Author: "Centre régional de pharmacovigilance" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Centre régional de pharmacovigilance"' showing total 926 results

Start Over Author "Centre régional de pharmacovigilance"

926 results on '"Centre régional de pharmacovigilance"'

1. ATAPAC Study (TauroLock Activity in Adult Cancer Patients) (ATAPAC)

Author: centre régional de pharmacovigilance de Nancy and Theradial
Published: 2016

2. Adverse drug reaction related to drug shortage: A retrospective study on the French National Pharmacovigilance Database

Author: Bourneau-Martin, Delphine, Babin, Marina, Grandvuillemin, Aurelie, Mullet, Charlotte, Salvo, Francesco, Singier, Allison, Cellier, Morgane, Fresse, Audrey, de Canecaude, Claire, Pietri, Tessa, Drablier, Guillaume, Geniaux, Helene, Lagarce, Laurence, Laroche, Marie-Laure, Briet, Marie, Admin, Oskar, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Régional de Pharmacovigilance, de Renseignement sur le Médicament et de Pharmaco épidémiologie de Bourgogne [Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Dijon, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine), CRHU Nancy, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service Pharmacologie Clinique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Centre régional de pharmacovigilance, de pharmaco-épidémiologie et d'information sur les médicaments [Limoges], CHU Limoges, Vieillissement Fragilité Prévention e-Santé (VieSanté), OmégaHealth (ΩHealth), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Laboratoire de Biologie Neurovasculaire Intégrée [Angers] (CNRS UMR6214 - INSERM U771), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers
Subjects: Pharmacology, Pharmacovigilance, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Adverse drug reaction, Drug shortage, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pharmacology (medical), Medication error
Abstract: International audience; AIM: Drug shortage is a growing global health issue. The aim of the study was to evaluate the consequences of drug shortages on patient safety based on data recorded in the French Pharmacovigilance Database. METHODS: All cases involving drug shortages reported from 1985 to the end of 2019 were extracted from the database. RESULTS: Following the selection process, 462 cases were included. The number of cases increased significantly from 2004 to 2019. Cases mainly involved drugs from the nervous system (22.1%, CI95[17.5;27.0]), the cardiovascular system (16.4%, CI95[11.9;21.4]), and anti-infectives for systemic use (14.3%, CI95[9.7;19.2]) ATC classes. Most of the cases reported an adverse drug reaction (ADR) belonging to the SOC nervous system (21%, CI95[18;24]), skin and subcutaneous (14%, CI95[11;17]), general (13%, CI95[10;17]), and gastrointestinal (8%, CI95[5;11]) disorders. Disease worsening was observed in 15.9% of the cases, mostly related to a lack of efficacy of the replacement drug. Half of the cases were considered as serious. Evolution was favourable in 79.4% of the cases. Death and/or life-threatening situations were reported in 5.8% of the cases. Medication errors (ME) were identified in 51 cases (11%), mostly occurring at the administration step and involving a human factor. CONCLUSION: This study emphasises the clinical impact of drug shortage in terms of ADRs, ME and inefficiency. These observations underline the importance of a global health policy programme to limit the occurrence of drug shortages and to reinforce the information provided to patients and health care professionals in this context to limit risk.
Published: 2022
Full Text: View/download PDF

3. Determinants of diaphragm inspiratory motion, diaphragm thickening, and its performance for predicting respiratory restrictive pattern in <scp>Duchenne</scp> muscular dystrophy

Author: Nicolas Mansencal, Abdallah Fayssoil, Frédéric Lofaso, H. Prigent, Robert Carlier, Karim Wahbi, Pascal Laforêt, Jean Bergounioux, Tanya Stojkovic, Helge Amthor, Anthony Behin, Guillaume Bassez, Guillaume Nicolas, Djillali Annane, Lee S. Nguyen, Rabah Ben Yaou, Sebastien Damez-Fontaine, David Orlikowski, Justine Zini, Service de réanimation medico-chirurgicale [CHU Raymond-Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie et maladies vasculaires [CHU Ambroise Paré], Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CMC Ambroise Paré [Neuilly-sur-Seine], Service de physiologie et d'explorations fonctionnelles [CHU Raymond-Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Service d'Imagerie Médicale [Raymond-Poincaré], Hôpital Raymond Poincaré [AP-HP], Filière Neuromusculaire (FILNEMUS), Service de Cardiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Analysis-Synthesis Approach for Virtual Human Simulation (MIMETIC), Université de Rennes 2 (UR2)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-RÉALITÉ VIRTUELLE, HUMAINS VIRTUELS, INTERACTIONS ET ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Service de biochimie et de génétique moléculaire [CHU Cochin], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre d’Investigation Clinique 1429 [Garches] (CIC 1429), Hôpital Raymond Poincaré [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), CIC Paris Est, Centre régional de Pharmacovigilance [CHU Pitié] (CRPV Paris), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Dpt Radiologie [CHU Poincaré], Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-MEDIA ET INTERACTIONS (IRISA-D6), Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Centre d'investigation clinique Paris Est (CIC Paris-Est), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre régional de Pharmacovigilance [CHU Pitié] (CRPV Paris Pitié), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Inria Rennes – Bretagne Atlantique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique)
Subjects: Duchenne muscular dystrophy, medicine.medical_specialty, Vital capacity, pulmonary, Physiology, Vital Capacity, Pulmonary insufficiency, Inspiratory Capacity, 03 medical and health sciences, Cellular and Molecular Neuroscience, FEV1/FVC ratio, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Humans, Respiratory system, Retrospective Studies, 2. Zero hunger, ultrasound, business.industry, Area under the curve, medicine.disease, Respiratory Function Tests, 3. Good health, Diaphragm (structural system), Muscular Dystrophy, Duchenne, 030228 respiratory system, diaphragm, Cardiology, Neurology (clinical), business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; Introduction/aims: Respiratory status is a key determinant of prognosis in patients with Duchenne muscular dystrophy (DMD). We aimed to evaluate the determinants of diaphragm ultrasound and its performance in predicting restrictive respiratory patterns in DMD.Methods: This was a retrospective study of DMD patients followed in our center and admitted for an annual checkup from 2015 to 2018. We included DMD patients who underwent diaphragm ultrasound and pulmonary functional tests.Results: This study included 74 patients with DMD. The right diaphragm thickening fraction (TF) was significantly associated with age (P = .001), Walton score (P = .012), inspiratory capacity (IC) (P = .004), upright forced vital capacity (FVC) (P < .0001), supine FVC (P = .038), and maximal inspiratory pressure (MIP) (P = .002). Right diaphragm excursion was significantly associated with age (P < .0001), steroid use (P = .008), history of spinal fusion (P < .0001), body mass index (BMI) (P = .002), Walton score (P < .0001), IC (P < .0001), upright FVC (P < .0001), supine FVC (P < .0001), and MIP (P < .0001). A right diaphragm TF >28% and a right diaphragm excursion>25.4 mm were associated with an FVC >50% with, respectively, an area under the curve (AUC) of 0.95 (P = .001) and 0.93 (P < .001). A left diaphragm TF >26.8% and a left diaphragm excursion >21.5 mm were associated with an FVC >50% with, respectively, an AUC of 0.95 (P = .011) and 0.97 (P < .001).Discussion: Diaphragm excursion and diaphragm TF can predict restrictive pulmonary insufficiency in DMD.
Published: 2021
Full Text: View/download PDF

4. Erreurs médicamenteuses en Auvergne Rhône-Alpes : étude pilote descriptive collaborative entre structures régionales de vigilance et d’appui (SRVA)

Author: Pauline Rascle, Nathalie Paret, Marie Zenut, Benjamin Grenier, Michel Roy, Amélie Faudel, Marion Lepelley, Jean-Marc Sapori, Catherine Stamm, Laurence Gilles-Afchain, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hospices Civils de Lyon (HCL), Centre Régional de Pharmacovigilance [CHU Clermont-Ferrand] (CRPV), CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand
Subjects: business.industry, [SDV]Life Sciences [q-bio], Poison control, medicine.disease, 030226 pharmacology & pharmacy, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Pharmacovigilance, Ambulatory, Health care, Medicine, Pharmacology (medical), 030212 general & internal medicine, Medical emergency, business
Abstract: Medication errors (ME) are frequently encountered and present at every step of the therapeutic process. This study's aims were to take stock of the ME reported to the region's pharmacovigilance (CRPV) and poison control centers (CAPTV) and to identify potential regional actions. A 2-months (January and February 2017) prospective gathering of the calls to the CAPTV regarding the ME and of the ME declarations to the region's CRPV (Clermont-Ferrand, Grenoble, Lyon, Saint-Etienne) has been carried out. The place of occurrence, the event's description and its consequences and data regarding the patient were collected. In addition to that, the regional drug observatory OMEDIT analysis has allowed to determine the ME's types (REMED characterization, never event?) and to look for the results of a potential thorough analysis. The study reported 580 calls for 590 ME and 583 patients. ME mostly affected the ambulatory/domicile sector (76%), the medico-social sector (14%) and the healthcare facilities sector (7%). It usually was about dose errors, medication errors and patient errors with a different profile in each sector. The majority of errors (85%) occurred at the administration step. Almost all the observed ME were confirmed errors having reached the patient (99.5%) but only a few had serious consequences. One out of 5 ME was eligible for a thorough analysis but even less were subjected to that kind of analysis. The main never event concerned the unidose in the ambulatory sector. The health products involved were mostly a single medication (75%) and then the patient's full treatment (12%). The CRPV/CAPTV/OMEDIT's skills are complementary for the gathering, the analysis and the management of the ME. Training campaigns and support are to be considered for the professionals and especially within the medico-social facilities.
Published: 2020
Full Text: View/download PDF

5. Safety of immune checkpoint inhibitor rechallenge after discontinuation for grade ≥2 immune-related adverse events in patients with cancer

Author: Marion Allouchery, Ghada Miremont-Salamé, Franck Rouby, Mathieu Puyade, Celia Bertin, Thomas Lombard, Marion Sassier, Mickael Martin, Marie-Christine Perault-Pochat, Marina Atzenhoffer, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Centre régional de pharmacovigilance de Caen Basse-Normandie (CRPV), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Henri Mondor, Hospices Civils de Lyon (HCL), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Laboratoire de neurosciences expérimentales et cliniques (LNEC), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Otten, Lisa
Subjects: Male, Cancer Research, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, medicine.medical_treatment, Immunology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Internal medicine, Neoplasms, Pharmacovigilance, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Adverse effect, Prospective cohort study, Immune Checkpoint Inhibitors, RC254-282, Aged, Pharmacology, business.industry, Melanoma, [SCCO.NEUR]Cognitive science/Neuroscience, autoimmunity, [SCCO.NEUR] Cognitive science/Neuroscience, Cancer, Correction, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunotherapy, Middle Aged, medicine.disease, Discontinuation, Oncology, 030220 oncology & carcinogenesis, Molecular Medicine, Female, immunotherapy, business, hormones, hormone substitutes, and hormone antagonists
Abstract: BackgroundSafety of rechallenge of immune checkpoint inhibitor (ICI) after grade ≥2 immune-related adverse events (irAEs) leading to ICI discontinuation remains unclear.MethodsAll adverse drug reactions involving at least one ICI reported up to December 31, 2019 were extracted from the French pharmacovigilance database. Patients were included if they experienced at least one grade ≥2 irAE resulting in ICI discontinuation, with subsequent ICI rechallenge. The primary outcome was the recurrence of at least one grade ≥2 irAE in these patients after ICI rechallenge.ResultsWe included 180 patients: 61.1% were men (median age of 66 years), 43.9% had melanoma and 78.9% were receiving anti-programmed cell death 1. First ICI discontinuation was related to 191 irAEs. After ICI rechallenge, 38.9% of the patients experienced at least one grade ≥2 irAE. Among them, 70.0% experienced the same irAE, 25.7% a distinct irAE, and 4.3% both the same and a distinct irAE. Lower recurrence rates of irAEs were associated with rechallenge with the same ICI treatment (p=0.02) or first endocrine irAEs (p=0.003). Gastrointestinal irAEs were more likely to recur (p=0.007). The median duration from ICI discontinuation to rechallenge and the severity of the initial irAE did not predict recurrent irAEs after ICI rechallenge (p=0.53 and p=0.40, respectively).ConclusionsIn this study, 61.1% of the patients who discontinued ICI treatment for grade ≥2 irAEs experienced no recurrent grade ≥2 irAEs after ICI rechallenge. Although ICI rechallenge appears to be safe under close monitoring, it should always be discussed balancing usefulness of rechallenge, patient comorbidities and risk of recurrence of first irAE(s). Due to inherent bias associated with pharmacovigilance studies, further prospective studies are needed to assess risk factors that may influence patient outcomes after ICI rechallenge.
Published: 2020
Full Text: View/download PDF

6. Thyroiditis and immune check point inhibitors: the post-marketing experience using the French National Pharmacovigilance database

Author: Nadine Petitpain, Julie Garon-Czmil, Franck Rouby, Marion Sassier, Georges Weryha, Marc Klein, Pierre Gillet, Samy Babai, Melissa Yelehe-Okouma, Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Endocrinologie et Gynécologie Médicale [CHRU Nancy], Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Pharmacologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre régional de pharmacovigilance [CHU Henri-Mondor], CHU Henri Mondor [Créteil], Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), and CHU Henri Mondor
Subjects: Adult, Male, Thyroiditis, Time Factors, Databases, Factual, Levothyroxine, Ipilimumab, Pembrolizumab, Antibodies, Monoclonal, Humanized, computer.software_genre, Risk Assessment, 030226 pharmacology & pharmacy, Pharmacovigilance, Young Adult, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Risk Factors, Product Surveillance, Postmarketing, Adverse Drug Reaction Reporting Systems, Humans, Medicine, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, Pharmacology, Database, business.industry, Thyroid, Middle Aged, medicine.disease, 3. Good health, Discontinuation, Nivolumab, medicine.anatomical_structure, Female, France, business, computer, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, medicine.drug
Abstract: Immunotherapy with immune checkpoint inhibitors (ICIs) for cancer has become increasingly prescribed in recent years. Indeed, it is used to treat both solid and hematological malignancies due to their considerable potential in treating melanoma, non-small cell lung and other cancers. Immune-mediated related adverse endocrine toxicity, and especially thyroiditis, is seen as a growing problem needing specific screening and management. This study aims at describing thyroid dysfunctions induced by the ICIs marketed in France, which are registered in the French Pharmacovigilance database. This database was queried for nivolumab, pembrolizumab, and ipilimumab-induced adverse drug reactions reported before April 30, 2017. Both a pharmacologist and an endocrinologist have reviewed each case to select only those of peripheral thyroiditis (thyrotoxicosis and hypothyroidism). During this period, 110 thyroiditis following ICI therapy were reported. Sex/ratio was around one. Most of the cases (47.2%) were asymptomatic. Although some thyrotoxicosis cases were severe, no orbitopathy was reported. Hypothyroidism and thyrotoxicosis were equally described. Antithyroid antibodies were positive in only 16% patients. The ultrasonography was informative in 19% patients. Levothyroxine supplementation was necessary in 57% patients, leading to 19% recovery. With a dedicated optimized management, most of the cases did not require immunotherapy discontinuation. Finally, immune-mediated related thyroiditis is increasing due to a wider prescription of ICI therapy in various cancer conditions and systematic screening. Often asymptomatic, they lead to a local activation accompanied by hormonal deficiency in the long run. It is necessary to carry out an early and sustained multidisciplinary screening to allow immunotherapy continuation.
Published: 2018
Full Text: View/download PDF

