Sujet(s)
Agonistes de canaux chlorure , Mucoviscidose , Troubles de la veille et du sommeil , Enfant , Enfant d'âge préscolaire , Femelle , Humains , Mâle , Aminophénols/effets indésirables , Aminophénols/usage thérapeutique , Benzodioxoles/effets indésirables , Benzodioxoles/usage thérapeutique , Agonistes de canaux chlorure/effets indésirables , Agonistes de canaux chlorure/usage thérapeutique , Mucoviscidose/traitement médicamenteux , Association médicamenteuse , Indoles/effets indésirables , Indoles/usage thérapeutique , Pyrazoles/usage thérapeutique , Pyrazoles/effets indésirables , Pyridines/usage thérapeutique , Pyridines/effets indésirables , Quinoléines/usage thérapeutique , Quinoléines/effets indésirables , Troubles de la veille et du sommeil/induit chimiquementRÉSUMÉ
The misuse of benzodiazepines and opioid medications is frequent in students. To improve our understanding of this behavior, we aimed to identify factors associated with separate and concomitant use of these substances. Anonymous self-reported questionnaires were e-mailed to students enrolled at a French university between March and July 2021, covering: sociodemographic characteristics, academics, psychoactive substance use, ADHD symptomatology (adulthood and childhood), and psychiatric/psychological or addiction follow-up. Factors associated with the use of benzodiazepines and opioid medications included female sex (OR = 1.41 [1.08; 1.86]) and OR = 1.38 [1.06; 1.79], respectively), older age (OR = 1.65 [1.04; 2.6] and OR = 2.17 [1.4; 3.36], respectively), current psychiatric/psychological follow-up (OR = 6.53 [5.18; 8.24] and OR= 1.5 [1.12; 2.0], respectively), ADHD symptomatology (OR= 2.33 [1.71;3.16] and OR= 1.61 [1.15; 2.24], respectively), polyconsumption (tobacco use for benzodiazepine users, OR = 1.38 [1.04; 1.82]; alcohol use OR = 1.67 [1.17; 2.39] and tobacco use OR = 1.62 [1.23; 2.14] for opioid users). These factors were even more strongly associated with the concomitant use of benzodiazepines and opioid medications: older age (OR = 3.64 [2.22; 5.99]), female sex (OR = 1.54 [1.1; 2.14]), grade repetition (OR = 1.7 [1.14; 2.54]), psychiatric/psychological follow-up (OR = 4.51 [3.35;6.06]), ADHD symptomatology (OR = 5.3 [3.69; 7.63]), polyconsumption (tobacco use OR = 2.05 [1.39; 3] and cannabis use, OR = 2.07 [1.97; 4.16]. The factors associated with the use of benzodiazepines and prescription opioids identified in this study could lead to the development of targeted prevention methods.
Sujet(s)
Analgésiques morphiniques , Benzodiazépines , Étudiants , Humains , Benzodiazépines/effets indésirables , Benzodiazépines/usage thérapeutique , Femelle , Mâle , Études transversales , Analgésiques morphiniques/effets indésirables , Analgésiques morphiniques/usage thérapeutique , Jeune adulte , Étudiants/psychologie , Adulte , Adolescent , Troubles liés à une substance/épidémiologie , Enquêtes et questionnaires , France/épidémiologie , Surdose/statistiques et données numériques , Médicaments sur ordonnance , Trouble déficitaire de l'attention avec hyperactivité/épidémiologieRÉSUMÉ
We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in COVID-19-vaccinated individuals. First, based on the French pharmacovigilance database, we estimated the RR of PMR and GCA cases in individuals aged over 50 who developed their initial symptoms within one month of receiving the BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. We then conducted a nationwide survey to gather clinical profiles, therapeutic management, and follow-up data from individuals registered in the pharmacovigilance study. A total of 70 854 684 COVID-19 vaccine doses were administered to 25 260 485 adults, among which, 179 cases of PMR (RR 7. 1 cases/1 000 000 persons) and 54 cases of GCA (RR 2. 1 cases/1 000 000 persons) have been reported. The nationwide survey allowed the characterization of 60 PMR and 35 GCA cases. Median time to the onset of first symptoms was 10 (range 2-30) and 7 (range 2-25) days for PMR and GCA, respectively. Phenotype, GCA-related ischemic complications and -large vessel vasculitis as well as therapeutic management and follow-up seemed similar according to the number of vaccine shots received and when compared to the literature data of unvaccinated population. Although rare, the short time between immunization and the onset of first symptoms of PMR and GCA suggests a temporal association. Physician should be aware of this potential vaccine-related phenomenon.
