. Par ailleurs, une augmentation des interruptions de traitement a été observée dès les premières semaines de l’épidémie, parallèlement à une baisse très importante des initiations de traitements, et ce quelle que soit la classe pharmacologique. Dans une seconde étude, nous avons étudié, toujours à l’aide de séries chronologiques interrompues, l’impact qualitatif potentiel de l’épidémie et des mesures associés sur les traitements cardiovasculaires. Nous nous sommes pour cela intéressé aux interruptions de traitement concernant les médicaments antihypertenseurs et avons retrouvé des résultats rassurants. Malgré un excès du nombre d’interruptions d’antihypertenseurs, l’épidémie de COVID-19 semble n’avoir eu aucun impact significatif ni sur la fréquence de reprise ou de changement de traitement après une interruption, ni sur le délai entre l'interruption et la reprise du traitement après celle-ci. Les caractéristiques de la population ayant présenté des interruptions pendant l’épidémie ne semblaient en outre pas différentes de celles de la population ayant présenté des interruptions avant celle-ci, dans un contexte normal de prise en charge et d’accès aux soins. Ces résultats étaient rassurants concernant l’impact potentiel que l’épidémie de COVID-19 et des mesures associées auraient pu avoir, via leurs conséquences sur les traitements médicamenteux, sur la santé cardiovasculaire, impact qui a été étudié dans la troisième étude menée dans cette thèse et dans lequel nous avons recherché, dans une étude de cohorte, une modification de l’effet des interruptions des antihypertenseurs liée à l’épidémie de COVID-19 (...).Since January 2020, the COVID-19 pandemic has led to unprecedented epidemic control measures and major lifestyle changes worldwide to cope with successive waves of the pandemic. Daily monitoring of the pandemic's spread and the effectiveness of its control has made it possible to assess its direct consequences on health in terms of infections, hospitalisations, deaths and, in the longer term, its impact on life expectancy. Questions have emerged concerning other impacts of the epidemic. For example, a significant drop in the number of hospitalizations for cardiovascular accidents was quickly observed during the most stringent periods of mobility restrictions. This led to fears of reduced access to care due to these restrictions or the embolisation of the health system by the epidemic itself. Subsequently, published studies have shown that the health consequences of the pandemic far exceeded the daily case counts. In the case of cardiovascular diseases, one of the main fears about the impact of the pandemic is a delay in treatment or a loss of continuity of care for patients already being treated. In these diseases, for which treatment plays an essential preventive role, the optimisation and continuity of treatment are decisive in terms of the risk of events occurring. In this context, we wanted to assess the impact of the pandemic on cardiovascular preventive drug treatments in France and to estimate the health consequences. We used data from the French National Health Data System (SNDS). In a first study, we investigated the potential quantitative impact of the epidemic and associated measures on cardiovascular treatments by means of interrupted time series analyses. We found an initial massive stockpiling of these treatments immediately preceding the first lockdown. Subsequently, we observed a decrease in the use of these drugs compared to what was expected during the first lockdown, before a return to a usual level in the months that followed. Furthermore, an increase in treatment interruptions was observed from the first weeks of the epidemic, in parallel with a very significant decrease in treatment initiations, regardless of the pharmacological class. In a second study, we investigated the potential qualitative impact of the epidemic and associated measures on cardiovascular treatments, again using interrupted time series. For this purpose, we looked at treatment interruptions for antihypertensive drugs and found reassuring results. Despite an excess in the number of interruptions of antihypertensive drugs, the COVID-19 epidemic seems to have had no significant impact on the frequency of resumption or change of treatment after an interruption, nor on the time between the interruption and the resumption of treatment after it. Furthermore, the characteristics of the population that interrupted during the epidemic did not appear to differ from those of the population that interrupted before the epidemic, in a normal context of management and access to care. These results were reassuring regarding the potential impact that the COVID-19 epidemic and associated measures might have had on cardiovascular health via their consequences on drug therapy, which was investigated in the third study conducted in this thesis, in which we looked for a modification of the effect of antihypertensive drug interruptions related to the COVID-19 epidemic and associated measures in a cohort study