7. Cutaneous pigmentation related to intravenous iron extravasation: Analysis from the French pharmacovigilance database

Author: Nadine Petitpain, Pierre Gillet, Alexia Hermitte-Gandoliere, Marion Lepelley, Jacqueline Ponte Astoul, Christine Le Beller, Laure Thomas, Service de pharmacie [CHR de Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine), CRHU Nancy, Centre régional de pharmacovigilance de Grenoble [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Centre régional de pharmacovigilance [CHU Henri-Mondor], CHU Henri Mondor, Department of pharmacovigilance, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Necrosis, business.industry, Extravasation IronSkin pigmentation, Intravenous iron, Dermatology, Extravasation, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Pharmacovigilance, medicine, Pharmacology (medical), 030212 general & internal medicine, medicine.symptom, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Summary Introduction Intravenous iron infusion may be complicated by extravasation and lead to cutaneous pigmentation. Methods We queried the French pharmacovigilance database to assess the spontaneously reported cases over the 2000–2016 period. Results Fifty-one cases of cutaneous pigmentation related to intravenous iron extravasation were retrieved, none was associated to necrosis. Most of patients were women aged 20 to 49 years old. The pigmentation was mostly a brown coloration, persisting over one month in 19 cases (37.2%) and over 6 months in 9 cases (17.6%). The management of extravasation and pigmentation was heterogeneous and was rarely followed by a decrease of the coloration. Conclusion Cutaneous pigmentation after intravenous iron extravasation can persist over time and create an aesthetic prejudice, particularly in young women. Standardized extravasation and iron-induced pigmentation management procedures appear necessary.
Published: 2018
Full Text: View/download PDF

8. Heart failure and atrial tachyarrhythmia on abiraterone: A pharmacovigilance study

Author: Dan M. Roden, Marie Bretagne, Javid Moslehi, Antoine Pariente, Camille Potey, Pauline Dureau, Christian M. Shaffer, Gabriel G. Malouf, Joe-Elie Salem, Bénédicte Lebrun-Vignes, Christian Funck-Brentano, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], CHU Strasbourg, Centre Régional de PharmacoVigilance Nord-Pas-de-Calais [CHU Lille] (CRPV), and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine
Subjects: Male, Time Factors, Databases, Factual, 030204 cardiovascular system & hematology, Androgen deprivation therapy, chemistry.chemical_compound, Prostate cancer, Pharmacovigilance, 0302 clinical medicine, Risk Factors, Tachycardia, Supraventricular, Medicine, 030212 general & internal medicine, Abiraterone, Aged, 80 and over, Atrial fibrillation, General Medicine, Middle Aged, 3. Good health, Benzamides, Androstenes, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Antineoplastic Agents, Hormonal, Abiratérone, Heart failure, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Nitriles, Phenylthiohydantoin, Enzalutamide, Adverse Drug Reaction Reporting Systems, Humans, Aged, Retrospective Studies, PharmacoEpi-Drugs, business.industry, Prostatic Neoplasms, Androgen Antagonists, Odds ratio, medicine.disease, Cardiotoxicity, Insuffisance cardiaque, Fibrillation auriculaire, chemistry, Anti-androgène, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Observational study, business
Abstract: International audience; Background: Abiraterone and enzalutamide are recently-approved androgen deprivation therapies (ADTs) for metastatic prostate cancer, with unknown cardiac safety profiles. Abiraterone has a propensity to hypermineralocorticism on top of androgen deprivation, so might carry an additional risk for atrial tachyarrhythmia (AT) and heart failure (HF) compared with other ADTs.Aim: To determine if abiraterone was associated with an increased proportion of AT and HF reports among all suspected adverse drug reactions (ADRs) reported in several pharmacovigilance databases compared with enzalutamide, other ADTs and all other drugs.Methods: In this observational retrospective pharmacovigilance study, we performed a disproportionality analysis of reports of suspected ADRs in men in the French pharmacovigilance database, the European pharmacovigilance database and the international pharmacovigilance database VigiBase, to evaluate the reporting odds ratios (RORs) of AT and HF for abiraterone compared with enzalutamide, other ADTs and all other drugs.Results: In the 5,759,781 ADR reports in men in VigiBase, 55,070 pertained to ADTs. The RORs for AT for abiraterone versus enzalutamide, other ADTs and all other drugs were 4.1 (95% confidence interval 3.1-5.3), 3.7 (3-4.5) and 3.2 (2.7-3.7), respectively (P
Published: 2020
Full Text: View/download PDF

9. Liquid formulation of ifosfamide increased risk of encephalopathy: A case-control study in a pediatric population

Author: Anne Default, Aurélie Grandvuillemin, Nathalie Massy, Geneviève Durrieu, Mégane Mousset, Marion Allouchery, Marina Babin, Aude Lambert, G. Veyrac, Marie-Blanche Valnet-Rabier, Valérie Gras-Champel, Marie-Christine Zenut, Marion Sassier, Fanny Rocher, Louise Triquet, Paola Sanchez-Pena, Brahim Azzouz, Hélène Géniaux, Corinne Simon, Johana Béné, Florelle Bellet, Dominique Hillaire-Buys, Nadine Petitpain, Marion Lepelley, Hélène Jantzem, Jean-Luc Faillie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance Publique - Hôpitaux de Marseille (APHM), Laboratoire de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de PharmacoVigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, Unité de Pharmacoépidémiologie, INSERM 1027, Université de Toulouse, Faculté de Médecine, Centre Hospitalier Universitaire, CHU Toulouse [Toulouse], CHU Limoges, Centre Régional de Pharmacovigilance, de Renseignement sur le Médicament et de Pharmaco épidémiologie de Bourgogne [Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Amiens-Picardie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Strasbourg, Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Bordeaux [Bordeaux], Département de Pharmacologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Montpellier, Pôle de biologie médicale et d'anatomie pathologique, CHU Clermont-Ferrand, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)
Subjects: Pediatrics, medicine.medical_specialty, Chloroethanamine, Encephalopathy, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Pharmacovigilance, medicine, Humans, Pharmacology (medical), Ifosfamide, Child, Antineoplastic Agents, Alkylating, Children, Retrospective Studies, Brain Diseases, Liquid formulation, business.industry, Case-control study, Case-control, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, 3. Good health, Residual risk, Increased risk, Case-Control Studies, Observational study, business, Chloroethylamine, medicine.drug, Pediatric population
Abstract: International audience; BACKGROUND:Several clusters of encephalopathy occurred after the market change from Holoxan® (ifosfamide lyophilized powder) to Ifosfamide EG® (liquid formulation) and justified a formal survey in 2015. In June 2016, the regulatory authority decided to apply a precautionary measure in reducing the shelf life of Ifosfamide EG® at 7 months. One-year study from spontaneous reports lead to suspect a potential residual risk. Due to the many limitations associated with spontaneous notifications, we performed a multicentric observational study, aiming to better explore this pharmacovigilance signal.METHODS:We performed a case-control study in pediatric oncology Departments of 25 university hospitals between July 1st, 2016 and July 1st, 2018. All children (
Published: 2019
Full Text: View/download PDF

10. Moderate-to-severe eosinophilia induced by treatment with immune checkpoint inhibitors: 37 cases from a national reference center for hypereosinophilic syndromes and the French pharmacovigilance database

Author: Franck Morschhauser, Chouki Chenaf, Alexis B. Cortot, Nicolas Etienne, Laurent Mortier, Aurélie Grandvuillemin, Christine Le Beller, Delphine Staumont-Sallé, David Launay, Solenn Brousseau, Guillaume Lefèvre, Matthieu Groh, Johana Béné, Sophie Gautier, Jean-Emmanuel Kahn, Eric Hachulla, Alexandra Forestier, Myriam Labalette, Quentin Scanvion, service de médecine interne et immunologie clinique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de référence des maladies auto-immunes systémiques rares du Nord et Nord Ouest [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de PharmacoVigilance Nord-Pas-de-Calais [CHU Lille] (CRPV), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Centre Régional de Pharmacovigilance, de Renseignement sur le Médicament et de Pharmaco épidémiologie de Bourgogne [Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Régional de Pharmacovigilance [CHU Clermont-Ferrand] (CRPV), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre de Référence National des Syndromes Hyperéosinophiliques (CEREO), Service d’oncologie thoracique et essais précoces [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Hôpital Foch [Suresnes], Institut d'Immunologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Ambroise Paré [AP-HP], The authors would like to thank all the physicians who contributed adverse drug reaction reports to the French pharmacovigilance system., Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Faculté de Médecine Henri Warembourg - Université de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-UNICANCER
Subjects: 0301 basic medicine, Moderate to severe, medicine.medical_specialty, Databases, Factual, Immune checkpoint inhibitors, Immunology, Early detection, emergent adverse event, immune checkpoint inhibitors, 03 medical and health sciences, Pharmacovigilance, 0302 clinical medicine, Antineoplastic Agents, Immunological, Internal medicine, Hypereosinophilic Syndrome, Eosinophilia, Immunology and Allergy, Medicine, Humans, Adverse effect, RC254-282, business.industry, Brief Report, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, RC581-607, respiratory system, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, immune-related adverse events, Observational study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, Immunologic diseases. Allergy, business
Abstract: International audience; A better understanding of immune-related adverse events is essential for the early detection and appropriate management of these phenomena. We conducted an observational study of cases recorded at the French reference center for hypereosinophilic syndromes and in the French national pharmacovigilance database. Thirty-seven reports of eosinophilia induced by treatment with immune checkpoint inhibitors (ICIs) were included. The median [range] time to the absolute eosinophil count (AEC) peak was 15 [4─139] weeks. The median AEC was 2.7 [0.8─90.9] G/L. Eosinophil-related manifestations were reported in 21 of the 37 cases (57%). If administered, corticosteroids were always effective (n = 10 out of 10). Partial or complete remission of eosinophilia was obtained in some patients not treated with corticosteroids, after discontinuation (n = 12) or with continuation (n = 4) of the ICI. The AEC should be monitored in ICI-treated patients. If required by oncologic indications, continuation of ICI may be an option in asymptomatic hypereosinophilic patients, and in corticosteroid responders.
Published: 2019
Full Text: View/download PDF

11. Exploiting heterogeneous publicly available data sources for drug safety surveillance: computational framework and case studies

Author: Vassilis Koutkias, Agnès Lillo-Le Louët, Marie-Christine Jaulent, Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece, Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris 13 (UP13), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé ( LIMICS ), Université Paris 13 ( UP13 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Régional de Pharmacovigilance ( CRPV ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris 13 ( UP13 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Université Paris 13 (UP13)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Drug-Related Side Effects and Adverse Reactions, Pyridones, social media, Information Storage and Retrieval, joint exploitation, Adverse drug events, 030226 pharmacology & pharmacy, case studies, computational framework, Pharmacovigilance, 03 medical and health sciences, Adverse Event Reporting System, 0302 clinical medicine, Data acquisition, emerging data sources for pharmacovigilance, Robustness (computer science), Adverse Drug Reaction Reporting Systems, Humans, Medicine, Pharmacology (medical), Social media, 030212 general & internal medicine, spontaneous reporting systems, Clozapine, Cerebral Hemorrhage, heterogeneous public data, Safety surveillance, business.industry, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, General Medicine, Data science, Cardiotoxicity, 3. Good health, Visualization, Identification (information), [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Haloperidol, Pyrazoles, bibliographic databases, business, Antipsychotic Agents, Factor Xa Inhibitors
Abstract: International audience; Objective: Driven by the need of pharmacovigilance centres and companies to routinely collect and review all available data about adverse drug reactions (ADRs) and adverse events of interest, we introduce and validate a computational framework exploiting dominant as well as emerging publicly available data sources for drug safety surveillance.Methods: Our approach relies on appropriate query formulation for data acquisition and subsequent filtering, transformation and joint visualization of the obtained data. We acquired data from the FDA Adverse Event Reporting System (FAERS), PubMed and Twitter. In order to assess the validity and the robustness of the approach, we elaborated on two important case studies, namely, clozapine-induced cardiomyopathy/myocarditis versus haloperidol-induced cardiomyopathy/myocarditis, and apixaban-induced cerebral hemorrhage.Results: The analysis of the obtained data provided interesting insights (identification of potential patient and health-care professional experiences regarding ADRs in Twitter, information/arguments against an ADR existence across all sources), while illustrating the benefits (complementing data from multiple sources to strengthen/confirm evidence) and the underlying challenges (selecting search terms, data presentation) of exploiting heterogeneous information sources, thereby advocating the need for the proposed framework.Conclusions: This work contributes in establishing a continuous learning system for drug safety surveillance by exploiting heterogeneous publicly available data sources via appropriate support tools.
Published: 2016
Full Text: View/download PDF

12. Thrombotic microangiopathy associated with gemcitabine use: Presentation and outcome in a national French retrospective cohort

Author: Julien Mancini, Pascale Poullin, Joëlle Micallef, Florence Daviet, Marion Sallée, Paul Coppo, Aurélie Grandvuillemin, Franck Rouby, Noémie Jourde-Chiche, Renaud Sabatier, Steven Grangé, Véronique Frémeaux-Bacchi, Bertrand Pourroy, Stéphane Burtey, Florence Duffaud, Julie Moussi-Frances, Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM), Centre régional de pharmacovigilance de Marseille [CHU de Marseille], CHU Marseille, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d\'hémaphérèse, Hôpital de la Conception, APHM, Marseille, France, Service d'hémaphérèse, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chirurgie urologique et transplantation rénale [Hôpital de la Conception - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Service Pharmacie [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Régional de Pharmacovigilance, de Renseignement sur le Médicament et de Pharmaco épidémiologie de Bourgogne [Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de réanimation médicale [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Saint-Antoine [APHP], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de réanimation médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), and Prémilleux, Annick
Subjects: Male, medicine.medical_specialty, Antimetabolites, Antineoplastic, Thrombotic microangiopathy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], chemotherapy, 030226 pharmacology & pharmacy, Gastroenterology, Deoxycytidine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Neoplasms, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Adverse effect, Dialysis, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Pharmacology, adverse drug reactions, business.industry, Thrombotic Microangiopathies, Acute kidney injury, Retrospective cohort study, Original Articles, Eculizumab, Middle Aged, medication safety, medicine.disease, Gemcitabine, 3. Good health, [SDV] Life Sciences [q-bio], acute kidney injury, pharmacovigilance, Female, Fresh frozen plasma, France, business, medicine.drug
Abstract: International audience; Aims Gemcitabine has been associated with thrombotic microangiopathy (TMA). We conducted a national retrospective study of gemcitabine-associated TMA (G-TMA). Methods From 1998 to 2015, all cases of G-TMA reported to the French Pharmacovigilance Network and the French TMA Reference Center, and cases explored for complement alternative pathway abnormalities, were analysed. Results G-TMA was diagnosed in 120 patients (median age 61.5 years), after a median of 210 days of treatment, and a cumulative dose of 12 941 mg m(-2). Gemcitabine indications were: pancreatic (52.9%), pulmonary (12.6%) and breast (7.6%) cancers, metastatic in 34.2% of cases. Main symptoms were oedema (56.7%) and new-onset or exacerbated hypertension (62.2%). Most patients presented with haemolytic anaemia (95.6%) and thrombocytopenia (74.6%). Acute kidney injury was reported in 97.4% and dialysis was required in 27.8% of patients. Treatment consisted of: plasma exchange (PE; 39.8%), fresh frozen plasma (21.4%), corticosteroids (15.3%) and eculizumab (5.1%). A complete remission of TMA was obtained in 42.1% of patients and haematological remission in 23.1%, while 34.7% did not improve. The survival status was known for 52 patients, with 29 deaths (54.7%). Patients treated with PE, despite a more severe acute kidney injury, requiring dialysis more frequently, displayed comparable rates of remission, but with more adverse events. No abnormality in complement alternative pathway was documented in patients explored. Conclusion This large cohort confirms the severity of G-TMA, associated with severe renal failure and death. Oedema and hypertension could be monitored in patients treated with gemcitabine to detect early TMA. The benefit of PE or eculizumab deserves further investigation.
Published: 2018
Full Text: View/download PDF