Sujet(s)
COVID-19 , Artérite à cellules géantes , Rhumatisme inflammatoire des ceintures , Adulte , Humains , Adulte d'âge moyen , Artérite à cellules géantes/épidémiologie , Rhumatisme inflammatoire des ceintures/épidémiologie , Vaccins contre la COVID-19/effets indésirables , Ad26COVS1 , Vaccin BNT162 , Vaccin ChAdOx1 nCoV-19 , COVID-19/épidémiologie , COVID-19/prévention et contrôle , Vaccination/effets indésirablesRÉSUMÉ
OBJECTIVES: Drug shortages are of increasing concern to worldwide public health. The consequences of drug shortages for patient safety have been little studied, especially from a pharmacovigilance point of view. In this context, the network of French pharmacovigilance centres conducted the CIRUPT study (Conséquences Iatrogènes des RUPTures de stock/iatrogenic consequences of drug shortages) based on a prospective campaign of adverse effects occurring in the context of drug shortage notifications. METHODS: All notifications involving a shortage drug submitted to the French pharmacovigilance centres between 1 January 2020 and 30 June 2021 were collected and registered in the French national pharmacovigilance database with the standardised high level term 'product supply and availability issues' and with predefined keywords in the narrative section. RESULTS: 224 cases were included, involving mainly adverse drug reactions (ADRs) (n=131/224, 59%) and medication errors (n=51/224, 23%); 29% of the cases were serious. The most represented classes of shortage drugs were: vaccines (n=78/224, 35%); drugs for acid-related disorders (H2-receptor antagonists) (n=27/224, 12%); antineoplastic agents (n=17/224, 8%); and antiepileptics (n=15/224, 7%). In 82% of cases, the involved shortage drug was the subject of information delivered to health professionals by the National Agency for the Safety of Medicines and Health Products. Drug shortages were associated with an ADR related to replacement drugs in 59% (n=131/224) of the cases, drug inefficacy in 18% (n=41/224), and/or an aggravation of the underlying disease in 11% (n=25/224). CONCLUSIONS: From a pharmacovigilance point of view, a large diversity of anatomical therapeutic classes is involved and the risk related to drug shortages is not limited to drugs registered on 'major therapeutic interest or essential drug' lists. Information from health agencies is not sufficient to avoid the risks, and further strategies should be developed.
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BACKGROUND: Cardiovascular diseases (CVDs) are currently the leading cause of maternal death in Western countries. Although multidisciplinary cardio-obstetric teams are recommended to improve the management of pregnant women with CVD, data supporting this approach are scarce. AIMS: To describe the characteristics and outcomes of pregnant patients with CVD managed within the cardio-obstetric programme of a tertiary centre. METHODS: We included every pregnant patient with history of CVD managed by our cardio-obstetric team between June 2017 and December 2019, and collected all major cardiovascular events (death, heart failure, acute coronary syndromes, stroke, endocarditis and aortic dissection) that occurred during pregnancy, peripartum and the following year. RESULTS: We included 209 consecutive pregnancies in 202 patients. CVDs were predominantly valvular heart diseases (37.8%), rhythm disorders (26.8%), and adult congenital heart diseases (22.5%). Altogether, 47.4% were classified modified World Health Organization (mWHO)>II, 66.5% had CARdiac disease in PREGnancy score (CARPREG II)≥2 and 80 pregnancies (38.3%) were delivered by caesarean section. Major cardiovascular events occurred in 16 pregnancies (7.7%, 95% confidence interval [CI] 4.5-12.2) during pregnancy and in three others (1.5%, 95% CI 0.3-4.1) during 1-year follow-up. Most events (63.1%) occurred in the 16.3% of patients with unknown CVD before pregnancy. CONCLUSIONS: The management of pregnant patients with CVD within a cardio-obstetric team seems encouraging as we found a relatively low rate of cardiovascular events compared to the high-risk profile of our population. However, most of the remaining events occurred in patients without cardiac monitoring before pregnancy.