Estimation de la prévalence et descriptions des situations à risque d’interactions médicamenteuses en France à partir des données de l’assurance maladie
No full textSome studies report that Drug Drug Interactions (DDIs) are estimated to cause 2 to 5% of hospital admissions in elderly patients and 1% in the general population. However, very little data are available on the drugs concerned and on the severity of the interactions encountered. Our aim was to assess the prevalence of drug delivery with Potential Drug Drug Interaction (PDDI) in France and to know which drug combinations are the most concerned. We conducted a transversal study using a random dataset from the Echantillon Généraliste de Bénéficiaires (EGB) to look at PDDIs prevalence in France between 2010 and 2015. PDDI prevalence was studied directly and using an probabilistic indicator called Dips-Score (DS) which is a relative risk between theoretical and observational co-prescription probabilities. In practice, a drug pair with a DS > 1 is more frequent than expected and a drug pair with a DS < 1 is less frequent. Analysis were based on ATC level 2 (therapeutic main group) and 5 (chemical substance). 6,908,910 drug dispensations were analyzed over the considered time period. Among them, 13,196 implied the concomitant delivery of contraindicated drugs (0.2%), and 95,410 the concomitant delivery of drugs which association is not recommended (1.4%). Median DS of contra-indications and not recommended associations were respectively 0.4 and 0.6. Among the 20 most frequent contra-indicated drug pairs, the pair with the highest prevalence was bisoprolol+flecainide for which 5,036 dispensations were identified. The drug pair associated with the highest DS was citalopram+hydroxyzine (DS: 3.7; 2.9 - 4.6); that associated with the lowest one was clarythromycine+simvastatine (DS: 0.2; 0.2 - 0.3). ATC level 2 analysis found more than 50% of contra-indications between beta blocking agents and cardiac therapy and 10% of contra-indications between diuretics and mineral supplements. The prevalence of some IMPs indicates the need for new prevention actions for the proper use of drugs. In this perspective, the Dips-Score indicator, which we present in this paper, can help to identify the IMPs least considered in practice and to consider specific studies or preventive actions on them.Les interactions médicamenteuses seraient à l’origine de 2 à 5 % des hospitalisations chez les personnes âgées et de 1 % des hospitalisations en population générale. Cependant, très peu de données sont disponibles sur les médicaments concernés et sur la gravité des interactions rencontrées. L’objectif de cette étude était d’estimer la prévalence des Interactions Médicamenteuses Potentielles (IMP) de niveau de sévérité élevée en France et d’identifier les couples de médicaments les plus à risques.Cette étude transversale a été réalisée à partir d’un échantillon de délivrances de médicaments délivrés entre 2010 et 2015 en France, identifié dans la base de données de l’Echantillon Généraliste de Bénéficiaires de l’assurance maladie (EGB). La prévalence des IMP de haut niveau de sévérité a été estimée de manière brute et à l’aide d’un indicateur de risque d’association développé pour l’étude : le DIPS-Score (DS). Les analyses ont été réalisées à l’échelle des substances actives et des classes pharmacologiques (niveau 2 de l’Anatomical Therapeutical Chemical classification). Nous avons identifié et analysé 6 908 910 délivrances dont 13 196 (0,2 %) comprenaient des associations de médicaments contre-indiquées (CI) et 95 410 (1,4 %) des associations de médicaments déconseillées (AD). Le DS médian était de 0,4 pour les CI et de 0,6 pour les AD. Parmi les 20 CI les plus fréquentes, la co-délivrance contre-indiquée présentant la plus forte prévalence correspondait à l’association bisoprolol + flecainide (n = 5 036 co-délivrances) ; celle présentant le DS le plus élevé correspondait à l’association citalopram + hydroxyzine (DS = 3,7 ; 2,9 - 4,6) et celle présentant le DS le plus faible correspondait à l’association clarithromycine + simvastattine (DS = 0,2 ; 0,2 - 0,3). L’analyse par classes ATC retrouvait plus de 50 % des CI entre bétabloquants et médicaments en cardiologie et 10 % des CI entre diurétiques et suppléments minéraux. La prévalence de certaines IMP de haut niveau de sévérité indique la nécessité de nouvelles actions de prévention autour du risque d’interaction médicamenteuse. Dans cette optique, l’utilisation de l’indicateur d’association médicamenteuse DIPS-Score, que nous présentons dans cette thèse, peut permettre d’identifier les IMP les moins prises en compte en situation réelle de soins et d’envisager des études spécifiques ou des actions de préventions les concernant