13. Neuromuscular blocking agents induced anaphylaxis: Results and trends of a French pharmacovigilance survey from 2000 to 2012

Author: Petitpain, N., Argoullon, L., Masmoudi, K., Fedrizzi, S., Cottin, J., Latarche, C., Mertes, P., Pierre GILLET, French Network of Regional Pharmacovigilance Centres Network, Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Amiens-Picardie, Centre régional de pharmacovigilance de Caen Basse-Normandie (CRPV), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Pharmacie Hospitalière et Pharmacovigilance, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France, parent, Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] (Pôle S2R), CHU Strasbourg, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2018

14. Curares et anaphylaxie : données de pharmacovigilance sur une période de 13 ans

Author: P. Gillet, Judith Cottin, K. Masmoudi, S Fedrizzi, C. Latarche, N. Petitpain, Paul-Michel Mertes, Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine), CRHU Nancy, Service d’anesthésie-réanimation chirurgicale, Centre régional de pharmacovigilance de Caen Basse-Normandie (CRPV), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de physique des matériaux (GPM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre régional de pharmacovigilance, Pharmacie Hospitalière et Pharmacovigilance, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France, parent, Coordination qualité risques et vigilances [CHRU de Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Pharmacologie Clinique et Toxicologie [CHRU Nancy], Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), and Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, [SDV]Life Sciences [q-bio], Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract: Introduction L’anaphylaxie peroperatoire est souvent associee au curare injecte et releve frequemment d’un mecanisme IgE dependant. En France, les anesthesistes et les allergologues declarent volontiers les cas d’anaphylaxie au reseau des centres regionaux de pharmacovigilance, generant ainsi 2 alertes concernant le suxamethonium en 2011 et en 2012. Ce travail porte sur les resultats d’une analyse descriptive retrospective des cas d’anaphylaxie peroperatoire declares entre 2000 et 2012. Methodes Une requete a ete effectuee dans la base nationale de pharmacovigilance pour identifier tous les cas d’anaphylaxie survenus entre le 01/01/2000 et le 31/12/2012, impliquant un des 7 curares alors disponibles (atracurium, cisatracurium, mivacurium, pancuronium, rocuronium, suxamethonium, vecuronium). Un cas etait retenu des lors qu’aucune autre substance n’avait une imputabilite superieure au curare, et il etait considere comme « (IgE) confirme » si a la fois le taux de tryptase etait augmente et les tests cutanes etaient positifs pour le curare implique ; un cas n’ayant pas ces 2 criteres etait considere comme « non (IgE) confirme ». Resultats Sur cette periode de 13 ans, 680 cas « confirmes » et 944 cas « non confirmes » etaient identifies. L’incidence globale de l’anaphylaxie, tous curares confondus, etait de 29,5 cas/million d’ampoules vendues (IC 95 % 28,0–30,9) et le suxamethonium etait le curare le plus implique en nombre absolu de cas (64 %). Mais en tenant compte des donnees de ventes, les incidences observees avec le suxamethonium et le rocuronium etait voisines (respectivement 147,6 et 117,6/million d’ampoules vendues) et se demarquaient nettement de celles des autres curares (11,2/million pour l’atracurium et 6,3/million pour le cisatracurium). Cette difference etait constatee independamment du statut « confirme » ou « non confirme » selon nos criteres. Conclusion Suxamethonium et rocuronium sont clairement les deux curares les plus impliques actuellement dans l’anaphylaxie, que celle-ci soit confirmee par les tests cutanes ou non. La reemergence de l’anaphylaxie au rocuronium, suite a la mise a disposition du sugammadex, est preoccupante et merite d’etre prise en compte dans les recommandations actuelles et a venir.
Published: 2018
Full Text: View/download PDF

15. Hypophysites survenant au décours d’un traitement par inhibiteurs du point de contrôle immunitaire : étude rétrospective à partir de la Base française de pharmacovigilance

Author: Marc Klein, S. Babai, Nadine Petitpain, G. Werhya, M. Sassier, Melissa Yelehe-Okouma, F. Rouby, Pierre Gillet, J. Garon Czmil, Service d'Endocrinologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine), CRHU Nancy, Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Centre régional de pharmacovigilance de Caen Basse-Normandie (CRPV), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CRPV, Créteil, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 03 medical and health sciences, 0302 clinical medicine, Endocrinology, 030220 oncology & carcinogenesis, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, General Medicine, ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract: Introduction Les inhibiteurs du point de controle immunitaire (ICI) representent une avancee considerable dans la prise en charge et la survie de cancers comme le melanome ou le carcinome bronchique non a petites cellules. Cependant ils induisent des effets indesirables inhabituels, tels que des hypophysites, peu decrites par ailleurs. Notre etude retrospective decrit les caracteristiques des hypophysites declarees au reseau des centres regionaux de pharmacovigilance. Materiel et methodes Requete sur l’ensemble des cas d’endocrinopathies enregistres dans la Base nationale de pharmacovigilance avant le 30 avril 2017, avec selection des cas d’hypophysite imputables au nivolumab, a l’ipilimumab ou au pembrolizumab et revues par un endocrinologue et un pharmacologue. Resultats Environ 61 hypophysites ont ete retenues, concernant 31 femmes et 30 hommes. L’ipilimumab etait la molecule la plus representee (59 %). La plupart des cas (51 %) correspondait a une atteinte de grade 3 et la majorite (88 %) a un deficit corticotrope. Les cas avec atteinte thyreotrope et/ou gonadotrope etaient respectivement de 20 et 2 %. Cinq patients (8 %) ont presente un panhypopituitarisme. L’IRM hypophysaire etait en faveur d’une hypophysite dans 50 % lorsqu’elle etait realisee. Aucun patient n’a recupere sa fonction hormonale anterieure. Le delai moyen de survenue etait significativement plus court avec l’ipilimumab (93 jours vs. 213 p = 0,005). Conclusion Les hypophysites sont des effets indesirables caracteristiques des ICI et generent des deficits qui ne recuperent pas a distance de l’evenement, contrairement a ce qui est observe avec les thyroidites. Les patients doivent alors beneficier d’une prise en charge coordonnee et adaptee aux deficits du patient.
Published: 2018
Full Text: View/download PDF

16. Pholcodine exposure increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: the ALPHO case-control study

Author: Paul Michel Mertes, Nadine Petitpain, Charles Tacquard, Marion Delpuech, Cédric Baumann, Jean Marc Malinovsky, Dan Longrois, Aurélie Gouel-Cheron, Diane Le Quang, Pascal Demoly, Jean Louis Guéant, Pierre Gillet, Emmanuelle Aguinet, Pol André Apoil, Jean Eric Autegarden, Faiza Bettayeb, Céline Biermann, Maryline Bordes-demolis, Anca Chiriac, Pierre Antoine Darene, Frédéric Deblay, Sabrina Dessard, Charles Dzviga, Hassan El Hanache, Alain Facon, Yannick Fuhrer, Noémie Gest, Marion Gouitaa, Adela Harpan, Cyrille Hoarau, Lisa Le Guillou, Laurence Lepeltier, Claire Mailhol, Delphine Mariotte, Yannick Meunier, Isabelle Migueres, Martine Morisset, Catherine Neukirch, Dalila Nouar, Yann Ollivier, Isabelle Orsel, Omar Outtas, Minaxi Patel, Christelle Pellerin, Isabelle Petit, Anaïs Pipet, Cécile Rochefort-Morel, Claire Schwartz, Sandrine Seltzer, Alice Seringulian, Angèle Soria, Lilia Soufir, Rodolphe Stenger, Céline Tummino, Marion Verdaguer, Les Hôpitaux Universitaires de Strasbourg (HUS), Biologie et Pharmacologie des Plaquettes sanguines : hémostase, thrombose, transfusion (BPP), Université de Strasbourg (UNISTRA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Nouvel Hôpital Civil de Strasbourg, Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département Méthodologie Promotion Investigation [CHRU Nancy] (MPI), Centre Hospitalier Universitaire de Reims (CHU Reims), Hémostase et Remodelage Vasculaire Post-Ischémie (HERVI - EA 3801), Université de Reims Champagne-Ardenne (URCA), Service d'anesthésie - réanimation chirurgicale [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre de référence des maladies héréditaires du métabolisme (MaMEA Nancy-Brabois), Service d'Hépato-gastro-entérologie [CHRU Nancy], Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Pharmacologie Clinique et Toxicologie [CHRU Nancy], The ALPHO study NCT02250729 was requested and supported by the European Medicines Agency (EMA). It was funded by a consortium of pharmaceutical companies marketing pholcodine (Zambon, Urgo, Les Laboratoires Pierre Fabre, Boots, Hepatoum, Biocodex, Sanofi, Laboratoires Bouchara Recordati, GlaxoSmithKline, Alliance Pharmaceuticals Ltd, Bells Healthcare, Pinewood, T & R, Ernest Jackson, Vemedia)., and ALPHO Study Group: Emmanuelle Aguinet, Pol André Apoil, Jean Eric Autegarden, Faiza Bettayeb, Céline Biermann, Maryline Bordes-Demolis, Anca Chiriac, Pierre Antoine Darene, Frédéric Deblay, Sabrina Dessard, Charles Dzviga, Hassan El Hanache, Alain Facon, Yannick Fuhrer, Noémie Gest, Marion Gouitaa, Adela Harpan, Cyrille Hoarau, Lisa Le Guillou, Laurence Lepeltier, Claire Mailhol, Delphine Mariotte, Yannick Meunier, Isabelle Migueres, Martine Morisset, Catherine Neukirch, Dalila Nouar, Yann Ollivier, Isabelle Orsel, Omar Outtas, Minaxi Patel, Christelle Pellerin, Isabelle Petit, Anaïs Pipet, Cécile Rochefort-Morel, Claire Schwartz, Sandrine Seltzer, Alice Seringulian, Angèle Soria, Lilia Soufir, Rodolphe Stenger, Céline Tummino, Marion Verdaguer
Subjects: Anesthesiology and Pain Medicine, [SDV]Life Sciences [q-bio], anaphylaxis, anaesthesia, quaternary ammonium compounds, neuromuscular blocking agents, pholcodine
Abstract: International audience; BackgroundNeuromuscular blocking agents (NMBAs) are among the leading cause of perioperative anaphylaxis, and most of these reactions are IgE mediated. Allergic sensitisation induced by environmental exposure to other quaternary ammonium-containing compounds, such as pholcodine, has been suggested. The aim of this study was to assess the relationship between pholcodine exposure and NMBA-related anaphylaxis.MethodsALPHO was a multicentre case-control study, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related perioperative anaphylaxis (cases) and control patients with uneventful anaesthesia in France. Each case was matched to two controls by age, sex, type of NMBA, geographic area, and season. Pholcodine exposure was assessed by a self-administered questionnaire and pharmaceutical history retrieved from pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated.ResultsOverall, 167 cases were matched with 334 controls. NMBA-related anaphylaxis was significantly associated with pholcodine consumption (odds ratio 4.2; 95% confidence interval 2.3–7.0) and occupational exposure to quaternary ammonium compounds (odds ratio 6.1; 95% confidence interval 2.7–13.6), suggesting that apart from pholcodine, other environmental factors can also lead to sensitisation to NMBAs. Pholcodine and quaternary ammonium sIgEs had a high negative predictive value (99.9%) but a very low positive predictive value (
Published: 2023
Full Text: View/download PDF

17. Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): a randomised, double-blind, placebo-controlled, phase 3 trial

Author: Abdellatif Tazi, Aurélie Le Borgne-Krams, Marine Cachanado, Tabassome Simon, Sylvain Marchand-Adam, Morgane Didier, Lidwine Wemeau-Stervinou, Sandrine Hirschi, Frédéric Rivière, Arnaud Bourdin, François Lebargy, Stéphane Dominique, Aude Gibelin, Alexandre Chabrol, Tristan Dégot, Jacques Cadranel, Martine Reynaud-Gaubert, Marie-Pierre Debray, Sylvie Leroy, Frédéric Gagnadoux, Emmanuel Bergot, François-Xavier Blanc, Alexandra Rousseau, Raphael Borie, Pierre Yves Brillet, Guillaume Beltramo, Mallorie Kerjouan, Hilario Nunes, Olivia Freynet, Julie Traclet, Bruno Crestani, Anne-Sophie Gamez, Grégoire Prévot, Jean Pastré, Dominique Israel-Biet, Marie-Christine Dombret, Laurent Plantier, Cécile Chenivesse, Laurence Berard, Ana Nieves, Emmanuel Gomez, Dominique Valeyre, Stéphane Jouneau, Anne Gondouin, Elodie Blanchard, C. Launois, Nathalie Bautin, Jean-Marc Naccache, Vincent Cottin, Antoine Parrot, Philippe Bonniaud, Centre de référence maladies rares des maladies pulmonaires rares de l’adulte (CHU Dijon) (CRMR des maladies pulmonaires rares de l’adulte), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Sorbonne Université (SU), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Foch [Suresnes], CHU Pontchaillou [Rennes], École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Avicenne [AP-HP], Laboratoire d'Excellence INFLAMEX [Paris], Université Sorbonne Paris Cité (USPC), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Saint-Antoine [AP-HP], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, CHU Dijon, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Les Hôpitaux Universitaires de Strasbourg (HUS), Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Lille, Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Référence des Maladies Pulmonaires Rares [Hôpital Louis Pradel - HCL], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Université de Lyon, CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital JeanMinjoz, CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque [CHU Bordeaux], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Rouen, Normandie Université (NU), CHU Tenon [AP-HP], Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), CHU Montpellier, Université de Lille, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Roche, Ministere de la Sante et des Solidarites, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, education.field_of_study, Exacerbation, Cyclophosphamide, business.industry, [SDV]Life Sciences [q-bio], Population, medicine.disease, Placebo, 3. Good health, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, 030228 respiratory system, Methylprednisolone, Internal medicine, Clinical endpoint, Medicine, 030212 general & internal medicine, business, education, Adverse effect, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: Summary Background The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population. Methods In this double-blind, placebo-controlled trial done in 35 departments across 31 hospitals in France, adult patients (≥18 years) with acute exacerbation of IPF and those with suspected acute exacerbation of IPF were randomly assigned in a 1:1 ratio using a web-based system to receive either intravenous pulses of cyclophosphamide (600 mg/m2) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m2) at the time of cyclophosphamide administration and then again, 4 h later, or placebo at days 0, 15, 30, and 60. Random assignment was stratified according to the severity of IPF and was block-balanced with variable block sizes of four or six patients. Patients receiving mechanical ventilation, with active infection, with active cancer, or who were registered on the lung transplant waiting list were excluded. All patients received standardised high-dose glucocorticoids. The investigators, patients, and the sponsor were masked to the treatment assignments. The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle. The trial is now complete and registered with ClinicalTrials.gov , NCT02460588 . Findings Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients (62 [52%] with severe IPF) received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis. The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group (difference 14·5% [95% CI −3·1 to 31·6]; p=0·10). Similar results were found after adjustment by IPF severity (odds ratio [OR] 1·89 [95% CI 0·89–4·04]). The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF (OR 2·62 [1·12–6·12]) and was lower with the use of antifibrotic therapy (OR 0·33 [0·13–0·82]). Adverse events were similar between groups by 6 months (25 [42%] in the cyclophosphamide group vs 30 [51%] in the placebo group) and their proportion, including infections, did not differ. Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group. Interpretation In patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients. Funding Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC 2014–502), Roche Pharmaceuticals.
Published: 2022
Full Text: View/download PDF