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Équipe soignante , Complications cardiovasculaires de la grossesse , Humains , Femelle , Grossesse , Complications cardiovasculaires de la grossesse/épidémiologie , Complications cardiovasculaires de la grossesse/thérapie , Complications cardiovasculaires de la grossesse/diagnostic , Complications cardiovasculaires de la grossesse/mortalité , Complications cardiovasculaires de la grossesse/physiopathologie , Adulte , Facteurs de risque , Facteurs temps , Résultat thérapeutique , Prestation intégrée de soins de santé , Appréciation des risques , Études rétrospectives , Maladies cardiovasculaires/épidémiologie , Maladies cardiovasculaires/diagnostic , Maladies cardiovasculaires/thérapie , Maladies cardiovasculaires/mortalité , Jeune adulteSujet(s)
Épinéphrine , Centres antipoison , Humains , Épinéphrine/administration et posologie , Épinéphrine/effets indésirables , France/épidémiologie , Centres antipoison/statistiques et données numériques , Femelle , Mâle , Adulte , Anaphylaxie/épidémiologie , Adulte d'âge moyen , Adolescent , Jeune adulte , Enfant , Sujet âgé , AutoadministrationRÉSUMÉ
We aimed to explore if psychostimulant use among student could be linked to attention deficit-hyperactivity disorder (ADHD) symptoms using a self-administered questionnaire sent by email to French students in 2021. Participants were asked about their psychostimulant use and the presence of ADHD symptoms using the Wender Utah Rating Scale and the Adult Self-Report Scale. Among the 4431 respondents, the prevalence of psychostimulant use was concerning and significantly associated with ADHD symptoms. This association could be related to undiagnosed ADHD or to psychobehavioral impairments induced by psychostimulant use underlining the need of ADHD screening and targeted prevention measures.
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Trouble déficitaire de l'attention avec hyperactivité , Stimulants du système nerveux central , Troubles liés à une substance , Adulte , Humains , Trouble déficitaire de l'attention avec hyperactivité/épidémiologie , Trouble déficitaire de l'attention avec hyperactivité/traitement médicamenteux , Universités , Stimulants du système nerveux central/effets indésirables , Troubles liés à une substance/traitement médicamenteux , ÉtudiantsRÉSUMÉ
Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity characterized by nonspecific symptomatology (eg, headache, visual disturbances, encephalopathy, and seizures) and classically cortical and subcortical vasogenic edema predominantly affecting the parietooccipital region. PRES etiologies are usually dichotomized into toxic PRES (eg, antineoplastic drugs, illicit drugs) and clinical condition-associated PRES (eg, acute hypertension, dysimmune disorders). Although the pathophysiology of PRES remains elusive, 2 main pathogenic hypotheses have been suggested: cerebral hyperperfusion due to acute hypertension and cerebral hypoperfusion related to endothelial dysfunction. Research into the pathogenesis of PRES has emerged through the development of animal models in the last decade. The motivation for developing a suitable PRES model is 2-fold: to fill in knowledge gaps of the pathophysiological mechanisms involved, and to open new perspectives for clinical assessment of pharmacological targets to improve therapeutic management of PRES. All current models of PRES have a hypertensive background, on which other triggers (acute hypertension, inflammatory, drug toxicity) have been added to address specific facets of PRES (eg, seizures). The initial model consisted in inducing a reduced uterine perfusion pressure that mimics preeclampsia, a leading cause of PRES. More recently, a model of stroke-prone spontaneously hypertensive rats on high-salt diet, originally developed for hypertensive small vessel disease and vascular cognitive impairment, has been studied in PRES. This review aims to discuss, depending on the research objective, the benefits and limitations of current experimental approaches and thus to define the desirable characteristics for studying the pathophysiology of PRES and developing new therapies.
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Hypertension artérielle , Leucoencéphalopathie postérieure , Accident vasculaire cérébral , Rats , Animaux , Leucoencéphalopathie postérieure/imagerie diagnostique , Leucoencéphalopathie postérieure/étiologie , Leucoencéphalopathie postérieure/anatomopathologie , Imagerie par résonance magnétique/effets indésirables , Hypertension artérielle/complications , Crises épileptiques , Accident vasculaire cérébral/complications , Modèles théoriques , Rats de lignée SHRRÉSUMÉ
OBJECTIVES: Students represent a population at risk for substance abuse. That risk may have been exacerbated by the COVID-19 pandemic. We aimed to describe substance abuse among students and to compare consumption according to the university field. METHODS: A self-administered questionnaire was sent by email to all students at the University of Lille, France, between March and July 2021. This anonymous questionnaire included questions about sociodemographic characteristics, university courses and the use of psychoactive substances (frequency, reasons, routes of administration) since the first university year. RESULTS: Among the 4431 students who responded (response rate 6.1%), eighty percent declared having used alcohol since the first university year, 34% cannabis, 15.4% benzodiazepines, 14.7% opioid drugs, 7.5% cocaine, 6.8% nitrous oxide and 6.5% MDMA. More than 20% of the users of cannabis, benzodiazepines, amphetamines and cocaine reported having already felt dependent. Recreational use was described by more than 10% of benzodiazepine or opioid drug users. Nitrous oxide use was significantly more frequent in the health and sport field (p < 0.001). Tobacco, benzodiazepine, cannabis and MDMA uses were significantly more frequent in the humanities and social sciences/art, language and literature fields (p < 0.001). CONCLUSION: Prevention measures focusing on alcohol, cannabis, illicit psychostimulants, nitrous oxide and prescription drugs are required in the student population.
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COVID-19 , Cannabis , Cocaïne , Hallucinogènes , N-Méthyl-3,4-méthylènedioxy-amphétamine , Troubles liés à une substance , Humains , Analgésiques morphiniques , Protoxyde d'azote , Pandémies , COVID-19/épidémiologie , Troubles liés à une substance/épidémiologie , Étudiants , BenzodiazépinesRÉSUMÉ
BACKGROUND: The intravenous form of fosfomycin, a bactericide antibiotic used to treat multiresistant bacterial infections is little prescribed. The most common reported adverse effects are hypokaliemia and hypernatremia. We describe a case of agranulocytosis, a rarely described side effect that may be fatal. CASE PRESENTATION: A 45 year-old woman was admitted to the intensive care unit for post-surgical meningitis following meningioma resection. Meropenem and vancomycin were first introduced. A DRESS-syndrom with meropenem was suspected. Neutropenia was diagnosed three days after the introduction of parenteral fosfomycin and agranulocytosis four days later. Eosinophilia was also observed. A bone marrow aspiration was performed showing a disappearance of the neutrophil granulocyte line and a significant eosinophilia. Meropenem was discontinued. Fosfomycin was maintained and filgrastim was added. As filgrastim had no effect, the relationship with fosfomycin was suspected, so it was then withheld. An increase of the neutrophil count was observed. Because of the complexity of the case, the unfavorable course of the illness and the urgent need for revision surgery, a rechallenge with fosfomycin was done followed by a decrease of the neutrophil count. CONCLUSION: This is the third paper reporting agranulocytosis induced by fosfomycin, and the first detailed description of a case. Based on chronological and semiological criteria and bibliographic data, the event was qualified as probable with the Naranjo adverse drug probability scale. Literature data is scarce. The summary of product characteristics mentions that only a few cases of transient neutropenia and agranulocytosis have been reported. An analysis of the FDA Adverse Event Reporting System Database highlighted a higher than expected frequency of agranulocytosis in patients treated with fosfomycin. Parenteral fosfomycin is often used in patients receiving other medications, so that it is rarely the only suspect. In our case, the results of the bone marrow aspiration, the sudden drop of the neutrophil count with concomitant eosinophilia and the absence of improvement despite the dose decrease, point towards an immuno-allergic mechanism. However, the overlap between the suspected DRESS induced by meropenem and the agranulocytosis do not allow to conclude with certainty on the causality. Awareness should be raised about this side effect.
Sujet(s)
Effets secondaires indésirables des médicaments , Éosinophilie , Fosfomycine , Neutropénie , Femelle , Humains , Adulte d'âge moyen , Fosfomycine/effets indésirables , Filgrastim/effets indésirables , Méropénème/effets indésirables , Neutropénie/induit chimiquement , Antibactériens/effets indésirablesRÉSUMÉ
INTRODUCTION: Ischemic or hemorrhagic stroke can occur to patients treated with oral anticoagulants (OAC), through lack of effectiveness or overdosing. OBJECTIVE: To evaluate the impact of clinical pharmacist's intervention on pharmacovigilance (PV) reporting for OAC-treated patients hospitalized for stroke. METHODS: Monocentric prospective study in which a clinical pharmacist's intervention was performed in a stroke unit, with a focus on patients treated by OAC prior admission. A PV report was made with all data collected for cases of stroke suspected to be related to OAC therapy. Data provided by pharmacist were compared with data initially available in the patient's electronic medical records. PV reports with pharmacist intervention were compared to those without. RESULTS: During the study period, 48 patients were included in the study: 43 (89.6%) ischemic strokes with an embolic or unknown etiology, four hemorrhage strokes (8.33%), and one medication error (2.08%). A clinical pharmacist intervention was performed for 19 patients (39.6%) and provided significant additional data in all of them (100%). The information was related to adherence to treatment for 17 cases (89.5%), OAC's initial prescription date for 11 cases (57.9%) and identifying event(s) that could have interfered with the efficacy of the OAC in five cases (26.3%). For patients with pharmacist intervention, PV reports were significantly more informative in terms of date's introduction of anticoagulant, adherence to treatment, reference to weight change or concomitant event. CONCLUSIONS: clinical pharmacist's intervention with patients taking oral anticoagulants and hospitalized for acute stroke contributes to collect high-quality data for pharmacovigilance reporting.
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INTRODUCTION: Two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines, tozinameran/BNT162b2 (Comirnaty®, Pfizer-BioNTech) and elasomeran/mRNA-1273 (Spikevax®, Moderna), were approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) at the end of 2020, less than a year after the start of the coronavirus disease 2019 (COVID-19) pandemic. In France, the health authorities have requested an intensive vaccination campaign, accompanied by a reinforced and active pharmacovigilance surveillance. This surveillance and analysis of real-life data, based on spontaneous reports received by the French Network of Regional PharmacoVigilance Centers (RFCRPV), has enabled to identify numerous pharmacovigilance signals. Some of them, such as myocarditis and heavy menstrual bleeding, have been confirmed as adverse effects of these vaccines. METHOD: We propose a descriptive review of the main pharmacovigilance signals identified by the RFCRPV concerning vaccines from the mRNA platform. RESULTS: Most pharmacovigilance signals were common to both mRNA vaccines: myocarditis, menstrual disorders, acquired haemophilia, Parsonage-Turner syndrome, rhizomelic pseudo-polyarthritis and hearing disorders. Other signals were more specific, such as arterial hypertension with tozinameran or delayed reaction site injection with elasomeran. CONCLUSION: This non-exhaustive review illustrates the experience of RFCRPV in identifying and monitoring pharmacovigilance signals related to mRNA vaccines in France during the COVID-19 pandemics, and the crucial role of pharmacological and clinical expertise in this area. It also highlights the predominant contribution of spontaneous reporting in the generation of pharmacovigilance signals, particularly for serious and rare adverse events not detected before marketing.
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AIM OF THE STUDY: Post-mRNA coronavirus diseases 2019 (COVID-19) vaccines myocarditis emerged as a rare adverse effect, particularly in adolescents and young adults, and was labeled as such for both vaccines in the summer of 2021. This study aims to summarize the timeline and process of signal detection, substantiation, and quantification of myocarditis cases related to mRNA vaccines in France. METHODS: The intensive monitoring plan for COVID-19 vaccine safety was based on case-by-case analysis of all cases collected in the French spontaneous reporting database (Base nationale de pharmacovigilance, BNPV). Cases were evaluated by drug safety medical professionals and discussed at a national level for signal detection purposes. Reported cases were compared to the number of vaccine-exposed persons up to September 30th, 2021. Reporting rates (Rr) of myocarditis per 100,000 injections were calculated and stratified according to age, gender, and injection rank of BNT162b2 and mRNA-1273 vaccines. Poisson distribution was used to compute Rrs 95% Confidence Interval (95% CI). RESULTS: The case-by-case analysis detected a possible cluster of myocarditis in April 2021 (5 cases, 4 after the 2nd injection). In June 2021, the signal was substantiated with 12 cases (9 related to BNT162b2, and 3 to mRNA-1273). As of September 2021, almost 73 million BNT162b2 and 10 million mRNA-1273 doses had been injected. The Rr per 100,000 injections was 0.5 (0.5-0.6) for BNT162b2 and 1.1 (95% CI 0.9-1.3) for mRNA-1273. The difference among vaccines was more pronounced after the second injection, particularly in men aged 18-24 years (4.3 [3.4-5.5] for BNT162b2 vs. 13.9 [9.2-20.1] for mRNA-1273) and aged 25-29 years (1.9 [1.2-2.9] vs. 7.0 [3.4-12.9]). CONCLUSION: The study highlighted the role of the spontaneous reporting system in the detection, assessment, and quantification of myocarditis related to m-RNA vaccines. It suggested from September 2021 that mRNA-1273 was reasonably related to a higher risk of myocarditis than BNT162b2 in people under 30, particularly after the second injection.
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic virus was a "health crisis" and a significant burden also for the French pharmacovigilance system. It took its toll in 2 phases, the first being in early 2020 when very little was known, and during which the missions of the 31 Regional Pharmacovigilance Centers (RPVCs) from university hospitals were to detect adverse reactions of drugs used in the context of the disease. Whether as a possible aggravating role on COVID-19, or displaying a different safety profile during its course, or to assess safety of curative treatment, this phase preceded that of the arrival of dedicated vaccines. Then the RPVCs' missions were to detect, as early as possible, any new serious adverse effect leading to a potential signal that would modify the benefit/risk ratio of a vaccine and require the implementation of health safety measures. During these two distinct periods, signal detection remained the core business of the RPVCs. Each RPVC had to organize itself to handle an unprecedented surge of declarations and requests for advice, from health care professionals and patients alike. "Leading" RPVCs, who were in charge of monitoring vaccines, had to deal with an extraordinary workload (still going on to this date), to generate in real-time and on a weekly basis, a summary of all the adverse drug reaction (ADR) reports as well as an extended analysis of the different safety signals. The organization put in place at the beginning of the health crisis, adapted to the context of the vaccines, allowed to meet the challenge of real-time pharmacovigilance monitoring, and to identify many safety signals. Efficient "short-circuits exchanges" with the French Regional Pharmacovigilance Centers Network (RPVCN) were paramount to the National Agency for the Safety of Medicines and Health Products (ANSM) to develop an optimal collaborative partnership. The French RPVCN has shown at this occasion both agility and flexibility, swiftly adapting to vaccine- and media-related unrest, and demonstrated its effectiveness in the early detection of safety signals. This crisis also confirmed the superiority of manual/human signal detection over automated ones, as the most effective and powerful tool to date to rapidly detect and validate a new ADR and enable to elaborate rapid risk reduction measures. To maintain the performance of French RPVCN in signal detection and to monitor all drugs as they should, and as expected by our fellow citizens, a new funding model should be considered.