Standardizing and Comparing Management Recommendations for Potential Drug-Drug Interactions Across Different Interaction Checkers
No full textBackground: Potential drug-drug interactions (pDDIs) are frequent in clinical care, particularly among older patients. Accurate identification and management of pDDIs are essential for patient safety. Prescribers often rely on interaction checkers (ICs) to screen for pDDIs. However, these tools may provide inconsistent recommendations, potentially leading to suboptimal clinical decisions. Objective: This study aimed to develop a standardized approach for classifying and prioritizing pDDIs based on the clinical relevance of their management recommendations and to compare how these pDDIs are categorized across ICs. Methods: A scale was developed through a structured iterative process to classify pDDIs into four management categories (high priority, intermediate priority, low priority, data unavailable), based on the management recommendations extracted from six ICs. This scale was applied to 218 real-world pDDIs identified from 1923 patients, and the agreement was primarily assessed using Gwet's AC1. Main results: Overall agreement among the ICs was moderate (Gwet's AC1 = 0.44; 95% CI 0.39-0.50), with values ranging from 0.58 (0.51, 0.65) to 0.38 (0.31, 0.44) in leave-one-out analyses. The agreement was higher in binary analyses dichotomizing the scale into high- and intermediate-priority versus low-priority pDDIs (AC1 = 0.72; 95% CI 0.65-0.79), and in the classification of high-priority versus all other pDDIs (AC1 = 0.62; 95% CI 0.54-0.69). Conclusion: This study developed and tested a structured approach to systematically compare pDDI management across ICs and prioritize clinically relevant interactions. Its application revealed a generally limited agreement between ICs, pointing to the need for harmonized approaches and further studies to support more consistent, evidence-aligned pDDI management
Interactions médicamenteuses : étude de la prévalence, des risques encourus et développement d’outils de prévention
No full textScientific problem Drug-drug interactions (DDIs) are estimated to cause of 2 to 5% of hospital admissions in elderly patients and 1% in the general population. However, very little data are available on the drugs concerned and on the severity of the interactions encountered. Objectives The general objectives of this thesis were: i) to describe and assess the prevalence and risks associated with DDIs and potential DDIs (pDDIs) in France, and ii) to develop and evaluate IT tools for the prevention of DDIs and pDDIs in the hospital. To satisfy the first, we had the specific objectives of: i) measuring the prevalence of major pDDIs in France, ii) evaluating the association between exposure to contraindicated pDDIs (CI) and the risk of emergency hospitalization in the general population, iii) describe the adverse drug reactions (ADRs) reported to the French network of Pharmacovigilance Centers and considered as resulting from DDIs, iv) study the proportion of major DDI causing emergency room admissions in the elderly. Methods The first part of this work was carried out via four studies using different databases: two studies based on the Echantillon Généraliste des Bénéficiaires (EGB); a cross-sectional study and a self-controlled case series, a study based on the national pharmacovigilance database (cross-sectional study), and a study based on the Bordeaux University Hospital electronic health record (cross-sectional study). The second part of this work consisted in developing digital tools in collaboration with the start-up Synapse Medicine and setting up evaluation studies of these tools in collaboration with hospitals. Results Among the 7 million dispensations of drugs studied using French data from the EGB, 0.2% included the co-dispensing of contraindicated drugs due to pDDIs and 1.4% the co-dispensing of drug combinations advised against which would correspond annually to approximately 900,000 contraindicated combinations and six million combinations advised against. The evaluation of the risk of hospitalization in the emergency room associated with CIs revealed a strong increase in risk during the exposure period compared to the other follow-up periods with an IRR of 2.41 (95% CI 1.55-3.76). Analysis of pharmacovigilance data showed that the main ADRs attributed to DDI were hemorrhage (46%), renal failure (8%), pharmacokinetic alteration (5%) and cardiac arrhythmias (4%). Data from the emergency room of the Bordeaux University Hospital revealed a prevalence of contraindicated or advised against pDDIs of 6.4% in patients aged 75 and over, 16% of whom had been deemed responsible for the admission (45% in the context of arrhythmias and long QT syndrome, 16% related to drug overdose, and 14% related to hemorrhage). The tool developments were of two types: a tool for analyzing the practices of hospital practitioners; a prescription support tool for geriatricians. These tools now developed are used in two research projects, one being funded by a PREPS, and the other being a clinical trial sponsored by the Bordeaux University Hospital. Conclusion Our studies lead to the following findings: i) a high prevalence of contraindicated and advised against pDDIs in France and in particular in elderly patients, ii) the identification of DDIs at risk of bleeding and situations at risk of QT prolongation and of Tdp as the main ones to be considered in terms of prevention, iii) a wide variety of DDI situations outside of these situations with a low proportion of pharmacokinetic DDIs, and iv) demonstration of a greatly increased risk of hospitalization during exposure to CI DDIs.Contexte Les interactions médicamenteuses (IM) seraient à l'origine de 2 à 5 % des hospitalisations chez les patients âgés et de 1 % des hospitalisations en population générale. Cependant, peu de données sont disponibles sur les médicaments concernés et sur la gravité des interactions rencontrées. Objectifs Les objectifs généraux de ce travail de thèse étaient : i) de décrire et évaluer la prévalence et les risques associés aux IM et IM potentielles (IMP) en France, et ii) de développer et évaluer des outils informatiques de prévention des IM et IMP à l'hôpital. Pour satisfaire au premier, nous avions pour objectifs spécifiques de : i) mesurer la prévalence des IMP de niveau de sévérité élevé en France, ii) évaluer l'association entre l’exposition aux IMP contre-indiquées (CI) et le risque d'hospitalisation en urgence dans la population générale, iii) décrire les événements indésirables (EI) rapportés au réseau français des Centres de pharmacovigilance et considérés comme résultants d’IM, iv) étudier la proportion des IMP classées comme sévères à l'origine d'une admission aux urgences chez les personnes âgées. Méthode La première partie de ce travail a été réalisée via quatre études utilisant différentes bases de données : deux études à partir de l'Echantillon Généraliste des Bénéficiaires (EGB) ; une étude transversale et une série de cas autocontrôlée, une étude à partir de la base de données nationale de pharmacovigilance (étude transversale), et une étude à partir du système d'information hospitalier du CHU de Bordeaux (étude transversale). La deuxième partie de ce travail a consisté à développer des outils numériques en collaboration avec la startup Synapse Medicine et à mettre en place des études d'évaluation de ces outils en collaboration avec des établissements hospitaliers. Résultats Parmi les 7 millions de délivrances de médicaments en villes étudiées à partir des données françaises de l'EGB, 0,2 % incluaient la co-délivrance de médicaments contre-indiqués en raison d’interactions et 1,4 % la co-délivrances d’associations de médicaments déconseillées, ce qui correspondrait annuellement à environ 900 000 associations contre-indiquées et six millions d’associations déconseillées. L’évaluation du risque d’hospitalisation aux urgences associé aux CI a permis de retrouver une forte augmentation du risque pendant la période d’exposition comparativement aux autres périodes de suivi avec un IRR à 2,41 (IC95% 1,55-3,76). L’analyse des données de pharmacovigilance a montré que les principaux EI attribués à des IM étaient de type hémorragique (46%), insuffisance rénale (8 %), altération pharmacocinétique (5 %) et arythmie cardiaque (4%). Celle des informations issues des urgences du CHU de Bordeaux a révélé une prévalence d'IMP contre-indiquées ou déconseillées de 6,4 % chez les patients de 75 ans et plus, dont 16 % avaient été jugées responsables de l’admission (45 % dans le cadre d’arythmies et de syndrome du QT long, 16 % liées à un surdosage médicamenteux, et 14 % liées à une hémorragie). Les développements d’outils étaient de deux natures : un outil d’analyse des pratiques des praticiens hospitaliers ; un outil d’aide à la prescription pour les gériatres. Ces outils aujourd’hui développés sont utilisés dans deux projets de recherche, l’un faisant l’objet d’un financement PREPS, et l’autre étant un essai clinique dont le promoteur est le CHU de Bordeaux. Conclusion Nos études conduisent aux constats suivants : i) une prévalence des IMP contre-indiquées et déconseillées élevée en France et en particulier chez les patients âgés, ii) l’identification des IM à risque hémorragique et des situations à risques d'allongement du QT et de Tdp comme les principales à considérer en termes de prévention, iii) une grande variété des situations d’IM en dehors de ces situations avec une part faible des IM de nature pharmacocinétique, et iv) la démonstration d’un risque très augmenté d’hospitalisation en période d’exposition aux IM CI
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