18. Changing spectrum of suspected drugs of epidermal necrolysis: A World Health Organization pharmacovigilance database analysis from 1997-2020

Author: N. de Prost, T. Bettuzzi, C. Chinchilla Purtillo, Bénédicte Lebrun-Vignes, P. Maison, Laurence Le Cleach, Emilie Sbidian, Pierre Wolkenstein, S. Ingen-Housz Oro, Service de dermatologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: medicine.medical_specialty, Databases, Factual, Drug-Related Side Effects and Adverse Reactions, business.industry, Database analysis, MEDLINE, Dermatology, Antibodies, Monoclonal, Humanized, World Health Organization, medicine.disease, Toxic epidermal necrolysis, Pharmacovigilance, Pharmaceutical Preparations, Epidermal necrolysis, Stevens-Johnson Syndrome, medicine, Adverse Drug Reaction Reporting Systems, Humans, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Retrospective Studies
Abstract: International audience
Published: 2021
Full Text: View/download PDF

19. Avis de l'Anses relatif à des nouveaux cas d’intoxications à la vitamine D chez des nourrissonspar mésusage de compléments alimentaires

Author: Danel-Buhl, Nicolas, Boissonnas, Alain, Boltz, Patricia, Crenn, Pascal, Gaboriau, Louise, Jacquesson-Fournols, Laetitia, Jian, Raymond, Kanny, Gisèle, Koppe-Guichard, Laetitia, Morisset, Martine, Plan, Pascal, Renaudin, Jean-Marie, Richard, Ruddy, Rocher, Fanny, Scherer, Philippe, Zazzo, Jean-Fabien, Mondier Casini, Aurélien, Dopter, Aymeric, Huret, Fanny, Nadaud, Perrine, Vo Van Regnault, Gwenn, GHT de l'Artois, Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), AP-HP. Université Paris Saclay, Centre Régional de PharmacoVigilance Nord-Pas-de-Calais [CHU Lille] (CRPV), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Faculté de Médecine Henri Warembourg - Université de Lille, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Emile Durkheim [Epinal] (CH Epinal / CHED), Université Clermont Auvergne (UCA), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Retraité, AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and Anses
Subjects: Compléments alimentaires, intoxication, mésusage, Food supplement, vitamine D, Nutrivigilance, vitamin D, misuse, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Citation suggérée : Anses. 2023. Avis de l’Anses relatif à « des intoxications à la vitamine D chez des nourrissons par mésusage de compléments alimentaires » (saisine 2022-VIG-0166). Maisons-Alfort: Anses, 13 p; Dans le cadre de son dispositif de nutrivigilance créé en 2009 et depuis la publication de sonavis du 28 juillet 2021 relatif à trois cas de signalements d’effets indésirables sévèresa chezdes nourrissons à la suite du mésusage de compléments alimentaires contenant de lavitamine Db (Anses 2021b), l’Anses a reçu trois nouveaux signalements d’effets indésirablessévères (sévérité de niveau 3, dont deux cas avec menace du pronostic vital) chez desnourrissons susceptibles d’être liés au mésusage de compléments alimentaires achetés surinternet contenant 5 000 UI et 10 000 UI par goutte de vitamine D. Ces trois cas, enregistrésdans la base de données de nutrivigilance sous les numéros 2022-140, 2022-335 et 2022-380ont été jugés d’imputabilité très vraisemblable.En raison de la sévérité des effets indésirables rapportés (hypercalcémies sévères associéesà une néphrocalcinose, anorexie, hypokaliémie, trouble de la repolarisation cardiaque),l’Anses s’est à nouveau autosaisie le 21 septembre 2022, estimant nécessaire de porter cescas de mésusage à la connaissance du public, des metteurs en marché et des professionnelsde santé, dans un but d’amélioration de la sécurité sanitaire du consommateur.
Published: 2023

20. A cell-contact-regulated operon is involved in genetic variability in Neisseria meningitidis

Author: Xavier Nassif, Eric Frapy, Dominique Schneider, Anne Jamet, Patricia Martin, Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Universite Paris Descartes, INSERM, Region Ile-De-France, Foundation pour la Recherche Medicale, Centre Régional de Pharmacovigilance ( CRPV ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Pathogénie des infections systémiques ( UMR_S 570 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] ( LAPM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : Operon, Operon, TOPOISOMERASES, Cell, Neisseria meningitidis, medicine.disease_cause, Bacterial Adhesion, MESH : Host-Pathogen Interactions, Genetics, 0303 health sciences, Mutation, MESH: Gene Expression Regulation, Bacterial, SEROGROUP-A, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], General Medicine, GENOME, [ SDV.BID.EVO ] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], medicine.anatomical_structure, Interaction with host, Meningococcus, ESCHERICHIA-COLI, Host-Pathogen Interactions, MESH : Gene Expression Regulation, Bacterial, MESH: Operon, PHASE VARIATION, OUTER-MEMBRANE PROTEIN, MESH : Bacterial Adhesion, Biology, Microbiology, MESH: Neisseria meningitidis, 03 medical and health sciences, MESH: Gene Expression Profiling, Downregulation and upregulation, medicine, HIGH MUTATION-RATES, Humans, Genetic variability, MESH: Bacterial Adhesion, Molecular Biology, Gene, 030304 developmental biology, MESH: Humans, MESH : Neisseria meningitidis, 030306 microbiology, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Humans, MESH: Host-Pathogen Interactions, Gene Expression Regulation, Bacterial, EVOLUTION, bacteria, HOST-CELLS, SYSTEM
Abstract: International audience; The ability of Neisseria meningitidis to establish efficient interaction with host cells is crucial for its survival. We recently demonstrated that an entire operon containing genes NMA1802 to NMA1806 was overexpressed during the early stage of the colonization process. In this work, we investigated whether upregulation of the expression of this operon facilitated the ability of N. meningitidis to adapt to growth on host cells. Using a strain displaying an inducible operon, we demonstrated that the NMA1802-NMA1806 cell-contact-regulated operon could potentially improve the adaptability of meningococcus during growth on the cell surface through enhanced generation of variants.
Published: 2012
Full Text: View/download PDF

21. Real-world safety profiles of pirfenidone and nintedanib in idiopathic pulmonary fibrosis patients

Author: Dorine Fournier, Stéphane Jouneau, Guillaume Bouzillé, Elisabeth Polard, Marie-Noëlle Osmont, Lucie-Marie Scailteux, CHU Pontchaillou [Rennes], Centre Régional de Pharmacovigilance [Rennes] (CRPV), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), None, Jonchère, Laurent, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), and Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)
Subjects: Pulmonary and Respiratory Medicine, [SDV.IB] Life Sciences [q-bio]/Bioengineering, MESH: Indoles, Indoles, MESH: Humans, Pyridones, Nintedanib, MESH: Idiopathic Pulmonary Fibrosis, Biochemistry (medical), Adverse drug reaction, Idiopathic pulmonary fibrosis, Pirfenidone, Treatment Outcome, Safety profile, MESH: Pyridones, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Humans, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Pharmacology (medical), MESH: Treatment Outcome
Abstract: Introduction: While pirfenidone and nintedanib have greatly influenced the treatment of idiopathic pulmonary fibrosis (IPF), both drugs have significant early adverse drug reactions (ADRs) and almost nothing is known of their rare and delayed ADRs. We collected and analyzed pirfenidone- or nintedanib-related ADRs identified in a French rare lung disease center, recorded their profiles and identified potential safety signals.Methods: We analyzed the medical records of IPF patients treated with pirfenidone or nintedanib between January 2011 and January 2020 at the Rennes University Hospital to estimate the incidence of serious and non-serious ADRs cases due to each drug and the incidence of ADRs involving the cardiovascular, hepatobiliary, gastro-intestinal, dermatological, and metabolic/nutritional systems.Results: The 176 patients included 115 (65%) initially treated with pirfenidone and 61 (35%) given nintedanib. ADRs occurred in 78.3% of those given pirfenidone and in 70.5% of those given nintedanib. The incidence of first serious ADRs cases was about 33 per 100 person-years (100 PY) for both drugs; first non-serious pirfenidone ADRs cases were 102 per 100 PY and 130 per 100 PY for nintedanib. The incidence involving each organ system were quite similar, except for the gastro-intestinal and skin disorders. Cardiovascular disorders occurred in about 10 cases per 100 PY in both pirfenidone and nintedanib patients.Discussion: Most ADRs were consistent with the expected antifibrotic drug safety profiles. As arterial and venous thromboembolic events are rare, it is important to assess the risk associated with using antifibrotics by a dedicated pharmacoepidemiological study.
Published: 2022
Full Text: View/download PDF

22. Documentation in pharmacovigilance: using an ontology to extend and normalize Pubmed queries

Author: Delamarre, Denis, Lillo-Le Louët, Agnès, Guillot, Laetitia, Jamet, Anne, Sadou, Eric, Ouazine, Theo, Burgun, Anita, Jaulent, Marie-Christine, Modélisation Conceptuelle des Connaissances Biomédicales, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Régional de Pharmacovigilance ( CRPV ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Laboratoire de Santé Publique et Informatique Médicale ( SPIM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire de Santé Publique et Informatique Médicale (SPIM), Institut National de la Santé et de la Recherche Médicale (INSERM), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: MESH: Terminology as Topic, PubMed, Drug-Related Side Effects and Adverse Reactions, Adverse drug reaction reporting, Adverse drug reaction, MESH: Documentation, Documentation, MESH: Drug Toxicity, MESH: Natural Language Processing, MESH : Database Management Systems, Terminology as Topic, MESH : Vocabulary, Controlled, Data Mining, Humans, Information retrieval, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, Natural Language Processing, MESH: Humans, Ontology, MESH : Data Mining, MESH: Data Mining, MESH : Humans, MESH : Drug Toxicity, MESH: PubMed, MESH: Vocabulary, Controlled, MESH : Natural Language Processing, MESH : PubMed, MESH : Terminology as Topic, Vocabulary, Controlled, Database Management Systems, [SDV.IB]Life Sciences [q-bio]/Bioengineering, MESH : Documentation, Databases bibliographic, MESH: Database Management Systems
Abstract: International audience; OBJECTIVES: To assess and understand adverse drug reactions (ADRs), a systematic review of reference databases like Pubmed is a necessary and mandatory step in Pharmacovigilance. In order to assist pharmacovigilance team with a computerized tool, we performed a comparative study of 4 different approaches to query Pubmed through ADR-drug terms. The aim of this study is to assess how an ontology of adverse effects, used to normalize and extend queries, could improve this search. MATERIAL AND METHOD: The ontological resource OntoEIM contains 58,000 classes and integrates MedDRA terminology. The entry point is a ADR-Drug term and the four methods are (i) a direct search on Pubmed (ii) a search with a normalized query enhanced with domain-specific Mesh Heading criteria, (iii) a search with the same elaborated query extended to the MeSH sub-hierarchy of the adverse effect entry and (iv) a search with a set of MedDRA terms grouped by subsomption in the OntoEIM ontology. For each of the 16 queries performed and analysed, relevant publications are selected "manually" by two pharmacovigilant experts. RESULTS: The recall is respectively of 63%, 50%, 67% and 74%, the precision of 13%, 26%, 29% and 4%. The best recall is provided by the ontology-based method, for 4 cases out of 16 this method returns relevant publications when the others return no results. CONCLUSION: Results show that an ontology-based search tool improves the recall performance, but other tools and methods are needed to raise the precision.
Published: 2010
Full Text: View/download PDF

23. Gastroenterological safety of IL-17 inhibitors: a systematic literature review

Author: Pierre Miossec, Bénédicte Caron, Patrick Netter, Jean-Yves Jouzeau, Pierre Gillet, Laurent Peyrin-Biroulet, Nadine Petitpain, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine), CRHU Nancy, Hôpital Edouard Herriot [CHU - HCL], and Hospices Civils de Lyon (HCL)
Subjects: medicine.medical_specialty, Gastrointestinal Diseases, [SDV]Life Sciences [q-bio], Inflammatory bowel disease, 030207 dermatology & venereal diseases, 03 medical and health sciences, Psoriatic arthritis, 0302 clinical medicine, Internal medicine, Psoriasis, medicine, Humans, Spondylitis, Ankylosing, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, Randomized Controlled Trials as Topic, 030203 arthritis & rheumatology, Ankylosing spondylitis, Crohn's disease, business.industry, Arthritis, Psoriatic, Interleukin-17, Antibodies, Monoclonal, General Medicine, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, 3. Good health, Ixekizumab, Secukinumab, business
Abstract: Introduction Interleukin 17 is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of many chronic immune-mediated disorders. Interleukin 17 inhibitors provide an excellent treatment option for patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis. However, Interleukin 17 inhibitors have been suspected of worsening or triggering new-onset inflammatory bowel disease. Areas covered A literature search was conducted until March 2021 to investigate reporting prevalence, and characteristics of all gastroenterological adverse events in patients treated with Interleukin 17 inhibitors. One hundred and six clinical randomized trials were included, involving 40,053 patients. Inflammatory bowel disease cases were reported in 0.4% of patients exposed to Interleukin 17 inhibitors. The most frequent other gastrointestinal adverse events were diarrhea (2.5%), nausea or vomiting (0.7%), and gastroenteritis (0.2%). Sixty-one uncontrolled or retrospective studies were included, involving 16,791 patients. Sixty (0.36%) inflammatory bowel disease cases were reported, 0.6% of patients reported other gastrointestinal adverse events. Expert opinion Interleukin 17 inhibitors are safe and effective in the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis. Low incidence rate of developing new-onset inflammatory bowel disease or exacerbating preexisting inflammatory bowel disease with anti-IL-17 agents has been reported. Clinicians should be aware of the possibility of these concerns when considering this therapy.
Published: 2021
Full Text: View/download PDF

24. Risk of Tuberculosis Is Higher With Anti-Tumor Necrosis Factor Monoclonal Antibody Therapy Than With Soluble Tumor Necrosis Factor Receptor Therapy The Three-Year Prospective French Research Axed on Tolerance of Biotherapies Registry

Author: F, Tubach, D, Salmon, P, Ravaud, Y, Allanore, P, Goupille, M, Bréban, B, Pallot-Prades, S, Pouplin, A, Sacchi, R M, Chichemanian, S, Bretagne, D, Emilie, M, Lemann, O, Lortholary, O, Lorthololary, X, Mariette, Zeller, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cytokines, chimiokines et immunopathologie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Immunologie antivirale systémique et cérébrale, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service de rhumatologie [CHU Cochin], Service de rhumatologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Hôpital Bellevue, Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de médecine interne (CH F. Quesnay), Centre hospitalier F. Quesnay, Centre régional de pharmacovigilance, Centre Régional de Pharmacovigilance, Service de parasitologie [Mondor], Service d'hépato-gastro-entérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris-Sud - Paris 11 (UP11)-IFR13-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 (UP7) - Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Cochin [APHP], Génétique, Immunothérapie, Chimie et Cancer (GICC), Université François Rabelais - Tours - Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Diderot - Paris 7 (UP7), Université Paris-Sud - Paris 11 (UP11) - Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Necker - Enfants malades, Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5), Université Paris-Sud - Paris 11 (UP11) - IFR93 - Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Cambefort, Jeanne, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], CHRU Tours, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Service de rhumatologie [Rouen], Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Rouen, Service de médecine interne ( CH F. Quesnay ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Université Paris-Sud - Paris 11 ( UP11 ) -IFR13-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Gillet, Catherine, Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Male, rheumatoid arthritis, Oncology, [SDV]Life Sciences [q-bio], Receptors, Tumor Necrosis Factor, anti-TNF-alpha, Etanercept, Arthritis, Rheumatoid, 0302 clinical medicine, Risk Factors, Immunology and Allergy, Pharmacology (medical), Prospective Studies, Registries, 030212 general & internal medicine, Monoclonal antibody therapy, Behcet Syndrome, Antibodies, Monoclonal, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Middle Aged, Colitis, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, tuberculosis, Rheumatoid arthritis, Female, Tumor necrosis factor alpha, France, medicine.drug, Adult, safety, medicine.medical_specialty, Tuberculosis, Immunology, Antibodies, Monoclonal, Humanized, inflammatory chronic diseases, 03 medical and health sciences, Rheumatology, Internal medicine, Spondylarthritis, medicine, Adalimumab, Humans, Risk factor, Aged, 030203 arthritis & rheumatology, Tumor Necrosis Factor-alpha, business.industry, medicine.disease, Infliximab, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Immunoglobulin G, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: International audience; Objective. Tuberculosis (TB) is associated with anti-tumor necrosis factor (anti-TNF) monoclonal anti-body (mAb) therapy, but whether this association is drug-specific remains a concern. Our objective was to describe cases of TB associated with anti-TNF mAb therapy, identify risk factors, and estimate the incidence. Methods. We conducted an incidence study and a case-control analysis to investigate the risk of newly diagnosed TB associated with the use of anti-TNF agents. As part of the French Research Axed on Tolerance of Biotherapies (RATIO) registry, for 3 years we collected cases of TB among French patients receiving anti-TNF mAb therapy for any indication; for each case, 2 patients treated with anti-TNF agents served as control subjects. Results. We collected 69 cases of TB in patients treated for rheumatoid arthritis (n = 40), spondylarthritides (n = 18), inflammatory colitis (n = 9), psoriasis (n = 1) and Behcet's disease (n = 1) with infliximab (n = 36), adalimumab (n = 28), and etanercept (n = 5). None of the patients had received correct chemoprophylactic treatment. The sex- and age-adjusted incidence rate of TB was 116.7 per 100,000 patient-years. The standardized incidence ratio (SIR) was 12.2 (95% confidence interval [95% CI] 9.7-15.5) and was higher for therapy with infliximab and adalimumab than for therapy with etanercept (SIR 18.6 [95% CI 13.4-25.8] and SIR 29.3 [95% CI 20.3-42.4] versus SIR 1.8 [95% CI 0.7-4.3], respectively). In the case-control analysis, exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB (odds ratio [OR] 13.3 [95% CI 2.6-69.0] and OR 17.1 [95% CI 3.6-80.6], respectively). Other risk factors were age, the first year of anti-TNF mAb treatment, and being born in an endemic area. Conclusion. The risk of TB is higher for patients receiving anti-TNF mAb therapy than for those receiving soluble TNF receptor therapy. The increased risk with early anti-TNF treatment and the absence of correct chemoprophylactic treatment favor the reactivation of latent TB.
Published: 2009
Full Text: View/download PDF

25. Immunomodulatory and/or immunosuppressive drugs should not be stopped prior to skin tests for the assessment of drug allergy

Author: S El Mesbahi, Delphine Staumont-Sallé, J Grosjean, Damien Lannoy, C Nassar, Florence Tetart, B. Tedbirt, F. Dezoteux, Sophie Gautier, Département de Dermatologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Département d'Informatique Médicale (D2IM), Centre Régional de PharmacoVigilance Nord-Pas-de-Calais [CHU Lille] (CRPV), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Faculté de Médecine Henri Warembourg - Université de Lille, CHU Lille, Institut de Pharmacie, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Drug, medicine.medical_specialty, media_common.quotation_subject, Drug allergy, Dermatology, Chronic inflammatory disease, Drug Hypersensitivity, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, medicine, Humans, In patient, Skin Tests, media_common, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Skin test, medicine.disease, 3. Good health, Skin reaction, 030228 respiratory system, Underlying disease, business, Immunosuppressive Agents
Abstract: International audience; The use of immunomodulatory and/or immunosuppressive therapy (IT) is increasingly common in the management of chronic inflammatory disease. Skin reactions to any drug (IT or not) are not rare in these patients, justifying allergological investigations. The influence of IT on allergological tests for drugs is not clearly described. IT cannot be interrupted due to the underlying disease. The data assessing the benefit and the safety of allergological test for drug allergy in patients under IT are missing.
Published: 2022
Full Text: View/download PDF

26. Impact of OSA primary therapy on antihypertensive drugs use

Author: Bruno Revol, Christel Castelli, Marie Joyeux-Faure, Jean-Louis Pépin, Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Laboratoire d’EFCR [Grenoble], Pôle Thorax et Vaisseaux [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre Hospitalier Universitaire [Grenoble] (CHU), Centre régional de pharmacovigilance de Grenoble [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Clinique Médicale Beausoleil, Dynamiques du droit (DD), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and SALAS, Danielle
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Physiology (medical), Neurology (clinical)
Abstract: International audience; No abstract available
Published: 2022
Full Text: View/download PDF

27. Investigating ADR mechanisms with Explainable AI: a feasibility study with knowledge graph mining

Author: Emmanuel Bresso, Pierre Monnin, Cédric Bousquet, François-Elie Calvier, Ndeye-Coumba Ndiaye, Nadine Petitpain, Malika Smaïl-Tabbone, Adrien Coulet, Computational Algorithms for Protein Structures and Interactions (CAPSID), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Knowledge representation, reasonning (ORPAILLEUR), Department of Natural Language Processing & Knowledge Discovery (LORIA - NLPKD), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Orange Labs [Belfort] (Orange Labs), France Télécom, Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), ANR-15-CE23-0028,PractiKPharma,Confrontation entre connaissances de l'état de l'art et connaissances extraites de dossiers patients en pharmacogénomique(2015), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Natural Language Processing & Knowledge Discovery (LORIA - NLPKD), Orange Labs, ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CRHU Nancy, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Monnin, Pierre, Interactions humain-machine, objets connectés, contenus numériques, données massives et connaissance - Confrontation entre connaissances de l'état de l'art et connaissances extraites de dossiers patients en pharmacogénomique - - PractiKPharma2015 - ANR-15-CE23-0028 - AAPG2015 - VALID, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Coulet, Adrien, and Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID
Subjects: [INFO.INFO-AI] Computer Science [cs]/Artificial Intelligence [cs.AI], Knowledge graph, [INFO.INFO-DB]Computer Science [cs]/Databases [cs.DB], Drug-Related Side Effects and Adverse Reactions, Explanation, Computer applications to medicine. Medical informatics, R858-859.7, Adverse drug reaction, Mechanism of action, Pattern Recognition, Automated, Molecular mechanism, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Pharmacovigilance, Artificial Intelligence, Machine learning, Explainable AI, Adverse Drug Reaction Reporting Systems, Feasibility Studies, Humans, [INFO.INFO-DB] Computer Science [cs]/Databases [cs.DB], Drug mechanism of action, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Data mining, Research Article, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: Background Adverse drug reactions (ADRs) are statistically characterized within randomized clinical trials and postmarketing pharmacovigilance, but their molecular mechanism remains unknown in most cases. This is true even for hepatic or skin toxicities, which are classically monitored during drug design. Aside from clinical trials, many elements of knowledge about drug ingredients are available in open-access knowledge graphs, such as their properties, interactions, or involvements in pathways. In addition, drug classifications that label drugs as either causative or not for several ADRs, have been established. Methods We propose in this paper to mine knowledge graphs for identifying biomolecular features that may enable automatically reproducing expert classifications that distinguish drugs causative or not for a given type of ADR. In an Explainable AI perspective, we explore simple classification techniques such as Decision Trees and Classification Rules because they provide human-readable models, which explain the classification itself, but may also provide elements of explanation for molecular mechanisms behind ADRs. In summary, (1) we mine a knowledge graph for features; (2) we train classifiers at distinguishing, on the basis of extracted features, drugs associated or not with two commonly monitored ADRs: drug-induced liver injuries (DILI) and severe cutaneous adverse reactions (SCAR); (3) we isolate features that are both efficient in reproducing expert classifications and interpretable by experts (i.e., Gene Ontology terms, drug targets, or pathway names); and (4) we manually evaluate in a mini-study how they may be explanatory. Results Extracted features reproduce with a good fidelity classifications of drugs causative or not for DILI and SCAR (Accuracy = 0.74 and 0.81, respectively). Experts fully agreed that 73% and 38% of the most discriminative features are possibly explanatory for DILI and SCAR, respectively; and partially agreed (2/3) for 90% and 77% of them. Conclusion Knowledge graphs provide sufficiently diverse features to enable simple and explainable models to distinguish between drugs that are causative or not for ADRs. In addition to explaining classifications, most discriminative features appear to be good candidates for investigating ADR mechanisms further. Supplementary Information The online version contains supplementary material available at 10.1186/s12911-021-01518-6.
Published: 2022
Full Text: View/download PDF

28. Validation of Artificial Intelligence to Support the Automatic Coding of Patient Adverse Drug Reaction Reports, Using Nationwide Pharmacovigilance Data

Author: Guillaume L, Martin, Julien, Jouganous, Romain, Savidan, Axel, Bellec, Clément, Goehrs, Mehdi, Benkebil, Ghada, Miremont, Joëlle, Micallef, Francesco, Salvo, Antoine, Pariente, Louis, Létinier, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Agence nationale de sécurité du médicament et des produits de santé [Saint-Denis] (ANSM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Assistance Publique - Hôpitaux de Marseille (APHM), Agence Nationale de Sécurité du Médicament et des Produits de Santé, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Neurosciences des Systèmes (INS), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pharmacology, Pharmacovigilance, COVID-19 Vaccines, Drug-Related Side Effects and Adverse Reactions, Artificial Intelligence, Adverse Drug Reaction Reporting Systems, COVID-19, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pharmacology (medical), Toxicology
Abstract: International audience; INTRODUCTION: Adverse drug reaction reports are usually manually assessed by pharmacovigilance experts to detect safety signals associated with drugs. With the recent extension of reporting to patients and the emergence of mass media-related sanitary crises, adverse drug reaction reports currently frequently overwhelm pharmacovigilance networks. Artificial intelligence could help support the work of pharmacovigilance experts during such crises, by automatically coding reports, allowing them to prioritise or accelerate their manual assessment. After a previous study showing first results, we developed and compared state-of-the-art machine learning models using a larger nationwide dataset, aiming to automatically pre-code patients' adverse drug reaction reports. OBJECTIVES: We aimed to determine the best artificial intelligence model identifying adverse drug reactions and assessing seriousness in patients reports from the French national pharmacovigilance web portal. METHODS: Reports coded by 27 Pharmacovigilance Centres between March 2017 and December 2020 were selected (n = 11,633). For each report, the Portable Document Format form containing free-text information filled by the patient, and the corresponding encodings of adverse event symptoms (in Medical Dictionary for Regulatory Activities Preferred Terms) and seriousness were obtained. This encoding by experts was used as the reference to train and evaluate models, which contained input data processing and machine-learning natural language processing to learn and predict encodings. We developed and compared different approaches for data processing and classifiers. Performance was evaluated using receiver operating characteristic area under the curve (AUC), F-measure, sensitivity, specificity and positive predictive value. We used data from 26 Pharmacovigilance Centres for training and internal validation. External validation was performed using data from the remaining Pharmacovigilance Centres during the same period. RESULTS: Internal validation: for adverse drug reaction identification, Term Frequency-Inverse Document Frequency (TF-IDF) + Light Gradient Boosted Machine (LGBM) achieved an AUC of 0.97 and an F-measure of 0.80. The Cross-lingual Language Model (XLM) [transformer] obtained an AUC of 0.97 and an F-measure of 0.78. For seriousness assessment, FastText + LGBM achieved an AUC of 0.85 and an F-measure of 0.63. CamemBERT (transformer) + Light Gradient Boosted Machine obtained an AUC of 0.84 and an F-measure of 0.63. External validation for both adverse drug reaction identification and seriousness assessment tasks yielded consistent and robust results. CONCLUSIONS: Our artificial intelligence models showed promising performance to automatically code patient adverse drug reaction reports, with very similar results across approaches. Our system has been deployed by national health authorities in France since January 2021 to facilitate pharmacovigilance of COVID-19 vaccines. Further studies will be needed to validate the performance of the tool in real-life settings.
Published: 2022
Full Text: View/download PDF

29. Systematic analysis of drug-associated myocarditis reported in the World Health Organization pharmacovigilance database

Author: Lee S. Nguyen, Leslie T. Cooper, Mathieu Kerneis, Christian Funck-Brentano, Johanne Silvain, Nicolas Brechot, Guillaume Hekimian, Enrico Ammirati, Badr Ben M’Barek, Alban Redheuil, Estelle Gandjbakhch, Kevin Bihan, Bénédicte Lebrun-Vignes, Stephane Ederhy, Charles Dolladille, Javid J. Moslehi, Joe-Elie Salem, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CMC Ambroise Paré [Neuilly-sur-Seine], Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Mayo Clinic [Jacksonville], Groupe Action, Institut de cardiologie [CHU Pitié-Salpêtrière], Service de Réanimation Médicale [CHU Pitié-Salpétrière], Ospedale Niguarda, Service de Radiologie Polyvalente et Oncologique = Service d'Imagerie Spécialisées et des Urgences [CHU Pitié-Salpêtrière] (SISU), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Cardiologie [CHU Pitié-Salpêtrière], Département de Pharmacologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Vanderbilt University [Nashville], Gestionnaire, Hal Sorbonne Université, and Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN)
Subjects: Systems Analysis, Databases, Factual, Science, Cardiology, General Physics and Astronomy, Antineoplastic Agents, World Health Organization, Article, General Biochemistry, Genetics and Molecular Biology, Pharmacovigilance, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Adverse Drug Reaction Reporting Systems, Humans, Data Management, Multidisciplinary, Adverse effects, Bayes Theorem, General Chemistry, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Myocarditis, Cross-Sectional Studies, Pharmaceutical Preparations, Risk factors, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Immunotherapy, Antipsychotic Agents
Abstract: While multiple pharmacological drugs have been associated with myocarditis, temporal trends and overall mortality have not been reported. Here we report the spectrum and main features of 5108 reports of drug-induced myocarditis, in a worldwide pharmacovigilance analysis, comprising more than 21 million individual-case-safety reports from 1967 to 2020. Significant association between myocarditis and a suspected drug is assessed using disproportionality analyses, which use Bayesian information component estimates. Overall, we identify 62 drugs associated with myocarditis, 41 of which are categorized into 5 main pharmacological classes: antipsychotics (n = 3108 reports), salicylates (n = 340), antineoplastic-cytotoxics (n = 190), antineoplastic-immunotherapies (n = 538), and vaccines (n = 790). Thirty-eight (61.3%) drugs were not previously reported associated with myocarditis. Antipsychotic was the first (1979) and most reported class (n = 3018). In 2019, the two most reported classes were antipsychotics (54.7%) and immunotherapies (29.5%). Time-to-onset between treatment start and myocarditis is 15 [interquartile range: 10; 23] days. Subsequent mortality is 10.3% and differs between drug classes with immunotherapies the highest, 32.5% and salicylates the lowest, 2.6%. These elements highlight the diversity of presentations of myocarditis depending on drug class, and show the emerging role of antineoplastic drugs in the field of drug-induced myocarditis., Multiple drugs have been in the past associated with myocarditis. Here the authors perform a pharmacovigilance study and analyze 5108 reports of drug-induced myocarditis reporting temporal trends and overall mortality and identifying emerging drug classes among the treatments associated with myocarditis.
Published: 2022
Full Text: View/download PDF

30. Hospitalization for adverse events under abiraterone or enzalutamide exposure in real-world setting: a French population-based study on prostate cancer patients

Author: Boris Campillo-Gimenez, Emmanuel Oger, André Happe, Romain Mathieu, Lucie-Marie Scailteux, Fabien Despas, Sandrine Kerbrat, Sébastien Vincendeau, Emmanuel Nowak, Frédéric Balusson, CHU Pontchaillou [Rennes], Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Pharmaco-Épidémiologie des Produits de Santé (PEPS), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), French Drugs Agency, National Health Insurance, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], and Jonchère, Laurent
Subjects: Male, safety, medicine.medical_specialty, 030204 cardiovascular system & hematology, Rate ratio, QT interval, Brain Ischemia, 03 medical and health sciences, Prostate cancer, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, abiraterone, Atrial Fibrillation, Nitriles, Phenylthiohydantoin, Pharmacovigilance, medicine, Humans, Enzalutamide, castration-resistant prostate cancer, Pharmacology (medical), liver test monitoring, Adverse effect, Pharmacology, [SDV.IB] Life Sciences [q-bio]/Bioengineering, enzalutamide, business.industry, Atrial fibrillation, medicine.disease, adverse events, 3. Good health, Hospitalization, Stroke, Prostatic Neoplasms, Castration-Resistant, Treatment Outcome, chemistry, acute kidney injury, 030220 oncology & carcinogenesis, Heart failure, Benzamides, Androstenes, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business
Abstract: International audience; Aims - Safety profiles of abiraterone and enzalutamide rely mainly on Phase III clinical trials. Our objective was to estimate the incidence rate ratio (IRR) for certain adverse events leading in real life to hospitalization (atrial fibrillation, acute heart failure, ischaemic heart disease, acute kidney injury [AKI], ischaemic stroke, torsade de pointe/QT interval prolongation, hepatitis and seizure), comparing abiraterone to enzalutamide. We also set out to discuss previously identified safety signals. Method - Using the French National Health Insurance System database, all patients newly exposed to abiraterone or enzalutamide between 2013 and 2017 and followed until 31 December 2018 were targeted. IRRs for each event were estimated using a Poisson model in a sub-population of patients without contraindications or precautions for use for either treatment. Results - Among 11 534 new users of abiraterone and enzalutamide, AKI (IRR 1.42, 95% CI: 1.01-2.00), liver monitoring suggestive of hepatic damage (IRR 3.06, 95% CI: 2.66-3.53) and atrial fibrillation (IRR 1.12, 95% CI: 1.05-1.19) were significantly more often observed with abiraterone than with enzalutamide. Conclusion - Our study provides knowledge on abiraterone and enzalutamide real-life safety profiles, especially for events leading to hospitalization. Despite several limitations, including the lack of clinical data, the safety signal for AKI under abiraterone is in line with results of an analysis of the French pharmacovigilance database, which requires further specific investigations. Enlightening the clinicians' therapeutic choices for patients treated for prostate cancer, our study should lead to clinicians being cautious in the use of abiraterone.
Published: 2022
Full Text: View/download PDF

31. Immunomodulatory or/and immunosuppressive drugs should not avoid skin test for the assessment of drug allergy

Author: Dezoteux, F., El Mesbahi, S., Tedbirt, B., Grosjean, J., Gautier, S., Lannoy, D., Nassar, C., Tétart, F., Staumont‐Sallé, D., Département de Dermatologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), CHU de Rouen, Département d’informatique et d’information médicales, Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Centre Régional de PharmacoVigilance Nord-Pas-de-Calais [CHU Lille] (CRPV), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, CHU Lille, Institut de Pharmacie, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Abstract: International audience; The use of immunomodulatory and/or immunosuppressive therapy (IT) is increasingly common in the management of chronic inflammatory disease. Skin reactions to any drug (IT or not) are not rare in these patients, justifying allergological investigations. The influence of IT on allergological tests for drugs is not clearly described. IT cannot be interrupted due to the underlying disease. The data assessing the benefit and the safety of allergological test for drug allergy in patients under IT are missing.
Published: 2021
Full Text: View/download PDF

32. Psychotic Episode following Treatment with Hydroxychloroquine in a 17- Year-Old Female Adolescent with Cutaneous Lupus Erythematosus: A Drug Causality Supported by a Literature Review and a Worldwide Pharmacovigilance Database Search

Author: Miguel Hie, Bénédicte Lebrun-Vignes, David Cohen, Stéphane Barete, Cora Cravero, Julie Brunelle, Solène Spiers, Service de Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière] (SPEA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], Service de Dermatologie [CHU Pitié-Salpêtrière], Centre Hospitalier le Vinatier [Bron], Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Institut des Systèmes Intelligents et de Robotique (ISIR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière]
Subjects: Drug, medicine.medical_specialty, business.industry, Drug Imputability, media_common.quotation_subject, Hydroxychloroquine, Case Report, General Medicine, Female adolescent, Psychosis, Dermatology, Causality, 3. Good health, Suicide Attempt, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Pharmacovigilance, Cutaneous Lupus Erythematosus, Medicine, Database search engine, business, medicine.drug, media_common
Abstract: International audience; Background: Hydroxychloroquine (HCQ), a useful treatment for chronic dermatologic or rheumatologic diseases, has recently gathered widespread attention as a possible treatment for COVID-19 infection. However, its rare et severe neuropsychiatric side effects (NSE), such as psychosis and suicidal tendencies, are poorly documented, especially in youths.Case presentation: We present the first case on a 17-yearold girl of severe acute psychosis with a suicide attempt during HCQ treatment in association with thalidomide for chronic and refractory discoid lupus erythematosus. Drug causality was evaluated using the updated French causality assessment method. We performed a literature review and a worldwide pharmacovigilance database search on psychotic features after HCQ and thalidomide treatment. We found six cases in the literature and 53 cases (psychotic disorder: N=45, 3.7% and acute psychosis: N=8, 0.7%) in the pharmacovigilance database reporting the occurrence of psychotic symptoms under HCQ and none under thalidomide. The intrinsic and extrinsic imputability scores support the hypothesis that HCQ induced psychosis and suicide attempt in our patient. Withdrawing HCQ resulted in a dramatically improved situation, which remained perfectly stable after 3 years of follow-up.Conclusion: In HCQ-induced psychosis, recovery may be obtained with HCQ withdrawal, no future HCQ reintroduction, and, for the most serious manifestations, a short period of antipsychotic medication. Clinicians need to be aware of the NSE of HCQ and the appropriate interventions to be carried out.
Published: 2021
Full Text: View/download PDF

33. Anticancer drug-induced life-threatening ventricular arrhythmias: a World Health Organization pharmacovigilance study

Author: Javid Moslehi, Dan M. Roden, Christian Funck-Brentano, Paul Gougis, Bénédicte Lebrun-Vignes, Joe-Elie Salem, Stéphane Ederhy, Lee S. Nguyen, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe de REcherche en Cardio Oncologie [CHU Saint-Antoine] (GRC 27 GRECO), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Vanderbilt University School of Medicine [Nashville], Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CMC Ambroise Paré [Neuilly-sur-Seine], and Service de Cardiologie [CHU Saint-Antoine]
Subjects: medicine.medical_specialty, long QT, medicine.medical_treatment, Concordance, Torsades de pointes, Antineoplastic Agents, 030204 cardiovascular system & hematology, World Health Organization, Sudden death, QT interval, World health, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Torsades de Pointes, Neoplasms, Internal medicine, Pharmacovigilance, medicine, Adverse Drug Reaction Reporting Systems, Humans, Disproportionality analysis, business.industry, ventricular arrhythmias, Bayes Theorem, Immunotherapy, medicine.disease, 3. Good health, Clinical trial, Long QT Syndrome, anticancer drugs, 030220 oncology & carcinogenesis, pharmacovigilance, torsade de pointes, Cardiology and Cardiovascular Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Aims With the explosion of anticancer drugs, an emerging concern is the risk for drug-induced sudden death (SD) via ventricular arrhythmias (VA). Methods and results We used the international pharmacovigilance database VigiBase (n = 18 441 659 reports) to compare drug-induced long QT (diLQT, n = 18 123) and VA (n = 29 193) including torsade de pointes (TdP, n = 8163) reporting for 663 anticancer drugs vs. all other drugs until 01/01/2019. The analysis used the 95% lower-end credibility interval of the information component (IC025), an indicator for disproportionate Bayesian reporting; significant when IC025 >0. There were 2301 reports (13.8% fatal) for 40 anticancer drugs significantly associated with diLQT (with 27 also associated with VA or SD) and 9 drugs associated with VA without diLQT. Half of these (46.9%, 23/49) were associated with SD. Most (41%, 20/49) were kinase inhibitors, 8% (4/49) were hormonal therapies, 6% (3/49) were immunotherapies, 24% (12/49) were cytotoxics, and 20% (10/49) were miscellaneous. In VigiBase, reports of diLQT, TdP, or VA increased from 580 in the period 1967–83 to 15 070 in 2014–18 with the proportion related to anticancer drugs increasing from 0.9% (5/580) to 14.0% (2115/15 070) (P Conclusion This list of liable anticancer drugs may prove useful for physicians and regulatory authorities to re-evaluate cardiac monitoring requirements. Clinical trial registration NCT03530215.
Published: 2021
Full Text: View/download PDF

34. Transketolase of Staphylococcus aureus in the Control of Master Regulators of Stress Response During Infection

Author: Elodie Ramond, Xin Tan, Fabiola Tros, Jean-Philippe Barnier, Daniel Euphrasie, Jason Ziveri, Ivan Nemazanyy, Xavier Nassif, Anne Jamet, Baptiste Decaux-Tramoni, Alain Charbit, Marion Dupuis, Mathieu Coureuil, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Pathogénie des infections systémiques (Inserm U1002), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), SOGIP, SOGIP (ERC 249236)/Laboratoire d'Anthropologie des Institutions et des Organisations Sociales (IIAC-LAIOS), Institut interdisciplinaire d'anthropologie du contemporain (IIAC), École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Institut interdisciplinaire d'anthropologie du contemporain (IIAC), École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), U1002, Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Charbit, Alain
Subjects: 0301 basic medicine, Staphylococcus aureus, RNAIII, 030106 microbiology, Mutant, pentose phosphate pathway, Transketolase, Biology, Pentose phosphate pathway, Kidney, medicine.disease_cause, Microbiology, Mice, 03 medical and health sciences, Stress, Physiological, sigma B, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Transcription (biology), RpiRc, medicine, Animals, Humans, Metabolomics, Immunology and Allergy, Gene Silencing, Gene, ComputingMilieux_MISCELLANEOUS, Gene Expression Profiling, metabolic adaptation, Gene Expression Regulation, Bacterial, Staphylococcal Infections, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Carbon, 3. Good health, Disease Models, Animal, Phenotype, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030104 developmental biology, Infectious Diseases, Genes, Bacterial, Mutation, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, transketolase, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Intracellular, Signal Transduction
Abstract: Staphylococcus aureus is a leading cause of both acute and chronic infections in humans. The importance of the pentose phosphate pathway (PPP) during S. aureus infection is currently largely unexplored. In the current study, we focused on one key PPP enzyme, transketolase (TKT). We showed that inactivation of the unique gene encoding TKT activity in S. aureus USA300 (∆tkt) led to drastic metabolomic changes. Using time-lapse video imaging and mice infection, we observed a major defect of the ∆tkt strain compared with wild-type strain in early intracellular proliferation and in the ability to colonize kidneys. Transcriptional activity of the 2 master regulators sigma B and RpiRc was drastically reduced in the ∆tkt mutant during host cells invasion. The concomitant increased RNAIII transcription suggests that TKT—or a functional PPP—strongly influences the ability of S. aureus to proliferate within host cells by modulating key transcriptional regulators.
Published: 2019
Full Text: View/download PDF

35. Immune checkpoint inhibitor–associated hypophysitis—World Health Organisation VigiBase report analysis

Author: Elisa Guerrero, Anne Bachelot, Bénédicte Lebrun-Vignes, Douglas B. Johnson, Javid Moslehi, Joe-Elie Salem, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC Paris Est, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: Adult, Male, Cancer Research, Databases, Factual, Hypophysitis, [SDV]Life Sciences [q-bio], Immune checkpoint inhibitors, Programmed Cell Death 1 Receptor, MEDLINE, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, World Health Organization, B7-H1 Antigen, World health, Pharmacovigilance, Young Adult, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Humans, CTLA-4 Antigen, Young adult, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, biology, business.industry, Antibodies, Monoclonal, Middle Aged, medicine.disease, Ipilimumab, 3. Good health, Nivolumab, Oncology, 030220 oncology & carcinogenesis, Monoclonal, Immunology, biology.protein, Female, Antibody, business
Abstract: International audience
Published: 2019
Full Text: View/download PDF

36. Cells in urothelium tissue engineering

Author: N. Berte, P. Eschwege, Laurent Grossin, Astrid Pinzano, Pierre Gillet, J.L. Lemelle, C. Mazeaud, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), and Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine)
Subjects: Pathology, medicine.medical_specialty, Tissue engineering, Chemistry, [SDV]Life Sciences [q-bio], medicine, Urothelium, 3. Good health
Abstract: International audience; Urothelium is a highly specialized epithelium covering the entire urinary excretory system. Tissue engineering of this urinary tract may allow to consider its reconstruction to perform in vitro studies or in vivo replacement. Therefore, the question of specific reconstruction of the urothelium arises in order to guarantee the neotissue’s ability to act as a barrier against highly cytotoxic urine. This literature review describes the different cell types and strategies available for this reconstruction. The non-reconstruction of urothelium relies on the colonization of a biomaterial by the adjacent healthy tissue but allows only incomplete reconstruction and fibrosis. The use of autologous urothelial cells requires preliminary surgery and has not been successful enough in humans. Research has therefore focused on the use of stem cells. Adipose Derived Stem Cells (ADSCs) and Bone Marrow Derived Stem Cells (BMSCs) allow the reconstruction of the smooth muscle layer, but have little effect on urothelium reconstruction. Urine Derived Stem Cells (UDSCs) and Bladder mesenchymal Stem Cells (BSCs) are very promising because they allow the achievement of a differentiated urothelium. Induced Pluripotent Stem Cells (IPSCs) and Embryonic Stem Cells (ESCs) can be differentiated towards urothelial phenotype but their use is restricted by ethics.
Published: 2021
Full Text: View/download PDF

37. Ultrasound-guided catheterization and infectious risk in obese ICU patients

Author: Jean-François Timsit, Nicolas Mongardon, Niccolò Buetti, Jean-Jacques Parienti, Olivier Mimoz, Université de Paris, IAME, INSERM, Paris, France, Infection Control Programme and WHO Collaborating Centre on Patient Safety, University of Geneva [Switzerland], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), département d'anesthésiologie, Foie ICU, AP-HP GH Henri Mondor, Créteil, France, Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Régional de Pharmacovigilance [Hôpital Charles Nicolle, Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de contrôle infectieux [Bichat Claude Bernard], AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: medicine.medical_specialty, Icu patients, business.industry, Pain medicine, [SDV]Life Sciences [q-bio], 030231 tropical medicine, MEDLINE, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Critical Care and Intensive Care Medicine, Ultrasound guided, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology, Emergency medicine, medicine, Infectious risk, 030212 general & internal medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021
Full Text: View/download PDF

38. Influence of the Obesity Phenotype on the Adequacy of Antibiotic Prophylaxis with Cefoxitin for Obese Patients Undergoing Bariatric Surgery: Lessons Learnt and Future Considerations

Author: Julien Scala-Bertola, Amandine Luc, Jeffrey Lipman, Emmanuel Novy, Thibaut Belveyre, Mathieu Esposito, Service d'Anesthésiologie et de Soins Intensifs [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine), CRHU Nancy, and University of Queensland [Brisbane]
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Bariatric Surgery, 030226 pharmacology & pharmacy, Body Mass Index, Cohort Studies, 03 medical and health sciences, Cefoxitin, 0302 clinical medicine, Sex Factors, Pharmacokinetics, Tandem Mass Spectrometry, medicine, Humans, Pharmacology (medical), Obesity, Prospective Studies, Antibiotic prophylaxis, education, ComputingMilieux_MISCELLANEOUS, Chromatography, High Pressure Liquid, Pharmacology, Metabolic Syndrome, education.field_of_study, business.industry, Antibiotic Prophylaxis, Middle Aged, medicine.disease, 3. Good health, Surgery, Anti-Bacterial Agents, Phenotype, 030220 oncology & carcinogenesis, Pharmacodynamics, Lean body mass, Female, Metabolic syndrome, business, medicine.drug
Abstract: A high inter-individual variability in pharmacokinetic parameters in obese patients is observed. The objective of this study was to evaluate the effect of obesity parameters on the pharmacokinetics of cefoxitin administered for antibiotic prophylaxis during bariatric surgery. This a secondary analysis of a pharmacokinetic study involving 174 obese patients scheduled for bariatric surgery and receiving a 4-g dose of cefoxitin. Blood samples were collected at incision and wound closure. The total plasma concentrations were assessed utilising a validated high-performance liquid chromatography–tandem mass spectrometry method. The pharmacokinetic and pharmacodynamic target was defined as an estimated free concentration of cefoxitin at the time of wound closure >8 mg/L. Specific evaluated obesity parameters were fat body mass, fat body mass/height2, lean body mass, lean body mass/height2, visceral adipose tissue and presence of a metabolic syndrome. A total of 174 patients (median age 47 years) with a majority of women (75.3%) and a median BMI of 44 kg/m2 were analysed. The percentage of patients who met the pharmacokinetic and pharmacodynamic target was 85.1%. In the whole population, a tendency to fail to reach the target was observed with a higher lean mass over height2 [OR = 0.79; 95% CI (0.62–1.01); P = 0.060]. In the female subgroup, higher lean mass over height2 [OR = 0.63; 95% CI (0.41–0.97); P = 0.037] and the presence of a metabolic syndrome [OR = 0.17; 95% CI (0.03–0.83); P = 0.030] were associated with failure to reach the pharmacokinetic and pharmacodynamic target. Obese patients with a higher lean mass and a metabolic syndrome could constitute a subgroup at risk for cefoxitin under-dosage.
Published: 2021
Full Text: View/download PDF

39. Obesity and risk of catheter-related infections in the ICU. A post hoc analysis of four large randomized controlled trials

Author: Ambre Loiodice, Jean-Christophe Lucet, Stéphane Ruckly, Jean-François Timsit, Niccolò Buetti, Nicolas Mongardon, Leonard A. Mermel, Olivier Mimoz, Bertrand Souweine, Jean-Jacques Parienti, Université de Paris, IAME, INSERM, Paris, France, Infection Control Programme and WHO Collaborating Centre on Patient Safety, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Rhode Island Hospital [Providence, RI, États-Unis], Warren Alpert Medical School of Brown University, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), département d'anesthésiologie, Foie ICU, AP-HP GH Henri Mondor, Créteil, France, Unité de contrôle infectieux [Bichat Claude Bernard], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Régional de Pharmacovigilance [Hôpital Charles Nicolle, Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Services de Maladies Infectieuses et Tropicales [CHU Bichat]
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, BMI, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Post-hoc analysis, Medicine, 030212 general & internal medicine, Obesity, education, 2. Zero hunger, education.field_of_study, Catheter-related infections, business.industry, Hazard ratio, 030208 emergency & critical care medicine, Dialysis catheter, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Intensive care unit, Intravascular catheter infections, 3. Good health, Catheter, Catheter-related bloodstream infections, business, Body mass index
Abstract: International audience; Purpose: Obesity increases the risk of nosocomial infection, but data regarding the role of body mass index (BMI) in catheter related infections are scarce. We used the data gathered from four randomized, controlled trials (RCTs) to investigate the association between body mass index (BMI) and intravascular catheter infections in critically ill obese patients.Methods: Adult obese patients who required short-term central venous, arterial or dialysis catheter insertion in the intensive care unit (ICU) were analyzed. The association between BMI and major catheter-related infection (MCRI), catheter-related bloodstream infection (CRBSI) and catheter tip colonization was estimated using univariate and multivariate marginal Cox models. Exploratory analysis using dressing disruptions was added.Results: A total of 2282 obese patients and 4275 catheters from 32 centers were included in this post-hoc analysis. Overall, 66 (1.5%) MCRI, 43 (1%) CRBSI and 399 (9.3%) catheter colonizations were identified. The hazard ratio (HR) for MCRI, CRBSI and colonization increased with BMI. After adjustment for well-known infection risk factors, the BMI ≥ 40 group had an increased risk for MCRI (HR 1.88, 95% CI 1.13-3.12, p = 0.015), CRBSI (HR 2.19, 95% CI 1.19-4.04, p = 0.012) and colonization (HR 1.44, 95% CI 1.12-1.84, p = 0.0038) compared to the BMI < 40 group. The mean dressing disruption per catheter was increased in the BMI ≥ 40 group (2.03 versus 1.68 in the BMI < 40 group, p = 0.05).Conclusions: Using the largest dataset ever collected from large multicentric RCTs, we showed that patients with BMI ≥ 40 had an increased risk for intravascular catheter infections. Targeted prevention measures should focus on this population with a particular attention to catheter care and dressing disruption.
Published: 2021
Full Text: View/download PDF

40. Poor assessment of bone mineral density after a forearm fracture in women aged 50 years or older: Data from a French health insurance database

Author: Delphine Chu Miow Lin, Denis Mulleman, Philippe Goupille, Emmanuel Oger, André Happe, Elsa Cattelain-Lopez, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Pontchaillou [Rennes], This work was supported by grants from the Osteoporosis research and information group (GRIO – Groupe de recherche et d’information sur les ostéoporoses) in 2013 and the French league against rheumatism (AFLAR – Association française de lutte anti-rhumatismale) in 2014., Université de Tours, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)
Subjects: medicine.medical_specialty, MEDLINE, 030209 endocrinology & metabolism, 03 medical and health sciences, Fractures, Bone, 0302 clinical medicine, Absorptiometry, Photon, Rheumatology, Bone Density, medicine, Humans, Osteoporosis, Postmenopausal, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, Bone mineral, Insurance, Health, business.industry, Health insurance database, 3. Good health, Forearm, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Physical therapy, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Forearm fracture, business
Abstract: International audience
Published: 2021
Full Text: View/download PDF

41. Spontaneous Reports of Serious Adverse Drug Reactions Resulting From Drug–Drug Interactions: An Analysis From the French Pharmacovigilance Database

Author: Louis, Létinier, Amandine, Ferreira, Alexandre, Marceron, Marina, Babin, Joëlle, Micallef, Ghada, Miremont-Salamé, Antoine, Pariente, Otten, Lisa, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Institut de Neurosciences des Systèmes (INS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)
Subjects: Pharmacology, hemorrhages, immune system diseases, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, pharmacovigilance, adverse drug reaction, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, virus diseases, spontaneous reporting, drug–drug interaction, antithrombotic agents, drug-drug interaction, Original Research
Abstract: International audience; Few data are available on the clinical impact of drug–drug interactions (DDIs). Most of the studies are limited to the analysis of exposure to potential DDI or the targeted impact of the combination of a few drugs or therapeutic classes. The analysis of adverse drug reaction (ADR) reports could be a mean to study generally the adverse effects identified due to a DDI. Our objective was to describe the characteristics of ADRs resulting from DDIs reported to the French Pharmacovigilance system and to identify the drugs most often implicated in these ADRs. Considering all ADR reports from January 01, 2012, to December 31, 2016, we identified all cases of ADR resulting from a DDI (DDI-ADRs). We then described these in terms of patients’ characteristics, ADR seriousness, drugs involved (two or more per case), and ADR type. Of the 4,027 reports relating to DDI-ADRs, 3,303 were related to serious ADRs. Patients with serious DDI-ADRs had a median age of 76 years (interquartile range: 63–84); 53% were male. Of all serious DDI-ADRs, 11% were life-threatening and 8% fatal. In 36% of cases, the DDI causing the ADR involved at least three drugs. Overall, 8,424 different drugs were mentioned in the 3,303 serious DDI-ADRs considered. Altogether, drugs from the “antithrombotic agents” subgroup were incriminated in 34% of serious DDI-ADRs. Antidepressants were the second most represented therapeutic/pharmacological subgroup (5% of serious DDI-ADRs). Among the 3,843 ADR types reported in the 3,303 serious DDI-ADRs considered, the most frequently represented were hemorrhage (40% clinical hemorrhage; 6% biological hemorrhage), renal failure (8%), pharmacokinetic alteration (5%), and cardiac arrhythmias (4%). Hemorrhagic accidents are still an important part of serious ADRs resulting from DDIs reported in France. The other clinical consequences of DDIs seem less well identified by pharmacovigilance. Moreover, more than one-third of serious DDI-ADRs involved at least three drugs.
Published: 2021
Full Text: View/download PDF

42. Association of Antihypertensive Agents with the Risk of In-Hospital Death in Patients with Covid-19

Author: Elisa Salamanca, Nathanaël Beeker, Elisabeth Polard, Jean-Marc Treluyer, Bastien Rance, Anita Burgun, Nicolas Garcelon, Laurent Chouchana, Nicolas Paris, Antoine Neuraz, Département de Pharmacologie Clinique [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de recherche clinique / Centre d'investigation clinique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Régional de Pharmacovigilance [Rennes] (CRPV), CHU Pontchaillou [Rennes], Service d'informatique médicale et biostatistiques [CHU Necker], AP-HP/Universities/Inserm COVID-19 research collaboration, AP-HP Covid CDR Initiative, and 'Entrepôt de Données de Santé' AP-HP Consortium': Pierre-Yves Ancel, Alain Bauchet, Nathanaël Beeker, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Breant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Judith Leblanc, Leo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurelien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Bastien Rance, Helene Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien Van Gysel, Gaël Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal, Neuraz, Antoine, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE)
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, [INFO.INFO-RO] Computer Science [cs]/Operations Research [cs.RO], Coronavirus disease 2019 (COVID-19), Hospitalized patients, Short Communication, Population, Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, Angiotensin Receptor Antagonists, 0302 clinical medicine, Renin-angiotensin-aldosterone inhibitors, Internal medicine, Risk of mortality, medicine, Humans, Pharmacology (medical), In patient, Hospital Mortality, Drug safety, education, Antihypertensive Agents, Aged, Retrospective Studies, Pharmacology, In hospital death, education.field_of_study, SARS-CoV-2, business.industry, COVID-19, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], General Medicine, Calcium Channel Blockers, 3. Good health, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Hypertension, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Angiotensin Receptor Blockers, Cardiology and Cardiovascular Medicine, business, Cohort study
Abstract: Purpose The role of angiotensin receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACEi), or other antihypertensive agents in the case of Covid-19 remains controversial. We aimed to investigate the association between antihypertensive agent exposure and in-hospital mortality in patients with Covid-19. Methods We performed a retrospective multicenter cohort study on patients hospitalized between February 1 and May 15, 2020. All patients had been followed up for at least 30 days. Results Of the 8078 hospitalized patients for Covid-19, 3686 (45.6%) had hypertension and were included in the study. In this population, the median age was 75.4 (IQR, 21.5) years and 57.1% were male. Overall in-hospital 30-day mortality was 23.1%. The main antihypertensive pharmacological classes used were calcium channel blockers (CCB) (n=1624, 44.1%), beta-blockers (n=1389, 37.7%), ARB (n=1154, 31.3%), and ACEi (n=998, 27.1%). The risk of mortality was lower in CCB (aOR, 0.83 [0.70–0.99]) and beta-blockers (aOR, 0.80 [0.67–0.95]) users and non-significant in ARB (aOR, 0.88 [0.72–1.06]) and ACEi (aOR, 0.83 [0.68–1.02]) users, compared to non-users. These results remain consistent for patients receiving CCB, beta-blocker, or ARB as monotherapies. Conclusion This large multicenter retrospective of Covid-19 patients with hypertension found a reduced mortality among CCB and beta-blockers users, suggesting a putative protective effect. Our findings did not show any association between the use of renin-angiotensin-aldosterone system inhibitors and the risk of in-hospital death. Although they need to be confirmed in further studies, these results support the continuation of antihypertensive agents in patients with Covid-19, in line with the current guidelines. Supplementary Information The online version contains supplementary material available at 10.1007/s10557-021-07155-5.
Published: 2021
Full Text: View/download PDF

43. Drug adulteration of sexual enhancement supplements: a worldwide insidious public health threat

Author: Melissa Yelehe-Okouma, Elise Pape, Lisa Humbertjean, Nadine Petitpain, Julien Scala-Bertola, Marion Evrard, Pierre Gillet, Rabih El Osta, Souleiman El Balkhi, Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Poison control, Global Health, 030226 pharmacology & pharmacy, Suicide prevention, Occupational safety and health, Tadalafil, 03 medical and health sciences, 0302 clinical medicine, Erectile Dysfunction, Injury prevention, Humans, Medicine, Pharmacology (medical), Intensive care medicine, Adverse effect, ComputingMilieux_MISCELLANEOUS, Marketing, Pharmacology, business.industry, Public health, Human factors and ergonomics, Drug Adulteration, 3. Good health, Dietary Supplements, Public Health, Drug Contamination, business, 030217 neurology & neurosurgery
Abstract: Worldwide, the consumption of dietary supplements for the enhancement of sexual performance is common. Consumers are generally fond of these products because they often want to avoid drugs, preferring "natural" than "chemical" solutions. This is challenging, as many of these supplements labelled "herbal" or "natural" are actually adulterated with drugs, mainly phosphodiesterase-5 inhibitors. This phenomenon is facilitated by fewer demanding regulations for marketing supplements. Thus, consumers may be widely exposed to serious adverse events, such as acute liver injury, kidney failure, pulmonary embolism, stroke or even death. We aim to warn physicians about this issue. This multidisciplinary review simultaneously deals with clinical consequences of this phenomenon, analytical toxicology, and regulation. Indeed, after outlining this worldwide issue and highlighting that a drug-adulterated dietary supplement is actually a falsified drug, we discuss its main contributing factors. Then, we describe some examples of adverse events of which a case of sildenafil-tadalafil-induced ischaemic stroke that benefited medical care in our hospital. Furthermore, we present some means to avoid adulteration and discuss their limitations that may be explained by the heterogeneity of the regulation of dietary supplements between countries. Doing so, we point out the requirement of a global harmonization of this regulation for an efficient eradication of this public health threat. Meanwhile, dietary supplements should be considered adulterated until proven otherwise. Thus, we encourage physicians to investigate these products in the drug histories of their patients, especially when clinical conditions cannot be explained by classical aetiologies.
Published: 2021
Full Text: View/download PDF

44. Outcome of patients hospitalized for Covid‐19 and exposure to angiotensin‐converting enzyme inhibitors and angiotensin‐receptor blockers in France: Results of the ACECoV study

Author: Guillaume Moulis, Guillaume Martin-Blondel, Sandrine Charpentier, Agnès Sommet, Pierre Delobel, Margaux Lafaurie, Service de Pharmacologie Médicale et Clinique, CHU Toulouse [Toulouse]-Centre d'Investigation Clinique, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et tropicales [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service des Urgences (TOULOUSE - Urgences), Service de Médecine Interne [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre régional de pharmacovigilance de Grenoble [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service Pharmacologie Clinique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and PINIER, CHRISTINE
Subjects: Male, MESH: Hypertension / complications, pharmacoepidemiology, MESH: COVID-19 / drug therapy, Angiotensin-Converting Enzyme Inhibitors, MESH: Hospitalization, Disease, 030226 pharmacology & pharmacy, SARS‐CoV‐2, law.invention, Cohort Studies, MESH: Aged, 80 and over, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: COVID-19 / enzymology, Pharmacology (medical), MESH: Respiration, Artificial, MESH: Cohort Studies, MESH: Cardiovascular Diseases / complications, ComputingMilieux_MISCELLANEOUS, MESH: Treatment Outcome, Aged, 80 and over, education.field_of_study, Angiotensin Receptor Antagonists, biology, MESH: Peptidyl-Dipeptidase A / drug effects, Intensive care unit, 3. Good health, Hospitalization, MESH: Peptidyl-Dipeptidase A / metabolism, MESH: Angiotensin Receptor Antagonists / adverse effects, Treatment Outcome, Cardiovascular Diseases, Cohort, Hypertension, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Population study, Female, angiotensin‐receptor blockers, France, medicine.symptom, medicine.medical_specialty, Angiotensins, Critical Care, MESH: COVID-19 / mortality, Population, Subgroup analysis, Inflammation, Peptidyl-Dipeptidase A, MESH: Angiotensin-Converting Enzyme Inhibitors / adverse effects, angiotensin‐converting enzyme inhibitors, 03 medical and health sciences, MESH: Critical Care, COVID‐19, Internal medicine, Renin–angiotensin system, medicine, Humans, cardiovascular diseases, education, Propensity Score, Aged, Pharmacology, MESH: Humans, SARS-CoV-2, business.industry, COVID-19, Angiotensin-converting enzyme, MESH: Propensity Score, medicine.disease, Respiration, Artificial, MESH: Male, Discontinuation, COVID-19 Drug Treatment, MESH: France, Blood pressure, Heart failure, Propensity score matching, biology.protein, business, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; Data are lacking on the impact of ACEI/ARB exposure on unfavorable outcome in the population of patients hospitalized for COVID‐19 with hypertension/cardiovascular disease, particularly in Europe. The ACE‐CoV study was designed to assess this question. The study was conducted in the Covid‐Clinic‐Toul cohort, which contains data about all patients hospitalized at Toulouse University hospital, France with a SARS‐CoV‐2 infection since March, 2020. We selected the patients with a history of cardiovascular disease (heart failure or coronary disease) and/or arterial hypertension. We conducted a subgroup analysis in patients with arterial hypertension. ACEI/ARB exposures at admission were assessed. The outcome was composite: admission to intensive care unit, need of mechanical ventilation or death during the 14 days after admission to hospital. We used logistic regression models with propensity scores (PS) weighted by overlap weighting (OW) and inverse probability of treatment weighting (IPTW). Between March 2020 and April 20, 2020, the Covid‐Clinic‐Toul included 263 patients. Among them, 111 were included in the ACE‐CoV study population. In OW‐PS‐adjusted analyses, the association of exposure to ACEIs or ARBs with outcome occurrence was OR: 1.56 (95% CI: 0.73–3.33). It was 0.99 (95% CI: 0.68–1.45) for ACEIs and 1.64 (95% CI: 0.77–3.50) for ARBs. Analyses with weighting by the IPTW‐PS method gave similar results. Results were similar when considering the subgroup of patients with arterial hypertension. The ACE‐CoV study found no association between exposure to ACEIs or ARBs and unfavorable outcome in hospitalized patients for COVID‐19 with a history of cardiovascular disease/arterial hypertension.
Published: 2021
Full Text: View/download PDF

45. COMBINATION OF AMOXICILLIN/CLAVULANATE AND PREDNISOLONE IN SEVERE ALCOHOLIC HEPATITIS: RESULTS OF THE ANTIBIOCOR RANDOMIZED CONTROLLED TRIAL

Author: Louvet, Alexandre, Labreuche, Julien, Dao, Thong, Thevenot, Thierry, Oberti, Frederic, Bureau, Christophe, Paupard, Thierry, Nguyen-Khac, Eric, Franza, Anne Minello, Chabert, Brigitte Bernard, Anty, Rodolphe, Wartel, Faustine, Carbonell, Nicolas, Pageaux, Georges-Philippe, Leroy, Vincent, Legros, Ludivine, Nahon, Pierre, Potey, Camille, Duhamel, Alain, Mathurin, Philippe, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Toulouse [Toulouse], Centre Hospitalier de Dunkerque, Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre d'Endoscopie Digestive [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pontchaillou [Rennes], Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de PharmacoVigilance Nord-Pas-de-Calais [CHU Lille] (CRPV), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Faculté de Médecine Henri Warembourg - Université de Lille, Physiopathologie des Maladies Inflammatoires de l'Intestin, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

46. Atypical thrombosis associated with VaxZevria (R) (AstraZeneca) vaccine: Data from the French Network of Regional Pharmacovigilance Centres

Author: Anthony Bron, Joëlle Micallef, Nathalie Massy, Thomas Geeraerts, Thierry Vial, Francesco Salvo, Hugo Laujin, Mariette Baud, Sophie Liabeuf, Marie Blanche Valnet-Rabier, Marie Girot, Céline Mounier, Antoine El Kaddissi, Antoine Pariente, Mehdi Benkebil, Justine Perez, Kamel Masmoudi, Jean François Albucher, Sophie Gautier, François Montastruc, Annie Pierre Jonville-Béra, Aurélie Grandvuillemin, Evelyne Massardier, Nicolas Raposo, Charlène Boulay, Valérie Gras-Champel, CHU Amiens-Picardie, Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Agence nationale de sécurité du médicament et des produits de santé [Saint-Denis] (ANSM), CHU Rouen, Normandie Université (NU), Hôpital JeanMinjoz, CHU Lille, Toulouse Neuro Imaging Center (ToNIC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Roger Salengro [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Aix Marseille Université (AMU), CHU Marseille, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Centre régional de pharmacovigilance de Grenoble [CHU Grenoble], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), French Network of Pharmacovigilance Centres, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-21-CO17-0001,Vigi-Drugs COVID-19,Identification précoce du risque associé aux médicaments utilisés dans le cadre de COVID-19 : analyse des données mondiales de pharmacovigilance(2021), DESSAIVRE, Louise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: 2019-20 coronavirus outbreak, Time Factors, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Letter to Editor, Antiviral Agents, Pharmacovigilance, medicine, Adverse Drug Reaction Reporting Systems, Humans, Pharmacology (medical), Pandemics, ComputingMilieux_MISCELLANEOUS, Covid-19 vaccine, SARS-CoV-2, business.industry, COVID-19, VaxZevria®, medicine.disease, Atypical thrombosis, Thrombosis, Virology, [SDV] Life Sciences [q-bio], Anti-PF4 antibodies, France, business, Thrombopenia
Abstract: The current COVID-19 pandemic is an exceptional health situation including for drug use. As there was no known effective drug for COVID-19 at the beginning of the pandemic, different candidates were proposed. In this short article, we present the French public pharmacovigilance activities during this health crisis. Although COVID-19 is a confounding factor per se, owing to its potential for multi-organ damage including the heart and kidney, the quality of the transmitted data in adverse drug reaction reports, the timeliness of feedback from clinicians, and the real-time pharmacological and medical analysis by the French network of the regional pharmacovigilance centers made it possible to swiftly identify relevant safety signals. The French National Agency of Medicine was thus able to validate the data and convey their findings very early. This decentralized organization based on medical and pharmacological evaluation of case reports has proven to be efficient and responsive in this unique and challenging healthcare emergency.
Published: 2021
Full Text: View/download PDF

47. Risk Factors for Mortality after COVID-19 in Patients with Preexisting Interstitial Lung Disease

Author: Sylvain Marchand-Adam, Romain Lazor, Vincent Cottin, Yurdagul Uzunhan, Dominique Israel-Biet, Pierre Rigaud, Victor Valentin, Raphael Borie, Sandrine Hirschi, Laure Gallay, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Lausanne (UNIL), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Régional de PharmacoVigilance Nord-Pas-de-Calais [CHU Lille] (CRPV), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, 0302 clinical medicine, Aged, Aged, 80 and over, COVID-19/complications, COVID-19/mortality, Case-Control Studies, Female, France/epidemiology, Humans, Lung Diseases, Interstitial/complications, Middle Aged, Proportional Hazards Models, Retrospective Studies, Risk Factors, Fibrosis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Correspondence, medicine, In patient, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Proportional hazards model, business.industry, Interstitial lung disease, Case-control study, COVID-19, Retrospective cohort study, medicine.disease, 3. Good health, 030228 respiratory system, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Lung Diseases, Interstitial, business
Abstract: International audience
Published: 2021
Full Text: View/download PDF

48. Triptans and SCAD:An Analysis From the WHO Pharmacovigilance Database

Author: Perez, Justine, Lepelley, Marion, Revol, Bruno, Roustit, Mathieu, Cracowski, Jean Luc, Khouri, Charles, Centre régional de pharmacovigilance de Grenoble [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), and ANR-19-P3IA-0003,MIAI,MIAI @ Grenoble Alpes(2019)
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

49. Combination of amoxicillin/clavulanate and prednisolone in severe alcoholic hepatitis: results of the randomized controlled trial Antibiocor

Author: Louvet, Alexandre, Labreuche, Julien, Dao, Thong, Thevenot, Thierry, Oberti, Frederic, Bureau, Christophe, Paupard, Thierry, Nguyen-Khac, Eric, Franza, Anne Minello, Chabert, Brigitte Bernard, Anty, Rodolphe, Wartel, Faustine, Carbonell, Nicolas, Pageaux, Georges-Philippe, Leroy, Vincent, Legros, Ludivine, Nahon, Pierre, Potey, Camille, Duhamel, Alain, Mathurin, Philippe, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier de Dunkerque, Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pontchaillou [Rennes], Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de PharmacoVigilance Nord-Pas-de-Calais [CHU Lille] (CRPV), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Faculté de Médecine Henri Warembourg - Université de Lille, Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, and DESSAIVRE, Louise
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

50. Néphrotoxicité en pédiatrie

Author: Pierre Cochat, J Bacchetta, M Auffret, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: 03 medical and health sciences, [SCCO]Cognitive science, 0302 clinical medicine, 030225 pediatrics, Pediatrics, Perinatology and Child Health, 030232 urology & nephrology, 3. Good health
Abstract: Resume L’elimination des medicaments est essentiellement renale et hepatique, et 75 % des medicaments sont principalement elimines par les reins. La nephrotoxicite en pediatrie concerne surtout les medicaments, mais il est important de connaitre d’autres types de nephrotoxicite non medicamenteux, par ingestion accidentelle ou volontaire, ou par contact, avec des produits chimiques, des toxines environnementales, des drogues, des vegetaux ou des animaux. La nephrotoxicite peut etre aigue ou chronique, dose-dependante ou -independante, et peut atteindre tous les compartiments fonctionnels du rein, meme si la necrose tubulaire aigue est le mecanisme le plus frequemment observe. Chez l’enfant, les informations sont souvent extrapolees des observations faites chez l’adulte et parfois a partir de l’experimentation animale ; il importe donc de preciser les particularites de la nephrotoxicite en pediatrie, qui subissent des variations considerables entre la periode fœtale et l’adolescence. Nous proposons donc une mise au point sur la nephrotoxicite en pediatrie, avec des rappels de physiopathologie, le rappel des grandes situations de nephrotoxicite medicamenteuse, et enfin un expose des situations les plus frequentes de nephrotoxicite non medicamenteuse.
Published: 2020
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

926 results on '"Centre régional de pharmacovigilance"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources