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155 results on '"Centre d'investigation clinique de Toulouse (CIC 1436)"'

1. Revision of expert panel's guidelines on postoperative pain management

Author: Michel Olivier, Nada Sabourdin, Valeria Martinez, Karine Nouette-Gaulain, Anissa Belbachir, Frédéric Aubrun, Christophe Dadure, Gilles Lebuffe, Paul Zetlaoui, Hélène Beloeil, Michel Carles, Philippe Cuvillon, Dominique Fletcher, Emmanuel Marret, Hospices Civils de Lyon (HCL), Service de Réanimation Médicale [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Hôpital Raymond Poincaré [AP-HP], Service de réanimation médicale polyvalente [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut hospitalier Franco-Britannique [Levallois-Perret], Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Lille, Université de Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - EA 7365, Hôpital de la Croix-Rousse [CHU - HCL], CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Nice [CHU Nice], Hôpital Universitaire Carémeau [Nîmes] [CHU Nîmes], CHU Montpellier, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA], Hôpital Beaujon [AP-HP], and Centre d'investigation clinique de Toulouse [CIC 1436]
Subjects: Adult, medicine.medical_specialty, Adolescent, Postoperative pain, Vulnerability, Hemorrhage, Regional anaesthesia, Critical Care and Intensive Care Medicine, Dexamethasone, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, 030202 anesthesiology, Catheterization, Peripheral, medicine, Update of experts'' guidelines, Humans, Pain Management, Drug Interactions, Child, Intensive care medicine, Monitoring, Physiologic, Pain Measurement, Analgesics, Pain, Postoperative, business.industry, Update of experts’ guidelines, Drug Administration Routes, Anti-Inflammatory Agents, Non-Steroidal, Contraindications, Drug, Infant, Newborn, Infant, Lidocaine, 030208 emergency & critical care medicine, General Medicine, Perioperative, 3. Good health, Analgesia, Epidural, Analgesics, Opioid, Anesthesiology and Pain Medicine, Child, Preschool, Ketamine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The French Society of Anaesthesia and Intensive Care Medicine (SFAR) published experts' guidelines on the care of postoperative pain. This was an update of the 2008 guidelines. Fourteen experts analysed the literature (PubMed™, Cochrane™) on questions that had not been treated in the previous guidelines, or to modify the guidelines following new data in the published literature. The used method is invariably the GRADE© method, which guarantees a rigorous work. Seventeen recommendations were formalised on the assessment of perioperative pain, and most particularly in non-communicating patients, on opioid and non-opioid analgesics and on anti-hyperalgesic drugs, such as ketamine and gabapentinoids, as well as on local and regional anaesthesia. The concept of vulnerability and therefore the identification of the most fragile patients in terms of analgesics requirements were specified. Because of the absence of sufficient data or new information, no recommendation was made about analgesia monitoring, the procedures for the surveillance of patients in conventional care structures, or perinervous or epidural catheterism.
Published: 2019
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2. Design of Anti-infectious Agents from Lawsone in a Three-Component Reaction with Aldehydes and Isocyanides

Author: Christina L. Koumpoura, Michel Nguyen, Christian Bijani, Laure Vendier, Elena G. Salina, Silvia Buroni, Giulia Degiacomi, Sandrine Cojean, Philippe M. Loiseau, Françoise Benoit-Vical, Alfonso T. García-Sosa, null Anne Robert, Michel Baltas, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), New Antimalarial Molecules and Pharmacological Approaches (ERL1289), Centre d'investigation clinique de Toulouse (CIC 1436), 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)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Université Toulouse III - Paul Sabatier (UT3), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Russian Academy of Sciences [Moscow] (RAS), Dipartimento di Biologia e Biotecnologie 'Lazzaro Spallanzani' = Department of Biology and Biotechnology [Univ di Pavia] (DBB UNIPV), Università degli Studi di Pavia = University of Pavia (UNIPV), Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), University of Tartu, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier, Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation pour la Recherche Médicale (FRM), Paris Saclay University, Estonian Research Council, Italian Ministry of Education, University and Research (MIUR), University of Pavia, Gulli, Marie-Hélène, Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and 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]
Subjects: Aldehydes, Inorganic carbon compounds, General Chemical Engineering, Multicomponent reactions, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Reaction products, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, General Chemistry, Carbon
Abstract: International audience; The first effective synthetic approach to naphthofuroquinones via a reaction involving lawsone, various aldehydes, and three isocyanides under microwave irradiation afforded derivatives in moderate to good yields. In addition, for less-reactive aldehydes, two naphtho-enaminodione quinones were obtained for the first time, as result of condensation between lawsone and isocyanides. X-ray structure determination for 9 and 2D-NMR spectra of 28 confirmed the obtained structures. All compounds were evaluated for their anti-infectious activities against Plasmodium falciparum, Leishmania donovani, and Mycobacterium tuberculosis. Among the naphthofuroquinone series, 17 exhibited comparatively the best activity against P. falciparum (IC50 = 2.5 μM) and M. tuberculosis (MIC = 9 μM) with better (P. falciparum) or equivalent (M. tuberculosis) values to already-known naphthofuroquinone compounds. Among the two naphtho-enaminodione quinones, 28 exhibited a moderate activity against P. falciparum with a good selectivity index (SI > 36) while also a very high potency against L. donovani (IC50 = 3.5 μM and SI > 28), rendering it very competitive to the reference drug miltefosine. All compounds were studied through molecular modeling on their potential targets for P. falciparum, Pfbc1, and PfDHODH, where 17 showed the most favorable interactions.
Published: 2022
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3. Progressive multifocal leukoencephalopathy: epidemiology and spectrum of predisposing conditions

Author: Marine Joly, Cécile Conte, Charles Cazanave, Vincent Le Moing, Pierre Tattevin, Pierre Delobel, Agnès Sommet, Guillaume Martin-Blondel, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), 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 ), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio], epidemiology, Neurology (clinical), JC virus, progressive multifocal leukoencephalopathy
Abstract: Population-based data on the epidemiology of progressive multifocal leukoencephalopathy, its predisposing conditions and mortality rate are lacking, although such data are crucial to raise awareness among clinicians and to lay foundations for future therapeutic trials in immunomodulating therapies. In our study, patients were identified by interrogating the French national healthcare reimbursement database from 1 January 2008 to 31 December 2017, using progressive multifocal leukoencephalopathy International Classification of Diseases code and a patient’s selection algorithm. Overall incidence rate, 1-year all-cause mortality rate and survival patterns were calculated, and factors associated with death were identified using a multivariate Cox proportional hazards regression model. Our cohort is the largest to date, comprising 584 patients with incident progressive multifocal leukoencephalopathy. The overall incidence in France from 2010 to 2017 was stable during the study period at 0.11 per 100 000 person-years, 95% confidence interval [0.10–0.12]. Predisposing diseases were HIV infection (43.7%), followed by haematological malignancies (21.9%), chronic inflammatory diseases (20.2%), solid organ transplantation (4.3%), solid neoplasm (4.1%) and primary immune deficiency (1.5%). The 1-year mortality rate was 38.2%, with a 95% confidence interval (34.2–42.2). In multivariate analysis, factors independently associated with death were older age [adjusted hazard ratio 0.33 (0.20–0.53) for patients aged 20 to 40 compared with patients aged over 60], male gender [adjusted hazard ratio 0.73 (0.54–0.99) for females compared with males] and predisposing immunosuppressive disease, with the highest risk for solid neoplasms [adjusted hazard ratio 4.34 (2.25–8.37)], followed by haematological malignancies [adjusted hazard ratio 3.13 (1.85–5.30)] and HIV infection [adjusted hazard ratio 1.83 (1.12–3.00)], compared with chronic inflammatory diseases. Immune reconstitution inflammatory syndrome was notified in 7.0% of patients. In conclusion, incidence of progressive multifocal leukoencephalopathy is stable in France, and HIV infection remains the main predisposing disease. This large-size cohort uncovers a higher risk of mortality for male patients compared to females, and the worst prognosis for patients with solid neoplasm, while prognosis in patients with haematological malignancies appeared less dismal than in previous studies.
Published: 2022
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4. Joint models for the longitudinal analysis of measurement scales in the presence of informative dropout

Author: Tiphaine Saulnier, Viviane Philipps, Wassilios G. Meissner, Olivier Rascol, Anne Pavy-Le Traon, Alexandra Foubert-Samier, Cécile Proust-Lima, 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), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique de Toulouse (CIC 1436), 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)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Agence Nationale de la Recherche, ANR-18-CE36-0004,DyMES,Modèles Dynamiques pour les Etudes Epidémiologiques Longitudinales sur les Maladies Chroniques(2018), Admin, Oskar, and APPEL À PROJETS GÉNÉRIQUE 2018 - Modèles Dynamiques pour les Etudes Epidémiologiques Longitudinales sur les Maladies Chroniques - - DyMES2018 - ANR-18-CE36-0004 - AAPG2018 - VALID
Subjects: FOS: Computer and information sciences, Models, Statistical, Longitudinal data, Normal Distribution, Latent process, Neurodegenerative Diseases, General Biochemistry, Genetics and Molecular Biology, [STAT] Statistics [stat], [STAT]Statistics [stat], Methodology (stat.ME), Joint model, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Time-to-event data, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Ordinal data, Longitudinal Studies, Molecular Biology, Statistics - Methodology, Proportional Hazards Models
Abstract: International audience; In health cohort studies, repeated measures of markers are often used to describe the natural history of a disease. Joint models allow to study their evolution by taking into account the possible informative dropout usually due to clinical events. However, joint modeling developments mostly focused on continuous Gaussian markers while, in an increasing number of studies, the actual quantity of interest is non-directly measurable; it constitutes a latent variable evaluated by a set of observed indicators from questionnaires or measurement scales. Classical examples include anxiety, fatigue, cognition. In this work, we explain how joint models can be extended to the framework of a latent quantity measured over time by indicators of different nature (e.g. continuous, binary, ordinal). The longitudinal submodel describes the evolution over time of the quantity of interest defined as a latent process in a structural mixed model, and links the latent process to each observation of the indicators through appropriate measurement models. Simultaneously, the risk of multi-cause event is modelled via a proportional cause-specific hazard model that includes a function of the mixed model elements as linear predictor to take into account the association between the latent process and the risk of event. Estimation, carried out in the maximum likelihood framework and implemented in the R-package JLPM, has been validated by simulations. The methodology is illustrated in the French cohort on Multiple-System Atrophy (MSA), a rare and fatal neurodegenerative disease, with the study of dysphagia progression over time stopped by the occurrence of death.
Published: 2022
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5. Impact of COVID-19 disease on clinical research in pediatric and congenital cardiology

Author: V. Pommier, H. Abassi, K. Lavastre, J. Calderon, S. Guillaumont, Y. Dulac, F. Auriol, C. Ovaert, A. Blondelon, S. Hascoet, F. Lecerf, C. Jore, M. Avesani, J.-B. Thambo, P. Amedro, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Harvard Medical School [Boston] (HMS), Institut Saint-Pierre, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'investigation clinique de Toulouse (CIC 1436), 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)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Marie-Lannelongue, CHU Bordeaux [Bordeaux], IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), and MORNET, Dominique
Subjects: [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Pandemic, SARS-CoV-2, Health Personnel, Cardiology, COVID-19, Drug trials, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Randomized controlled trial, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Pediatrics, Perinatology and Child Health, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Child, Pandemics, Congenital heart disease
Abstract: International audience; Background: COVID-19 triggered an unprecedented crisis affecting society at every level. Research in pediatric and congenital cardiology is currently in full development and may have been disrupted. The aim of the study was to determine the impact of COVID-19 on pediatric and congenital cardiology clinical research and to analyze decision-making and adaptation processes, from a panel of ongoing academic and industry-sponsored research at the time of the pandemic.Methods: This observational study was carried out in April 2020, from a CHD clinical research network involving five tertiary care pediatric and congenital cardiology centers. Investigators and clinical research assistants from each participating research center completed an online survey questionnaire, and each principal investigator underwent a 1-h web-based videoconference interview.Results: A total of 34 study questionnaires were collected, reporting that 18 studies were totally suspended. Upon the investigator's decision, after discussion on ethical issues and with facilitating support from health authorities, 16 studies were resumed. The rate of study suspension in interventional research (53%) was similar to that in non-interventional research (56%). Logistical problems were predominantly reported in both continued and suspended trials. Research protocols were adapted, largely thanks to telemedicine, which in some cases even improved the course of the study.Conclusion: The impact of the COVID-19 pandemic on clinical research in pediatric and congenital cardiology has been limited by a rapid adaptation of all research structures and an extensive use of telemedicine at all stages of the studies.
Published: 2022
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6. How to Define a Nanozyme

Author: Anne Robert, Bernard Meunier, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), New Antimalarial Molecules and Pharmacological Approaches (ERL1289), Centre d'investigation clinique de Toulouse (CIC 1436), 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)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Université Toulouse III - Paul Sabatier (UT3), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), School of Chemical Engineering and Light Industry, Guangdong University of Technology, CNRS, France, Guangdong University of Technology, P.R. China, Gulli, Marie-Hélène, Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and 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]
Subjects: General Engineering, Nanoparticles, General Physics and Astronomy, Nanozymes, [CHIM.COOR]Chemical Sciences/Coordination chemistry, General Materials Science, Hydrogen Peroxide, [CHIM.COOR] Chemical Sciences/Coordination chemistry, Turnover number, Catalysis, Catalytic activity
Abstract: International audience; Over the past 15 years, many articles have considered “nanozymes” as ferromagnetic nanoparticles having an “intrinsic peroxidase-like activity” in the presence of hydrogen peroxide. However, the definition and the catalytic activity of these nanozymes have been questioned. The present Perspective reports the main criteria that are essential to classify a nanoparticle as a nanozyme. It is important to consider that not all nanoparticles able to generate hydroxyl radicals in the presence of hydrogen peroxide without catalytic activity can be registered as nanozymes.
Published: 2022
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7. Increase of high‐risk tramadol use and harmful consequences in France from 2013 to 2018: Evidence from the triangulation of addictovigilance data

Author: Roussin, Anne, Soeiro, Thomas, Fouque, Charlotte, Jouanjus, Emilie, Frauger, Elisabeth, Fouilhé, Nathalie, Mallaret, Michel, Micallef, Joëlle, Lapeyre-Mestre, Maryse, Batisse, Anne, Chevallier, Cécile, Daveluy, Amélie, Deheul, Sylvie, Fournier-Choma, Christine, Guerlais, Marylène, Le Boisselier, Reynald, Pérault-Pochat, Marie‐christine, Roy, Sophie, Tournebize, Juliana, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), 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), Université de Toulouse (UT), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Equipe EQUITY, Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), 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 National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU), Addictovigilance Grenoble, Centre d'investigation clinique de Toulouse (CIC 1436), 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], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre antipoison et de toxicovigilance (Lyon) (CAPTV Lyon), 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), Addictovigilance de Lille, Service de Pharmacologie Clinique [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Addictovigilance [Caen], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Agence Nationale de Securite du Medicament et des Produits de Sante, ANSM
Subjects: Adult, Analgesics, Opioid, Male, Pharmacology, Cross-Sectional Studies, Substance-Related Disorders, Humans, Pain, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Pharmacology (medical), France, Tramadol
Abstract: The aim of this paper is to assess recent developments in non-medical tramadol use, tramadol use disorder, illegal procurement and deaths.This study used repeated cross-sectional analysis of data collected nationwide from 2013 to 2018. Analysis was conducted through multisource monitoring of the French Addictovigilance Network of: (1) validated reports of high-risk tramadol use, (2) record systems collecting information from toxicology experts investigating analgesic-related deaths (DTA) and deaths related to substance abuse (DRAMES), and pharmacists for forged prescriptions (OSIAP), and (3) survey of drug users, with investigation of patterns of use while visiting addiction-specialised institutions (OPPIDUM).Despite a plateauing level of tramadol exposure in the French population, the proportion of tramadol reports increased 1.7-fold (187 cases in 2018, 3.2% (95% confidence interval [CI]: 2.74-3.63%), versus 1.9% (95% CI: 1.49-2.42% in 2013). Trends were similar in OSIAP: 11.9% of forged prescriptions in 2018 (95% CI: 10.56-13.45%); 1.7-fold increase; in OPPIDUM: 0.76% (95% CI: 0.55-1.02); 2.2-fold increase; and DRAMES: 3.2% of drug abuse-related deaths in 2018 (95% CI: 1.89-5.16) versus 1.7% in 2013 (95% CI: 0.65-3.84). Tramadol was the primary opioid in analgesic-related deaths in DTA (45% in 2018). Two profiles of high-risk tramadol users were identified: (1) patients treated for pain or with tramadol persistence when pain disappeared (mainly women; mean age 44 years), and (2) individuals with non-medical use for psychoactive effects (mainly men; mean age 36 years).The triangulation of the data obtained through addictovigilance monitoring evidenced a recent increase in high-risk tramadol use. These findings have a practical impact on the limitation of the maximal duration of tramadol prescriptions.
Published: 2022
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8. Pharmacology and pharmacovigilance of protein kinase inhibitors

Author: Charles Khouri, Clara Locher, Fabien Despas, Laura Caquelin, Julien Mahé, Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], 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), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université de Toulouse (UT)-Université de Toulouse (UT)-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)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), 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: Databases, Factual, Drug-Related Side Effects and Adverse Reactions, business.industry, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Pharmacology, 3. Good health, [SDV] Life Sciences [q-bio], Pharmacovigilance, 03 medical and health sciences, 0302 clinical medicine, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Adverse Drug Reaction Reporting Systems, Humans, Medicine, On- and off-target, Pharmacology (medical), business, Protein kinase A, Protein Kinase Inhibitors, Protein kinases inhibitors
Abstract: International audience; Protein kinase inhibitors experienced their advent in the 2000s. Their market introduction made it possible to constitute a class of targeted therapies administered orally. This name was chosen to mark a break with conventional chemotherapy drugs, but it is important to stress that these are multi-target drugs with complex affinity profiles. Adverse effects can be explained by direct interactions with their targets of interest, chosen for their indications (on-target) but also interactions with other targets (off-target). The adverse effect profiles of these drugs are therefore varied and it is possible to identify common profiles related to inhibitions of common targets. Identification of these targets has improved the global understanding of the pathophysiological mechanisms underlying the onset of adverse drug reactions as well as of the related diseases, and makes it possible to predict the adverse effect profile of new protein kinase inhibitors based on their affinities. In this review, we describe the main adverse drug reactions associated with protein kinase inhibitors, their frequency and their plausible mechanisms of action.
Published: 2022
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9. Epidemiology of pre-existing multimorbidity in pregnant women in the UK in 2018: a population-based cross-sectional study

Author: Lee, S. I., Azcoaga-Lorenzo, A., Agrawal, U., Kennedy, J. I., Fagbamigbe, A. F., Hope, H., Subramanian, A., Anand, A., Taylor, B., Nelson-Piercy, C., Damase-Michel, C., Yau, C., Crowe, F., Santorelli, G., Eastwood, K-A., Vowles, Z., Loane, M., Moss, N., Brocklehurst, P., Plachcinski, R., Thangaratinam, S., Black, M., O'Reilly, D., Abel, K. M., Brophy, S., Nirantharakumar, K., McCowan, C., MuM-PreDiCT Group, University of St Andrews. Population and Behavioural Science Division, University of St Andrews. School of Medicine, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of Birmingham [Birmingham], University of St Andrews [Scotland], Swansea University, University of Ibadan, University of Manchester [Manchester], Guy's and St Thomas NHS Foundation Trust [London], Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), 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 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], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Bradford Institute for Health Research [Bradford, UK], Bradford Teaching Hospitals NHS Foundation Trust [Bradford, UK] (BTHFT), Queen's University [Belfast] (QUB), University Hospitals Bristol, University of Ulster, Patient and Public Representative [London, UK] (P&PR), Birmingham Women's and Children's NHS Foundation Trust, University of Aberdeen, Manchester University NHS Foundation Trust (MFT), MuM-PreDiCT Group, and Malbec, Odile
Subjects: Adult, Adolescent, Epidemiology, [SDV]Life Sciences [q-bio], Maternity, Datasets as Topic, E-DAS, RT, Young Adult, SDG 3 - Good Health and Well-being, RA0421, Pregnancy, RA0421 Public health. Hygiene. Preventive Medicine, Prevalence, Humans, MCC, Multiple long-term conditions, United Kingdom/epidemiology, Obstetrics and Gynecology, Multimorbidity, Gynecology and obstetrics, Middle Aged, United Kingdom, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, Multiple chronic conditions, RG Gynecology and obstetrics, RG1-991, Female, Pregnant Women, RG, Routinely Collected Health Data
Abstract: Background Although maternal death is rare in the United Kingdom, 90% of these women had multiple health/social problems. This study aims to estimate the prevalence of pre-existing multimorbidity (two or more long-term physical or mental health conditions) in pregnant women in the United Kingdom (England, Northern Ireland, Wales and Scotland). Study design Pregnant women aged 15–49 years with a conception date 1/1/2018 to 31/12/2018 were included in this population-based cross-sectional study, using routine healthcare datasets from primary care: Clinical Practice Research Datalink (CPRD, United Kingdom, n = 37,641) and Secure Anonymized Information Linkage databank (SAIL, Wales, n = 27,782), and secondary care: Scottish Morbidity Records with linked community prescribing data (SMR, Tayside and Fife, n = 6099). Pre-existing multimorbidity preconception was defined from 79 long-term health conditions prioritised through a workshop with patient representatives and clinicians. Results The prevalence of multimorbidity was 44.2% (95% CI 43.7–44.7%), 46.2% (45.6–46.8%) and 19.8% (18.8–20.8%) in CPRD, SAIL and SMR respectively. When limited to health conditions that were active in the year before pregnancy, the prevalence of multimorbidity was still high (24.2% [23.8–24.6%], 23.5% [23.0–24.0%] and 17.0% [16.0 to 17.9%] in the respective datasets). Mental health conditions were highly prevalent and involved 70% of multimorbidity CPRD: multimorbidity with ≥one mental health condition/s 31.3% [30.8–31.8%]). After adjusting for age, ethnicity, gravidity, index of multiple deprivation, body mass index and smoking, logistic regression showed that pregnant women with multimorbidity were more likely to be older (CPRD England, adjusted OR 1.81 [95% CI 1.04–3.17] 45–49 years vs 15–19 years), multigravid (1.68 [1.50–1.89] gravidity ≥ five vs one), have raised body mass index (1.59 [1.44–1.76], body mass index 30+ vs body mass index 18.5–24.9) and smoked preconception (1.61 [1.46–1.77) vs non-smoker). Conclusion Multimorbidity is prevalent in pregnant women in the United Kingdom, they are more likely to be older, multigravid, have raised body mass index and smoked preconception. Secondary care and community prescribing dataset may only capture the severe spectrum of health conditions. Research is needed urgently to quantify the consequences of maternal multimorbidity for both mothers and children.
Published: 2022
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10. Prolonged response after TPO-RA discontinuation in primary ITP: results of a prospective multicenter study

Author: Stephanie Guillet, Etienne Crickx, Imane Azzaoui, pascal chappert, Emmanuelle Boutin, Jean-François Viallard, Etienne Riviere, Delphine Gobert, Lionel Galicier, Marion Malphettes, Stéphane Cheze, Francois Lefrere, Sylvain Audia, Bernard Bonnotte, Olivier Lambotte, Nicolas Noel, Olivier Fain, Guillaume Moulis, Mohamed Hamidou, Mathieu Gerfaud-Valentin, Jean-Pierre Marolleau, Louis Terriou, Nihal Martis, Anne-Sophie Morin, Antoinette Perlat, Thomas Le Gallou, Frédérique Roy-Peaud, Ailsa Robbins, Jean-Christophe Lega, Mathieu Puyade, Thibault Comont, Nicolas Limal, Laetitia Languille, Anissa Zarour, Marine Luka, Mickaël Mathieu Ménager, Thibaut Belmondo, Sophie Hue, Florence Canoui-Poitrine, Marc Michel, Bertrand Godeau, Matthieu Mahevas, Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor [Créteil], 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), 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 Paris Cité (UPCité), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Necker - Enfants Malades [AP-HP], Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, 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), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hospices Civils de Lyon (HCL), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), and Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Immunology, Cell Biology, Hematology, Biochemistry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Sustained response off-treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in ITP. This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response on TPO-RAs. The primary endpoint was the proportion of patients achieving SROT (platelet count > 30x109/L and no bleeding) at W24 with no other ITP-specific medications. Secondary endpoints included the proportion of sustained complete response off-treatment (SCROT, platelet count > 100x109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with median (IQR) age 58.5 years (41-73.5); 30/48 (63%) had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27/48 (56.2%, 95% CI, 41.2-70.5) achieved SROT; 15/48 (31.3%; 95% CI, 18.9-44.5) achieved SCROT at W24, and 25/48 (52.1%; 95% CI, 37.2-66.7) achieved respectively SROT and 14/48 (29.2%; 95% CI, 17.2-42.3) SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients re-challenged with TPO-RA, 11/12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA-seq revealed enrichment of a "TNFα signaling via NF-κB" signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based of progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. Clinical trial number: NCT03119974
Published: 2023
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11. Overview of literature monitoring practice of clinical trials vigilance units in French institutional sponsors - A study from the REVISE working group

Author: Astrid Prioul, Dorine Fournier, Cécile Lefeuvre, Sophie Duranton, Pascale Olivier, Emeline Blanc, Laure Peyro-Saint-Paul, Sophie Ruault, Aurélie Jamet, Catherine Mouchel, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), 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), Centre d'investigation clinique de Toulouse (CIC 1436), 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), Hospices Civils de Lyon, Departement de Neurologie (HCL), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)
Subjects: Patient safety, Clinical trials, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Pharmacology (medical), Review Literature, Safety management
Abstract: International audience; INTRODUCTION: The evaluation of clinical trial (CT) safety is the main task of CT vigilance units. In addition to the management of adverse events, the units must review the literature to identify information that may impact the benefit-risk assessment of studies. In this survey, we investigated the literature monitoring (LM) activity of French Institutional Vigilance Units (IVU) from the working group "REflexion sur la VIgilance et la SEcurite des essais cliniques" (REVISE). MATERIAL AND METHODS: We sent a questionnaire of 26 questions, divided into four themes, to the 60 IVU: (1) Presentation of the IVU and the LM activity; (2) Used sources, queries and criteria for selecting articles; (3) Valuation of the LM and (4) Practical organisation. RESULTS: Of the 27 IVU that responded to the questionnaire, 85% of them carried out LM. This was mainly provided by medical staff to improve general knowledge (83%), to detect Adverse Reactions (AR) not listed in the reference documents (70%) and to detect new safety information (61%). Due to lack of time, staff, available recommendations and sources, only 21% of IVU conducted LM for all CT. On average, units reported four sources: ANSM information (96%), PubMed database (83%), EMA alerts (57%) and the subscription to APM international (48%). The LM had an impact on the CT of 57% of the IVU such as changing the conditions of a study (39%) or suspending a study (22%). DISCUSSION/CONCLUSION: LM is an important but time-consuming activity with heterogeneous practices. According to the results of this survey, we proposed seven ways to improve this practice: (1) Target the highest risk CT; (2) Refine the PubMed queries; (3) Use other tools; (4) Create a decision flowchart for the selection of PubMed articles; (5) Improve training; (6) Value the activity and (7) Outsource the activity.
Published: 2023
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12. Distribution in Rat Blood and Brain of TDMQ20, a Copper Chelator Designed as a Drug-Candidate for Alzheimer’s Disease

Author: Lan Huang, Yaoxun Zeng, Yongliang Li, Yingshan Zhu, Yan He, Yan Liu, Anne Robert, Bernard Meunier, Guangdong University of Technology, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), New Antimalarial Molecules and Pharmacological Approaches (ERL1289), Centre d'investigation clinique de Toulouse (CIC 1436), 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)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Université Toulouse III - Paul Sabatier (UT3), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), National Natural Science Foundation of China, Guangdong Provincial Key Laboratory of Plant Resources Biorefinery, Science, Technology and Innovation Commission of Shenzhen Municipality, Guangdong Province Program for Innovative Research Teams and Leading Talents Introduction, Centre National de la Recherche Scientifique, Gulli, Marie-Hélène, Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and 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]
Subjects: Blood, Oxidative stress, Copper chelator, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, [CHIM] Chemical Sciences, Pharmaceutical Science, Brain, [CHIM]Chemical Sciences, Pharmacokinetics, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Alzheimer’s disease, blood, brain, copper chelator, oxidative stress, pharmacokinetics
Abstract: International audience; (1) Background: TDMQ20 is a specific regulator of copper homeostasis in the brain, able to inhibit cognitive impairment in the early stages of Alzheimer’s disease (AD) in mouse models of AD. To promote the further development of this drug-candidate, preliminary data on the pharmacokinetics of TDMQ20 in a mammal model have been collected. Since TDMQ20 should be administered orally, its absorption by the gastrointestinal tract was evaluated by comparison of blood concentrations after administration by oral and IV routes, and its ability to reach its target (the brain) was confirmed by comparison between blood and brain concentrations after oral administration. (2) Methods: plasmatic and brain concentrations of the drug after oral or intravenous treatment of rats at pharmacologically relevant doses were determined as a function of time. (3) Results: oral absorption of TDMQ20 was rapid and bioavailability was high (66% and 86% for males and females, respectively). The drug accumulated in the brain for several hours (brain–plasma ratio 3 h after oral administration = 2.6), and was then efficiently cleared. (4) Conclusions: these data confirm that TDMQ20 efficiently crosses the brain–blood barrier and is a relevant drug-candidate to treat AD.
Published: 2022
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13. SNORD116 and growth hormone therapy impact IGFBP7 in Prader–Willi syndrome

Author: Lisa Cole Burnett, Françoise Conte Auriol, Eric Bieth, Jean Pierre Salles, Juliette Salles, Maithé Tauber, Gwenaelle Diene, Catherine Molinas, Rudolph L. Leibel, Boris V. Skryabin, Isabelle Gennero, Timofey S. Rozhdestvensky, Sanaa Eddiry, Centre d'investigation clinique de Toulouse (CIC 1436), 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)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), 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), Centre de Référence du Syndrome de Prader-Willi, Pôle Enfants [CHU Toulouse], Service Psychiatrie et psychologie médicale [CHU Toulouse], Pôle Psychiatrie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), University of Illinois [Chicago] (UIC), University of Illinois System, Columbia University [New York], and Pistre, Karine
Subjects: 0301 basic medicine, MESH: Prader-Willi Syndrome* / genetics, medicine.medical_specialty, MESH: RNA, Small Nucleolar, congenital, hereditary, and neonatal diseases and abnormalities, IGFBP7, [SDV]Life Sciences [q-bio], Induced Pluripotent Stem Cells, MESH: Neurons, MESH: Induced Pluripotent Stem Cells, Article, MESH: Prader-Willi Syndrome* / drug therapy, 03 medical and health sciences, Mice, 0302 clinical medicine, Neurodevelopmental disorder, Downregulation and upregulation, Internal medicine, medicine, Animals, Humans, RNA, Small Nucleolar, MESH: Animals, MESH: Mice, Genetics (clinical), Neurons, MESH: Humans, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Dopaminergic, nutritional and metabolic diseases, medicine.disease, Phenotype, Pathophysiology, nervous system diseases, [SDV] Life Sciences [q-bio], 030104 developmental biology, Endocrinology, MESH: Growth Hormone, Growth Hormone, Knockout mouse, business, Genomic imprinting, Prader-Willi Syndrome, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Purpose: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder with hypothalamic dysfunction due to deficiency of imprinted genes located on the 15q11-q13 chromosome. Among them, the SNORD116 gene appears critical for the expression of the PWS phenotype. We aimed to clarify the role of SNORD116 in cellular and animal models with regard to growth hormone therapy (GHT), the main approved treatment for PWS.Methods: We collected serum and induced pluripotent stem cells (iPSCs) from GH-treated PWS patients to differentiate into dopaminergic neurons, and in parallel used a Snord116 knockout mouse model. We analyzed the expression of factors potentially linked to GH responsiveness.Results: We found elevated levels of circulating IGFBP7 in naive PWS patients, with IGFBP7 levels normalizing under GHT. We found elevated IGFBP7 levels in the brains of Snord116 knockout mice and in iPSC-derived neurons from a SNORD116-deleted PWS patient. High circulating levels of IGFBP7 in PWS patients may result from both increased IGFBP7 expression and decreased IGFBP7 cleavage, by downregulation of the proconvertase PC1.Conclusion: SNORD116 deletion affects IGFBP7 levels, while IGFBP7 decreases under GHT in PWS patients. Modulation of the IGFBP7 level, which interacts with IGF1, has implications in the pathophysiology and management of PWS under GHT.
Published: 2021
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14. Multimodal management of surgery- and radiation-refractory meningiomas: an analysis of the French national tumor board meeting on meningiomas cohort

Author: Olivier Chinot, Marc Sanson, J. Jacob, Thomas Graillon, François Caire, Michel Kalamarides, Charlotte Bronnimann, Apolline Monfilliette, Ilyess Zemmoura, François Ducray, Charles-Henry Mallereau, Christelle Dufour, Sébastien Froelich, Mathieu Boone, Mélanie Dore, Aymeri Huchet, Anthony Joncour, Anne-Laure Boch, Denys Fontaine, Elodie Vauleon, Loïc Feuvret, Anna Luisa Di Stefano, Matthieu Helleringer, Emmanuel Jouanneau, Matthieu Peyre, Mariette Delaitre, Emmanuelle Le Fur, Amaury De Barros, Julien Boetto, Hugues Loiseau, Tuan Le Van, Julien Engelhardt, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Amiens-Picardie, CHU Bordeaux [Bordeaux], CHU Limoges, Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital pasteur [Colmar], Hôpital Foch [Suresnes], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Hospices Civils de Lyon (HCL), Institut Gustave Roussy (IGR), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Imagerie moléculaire et thérapies innovantes en oncologie (IMOTION), Université de Bordeaux (UB), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Strasbourg, CHU Lille, Clinique Armoricaine de Radiologie [St. Brieuc], CHU Trousseau [Tours], No funding, Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), Centre hospitalier Saint-Brieuc, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Cancer Research, medicine.medical_specialty, Palliative care, Bevacizumab, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Octreotide, Radiosurgery, Disease-Free Survival, Meningioma, 03 medical and health sciences, 0302 clinical medicine, Meningeal Neoplasms, medicine, Humans, Everolimus, Progression-free survival, Retrospective Studies, Atypical meningioma, business.industry, medicine.disease, Combined Modality Therapy, 3. Good health, Surgery, Radiation therapy, Treatment Outcome, Neurology, Oncology, 030220 oncology & carcinogenesis, Cohort, High-grade meningioma, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Malignant meningioma, Neurology (clinical), business, 030217 neurology & neurosurgery, Progressive disease, Follow-Up Studies, medicine.drug
Abstract: International audience; PURPOSE: Meningiomas represent the most frequent tumor of the central nervous system in adults. While most meningiomas are efficiently treated by surgery and radiotherapy/radiosurgery, there is a small portion of radiation- and surgery-refractory tumors for which there is no clear recommendation for optimal management. The French National Tumor Board Meeting on Meningiomas (NTBM) offers a glimpse on the current management of such patients. METHODS: We retrospectively reviewed the charts of patients presented to the multidisciplinary Meeting between 2016 and 2019. We selected patients with a progressive disease after at least two treatments, including surgery and radiotherapy. RESULTS: In this multicentric cohort of 86 cases, patients harbored 17 (19.8%) WHO Grade I, 48 (55.8%) WHO Grade II and 21 (24.4%) WHO Grade III tumors. The median number of treatments received before inclusion was 3 (range: 2 - 11). Following the Board Meeting, 32 patients (37.2%) received chemotherapy, 11 (12.8%) surgery, 17 (19.8%) radiotherapy, 14 (16.3%) watchful observation and 12 (13.9%) palliative care. After a mean follow-up of 13 months post-inclusion, 32 patients (37.2%) had died from their disease. The mean progression free survival was 27 months after radiotherapy, 10 months after surgery, 8.5 months after chemotherapy (Bevacizumab: 9 months - Octreotide/Everolimus: 8 months). CONCLUSIONS: Surgery- and radiation-refractory meningiomas represent a heterogeneous group of tumors with a majority of WHO Grade II cases. If re-irradiation and redo-surgery are not possible, bevacizumab and octreotide-everolimus appear as a valuable option in heavily pre-treated patients considering the current EANO guidelines.
Published: 2021
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15. Drug-related risks and immune thrombocytopenia : a pharmacoepidemiological approach of three issue

Author: Lafaurie, Margaux, Centre d'investigation clinique de Toulouse (CIC 1436), 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)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paul Sabatier - Toulouse III, Agnès Sommet, Guillaume Moulis, and STAR, ABES
Subjects: Vaccination antigrippal, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Pharmacoepidemiology, Thrombosis, Influenza vaccination, Agonistes du récepteur à la thrombopoïétine, Thrombopoietin receptor agonists, Pharmacoépidémiologie, Thrombose, French National Health Database, Système national des données de santé, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Purpura thrombopénique immunologique primaire, Primary immune thrombocytopenia, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Immune thrombocytopenia (ITP) is a rare autoimmune disease with a risk of spontaneous bleeding, but also of thrombosis, whose management is particularly challenging. First-line therapy is based on corticosteroids more or less intravenous immunoglobulin (IVIg). Thrombopoietin receptor agonists (TPO-RAs; eltrombopag and romiplostim) are the preferred second-line treatments. We selected three pharmacoepidemiological issues to better understand the disease and its management. Eltrombopag exposure was associated with risk of cataract since the preclinical studies, while the risk is unknown in patients. TPO-RAs as well as corticosteroids and IVIg are suspected to increase the risk of thrombosis, which has not been measured in the real-world, adjusted for other risk factors. As for many other autoimmune diseases, the risk of ITP following vaccination is debated, especially with the influenza vaccine. In our thesis, we aimed to assess these three important issues for clinical practice. We used a population-based pharmacoepidemiological approach based on the FAITH cohort (NCT03429660) including all adult patients with primary incident ITP since 2009 (n=9,885) built on the National Health Database (Système National des Données de Santé, SNDS); three studies with specific designs and methods dedicated to assess each issue were conducted. In a nested case-control study, we found no association between eltrombopag exposure and the occurrence of cataract surgery after adjustment for cataract risk factors such as diabetes and corticosteroids exposure (Lafaurie et al., Br J Haematol, 2020). Exposure to TPO-RAs was associated with hospitalization for venous and arterial thrombosis after adjustment for individual risk factors and other prothrombotic ITP treatments (corticosteroids, IgIV and splenectomy) in a cohort study using time-varying exposures (Lafaurie et al., Br J Haematol, 2021). Using self-controlled designs (self-controlled case series and case crossover) and a case-control design with controls from the general population, we found no association between influenza vaccination and the occurrence of ITP (Lafaurie et al., JAMA Intern Med, 2022). In conclusion, this thesis provided important findings for clinical practice on controversial issues., Le purpura thrombopénique immunologique (PTI) est une maladie auto-immune rare avec un risque de saignement spontané, mais aussi de thrombose dont la prise en charge est particulièrement difficile. Le traitement de première intention repose sur les corticoïdes, plus ou moins les immunoglobulines intraveineuses (IgIV). Les agonistes du récepteur de la thrombopoïétine (AR-TPO ; eltrombopag et romiplostim) sont les médicaments privilégiés en deuxième ligne. Nous avons sélectionné trois questions pharmacoépidémiologiques pour mieux comprendre la maladie et sa prise en charge. Dès les études précliniques, un risque de survenue de cataracte associé à l'exposition à l'eltrombopag a été évoqué, alors que le risque est inconnu chez les patients en vie réelle. Les AR-TPO ainsi que les corticoïdes et les IgIV sont suspectés d'augmenter le risque de thrombose, ce qui n'a pas été mesuré en vie réelle et ajusté sur les autres facteurs de risque. Enfin, à l'instar d'autres maladies auto-immunes, le risque de PTI après une vaccination est débattu, notamment après le vaccin contre la grippe. Nos travaux de thèse avaient pour objectif de répondre à ces trois questions importantes pour la pratique clinique. Nous avons utilisé une approche pharmacoépidémiologique basée sur la cohorte FAITH (NCT03429660) incluant tous les patients adultes présentant un PTI primaire incident depuis 2009 (n=9885), construite sur la base du Système des Données de Santé (SNDS) ; trois études ont été menées avec des méthodes spécifiques pour chacune des questions. Dans une étude cas-témoins nichée, nous n'avons trouvé aucune association entre l'exposition à l'eltrombopag et la survenue d'une chirurgie de cataracte après ajustement sur les facteurs de risque de cataracte tels que le diabète et l'exposition aux corticostéroïdes (Lafaurie et al., Br J Haematol, 2020). L'exposition aux AR-TPO était associée à la survenue d'hospitalisation pour thrombose veineuse et artérielle après ajustement pour les facteurs de risque individuels et les autres traitements prothrombotiques du PTI (corticoïdes, IgIV et splénectomie) dans une étude de cohorte utilisant des expositions variables dans le temps (Lafaurie et al. Br J Haematol, 2021). En utilisant des méthodes autocontrôlées (self-controlled case series et case crossover) et une méthode cas-témoins (témoins issus de la population générale), nous n'avons pas trouvé d'association entre la vaccination contre la grippe et la survenue du PTI (Lafaurie et al., JAMA Intern Med, 2022). Ainsi, ces travaux de thèse ont fourni des résultats importants pour la pratique clinique sur des questions controversées.
Published: 2022

16. Synthesis and Antimalarial Activities of New Hybrid Atokel Molecules

Author: Youzhi Li, Anthony Loureiro, Michel Nguyen, Marion Laurent, Christian Bijani, Françoise Benoit‐Vical, Anne Robert, Yan Liu, Bernard Meunier, School of Chemical Engineering and Light Industry, Guangdong University of Technology, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), New Antimalarial Molecules and Pharmacological Approaches (ERL1289), Centre d'investigation clinique de Toulouse (CIC 1436), 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)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Université Toulouse III - Paul Sabatier (UT3), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de pharmacologie et de biologie structurale (IPBS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), NSFC (grants 21977019 and 21502023), Guangdong Province (Program for Innovative Research Teams and Leading Talents Introduction, grant 2050205), Open Project of Guangdong Provincial Key Laboratory of New Drug Screening (No. GDKLNDS-2018OF004), University of Technology of the Guangdong (GDUT) (grant 220418037) of the P. R. China, CNRS, Fondation pour la Recherche Médicale, France (grant FRM Equipe EQU202103012596), ANR-17-CE18-0017,RADICAL,Stratégie thérapeutique par voie radicalaire pour combattre des maladies parasitaires(2017), Gulli, Marie-Hélène, Stratégie thérapeutique par voie radicalaire pour combattre des maladies parasitaires - - RADICAL2017 - ANR-17-CE18-0017 - AAPG2017 - VALID, Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), 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], and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Plasmodium, Plasmodium falciparum, Quinoline, General Chemistry, [CHIM.COOR] Chemical Sciences/Coordination chemistry, Artemisinins, Malaria, Antimalarials, Oxidative stress, parasitic diseases, Folic Acid Antagonists, Quinone, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Metal chelator, Atovaquone
Abstract: International audience; The currently spreading resistance of the malaria parasite Plasmodium falciparum to artemisinin-based combination therapies makes an urgent need for new efficient drugs. Aiming to kill artemisinin-resistant Plasmodium, a series of novel hybrid drugs named Atokels were synthesized and characterized. Atokels are based on an 8-amino- or 8-hydroxyquinoline entity covalently bound to a 1,4-naphthoquinone through a polyamine linker. These drugs have been designed to target the parasite mitochondrion by their naphthoquinone moiety reminiscent of the antimalarial drug atovaquone, and to trigger a damaging oxidative stress due to their ability to chelate metal ions in order to generate redox active complexes in situ. The most effective Atokel drug shown a promising antimalarial activity (IC50=622 nm on an artemisinin-resistant P. falciparum strain) and no cytotoxicity at 50 μm indicating a specific antiplasmodial mode of action.
Published: 2022
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17. Clinical phenotype and cytokine profile of adult IgA vasculitis with joint involvement

Author: Delapierre, Alice, Terrier, Benjamin, Pillebout, Evangéline, Baudart, Pauline, Jourde-Chiche, Noémie, Lioger, Bertrand, Martis, Nihal, Moulis, Guillaume, Rivière, Etienne, Le Gouellec, Noémie, Raffray, Loïc, Urbanski, Geoffrey, Sanges, Sébastien, Maurier, Francois, Deroux, Alban, Mekinian, Arsène, Monteiro, Renato, Marcelli, Christian, Guillevin, Loïc, Maillot, Francois, Lucas, Bruno, Aouba, Achille, Audemard-Verger, Alexandra, Université de Caen Normandie - UFR Santé (UNICAEN Santé), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Plateforme Cytométrie et Immunobiologie [Institut Cochin] (CYBIO), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Rhumatologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de pharmacologie moléculaire et cellulaire (IPMC), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), 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), CHU Bordeaux [Bordeaux], Centre hospitalier [Valenciennes, Nord], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Hôpital-Clinique Claude-Bernard [Metz], Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire d'Excellence INFLAMEX [Paris], Université Sorbonne Paris Cité (USPC), Biotechnologie des tissus conjonctifs et cutanés / Biology of Connective and Cutaneous Tissues (BioConnecT), Hôpital Cochin [AP-HP], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), Université de Tours (UT), Laboratoire d'Immunologie [CHU Caen], Immunologie parasitaire (TOURS UMR IMMUNOLOGIE PARASIT), and Faculte des Sciences Pharmaceutiques-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Henoch Schonlein purpura, Phenotype, IgA Vasculitis, Rheumatology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Cytokines, Humans, IgA vasculitisIL-1 beta, Prospective Studies, General Medicine, Gastrointestinal tract involvement, Joint involvement, Immunoglobulin A
Abstract: Joint involvement can be observed during the course of adult IgA vasculitis (IgAV). However, clinical picture, prognosis, or pathophysiological data associated with this condition have been overlooked. We aimed to describe the clinical characteristics and outcome of IgAV patients with joint involvement and look to a specific cytokine profile.We analyzed clinical and biological data from a nationwide study that included adult IgAV patients. Presentation and outcomes of patients with or without joint involvement were compared at baseline and during follow-up. Plasma cytokine measurements of IgAV patients included in a prospective study were also analyzed using multiplex assays.Among 260 patients, 62% had joint involvement. Among them, rheumatological manifestations included arthralgia (100%) or arthritis (16%), mostly involving the knees and ankles. In multivariate analysis, patients with joint involvement, compared to those without, were younger (p = 0.002; OR 0.87; 95% CI 0.80-0.95) and showed more frequent gastrointestinal tract involvement (p = 0.012; OR = 2.08; 95% CI 1.18-3.67). However, no difference in terms of clinical response, relapse, end-stage renal disease, or death was observed between groups. Among 13 cytokines measured, plasma interleukin (IL)-1β level was higher in patients with joint involvement compared to those without (mean ± SEM IL-1β, 3.5 ± 1.2 vs. 0.47 ± 0.1 pg/ml; p = 0.024) or healthy controls (vs. 1.2 ± 0.5 pg/ml; p = 0.076).Joint involvement is frequent in adult IgAV and is associated with more frequent gastrointestinal involvement. Increased plasma IL-1β levels raise the question of targeting this cytokine in patients with chronic and/or refractory joint involvement. Key Points • Joint involvement in adult IgAV is a frequent manifestation. • Joint involvement is associated with more frequent gastrointestinal manifestations. • Interleukin-1β (IL-1β) might orchestrate joint inflammation in adult IgAV. • IL-1β might be a therapeutic target in patients with chronic and/or refractory joint involvement.
Published: 2022
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18. Real-life data on protein kinase inhibitors in chronic myeloid leukemia : usage profile in France and impact of drug interactions with concomitant treatments

Author: Pajiep Tchapda, Marie Christelle, Centre d'investigation clinique de Toulouse (CIC 1436), 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)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paul Sabatier - Toulouse III, Maryse Lapeyre-Mestre, Fabien Despas, and STAR, ABES
Subjects: Interactions médicamenteuses, Pharmacoepidemiology, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Chronic myeloid leukemia, Drug drug interactions, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Inhibiteurs de protéine kinase, Protein Kinase Inhibitors, Leucémie myéloïde chronique, Pharmaco-épidémiologie
Abstract: The introduction of protein kinase inhibitors (PKIs) in the treatment of chronic myeloid leukemia (CML) has considerably changed the paradigm of this pathology, which has now become a chronic disease. This chronicity is accompanied over time by an increase in comorbidities in parallel with poly-medication. However, despite their effectiveness, PKIs are particularly at risk of drug interactions. The objective of this study was to study potential PKI-drug interactions (pPKI-DIs) in a real-life cohort of incident CML patients treated with PKIs on a national scale, using data from the French National Health Data System (SNDS). The pPKI-DIs were defined according to the information in the summary of product characteristics (SPC) and the Thesaurus of Drug Interactions of the ANSM. This information was completed by an exploration of international pharmacovigilance data (from Vigibase(r), the WHO pharmacovigilance database) and the French Pharmacovigilance Database. Data from the SNDS identified a cohort of 3633 patients newly diagnosed with CML between January 1, 2011, and December 31, 2014, with an estimated incidence of 1,37 [IC 95% 1,36-1,38] per 100 000 person-years in this period (54% male, mean age 60 years). Imatinib was the most frequently used drug in the 1st line (78% of patients) and remained so in the 1st year of follow-up. At inclusion, 25% of patients had an associated comorbidity, and the majority of them were polymedicated (2.8 drugs on average in addition to the KPI) at inclusion in the cohort, including 48% of patients treated with proton pump inhibitors (PPIs), 37% with antihypertensives, 25% with statins, 16% with allopurinol, and 11% with serotonin reuptake inhibitor antidepressants. The search for pPKI-DI-type situations in the first year following the initiation of a PKI treatment showed that 41% (co-dispensing) to 62% (co-medication with delivery within one month of the PKI prescription) of patients were concerned, the drugs most involved being statins, benzodiazepines and PPIs. Factors associated with this potential interaction situation were age, number of comorbidities, number of drugs and number of prescribers. Nilotinib and dasatinib were more likely to interact than imatinib. The search for adverse events related to interactions with PKIs showed that, beyond the list in the ANSM thesaurus, the main drugs involved in adverse events related to drug interactions were statins (with all KPIs and not just ponatinib as listed in the ANSM thesaurus), anticoagulants, PPIs and potent CYP 3A4 inhibitors. The results obtained confirm the research hypotheses on the involvement of drugs in comorbidities, and lead to the proposal of additional specific analyses of the impact of certain classes of drugs (PPIs, statins) on criteria such as survival, hospitalizations, switching of PKIs or specific complications (e.g. muscle damage)., L'introduction des inhibiteurs des protéines kinases (IPK) dans le traitement de la Leucémie Myéloïde Chronique (LMC) a considérablement changé le paradigme de cette pathologie, devenue aujourd'hui une maladie chronique. Cette chronicité s'accompagne dans le temps d'une augmentation des comorbidités en parallèle avec une polymédication. Cependant, malgré une efficacité certaine, les IPK sont particulièrement à risque d'interaction médicamenteuse. L'objectif de cette étude était d'étudier en vie réelle et à l'échelle nationale les situations d'interactions médicamenteuses potentielles (IMP) dans une cohorte de patients incidents pour la LMC et traités par IPK à partir des données du SNDS (Système National des Données de Santé). Les IMP ont été définies selon les informations du résumé des caractéristiques de produits (RCP) et du Thésaurus des Interactions Médicamenteuses de l'ANSM. Ces informations ont été complétées par une exploration des données de pharmacovigilance à l'échelle internationale (à partir de Vigibase(r), base de pharmacovigilance de l'OMS) et de la Base Française de Pharmacovigilance. Les données du SNDS ont permis d'identifier une cohorte de 3633 patients nouvellement diagnostiqués pour une LMC entre le 1er janvier 2011 et le 31 décembre 2014, soit une incidence estimée de 1,37 [IC 95% 1,36-1,38] pour 100000 personnes-années dans cette période (54 % d'hommes, âge médian 60 ans). L'imatinib était le médicament le plus fréquemment utilisé en 1ère intention (78% des patients) et le demeurait dans la 1ère année de suivi. A l'inclusion, 25% des patients présentaient une comorbidité associée, ils étaient polymédiqués en majorité (2,8 médicaments en moyenne en plus de l'IPK) à l'inclusion dans la cohorte, dont 48% des patients traités par inhibiteurs de la pompe à protons (IPP) ; 37% par antihypertenseurs, 25% par statines, 16% par allopurinol, 11% par antidépresseurs Inhibiteurs de la Recapture de la Sérotonine. La recherche des situations à type d'IMP dans la 1ère année suivant l'initiation d'un traitement par IPK a mis en évidence que 41% (co-prescription) à 62% (co-médication avec délivrance dans le mois suivant la prescription de l'IPK) des patients étaient concernés, les médicaments majoritairement impliqués étant les statines, les benzodiazépines et les IPP. Les facteurs associés à cette situation potentielle d'interaction étaient l'âge, le nombre de comorbidités, le nombre de médicaments et le nombre de prescripteurs. Le nilotinib et le dasatinib étaient plus à risque d'interactions que l'imatinib. La recherche des effets indésirables en relation avec une interaction avec les IPK a montré que au-delà de la liste du Thésaurus de l'ANSM, les principaux médicaments impliqués dans les effets indésirables liés à une interaction médicamenteuse étaient les statines (avec l'ensemble des IPK et pas seulement le ponatinib comme retenu dans le thésaurus de l'ANSM), les anticoagulants, les IPP et les inhibiteurs puissants du CYP 3A4. Les résultats obtenus confirment les hypothèses de recherche sur l'implication des médicaments des comorbidités, et conduisent à proposer des analyses spécifiques complémentaires de l'impact de certaines classes de médicaments (IPP, statines) sur des critères tels que la survie, les hospitalisations, le switch d'IPK ou des complications spécifiques (atteintes musculaires par exemple).
Published: 2022

19. Clinical characteristics and outcome of hospitalized patients with SARS-CoV-2 infection at Toulouse University hospital (France). Results from the Covid-clinic-Toul cohort

Author: A. Jourdes, Stein Silva, C. Thalamas, Sandrine Charpentier, Vincent Minville, Margaux Lafaurie, G. Moulis, Agnès Sommet, M. Faruch, Pierre Delobel, Guillaume Martin-Blondel, CCSD, Accord Elsevier, 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)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), and 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]
Subjects: Male, medicine.medical_specialty, Epidemiology, medicine.medical_treatment, 030204 cardiovascular system & hematology, COVID-2019, law.invention, Cohort Studies, Hospitals, University, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Interquartile range, law, Internal medicine, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Aged, Mechanical ventilation, SARS-CoV-2, business.industry, Gastroenterology, COVID-19, Middle Aged, medicine.disease, Intensive care unit, Comorbidity, 3. Good health, Épidémiologie, Hospitalization, Pneumonia, Treatment Outcome, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Original Article, Female, France, business, Cohort study
Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide from epicenter of Wuhan, China since December 2019. The aim of our study was to describe the clinical characteristics and outcome of hospitalized patients with SARS-CoV-2 pneumonia at the Toulouse university hospital, France. Patients and methods We selected the patients included from March 7, 2020 to April 20, 2020 in the retrolective Covid-clinic-Toul cohort that follows all hospitalized patients with SARS-CoV-2 infection at the Toulouse Hospital. Cases were confirmed by real-time reverse transcriptase polymerase chain reaction. We report demographics, clinical, biological and radiological features, as well as unfavorable outcome at Day 14 after admission (admission in an intensive care unit, mechanical ventilation, death). Results Among 263 hospitalized patients, the median age was 65 years and 155 (58.9%) were males. Two hundred and twenty-seven patients (86.3%) had at least one comorbidity. The median time from first symptom to hospital admission was 7.0 days (interquartile range: 4–10). On day 14 after admission, 111 patients (42.2%) had been transferred to intensive care unit (ICU), including 50 (19.0%) on Day 1; 61 (23.1%) needed mechanical ventilation and 19 patients (7.2%) had died. Patients admitted to ICU at Day 1 of admission (n = 50) were more frequently men (66.0% vs 57.3%), smokers (25.0% vs 7.1%), with obesity (42.0% vs 24.7%) and had a higher mean level of C-reactive protein (median: 110.9 mg/L vs 46.2 mg/L). Conclusion This cohort provides epidemiological data on SARS-CoV-2 in hospitalized patients in a University hospital in the South of France.
Published: 2020
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20. Le psychotraumatisme chez l’enfant et l’adolescent : donnés actuelles et perspectives

Author: Alexis Revet, Maryse Lapeyre-Mestre, Eric Bui, Bertrand Olliac, Jean-Philippe Raynaud, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), 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 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], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CH Esquirol [Limoges] (CH Esquirol), Harvard Medical School [Boston] (HMS), CCSD, Accord Elsevier, CHU Toulouse [Toulouse], 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 Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-CHU Limoges-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST)
Subjects: Enfants et adolescents, 05 social sciences, 16. Peace & justice, Trouble stress post-traumatique, [SHS]Humanities and Social Sciences, 030227 psychiatry, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Pediatrics, Perinatology and Child Health, Traumatismes psychiques, Developmental and Educational Psychology, 0501 psychology and cognitive sciences, Traumatisme complexe, [SHS] Humanities and Social Sciences, 050104 developmental & child psychology
Abstract: International audience; L’exposition au traumatisme est une expérience fréquemment vécue par les enfants et les adolescents, la prévalence du trouble stress post-traumatique (TSPT) dans cette population étant probablement sous-estimée. Si la plupart vont faire preuve de capacités de résilience leur permettant de surmonter ces épreuves, un certain nombre d’entre eux vont toutefois présenter des réactions très diverses, allant de perturbations minimes de la vie de l’enfant à des tableaux cliniques sévères interférant fortement avec le développement psychoaffectif, parmi lesquels le TSPT. Dans le DSM-5, les troubles liés à des traumatismes ont été autonomisés des autres troubles anxieux et des troubles du spectre obsessionnel. Plus récemment, la CIM-11 a proposé un nouveau diagnostic appelé TSPT complexe, qui rapproche du champ du psychotraumatisme certains troubles psychiatriques à forte composante traumatique développementale, en particulier les troubles de personnalité borderline. Malgré la grande hétérogénéité des réactions psychotraumatiques chez l’enfant et l’adolescent, une triade clinique est classiquement décrite, associant des symptômes de répétition, des manifestations d’évitement et une hyperactivité neurovégétative. De multiples approches thérapeutiques sont possibles, mais la trauma-focused cognitive behavioral therapy, une thérapie limitée dans le temps, qui associe des exercices d’exposition, de remodelage cognitif et d’augmentation des capacités d’adaptation et de résilience, est la plus validée et la plus largement utilisée. Beaucoup reste à faire concernant l’identification des facteurs de risque et des facteurs protecteurs, la description des différentes trajectoires possibles suites à un traumatisme, le développement d’instruments psychométriques et leur validation en français, et l’évaluation et l’implémentation de thérapies efficaces et accessibles.
Published: 2020
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21. X-Ray diffraction structure of Cu(II) and Zn(II) complexes of 8-aminoquinoline derivatives (TDMQ), related to the activity of these chelators as potential drugs against Alzheimer's disease

Author: Youzhi Li, Michel Nguyen, Laure Vendier, Anne Robert, Yan Liu, Bernard Meunier, School of Chemical Engineering and Light Industry, Guangdong University of Technology, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), New Antimalarial Molecules and Pharmacological Approaches (ERL1289), 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)-Université Toulouse III - Paul Sabatier (UT3), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), NSFC (grant 21502023), Guangdong Province (Program for Innovative Research Teams and Leading Talents Introduction, grant 2050205), GDUT (grant 220418037), CNRS, Gulli, Marie-Hélène, Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), 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], Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 010405 organic chemistry, Copper chelator, Organic Chemistry, [CHIM.COOR] Chemical Sciences/Coordination chemistry, Alzheimer's disease, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, 3. Good health, Analytical Chemistry, Inorganic Chemistry, Zinc, 8-aminoquinoline, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Spectroscopy, X-ray crystallography
Abstract: International audience; TDMQ chelators have been designed as drug-candidates for the regulation of copper homeostasis and for the reduction of the oxidative stress in the brain of Alzheimer's patients. To achieve suitable biological properties and high Cu(II) selectivity in a zinc-rich medium, TDMQ ligands must meet critical coordination chemistry requirements related to the structures of the CuII-TDMQ complexes. The correlation between X-ray diffraction structures of Cu- and Zn-TDMQ complexes and their physicochemical properties should therefore help to draw pertinent correlations between structure and properties of the drug-candidates, and to select the most promising ones for biological studies. Here we report the X-ray structures of single crystals of Cu-TDMQ36, and of the zinc complexes of TDMQ35, TDMQ36 and TDMQ22. Comparison with the already reported structures of other copper and zinc complexes of TDMQ then allows to specify the structure requirement for potentially more efficient drugs.
Published: 2022
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22. Resistance to artemisinin in falciparum malaria parasites: A redox-mediated phenomenon

Author: Egwu, Chinedu, Pério, Pierre, Augereau, Jean-Michel, Tsamesidis, Ioannis, Benoit-Vical, Françoise, Reybier, Karine, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Alex Ekwueme Federal University Ndufu-Alike, Ikwo (AE-FUNAI), Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), New Antimalarial Molecules and Pharmacological Approaches (ERL1289), Centre d'investigation clinique de Toulouse (CIC 1436), 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)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Université Toulouse III - Paul Sabatier (UT3), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de pharmacologie et de biologie structurale (IPBS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), CNRS (Centre National de la Recherche Scientifique, France), Université Paul Sabatier, Toulouse III (France), IRD (Institut de Recherche pour le Développement, France), ANR-16-CE35-0003,INMAR,Réseau intégré des mécanismes de quiescence & clairance impliqués dans la résistance à l'artémisinine chez Plasmodium(2016), ANR-17-CE18-0017,RADICAL,Stratégie thérapeutique par voie radicalaire pour combattre des maladies parasitaires(2017), Gulli, Marie-Hélène, Réseau intégré des mécanismes de quiescence & clairance impliqués dans la résistance à l'artémisinine chez Plasmodium - - INMAR2016 - ANR-16-CE35-0003 - AAPG2016 - VALID, Stratégie thérapeutique par voie radicalaire pour combattre des maladies parasitaires - - RADICAL2017 - ANR-17-CE18-0017 - AAPG2017 - VALID, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), 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], and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Redox, GSH Resistance, parasitic diseases, Superoxide, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Antioxidant, [CHIM.COOR] Chemical Sciences/Coordination chemistry, Artemisinin and Plasmodium
Abstract: International audience; Malaria remains a major public health disease due to its high yearly mortality and morbidity. Resistance to the gold standard drug, artemisinin, is worrisome and needs better understanding in order to be overcome. In this work, we sought to study whether redox processes are involved in artemisinin resistance. As artemisinin is known to act among others via production of reactive species, we first compared the production of reactive oxygen species and concomitant protein oxidation in artemisinin-sensitive and artemisinin-resistant parasites when treated with artemisinin. The results undoubtedly demonstrated, using different original methods, that the level of ROS, including superoxide production, and oxidized protein were lower in the resistant strain. Interestingly, the major in-between strain difference was reported at the earlier ring stages, which are the forms able to enter in a quiescence state according to the ART resistance phenomenon. Moreover, we demonstrated a better homeostasis regulation in relation with higher expression of antioxidants in the artemisinin-resistant parasites than their sensitive counterparts after artemisinin exposure, notably, superoxide dismutase and the glutathione (GSH) system. These findings enrich the body of knowledges about the multifaceted mechanism of artemisinin resistance and will help in the design and development of newer antimalarials strategies active against resistant parasites.
Published: 2022
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23. Mutation in the Plasmodium falciparum BTB/POZ Domain of K13 Protein Confers Artemisinin Resistance

Author: Nina F. Gnädig, Françoise Benoit-Vical, Romain Coppée, Jérôme Clain, David A. Fidock, Karamoko Niaré, Jean-Michel Augereau, Barbara H. Stokes, Lucie Paloque, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), New Antimalarial Molecules and Pharmacological Approaches (ERL1289), 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)-Université Toulouse III - Paul Sabatier (UT3), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de pharmacologie et de biologie structurale (IPBS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Columbia University Irving Medical Center (CUIMC), Malaria Research and Training Center [Bamako, Mali], Université de Bamako, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS), NIH (R01 AI109023), WorldWide Antimalarial Resistance Network (WWARN), ANR-17-CE15-0013,PlasmoPrim,Elucider les mécanismes d'action de deux agents redox antipaludiques aux propriétés gametocytocides et bloquant la transmission -- de la levure aux parasites du paludisme(2017), Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), 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], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Gulli, Marie-Hélène, and Elucider les mécanismes d'action de deux agents redox antipaludiques aux propriétés gametocytocides et bloquant la transmission -- de la levure aux parasites du paludisme - - PlasmoPrim2017 - ANR-17-CE15-0013 - AAPG2017 - VALID
Subjects: medicine.medical_treatment, Plasmodium falciparum, Drug Resistance, Protozoan Proteins, Dihydroartemisinin, medicine.disease_cause, Epidemiology and Surveillance, Antimalarials, parasitic diseases, medicine, Coding region, CRISPR, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Pharmacology (medical), Artemisinin, BTB/POZ domain, Gene, Pharmacology, Mutation, biology, K13 mutation, [CHIM.COOR] Chemical Sciences/Coordination chemistry, Editor's Pick, biology.organism_classification, Virology, Artemisinins, Malaria, Infectious Diseases, Artemisinin resistance, BTB-POZ Domain, medicine.drug
Abstract: International audience; Partial artemisinin resistance, defined in patients as a delayed parasite clearance following artemisinin-based treatment, is conferred by non-synonymous mutations in the Kelch beta-propeller domain of the Plasmodium falciparum k13 (pfk13) gene. Here, we carried out in vitro selection over a 1-year period on a West African P. falciparum strain isolated from Kolle (Mali) under a dose-escalating artemisinin regimen. After 18 cycles of sequential drug pressure, the selected parasites exhibited enhanced survival to dihydroartemisinin in the ring-stage survival assay (RSA0-3h = 9.2%). Sanger and whole-genome sequence analyses identified the PfK13 P413A mutation, localized in the BTB/POZ domain, upstream of the propeller domain. This mutation was sufficient to confer in vitro artemisinin resistance when introduced into the PfK13 coding sequence of the parasite strain Dd2 by CRISPR/Cas9 gene editing. These results together with structural studies of the protein demonstrate that the propeller domain is not the sole in vitro mediator of PfK13-mediated artemisinin resistance, and highlight the importance of monitoring for mutations throughout PfK13.
Published: 2022
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24. Neurofilament light levels predict clinical progression and death in multiple system atrophy

Author: Viorica Chelban, Elham Nikram, Alexandra Perez-Soriano, Carlo Wilke, Alexandra Foubert-Samier, Nirosen Vijiaratnam, Tong Guo, Edwin Jabbari, Simisola Olufodun, Mariel Gonzalez, Konstantin Senkevich, Brice Laurens, Patrice Péran, Olivier Rascol, Anne Pavy Le Traon, Emily G Todd, Alyssa A Costantini, Sondos Alikhwan, Ambreen Tariq, Bai Lin Ng, Esteban Muñoz, Celia Painous, Yaroslau Compta, Carme Junque, Barbara Segura, Kristina Zhelcheska, Henny Wellington, Ludger Schöls, Zane Jaunmuktane, Christopher Kobylecki, Alistair Church, Michele T M Hu, James B Rowe, P Nigel Leigh, Luke Massey, David J Burn, Nicola Pavese, Tom Foltynie, Sofya Pchelina, Nicholas Wood, Amanda J Heslegrave, Henrik Zetterberg, Martina Bocchetta, Jonathan D Rohrer, Maria J Marti, Matthis Synofzik, Huw R Morris, Wassilios G Meissner, Henry Houlden, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), 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), Toulouse Neuro Imaging Center (ToNIC), 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)-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), Université de Toulouse (UT), Centre d'investigation clinique de Toulouse (CIC 1436), 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), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical Research Council, Wellcome Trust, Alzheimer's Drug Discovery Foundation, Alzheimer's Association, Familjen Erling-Perssons Stiftelse, Stiftelsen för Gamla Tjänarinnor, UK Dementia Research Institute, Canada First Research Excellence Fund, Multiple System Atrophy Trust, Multiple System Atrophy Coalition, Guarantors of Brain, King Baudouin Foundation United States, European Research Council, and European Project: 825619,AI4EU
Subjects: multiple system atrophy, Intermediate Filaments, Multiple system atrophy, NfL, Cohort Studies, Cross-Sectional Studies, Neurofilament Proteins, MSA, Disease Progression, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ddc:610, Neurology (clinical), Biomarkers
Abstract: Supplementary material: Supplementary material is available at Brain online. Copyright © The Author(s) 2022. Disease-modifying treatments are currently being trialled in multiple system atrophy. Approaches based solely on clinical measures are challenged by heterogeneity of phenotype and pathogenic complexity. Neurofilament light chain protein has been explored as a reliable biomarker in several neurodegenerative disorders but data on multiple system atrophy have been limited. Therefore, neurofilament light chain is not yet routinely used as an outcome measure in multiple system atrophy. We aimed to comprehensively investigate the role and dynamics of neurofilament light chain in multiple system atrophy combined with cross-sectional and longitudinal clinical and imaging scales and for subject trial selection. In this cohort study, we recruited cross-sectional and longitudinal cases in a multicentre European set-up. Plasma and CSF neurofilament light chain concentrations were measured at baseline from 212 multiple system atrophy cases, annually for a mean period of 2 years in 44 multiple system atrophy patients in conjunction with clinical, neuropsychological and MRI brain assessments. Baseline neurofilament light chain characteristics were compared between groups. Cox regression was used to assess survival; receiver operating characteristic analysis to assess the ability of neurofilament light chain to distinguish between multiple system atrophy patients and healthy controls. Multivariate linear mixed-effects models were used to analyse longitudinal neurofilament light chain changes and correlated with clinical and imaging parameters. Polynomial models were used to determine the differential trajectories of neurofilament light chain in multiple system atrophy. We estimated sample sizes for trials aiming to decrease neurofilament light chain levels. We show that in multiple system atrophy, baseline plasma neurofilament light chain levels were better predictors of clinical progression, survival and degree of brain atrophy than the neurofilament light chain rate of change. Comparative analysis of multiple system atrophy progression over the course of disease, using plasma neurofilament light chain and clinical rating scales, indicated that neurofilament light chain levels rise as the motor symptoms progress, followed by deceleration in advanced stages. Sample size prediction suggested that significantly lower trial participant numbers would be needed to demonstrate treatment effects when incorporating plasma neurofilament light chain values into multiple system atrophy clinical trials in comparison to clinical measures alone. In conclusion, neurofilament light chain correlates with clinical disease severity, progression and prognosis in multiple system atrophy. Combined with clinical and imaging analysis, neurofilament light chain can inform patient stratification and serve as a reliable biomarker of treatment response in future multiple system atrophy trials of putative disease-modifying agents. This study was supported by the MSA Trust (PROSPECT-M-UK). We are grateful to the Multiple System Atrophy Coalition, Medical Research Council (MRC UK MR/J004758/1, G0802760, G1001253), The Wellcome Trust (Synaptopathies) (WT093205MA and WT104033/Z/14/Z), the French Clinical Research Programme (AOI 2011-BIOAMS, API 2012-BIOPARK) and the PSP Association (PROSPECT-M-UK) and ‘Solve-RD’ from the Horizon 2020 research and innovation programme (grant 779257 to M.S. and H.H.) for their support. V.C. received grants from the Multiple System Atrophy Trust/ABN Clinical Research Training fellowship grant F84 ABN 540868, Multiple System Atrophy Trust (PROSPECT-M-UK Project), Multiple System Atrophy Coalition grant 567540, The Guarantors of Brain grant 565908 and King Baudouin Foundation (Sophia Fund). H.Z. is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), King Baudouin Foundation (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the Alzheimer’s Association (AD Strategic Fund #ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C), the Olav Thon Stiftelsen, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 860197 (MIRIADE), European Union Joint Program for Neurodegenerative Disorders (JPND2021-00694) and the UK Dementia Research Institute at UCL. The Simoa instrument was funded by a Multi-User Equipment grant from the Wellcome Trust to H.Z. and A.H. J.D.R. is an MRC Clinician Scientist (MR/M008525/1) and has received funding from the NIHR Rare Diseases Translational Research Collaboration (BRC149/NS/MH), the Bluefield Project and the Association for Frontotemporal Degeneration. M.B. is supported by a Fellowship award from the Alzheimer’s Society, UK (AS-JF-19a-004-517). M.B.’s work was also supported by the UK Dementia Research Institute, which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. K.S. is supported by a postdoctoral fellowship from the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives initiative (HBHL) and the Fonds de recherche du Québec – Santé (FRQS) postdoctoral fellowship. C.W. and M.S. are members of the European Reference Network for Rare Neurological Diseases Project ID no. 739510. C.W. was supported by the Clinician Scientist Program of the Medical Faculty Tübingen (grant 480-0-0). M.J.M. and C.J. acknowledge the Centres de Recerca de Catalunya (CERCA) Programme/Generalitat de Catalunya, the Institute of Neurosciences and the Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) and CIBERNED. This study was sponsored by the PID2020-114640GB-I00/MCIN/AEI/10.13039/501100011033, by Generalitat de Catalunya (2017SGR748), and by María de Maeztu Unit of Excellence (Institute of Neurosciences, University of Barcelona) MDM-2017-0729, Ministry of Science, Innovation and Universities. Samples were generously donated by participants with MSA thanks to the funding by Fundacio Marato TV3 grant no. 20142730. C.P. received a grant Rio Hortega from Instituto de Salud Carlos III (CM18/00072). J.B.R. is supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014; The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care), Wellcome Trust (220258) and Medical Research Council (SUAG/092 G168768). For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Published: 2022
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25. Quantification of Head Tremors in Medical Conditions: A Comparison of Analyses Using a 2D Video Camera and a 3D Wireless Inertial Motion Unit

Author: David Amarantini, Isabelle Rieu, Giovanni Castelnovo, Frédérique Fluchère, Chloé Laurencin, Bertrand Degos, Aurélia Poujois, Alexandre Kreisler, Sophie Sangla, Mélissa Tir, Isabelle Benatru, Geneviève Blanchet-Fourcade, Dominique Guehl, Dominique Gayraud, Laurent Tatu, Christine Tranchant, Franck Durif, Marion Simonetta-Moreau, Toulouse Neuro Imaging Center (ToNIC), 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)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Rothschild [AP-HP], Département de Pharmacologie, PRES Université Lille Nord de France, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), 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), Centre Hospitalier de Narbonne, CHU Bordeaux [Bordeaux], Service de neurologie, Hôpital Général, Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Département Neurologie [CHU Toulouse], Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), DESSAIVRE, Louise, 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), Université de Toulouse (UT), CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Aix Marseille Université (AMU), CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, CHU Amiens-Picardie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHI Aix Pertuis CHPA-CHIAP, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital de Hautepierre [Strasbourg], Centre d'investigation clinique de Toulouse (CIC 1436), and 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]
Subjects: head tremor amplitude, head tremor frequency, 2D video motion analysis, miniature wireless inertial magnetic motion unit, Fourier transform, wavelet transform, [SDV]Life Sciences [q-bio], Biochemistry, Atomic and Molecular Physics, and Optics, Analytical Chemistry, [SDV] Life Sciences [q-bio], Motion, Head Movements, Tremor, Humans, Electrical and Electronic Engineering, Instrumentation
Abstract: International audience; This study compares two methods to quantify the amplitude and frequency of head movements in patients with head tremor: one based on video-based motion analysis, and the other using a miniature wireless inertial magnetic motion unit (IMMU). Concomitant with the clinical assessment of head tremor severity, head linear displacements in the frontal plane and head angular displacements in three dimensions were obtained simultaneously in forty-nine patients using one video camera and an IMMU in three experimental conditions while sitting (at rest, counting backward, and with arms extended). Head tremor amplitude was quantified along/around each axis, and head tremor frequency was analyzed in the frequency and time-frequency domains. Correlation analysis investigated the association between the clinical severity of head tremor and head linear and angular displacements. Our results showed better sensitivity of the IMMU compared to a 2D video camera to detect changes of tremor amplitude according to examination conditions, and better agreement with clinical measures. The frequency of head tremor calculated from video data in the frequency domain was higher than that obtained using time-frequency analysis and those calculated from the IMMU data. This study provides strong experimental evidence in favor of using an IMMU to quantify the amplitude and time-frequency oscillatory features of head tremor, especially in medical conditions.
Published: 2022
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26. 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
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27. Outcome of Progressive Multifocal Leukoencephalopathy Treated by Interleukin-7

Author: Lajaunie, Rébecca, Mainardi, Ilaria, Gasnault, Jacques, Rousseau, Vanessa, Tarantino, Andrea, Sommet, Agnès, Cinque, Paola, Martin-Blondel, Guillaume, Debard, Alexa, Delobel, Pierre, Pansu, Nathalie, Gollion, Cédric, Benaiteau, Marie, Jacomet, Christine, Mélé, Nicolas, Moulignier, Antoine, Suarez, Felipe, Ruch, Yvon, Tranchant, Christine, Lemaignen, Adrien, Langner-Lemercier, Sophie, Buzele, Rodolphe, Guffroy, Aurelien, Moluçon-Chabrot, Cécile, Tattevin, Pierre, Melica, Giovanna, Badiu, Carmen‐ionela, Cheraud-Bonfort, Chrystel, Salmon, Anne, Alstadhaug, Karl Bjornar, Kuhlmann, F. Matthew, Gorza, Lucas, Wang, Adrien, Wille, Heidi, Curlier, Elodie, Hessamfar, Mojgan, Valour, Florent, Perpoint, Thomas, Koralnik, Igor, Decaestecker, Kevin, Vindrios, William, Guilbert, Anne, Boulesteix, Jean Marc, Verdière, Sylvie Colin De, Roux, Antoine, Patel, Amila, Fabian, Michelle, Harel, Asaff, Wyplosz, Benjamin, Ader, Florence, 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)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), San Raffaele Scientific Institute, Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, Immunologie intégrative des tumeurs (UMR 1186), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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], Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), 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 ), and This study was not funded.
Subjects: MESH: Humans, Interleukin-7, MESH: Leukoencephalopathy, Progressive Multifocal, MESH: JC Virus, Leukoencephalopathy, Progressive Multifocal, MESH: Retrospective Studies, [SDV.CAN]Life Sciences [q-bio]/Cancer, HIV Infections, MESH: HIV Infections, JC Virus, MESH: Interleukin-7, Neurology, Hematologic Neoplasms, Humans, Neurology (clinical), MESH: Hematologic Neoplasms, Retrospective Studies
Abstract: International audience; Objective: Restoring anti-JC virus (JCV) immunity is the only treatment of progressive multifocal leukoencephalopathy (PML). Interleukin-7 is a cytokine that increases number and function of T cells. We analyzed a population of PML patients who received recombinant human IL-7 (rhIL-7) to estimate survival and its determinants.Methods: After exclusion of patients with missing data or receiving other immunotherapies, findings from 64 patients with proven PML who received rhIL-7 between 2007 and 2020 were retrospectively analyzed. Logistic regression was used to analyze variables associated with one-year survival.Results: Underlying conditions were HIV/AIDS (n = 27, 42%), hematological malignancies (n = 16, 25%), primary immunodeficiencies (n = 13, 20%), solid organ transplantation (n = 4, 6%) and chronic inflammatory diseases (n = 4, 6%). One-year survival was 54.7% and did not differ by underlying condition. Survival was not associated with baseline characteristics, but with a >50% increase in blood lymphocytes (OR 4.1, 95%CI 1.2-14.9) and CD4+ T cells (OR 5.9, 95%CI 1.7-23.3), and a > 1 log copies/mL decrease in cerebrospinal fluid JCV DNA (OR 7.6, 95%CI 1.6-56.1) during the first month after rhIL-7 initiation. Side effects were mainly local and flu-like symptoms (n = 8, 12.5%) and PML-immune reconstitution inflammatory syndrome (IRIS) (n = 5, 8%).Interpretation: In this non-controlled retrospective study, survival did not differ from that expected in HIV/AIDS patients, but might have been improved in those with hematological malignancies, primary immunodeficiencies and transplant recipients. RhIL-7 might have contributed to the increase in blood lymphocytes and decrease in CSF JCV replication that were associated with better survival. ANN NEUROL 2022;91:496-505.
Published: 2021
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28. Reactive Oxygen Species as the Brainbox in Malaria Treatment

Author: Françoise Benoit-Vical, Jean-Michel Augereau, Karine Reybier, Chinedu O. Egwu, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Alex Ekwueme Federal University Ndufu-Alike, Ikwo (AE-FUNAI), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), New Antimalarial Molecules and Pharmacological Approaches (ERL1289), Centre d'investigation clinique de Toulouse (CIC 1436), 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)-Université Toulouse III - Paul Sabatier (UT3), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), CNRS (Centre National de la Recherche Scientifique, France), Université Paul Sabatier, Toulouse III (France), IRD (Institut de Recherche pour le Développement, France), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), 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], Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), and Pagès, Nathalie
Subjects: malaria and oxidative stress, Physiology, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Plasmodium falciparum, RM1-950, Review, medicine.disease_cause, Biochemistry, antimalarials, parasitic diseases, medicine, Artemisinin, Molecular Biology, chemistry.chemical_classification, Reactive oxygen species, biology, ROS, Cell Biology, biology.organism_classification, medicine.disease, [SDV] Life Sciences [q-bio], chemistry, Immunology, Therapeutics. Pharmacology, Malaria control, Malaria, Oxidative stress, medicine.drug
Abstract: International audience; Several measures are in place to combat the worldwide spread of malaria, especially in regions of high endemicity. In part, most common antimalarials, such as quinolines and artemisinin and its derivatives, deploy an ROS-mediated approach to kill malaria parasites. Although some antimalarials may share similar targets and mechanisms of action, varying levels of reactive oxygen species (ROS) generation may account for their varying pharmacological activities. Regardless of the numerous approaches employed currently and in development to treat malaria, concerningly, there has been increasing development of resistance by Plasmodium falciparum, which can be connected to the ability of the parasites to manage the oxidative stress from ROS produced under steady or treatment states. ROS generation has remained the mainstay in enforcing the antiparasitic activity of most conventional antimalarials. However, a combination of conventional drugs with ROS-generating ability and newer drugs that exploit vital metabolic pathways, such antioxidant machinery, could be the way forward in effective malaria control.
Published: 2021
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29. Skeletal Ryanodine Receptors Are Involved in Impaired Myogenic Differentiation in Duchenne Muscular Dystrophy Patients

Author: Jean-Marie Cuisset, Jérôme Cottalorda, Stefan Matecki, Gérald Hugon, Alain Lacampagne, Pierre Meyer, Cécile Notarnicola, Hugues Chevassus, Albano C. Meli, Pascal Sabouraud, François Rivier, Léonard Féasson, Mirna Khalil, Gilles Carnac, Jérémy Salvador, Claude Cances, Isabelle Desguerre, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Reims (CHU Reims), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), 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], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris Cité (UPCité), Herrada, Anthony, Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), and Université de Paris (UP)
Subjects: Male, Duchenne muscular dystrophy, Muscle Fibers, Skeletal, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Muscle Development, Calcium in biology, Dystrophin, Myoblasts, 0302 clinical medicine, Myocyte, Biology (General), Child, Spectroscopy, Cells, Cultured, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Ryanodine receptor, Myogenesis, Cell Differentiation, General Medicine, musculoskeletal system, Computer Science Applications, Chemistry, Sarcoplasmic Reticulum, medicine.anatomical_structure, Child, Preschool, myogenesis, tissues, Intracellular, musculoskeletal diseases, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, QH301-705.5, Catalysis, Article, Inorganic Chemistry, Tacrolimus Binding Proteins, 03 medical and health sciences, ryanodine receptor, endomysial fibrosis, human, Internal medicine, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine, Humans, Calcium Signaling, Physical and Theoretical Chemistry, Muscle, Skeletal, Molecular Biology, QD1-999, 030304 developmental biology, RYR1, business.industry, Organic Chemistry, Skeletal muscle, Ryanodine Receptor Calcium Release Channel, medicine.disease, Muscular Dystrophy, Duchenne, Endocrinology, Calcium, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Duchenne muscular dystrophy (DMD) is characterized by progressive muscle wasting following repeated muscle damage and inadequate regeneration. Impaired myogenesis and differentiation play a major role in DMD as well as intracellular calcium (Ca2+) mishandling. Ca2+ release from the sarcoplasmic reticulum is mostly mediated by the type 1 ryanodine receptor (RYR1) that is required for skeletal muscle differentiation in animals. The study objective was to determine whether altered RYR1-mediated Ca2+ release contributes to myogenic differentiation impairment in DMD patients. The comparison of primary cultured myoblasts from six boys with DMD and five healthy controls highlighted delayed myoblast differentiation in DMD. Silencing RYR1 expression using specific si-RNA in a healthy control induced a similar delayed differentiation. In DMD myotubes, resting intracellular Ca2+ concentration was increased, but RYR1-mediated Ca2+ release was not changed compared with control myotubes. Incubation with the RYR-calstabin interaction stabilizer S107 decreased resting Ca2+ concentration in DMD myotubes to control values and improved calstabin1 binding to the RYR1 complex. S107 also improved myogenic differentiation in DMD. Furthermore, intracellular Ca2+ concentration was correlated with endomysial fibrosis, which is the only myopathologic parameter associated with poor motor outcome in patients with DMD. This suggested a potential relationship between RYR1 dysfunction and motor impairment. Our study highlights RYR1-mediated Ca2+ leakage in human DMD myotubes and its key role in myogenic differentiation impairment. RYR1 stabilization may be an interesting adjunctive therapeutic strategy in DMD.
Published: 2021
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30. Myocarditis and Pericarditis in Adolescents after First and Second doses of mRNA COVID-19 Vaccines

Author: Déborah Foltran, Clément Karsenty, François Montastruc, Clara Flumian, Pierre De Paoli, Sophie Gautier, Clément Delmas, Francesco Salvo, Milou-Daniel Drici, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), 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], CHU Lille, Université de Lille, Hôpital Pasteur [Nice] (CHU), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université de Toulouse (UT)-Université de Toulouse (UT)-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), 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], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), and Admin, Oskar
Subjects: Male, Myocarditis, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Adolescent, MEDLINE, Pericarditis, medicine, Humans, AcademicSubjects/MED00200, RNA, Messenger, Child, ComputingMilieux_MISCELLANEOUS, Messenger RNA, business.industry, SARS-CoV-2, Health Policy, Adolescent RNA messenger, COVID-19, medicine.disease, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Original Article, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Aims While some concerns about vaccination-related pericarditis and/or myocarditis have been raised, no published data are available on pericarditis and/or myocarditis with mRNA COVID-19 vaccines in the age group of adolescents, particularly 12–15 years. The objective of this study was to determine whether the risk of reporting pericarditis and/or myocarditis with mRNA COVID-19 vaccines varied according to dose of vaccination, age, sex, and type of pericarditis and/or myocarditis in adolescents between 12 and 17 years. Methods and results We performed an observational study reviewing all reports of adolescents vaccinated with mRNA COVID-19 vaccines and recorded in VigiBase®, the World Health Organization global database of individual case safety reports. We included all reports registered between 1 January 2021 and 14 September 2021. Reporting odds ratios (RORs) with their 95% confidence interval (CI) were calculated to estimate the risk of reporting pericarditis and/or myocarditis. Among 4942 reports with mRNA COVID-19 vaccines in adolescents, we identified 242 pericarditis and/or myocarditis. Compared with the first dose of mRNA COVID-19 vaccines, the second dose was associated with an increased risk of reporting pericarditis and/or myocarditis (ROR 4.95; 95% CI 3.14, 7.89). The risk of reporting pericarditis and/or myocarditis was 10 times higher in boys than in girls and no difference between the two types of vaccines could be demonstrated. Conclusion This investigation including only adolescent data suggests for the first time that the second dose of mRNA COVID-19 vaccines increases the risk of reporting myocarditis/pericarditis compared with the first dose particularly in boys without significant difference between tozinameran and elasomeran.
Published: 2021
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31. Exposure to inorganic particles in paediatric sarcoidosis: the PEDIASARC study

Author: Véronique Houdouin, Catherine Cavalin, Antoine Deschildre, Jean-Marc Naccache, Catherine Chapelon-Abric, Céline Delestrain, Julien Haroche, Ralph Epaud, Ulrich Meinzer, Simon Chauveau, Fleur Cohen-Aubart, Mickaël Catinon, Florence Jeny, Odile Macchi, Sylvain Le Jeune, Hilario Nunes, Michel Vincent, Paul-André Rosental, Manon Brocvielle, Marie-Hélène Odièvre, Marie-Emeline Montagne, S. Mattioni, Dominique Valeyre, Karine Juvin, Annick Clement, Dominique Israël-Biet, A. Dossier, Nadia Nathan, Jacques Brouard, François Lionnet, Lucile Sesé, Rola Abou Taam, Christophe Delacourt, Marie Mittaine, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Recherche Interdisciplinaire en Sciences Sociales (IRISSO), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Service de pneumologie [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Pneumologie et allergologie pédiatriques [CHU Jeanne de Flandre, Lille], Hôpital Jeanne de Flandre [Lille], Université de Lille, Service de Pneumologie et d'Allergologie Pédiatriques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Service de Pneumologie, soins intensifs (Pneumo - HEGP), 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), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], CHU Tenon [AP-HP], Centre d'études européennes et de politique comparée (Sciences Po, CNRS) (CEE), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPC), Centre d'histoire de Sciences Po (Sciences Po) (CHSP), Sciences Po (Sciences Po), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Observatoire du Samu Social de Paris, CHU Necker - Enfants Malades [AP-HP], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre des maladies respiratoires rares Respirare [CHI Créteil], 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), AP-HP - Hôpital Bichat - Claude Bernard [Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de médecine interne [Avicenne], Centre de Référence pour les Maladies Rhumatologiques Auto-Immunes et Systémiques [CHU Necker] (RAISE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de pneumologie [Hôpital Foch], Hôpital Foch [Suresnes], Groupe Hospitalier Paris Saint-Joseph (hpsj), Laboratoire interdisciplinaire d'évaluation des politiques publiques (Sciences Po) (LIEPP), Centre d'études de l'emploi et du travail (CEET), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Ministère du Travail, de l'Emploi et de la Santé, contract grant sponsor: European Research Council (ERC) / SILICOSISproject / Principal investigator: Paul-André Rosental, Contract grant number: ERC2011-ADG_20110406ˆProject ID: 295817. Statistical analysis: RespiFIL funds, European Project: 295449,EC:FP7:ERC,ERC-2011-ADG_20110406,DARTCH(2012), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'études européennes et de politique comparée (CEE), Centre d'histoire de Sciences Po (CHSP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], and Centre National de la Recherche Scientifique (CNRS)-Sciences Po (Sciences Po)
Subjects: Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, paediatric interstitial lung disease, [SDV]Life Sciences [q-bio], [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Occupational Exposure, medicine, Humans, sarcoidosis, Occupational lung disease, Occupations, Child, Inorganic particles, 030304 developmental biology, 0303 health sciences, Median score, rare lung diseases, business.industry, Dust, Environmental exposure, Environmental Exposure, medicine.disease, 3. Good health, 030228 respiratory system, Metal dust, Talc, Sarcoidosis, business, occupational lung disease
Abstract: International audience; Inorganic antigens may contribute to paediatric sarcoidosis. Thirty-six patients matched with 36 healthy controls as well as a group of 21 sickle-cell disease (SCD) controls answered an environmental questionnaire. Patients' indirect exposure to inorganic particles, through coresidents' occupations, was higher than in healthy and SCD controls (median score: 2.5 (0.5-7) vs 0.5 (0-2), p=0.003 and 1 (0-2), p=0.012, respectively), especially for construction, exposures to metal dust, talc, abrasive reagents and scouring products. Wood or fossil energies heating were also linked to paediatric sarcoidosis. This study supports a link between mineral environmental exposure due to adult coresident occupations and paediatric sarcoidosis.
Published: 2021
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32. Impact of aging on phenotype and prognosis in IgA vasculitis

Author: Stanislas Faguer, Noémie Le Gouellec, François Maurier, Bertrand Lioger, Patrice Cacoub, Noémie Jourde-Chiche, Sébastien Sanges, Christian Lavigne, Benjamin Terrier, Julie Goutte, Geoffrey Urbanski, Zahir Amoura, Aurélie Hummel, Evangeline Pillebout, Sophie Deriaz, Loic Raffray, Alban Deroux, Alexandra Audemard-Verger, Elisabeth Diot, Guillaume Moulis, Nicole Feirreira-Maldent, Johan Chanal, François Maillot, A. Baldolli, Loïc Guillevin, Jean-François Augusto, Eric Thervet, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier [Valenciennes, Nord], Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), LUNAM Université [Nantes Angers Le Mans], Département de Néphrologie-Dialyse-Transplantation [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), PRES Université Nantes Angers Le Mans (UNAM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), 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 [Grenoble] (CHU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe de recherche clinique Biomarqueurs d’urgence et de réanimation (GRC 14 - BIOSFAST), Sorbonne Université (SU), 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), Hôpital Ambroise Paré [AP-HP], Service de médecine interne et gérontologie clinique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Vasculaire [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Plateforme Histologie, Immunomarquage et Microdissection laser [Institut Cochin] (HistIM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Immunoglobulin A, Adult, Male, Vasculitis, medicine.medical_specialty, Aging, Henoch-Schonlein purpura, Disease, 03 medical and health sciences, IgA vasculitis, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Humans, Pharmacology (medical), Aged, Retrospective Studies, 030203 arthritis & rheumatology, biology, business.industry, Age Factors, Retrospective cohort study, Middle Aged, medicine.disease, renal involvement, Purpura, 030104 developmental biology, Phenotype, Quartile, age, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, biology.protein, outcome, Kidney Failure, Chronic, Female, prognosis, medicine.symptom, business, Henoch–Schönlein purpura
Abstract: Objectives Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis most frequently benign in children while more severe in adults. We aimed to study the impact of age on presentation and outcome of adult IgAV. Methods We conducted a nationwide retrospective study including 260 IgAV patients. Patients were divided into four quartiles according to the age at IgAV diagnosis: Results Mean age at diagnosis was 50.1 (18) years and 63% were male. IgAV diagnosed in the lowest quartile of age was associated with more frequent joint (P 6 months, clinical response and relapse rates were similar between the four groups. Median follow-up was of 17.2 months (9.1–38.3 months). Renal failure at the end of follow-up was significantly more frequent in the highest quartile of age (P = 0.02), but the occurrence of end-stage renal disease was similar in all groups. Last, overall and IgAV-related deaths were associated with increase in age. Conclusion Aging negatively impacts the severity and outcome of IgAV in adults. Younger patients have more frequent joint and gastrointestinal involvement, while old patients display more frequent severe purpura and glomerulonephritis.
Published: 2021
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33. Distortion of voiced obstruents for differential diagnosis between parkinson's disease and multiple system atrophy

Author: Daoudi, Khalid, Das, Biswajit, Milhé de Saint Victor, Solange, Foubert-Samier, Alexandra, Pavy-Le Traon, Anne, Rascol, Olivier, Meissner, Wassilios, Woisard, Virginie, Geometry and Statistics in acquisition data (GeoStat), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], This work is funded by the French research agency (ANR), project Voice4PD-MSA n° ANR-16-CE19-0010-01., ANR-16-CE19-0010,Voice4PD-MSA,Diagnostic différentiel entre la maladie de Parkinson et l'atrophie multisystématisée par analyse numérique de la parole(2016), 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], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Das, Biswajit, Diagnostic différentiel entre la maladie de Parkinson et l'atrophie multisystématisée par analyse numérique de la parole - - Voice4PD-MSA2016 - ANR-16-CE19-0010 - AAPG2016 - VALID, and 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]
Subjects: Pathological speech processing, Parkinson's disease, Dysarthria, Consonant distortion, [INFO]Computer Science [cs], Multiple system atrophy, [INFO] Computer Science [cs], nervous system diseases
Abstract: International audience; Parkinson's disease (PD) and the parkinsonian variant of Multiple System Atrophy (MSA-P) are two neurodegenerative diseases which share similar clinical features, particularly in early disease stages. The differential diagnosis can be thus very challenging. Dysarthria is known to be a frequent and early clinical feature of PD and MSA. It can be thus used as a vehicle to provide a vocal biomarker which could help in the differential diagnosis. In particular, distortion of consonants is known to be a frequent impairment in these diseases. The aim of this study is to investigate distinctive patterns in the distortion of voiced obstruents (plosives and fricatives). It is the first study which attempts to examine such distortions in the French language for the purpose of the differential diagnosis between PD and MSA-P (and among the very few studies if we consider all languages). We carry out a perceptual and objective analysis of voiced obstruents extracted from isolated pseudo-words initials. We first show that devoicing is a significant impairment which predominates in MSA-P. We then show that voice onset time (VOT) of voiced plosives (prevoicing duration) can be a complementary feature to improve the accuracy in discrimination between PD and MSA-P.
Published: 2021

34. Comparison of the first and second waves of coronavirus disease in Toulouse, France

Author: Guillaume Martin-Blondel, Pierre Delobel, Aurélie Jourdes, G. Moulis, Marie Faruch, Agnès Sommet, Margaux Lafaurie, 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)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service Pharmacologie Clinique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre d'investigation clinique de Toulouse (CIC 1436), 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)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Pistre, Karine
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Epidemiology, [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Disease, medicine.disease_cause, Article, MESH: COVID-19, Medicine, Humans, MESH: SARS-CoV-2, Coronavirus, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: France / epidemiology, MESH: Humans, business.industry, SARS-CoV-2, COVID-19, Virology, [SDV] Life Sciences [q-bio], Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business
Abstract: International audience; We conducted a retrospective Covid-clinic-Toul cohort study at Toulouse university hospital, in southern France (2800 beds, tertiary hospital covering an area of about 3 million inhabitants) and selected hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia from September 1st, 2020 to October 31st, 2020. We compared their demographics, clinical, biological and radiological features, as well as unfavorable outcome (admission in an intensive care unit, mechanical ventilation, death) at Day 14 after admission to those of hospitalized patients during the 1st wave (March 11, 2020 to April 20, 2020).
Published: 2021
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35. Metabolic and cardiovascular adaptations to an 8-wk lifestyle weight loss intervention in younger and older obese men

Author: Dominique Langin, Marie-Adeline Marques, Cédric Dray, Sylvie Caspar-Bauguil, Dominique Larrouy, Sophie Bonnel, Philippe Valet, Cécile Vindis, Nathalie Viguerie, Veronika Šrámková, Virginie Bourlier, Isabelle Harant, Laurent O. Martinez, Cedric Moro, Thibaut Duparc, Claire Thalamas, Joost P. Schanstra, Jean-Sébastien Saulnier-Blache, Emilie Montastier, Nabila Moussaoui, Julie Vion, Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), 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), Charles University [Prague] (CU), Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [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], Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Saulnier-Blache, Jean Sébastien, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Mégard, Roxane
Subjects: Gerontology, Adult, Male, medicine.medical_specialty, Physiology, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Calorie restriction, 030209 endocrinology & metabolism, Physical exercise, 030204 cardiovascular system & hematology, Cardiovascular System, 03 medical and health sciences, 0302 clinical medicine, Weight loss, physical exercise, Physiology (medical), Internal medicine, Intervention (counseling), cardiometabolic risk, Obesity management, medicine, Humans, Obesity, Life Style, Aged, 2. Zero hunger, Cardiometabolic risk, business.industry, Public health, aging, Age Factors, calorie restriction, Middle Aged, medicine.disease, Adaptation, Physiological, 3. Good health, [SDV] Life Sciences [q-bio], Weight Reduction Programs, Body Composition, medicine.symptom, business
Abstract: International audience; The number of older obese adults is increasing worldwide. Whether obese adults show similar health benefits in response to lifestyle interventions at different ages is unknown. The study enrolled 25 obese men (body mass index: 31-39 kg/m2) in two arms according to age (30-40 and 60-70 yr old). Participants underwent an 8-wk intervention with moderate calorie restriction (∼20% below individual energy requirements) and supervised endurance training resulting in ∼5% weight loss. Body composition was measured using dual energy X-ray absorptiometry. Insulin sensitivity was assessed during a hypersinsulinemic-euglycemic clamp. Cardiometabolic profile was derived from blood parameters. Subcutaneous fat and vastus lateralis muscle biopsies were used for ex vivo analyses. Two-way repeated-measure ANOVA and linear mixed models were used to evaluate the response to lifestyle intervention and comparison between the two groups. Fat mass was decreased and bone mass was preserved in the two groups after intervention. Muscle mass decreased significantly in older obese men. Cardiovascular risk (Framingham risk score, plasma triglyceride, and cholesterol) and insulin sensitivity were greatly improved to a similar extent in the two age groups after intervention. Changes in adipose tissue and skeletal muscle transcriptomes were marginal. Analysis of the differential response to the lifestyle intervention showed tenuous differences between age groups. These data suggest that lifestyle intervention combining calorie restriction and exercise shows similar beneficial effects on cardiometabolic risk and insulin sensitivity in younger and older obese men. However, attention must be paid to potential loss of muscle mass in response to weight loss in older obese men.NEW & NOTEWORTHY Rise in obesity and aging worldwide are major trends of critical importance in public health. This study addresses a current challenge in obesity management. Do older obese adults respond differently to a lifestyle intervention composed of moderate calorie restriction and supervised physical activity than younger ones? The main conclusion of the study is that older and younger obese men similarly benefit from the intervention in terms of cardiometabolic risk.
Published: 2021
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36. Cynomolgus macaque IL37 polymorphism and control of SIV infection

Author: Henri-Jean Garchon, Nicolas Tchitchek, Delphine Desjardins, Roger Le Grand, Bruno Vaslin, Takashi Shiina, Nicolas Congy-Jolivet, Nathalie Dereuddre-Bosquet, Brigitte Autran, Ioannis Theodorou, Olivier Lambotte, Antoine Blancher, Alice Aarnink, Shingo Suzuki, Tokai University, Japan, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Neurology, André Mignot Hospital, University of Versailles, St-Quentin-en-Yvelines, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Tokai University, Laboratoire d'Immunogénétique Moléculaire (LIMT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, CHU Toulouse [Toulouse], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Ambroise Paré [AP-HP], Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre de Physiopathologie Toulouse Purpan (CPTP), 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), ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), ANR-10-EQPX-0002,FlowCyTech,Plateforme de phénotypage en Mass cytométrie pour l'analyse multiparamétrique de biomarqueurs complexes de l'efficacité de nouvelles stratégies thérapeutiques ou vaccinales(2010), Université de Toulouse (UT)-Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI)
Subjects: MESH: Histocompatibility Antigens Class I / immunology, Male, 0301 basic medicine, Candidate gene, [SDV]Life Sciences [q-bio], Simian Acquired Immunodeficiency Syndrome, Gene Expression, lcsh:Medicine, MESH: Base Sequence, MESH: Linear Models, Exon, 0302 clinical medicine, Polymorphism (computer science), Gene expression, Odds Ratio, MESH: Animals, lcsh:Science, MESH: High-Throughput Nucleotide Sequencing, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, MESH: Host-Pathogen Interactions / immunology, High-Throughput Nucleotide Sequencing, Exons, Viral Load, MESH: Interleukin-1 / genetics, 3. Good health, MESH: Histocompatibility Antigens Class I / genetics, MESH: Interferon-Stimulated Gene Factor 3, gamma Subunit / immunology, Host-Pathogen Interactions, [SDV.IMM]Life Sciences [q-bio]/Immunology, Simian Immunodeficiency Virus, MESH: Interleukin-1 / immunology, HIV infections, MESH: Host-Pathogen Interactions / genetics, MESH: Gene Expression, Single-nucleotide polymorphism, Biology, MESH: Genetic Loci, Polymorphism, Single Nucleotide, MESH: Interferon-Stimulated Gene Factor 3, gamma Subunit / genetics, Article, 03 medical and health sciences, Immunogenetics, Animals, Gene, Base Sequence, Histocompatibility Antigens Class I, Haplotype, lcsh:R, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Haplotypes, Odds ratio, Virology, Interferon-Stimulated Gene Factor 3, gamma Subunit, Macaca fascicularis, 030104 developmental biology, Haplotypes, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Genetic Loci, Linear Models, lcsh:Q, MESH: Exons, Sequence Alignment, 030217 neurology & neurosurgery, Interleukin-1
Abstract: The association between gene polymorphisms and plasma virus load at the set point (SP-PVL) was investigated in Mauritian macaques inoculated with SIV. Among 44 macaques inoculated with 50 AID50, six individuals were selected: three with SP-PVL among the highest and three with SP-PVL among the lowest. The exons of 390 candidate genes of these six animals were sequenced. Twelve non-synonymous single nucleotide polymorphisms (NS-SNPs) lying in nine genes potentially associated with PVL were genotyped in 23 animals. Three NS-SNPs with probabilities of association with PVL less than 0.05 were genotyped in a total of 44 animals. One NS-SNP lying in exon 1 of the IL37 gene displayed a significant association (p = 3.33 × 10−4) and a strong odds ratio (19.52). Multiple linear regression modeling revealed three significant predictors of SP-PVL, including the IL37 exon 1 NS-SNP (p = 0.0004) and the MHC Class IB haplotypes M2 (p = 0.0007) and M6 (p = 0.0013). These three factors in conjunction explained 48% of the PVL variance (p = 4.8 × 10−6). The potential role of IL37 in the control of SIV infection is discussed.
Published: 2019
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37. Methods in pharmacoepidemiology

Author: Agnès Sommet, Antoine Pariente, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), and CHU Bordeaux [Bordeaux]
Subjects: Drug, Research design, medicine.medical_specialty, Databases, Factual, Drug-Related Side Effects and Adverse Reactions, Drug exposure, media_common.quotation_subject, MEDLINE, Context (language use), 030226 pharmacology & pharmacy, Databases, 03 medical and health sciences, 0302 clinical medicine, Environmental health, Epidemiology, Methods, Humans, Medicine, Pharmacology (medical), media_common, business.industry, Pharmacoepidemiology, Clinical study design, Study designs, 3. Good health, Research Design, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Phase IV, business
Abstract: International audience; Pharmacoepidemiology is the study of interactions between drugs and human populations, investigating, in real conditions of life, benefits, risks and use of drugs. Pharmacoepidemiology applies to drugs and their pharmacological evaluations, the different methods also used in epidemiology to assess in real conditions of life, benefits, risks and use of drugs. Pharmacoepidemiologic studies are ad-hoc studies or studies on databases. Specific methods exist to measure drug exposure, as well as indicators of compliance and misuse of drugs. Various designs for descriptive and explanatory studies exist, in a context in which a growing proportion of studies are carried out using medico-administrative data. The limits traditionally affecting the study designs are modified in this context, almost any design selected for the conduct of a study from these databases then deriving from a cohort in whom the information has been recorded prospectively and exhaustively.
Published: 2019
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38. Effects of proprotein convertase subtilisin kexin type 9 modulation in human pancreatic beta cells function

Author: Matthieu Wargny, Valentin Blanchard, Mikaël Croyal, Valery Gmyr, E. Nobecourt, Stéphane Ramin-Mangata, Cécile Vindis, Bertrand Cariou, Mathieu Armanet, Gilles Lambert, Stéphanie Billon-Crossouard, Nicolas Diotel, Olivier Meilhac, François Pattou, Philippe Hulin, Aurélie Thedrez, Cédric Le May, Brice Nativel, Audrey Aguesse, 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)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de La Réunion (UR), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Institut National de la Santé et de la Recherche Médicale (INSERM), Structure fédérative de recherche François Bonamy (SFR François Bonamy), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), Université Paris Diderot - Paris 7 (UPD7), Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, 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), Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Nutrition Humaine Ouest (CRNH Ouest), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut du Thorax [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Structure fédérative de recherche François Bonamy (Nantes Univ - SFR François Bonamy), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université (Nantes Univ), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), 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 National de la Recherche Scientifique (CNRS), and CHU Lille
Subjects: 0301 basic medicine, medicine.medical_specialty, Diabetes risk, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Flow cytometry, PCSK9, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Insulin-Secreting Cells, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Secretion, Subtilisins, ComputingMilieux_MISCELLANEOUS, medicine.diagnostic_test, Chemistry, Statins, LDL receptor, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Proprotein convertase, Beta cell, 030104 developmental biology, Endocrinology, Receptors, LDL, PCSK9 inhibitors, Kexin, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Proprotein Convertase 9, Cardiology and Cardiovascular Medicine
Abstract: International audience; Background and aims: Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) is an endogenous inhibitor of the LDL receptor (LDLR). Mendelian randomization studies suggest that PCSK9 deficiency increases diabetes risk, but the underlying mechanisms remain unknown. The aim of our study was to investigate whether PCSK9 or its inhibition may modulate beta cell function.Methods: We assessed PCSK9 and insulin colocalization in human pancreatic sections by epifluorescent and confocal microscopy. We also investigated the expression and the function of PCSK9 in the human EndoC-8H1 beta cell line, by ELISA and flow cytometry, respectively. PCSK9 was inhibited with Alirocumab or siRNA. LDLR expression and LDL uptake were assessed by flow cytometry.Results: PCSK9 was expressed and secreted from beta cells isolated from human pancreas as well as from EndoC-8H1 cells. PCSK9 secretion was enhanced by statin treatment. Recombinant PCSK9 decreased LDLR abundance at the surface of these cells, an effect abrogated by Alirocumab. Alirocumab as well as PCSK9 silencing increased LDLR expression at the surface of EndoC-8H1 cells. Neither exogenous PCSK9, nor Alirocumab, nor PCSK9 silencing significantly altered glucose-stimulated insulin secretion (GSIS) from these cells. High-low density lipoproteins (LDL) concentrations decreased GSIS, but the addition of PCSK9 or its inhibition did not modulate this phenomenon.Conclusions: While PCSK9 regulates LDLR abundance in beta cells, inhibition of exogenous or endogenous PCSK9 does not appear to significantly impact insulin secretion. This is reassuring for the safety of PCSK9 inhibitors in terms of beta cell function.
Published: 2021
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39. Superoxide: A major role in the mechanism of action of essential antimalarial drugs

Author: Karine Reybier, Pierre Perio, Chinedu O. Egwu, Ioannis Tsamesidis, Jean-Michel Augereau, Françoise Benoit-Vical, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Alex Ekwueme Federal University Ndufu-Alike, Ikwo (AE-FUNAI), Laboratoire de chimie de coordination (LCC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, New Antimalarial Molecules and Pharmacological Approaches (ERL1289), Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), 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 de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), 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)-Université Toulouse III - Paul Sabatier (UT3), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and ANR-16-CE35-0003,INMAR,Réseau intégré des mécanismes de quiescence & clairance impliqués dans la résistance à l'artémisinine chez Plasmodium(2016)
Subjects: 0301 basic medicine, Artemisinins, medicine.medical_treatment, Plasmodium falciparum, Drug Resistance, Dihydroartemisinin, Pharmacology, Mechanism of action, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Antimalarials, 0302 clinical medicine, Superoxides, Chloroquine, Physiology (medical), parasitic diseases, medicine, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Artemisinin, biology, Superoxide radicals, Superoxide, biology.organism_classification, 3. Good health, LC-MS, 030104 developmental biology, chemistry, medicine.symptom, Drugs, Essential, 030217 neurology & neurosurgery, Atovaquone, medicine.drug
Abstract: International audience; Understanding the mode of action of antimalarials is central to optimizing their use and the discovery of new therapeutics. Currently used antimalarials belong to a limited series of chemical structures and their mechanisms of action are coutinuously debated. Whereas the involvement of reactive species that in turn kill the parasites sensitive to oxidative stress, is accepted for artemisinins, little is known about the generation of such species in the case of quinolines or hydroxynaphtoquinone. Moreover, the nature of the reactive species involved has never been characterized in Plasmodium-infected erythrocytes. The aim of this work was to determine and elucidate the production of the primary radical, superoxide in Plasmodium-infected erythrocytes treated with artemisinin, dihydroartemisinin, chloroquine and atovaquone, as representatives of three major classes of antimalarials. The intracellular generation of superoxide was quantified by liquid chromatography coupled to mass spectrometry (LC-MS). We demonstrated that artemisinins, atovaquone and to a lesser extent chloroquine, generate significant levels of superoxide radicals in Plasmodium falciparum sensitive strains. More so, the production of superoxide was lowered in chloroquine-resistant strain of Plasmodium treated with chloroquine. These results consolidate the knowledge about the mechanism of action of these different antimalarials and should be taken into consideration in the design of future drugs to fight drug-resistant parasites.
Published: 2021
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40. Rational and Design of the SIMULATOR Study: A Multicentre Randomized Study to Assess the Impact of SIMULation-bAsed Training on Transoesophageal echocardiOgraphy leaRning for Cardiology Residents

Author: Théo Pezel, Anne Bernard, Yoan Lavie Badie, Julien Dreyfus, Etienne Audureau, Yohann Bohbot, Damien Fard, Arnaud Hubert, Lee S. Nguyen, Cécile Monteil, Loïc Bière, Florent Le Ven, Marjorie Canu, Sophie Ribeyrolles, Baptiste Mion, Basile Mouhat, Baptiste Bazire, Charles Fauvel, Julien Ternacle, Jennifer Cautela, Théo Cambet, Thierry Le Tourneau, Erwan Donal, Stéphane Lafitte, Nicolas Mansencal, Augustin Coisne, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Johns Hopkins University (JHU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours-Hôpital Bretonneau, Faculté de Médecine, Université de Tours, Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre cardiologique du Nord (CCN), 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), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor, CHU Amiens-Picardie, Université de Picardie Jules Verne (UPJV), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), 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), Hôpital Ambroise Paré [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut Mutualiste de Montsouris (IMM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Rouen, Normandie Université (NU), CHU Bordeaux [Bordeaux], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Marseille, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), 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, CHU Lille, Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Institut Pasteur de Lille, 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), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, 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), CHU Henri Mondor [Créteil], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD)
Subjects: medicine.medical_specialty, Randomization, education, 030204 cardiovascular system & hematology, Cardiovascular Medicine, Transoesophageal echocardiography, transesophageal echoardiography, law.invention, Likert scale, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, 030202 anesthesiology, law, Internal medicine, medicine, Methods, Diseases of the circulatory (Cardiovascular) system, Simulation based, Simulation, business.industry, 3. Good health, Test (assessment), Multicenter study, RC666-701, Cardiology, residents, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine, business, medical education, Educational program, human activities, simulation-based, randomized study
Abstract: Introduction: Simulation-based training in transesophageal echocardiography (TEE) seems promising. However, data are limited to non-randomized or single-center studies. To assess the impact of simulation-based vs. traditional teaching on TEE knowledge and performance for medical residents in cardiology.Materials and Methods: Nationwide prospective randomized multicenter study involving 43 centers throughout France allowing for the inclusion of >70% of all French cardiology residents. All cardiology residents naive from TEE will be included. Randomization with stratification by center will allocate residents to either a control group receiving theoretical knowledge by e-learning only, or to an intervention group receiving two simulation-based training sessions on a TEE simulator in addition.Results: All residents will undergo both a theoretical test (0–100 points) and a practical test on a TEE simulator (0–100 points) before and 3 months after the training. Satisfaction will be assessed by a 5-points Likert scale. The primary outcomes will be to compare the scores in the final theoretical and practical tests between the two groups, 3 months after the completion of the training.Conclusion: Data regarding simulation-based learning in TEE are limited to non-randomized or single-center studies. The randomized multicenter SIMULATOR study will assess the impact of simulation-based vs. traditional teaching on TEE knowledge and performance for medical residents in cardiology, and whether such an educational program should be proposed in first line for TEE teaching.
Published: 2021
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41. Influence of perceived barriers and facilitators for physical activity on physical activity levels in patients with rheumatoid arthritis or spondyloarthritis: a cross-sectional study of 150 patients

Author: Jérémie Sellam, Stéphane Mitrovic, Laure Gossec, Rawdha Tekaya, Anne Tournadre, Adeline Ruyssen-Witrand, Thomas Davergne, Sabrina Dadoun, Christophe Hudry, Jérôme Avouac, Bruno Fautrel, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tunis El Manar (UTM), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), CHU Clermont-Ferrand, Institut Mutualiste de Montsouris (IMM), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), MGEN, Clinique Geoffroy Saint-Hilaire, Service de rhumatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Rhumatologie [CHU Pitié Salpêtrière], and CHU Pitié-Salpêtrière [AP-HP]
Subjects: medicine.medical_specialty, Sports medicine, Cross-sectional study, medicine.medical_treatment, Inflammatory arthritis, MESH: Spondylarthritis, Diseases of the musculoskeletal system, Arthritis, Rheumatoid, 03 medical and health sciences, Psoriatic arthritis, 0302 clinical medicine, MESH: Cross-Sectional Studies, Rheumatology, Internal medicine, Epidemiology, Spondylarthritis, medicine, MESH: Arthritis, Psoriatic, Humans, Orthopedics and Sports Medicine, 030212 general & internal medicine, Rheumatoid arthritis, Exercise, 030203 arthritis & rheumatology, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MESH: Arthritis, Rheumatoid, Rehabilitation, MESH: Humans, MESH: Middle Aged, business.industry, Barriers and facilitators, Physical activity, Arthritis, Psoriatic, Middle Aged, medicine.disease, Patient reported outcome measures, Cross-Sectional Studies, RC925-935, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MESH: Exercise, Female, business, MESH: Female, Axial Spondyloarthritis, Research Article
Abstract: Background Barriers and facilitators to physical activity in inflammatory arthritis can be assessed through the Inflammatory arthritis FAcilitators and Barriers (IFAB) questionnaire. The objective was to measure the correlation between IFAB and self-reported physical activity levels. Methods This was an international, multicentric, cross-sectional study in 2019–20. Consecutive spondyloarthritis (axSpA), rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients completed the 10-item IFAB, which ranges from − 70 to 70 with lower scores indicating more barriers. Physical activity was measured by the IPAQ-S questionnaire, steps per day collected by smartphone, and psychological readiness to change by stages of behaviour change. Spearman correlations and multivariable linear regression were calculated. Results Of 245 patients included, 150 were analysed: 69 (46%) axSpA, 63 (42%) RA, 18 (12%) PsA. Mean age was 48.6 years (standard deviation, SD 17.1), mean disease duration 11.7 (10.1) years and 60% were women. Barriers to physical activity were moderate: mean IFAB, 6 (SD 19.2); 39 (26%) patients scored less than − 5, corresponding to significant barriers. The mean physical activity was 2837 (SD 2668, median 1784) MET-minutes per week. The IPAQ-S questionnaire was correlated with the IFAB (rho 0.28, p p Conclusion Perceived barriers and facilitators to physical activity were correlated with physical activity, indicating that targeting patients with high barriers and low facilitators to physical activity could be an effective option to improve physical activity levels. Trial registration ClinicalTrial NCT04426747. Registered 11 June 2020 - Retrospectively registered.
Published: 2021
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42. Fluoxetine for the Symptomatic Treatment of Multiple System Atrophy: The MSA-FLUO Trial

Author: Marc Vérin, Anne Pavy-Le Traon, Vanessa Rousseau, Margherita Fabbri, Alexandra Foubert-Samier, Wassilios G. Meissner, François Tison, Philippe Couratier, Agnès Sommet, Luc Defebvre, Valérie Cochen De Cock, Santiago Perez-Lloret, Franck Durif, Christine Tranchant, Claire Thalamas, Jean-Philippe Azulay, Philippe Remy, Jean-Christophe Corvol, Philippe Damier, Olivier Rascol, Jean-Luc Houeto, Christian Geny, Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), EuroMov - Digital Health in Motion (Euromov DHM), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Montpellier (UM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), CHU Bordeaux [Bordeaux], 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), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Limoges, Centre hospitalier universitaire de Nantes (CHU Nantes), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Clermont-Ferrand, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Euromov (EuroMov), Université de Montpellier (UM), CHI Créteil, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), CHU Pontchaillou [Rennes], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), NS-Park/FCRIN Network, UMS 015, Centre d’Excellence en Maladies Neurodégénératives (NeuroToul), CHU Toulouse [Toulouse], Clinique Beau Soleil [Montpellier], Pontifical Catholic University of Argentina (UCA), Institut du Cerveau = Paris Brain Institute (ICM), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Nord Laennec [CHU Nantes], Lille Neurosciences & Cognition - U 1172 (LilNCog), CHU Lille, CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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 Henri Mondor, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Les Hôpitaux Universitaires de Strasbourg (HUS), University of Otago [Dunedin, Nouvelle-Zélande], 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor [Créteil], and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)
Subjects: 0301 basic medicine, medicine.medical_specialty, Serotonin reuptake inhibitor, [SDV]Life Sciences [q-bio], multiple system atrophy, ENSAYO CLINICO, Placebo, law.invention, 03 medical and health sciences, NEUROBIOLOGIA, 0302 clinical medicine, Atrophy, Randomized controlled trial, Double-Blind Method, Rating scale, law, Internal medicine, Surveys and Questionnaires, medicine, ATROFIA MULTISISTÉMICA, Humans, symptomatic treatment, Fluoxetine, business.industry, Beck Depression Inventory, fluoxetine, ENFERMEDADES NEURODEGENERATIVAS, Parkinson Disease, clinical trial, medicine.disease, Confidence interval, 3. Good health, ENFERMEDAD DE PARKINSON, 030104 developmental biology, Treatment Outcome, Neurology, Quality of Life, placebo, TRATAMIENTO MEDICO, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Fil: Rascol, Olivier. Universidad de Toulouse. Hospital Universitario de Toulouse; Francia Fil: Rascol, Olivier. Centro NeuroToul COEN; Francia Fil: Rascol, Olivier. Clínica de Toulouse. Centro de Investigación. Departamentos de Neurociencias y Farmacología Clínica; Francia Fil: Cochen De Cock, Valérie. Clínica Beau Soleil. Departamento de Neurología; Francia Fil: Cochen De Cock, Valérie. Universidad de Montpellier. EuroMov Digital Health in Motion; Francia Fil: Pavy-Le Traon, Anne. Centro de referencia de atrofia multisistémica; Francia Fil: Pavy-Le Traon, Anne. Universidad de Toulouse. Hospital Universitario de Toulouse. Instituto de Enfermedades Cardiovasculares y Metabólicas. Centro de Investigación Clínica de Toulouse. Departamento de Neurociencias; Francia Fil: Foubert-Samier, Alexandra. Universidad de Toulouse. Hospital Universitario de Toulouse. Instituto de Enfermedades Cardiovasculares y Metabólicas. Departamento de Neurociencias, Centro de investigación Clínica de Toulouse; Francia Fil: Thalamas, Claire. Universidad de Toulouse. Hospital Universitario de Toulouse. Centro de Investigación Clínica de Toulouse; Francia Fil: Thalamas, Claire. Hospital Universitario de Burdeos; Francia Fil: Sommet, Agnès. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Pérez Lloret, Santiago. Universidad Abierta Interamericana. Centro de Investigaciones Biomédicas; Argentina Fil: Pérez Lloret, Santiago. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas; Argentina Fil: Fabbri, Margherita. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Azulay, Jean Philippe. Universidad de Aix-Marsella. Sistema de Hospitales Universitarios Públicos de Marsella; Francia Fil: Corvol, Jean-Christophe. Universidad de la Sorbona; Francia Fil: Corvol, Jean-Christophe. Hospital de la Pitié-Salpêtrière; Francia Fil: Corvol, Jean-Christophe. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Couratier, Philippe. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Damier, Philippe. Hospital Nord Laennec. Centro de Investigación Clínica; Francia Fil: Defebvre, Luc. Universidad en Lille; Francia Fil: Defebvre, Luc. Hospital Universitario de Marsella. Departamento de Neurología y Patología del Movimiento; Francia Fil: Durif, Franck. Centro Hospitalario Universitario, Clermont-Ferrand. Departamento de Neurología; Francia Fil: Durif, Franck. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Geny, Christian. Universidad de Montpellier. Departamento de Neurología; Francia Fil: Houeto, Jean-Luc. Centro Hospitalario Universitario de Limoges; Francia Fil: Houeto, Jean-Luc. Centro de referencia de atrofia multisistémica. Departamento de Neurología. Centro de Expertos en Parkinson; Francia Fil: Rascol, Olivier. Centro de referencia de atrofia multisistémica; Francia Fil: Remy, Philippe. Red Francesa de Infraestructura de Investigación Clínica. Centros Expertos en Parkinson; Francia Fil: Remy, Philippe. Instituto de Investigaciones Biomédicas Mondor; Francia Fil: Tranchant, Christine. Hospital Universitario de Estrasburgo. Red Francesa de Infraestructura de Investigación Clínica. Departamento de Neurología; Francia Fil: Verin, Marc. Universidad de Rennes. Hospital Universitario de Rennes. Red Francesa de Infraestructura de Investigación Clínica. Centro de expertos en Parkinson; Francia Fil: Tison, François. Centro de referencia de atrofia multisistémica. Departamento de Neurología de Enfermedades Neurodegenerativas; Francia Fil: Meissner, Wassilios G. Instituto de Investigación del Cerebro; Nueva Zelanda Fil: Meissner, Wassilios G. Universidad de Otago. Departamento de Medicina; Nueva Zelanda Abstract: Background: There are no effective treatments for multiple system atrophy (MSA). Objective: The objective of this study was to assess the efficacy and safety of the serotonin reuptake inhibitor fluoxetine (40 mg/d) for the symptomatic treatment of MSA. Methods: This was a double-blind, parallel-group, placebo-controlled, randomized trial in patients with "probable" MSA. The primary outcome was the change from baseline to week 12 in the mean total score of the Unified MSA Rating Scale (UMSARS Parts I + II). Secondary outcomes included change from baseline to week 6 in total UMSARS, and change from baseline to week 12 in the Scales for Outcomes in Parkinson Disease-Autonomic Dysfunction, Beck Depression Inventory, and different domains of the MSA-Quality of Life Questionnaire. Exploratory outcomes included change from baseline to week 12 in the UMSARS Parts I and II separately and change from baseline to week 24 in the total UMSARS score. Results: A total of 81 patients were randomly assigned, with no significant difference in the primary outcome (-2.13 units [95% confidence interval, CI, -4.55 to 0.29]; P = 0.08). There was a greater reduction on fluoxetine in the change from baseline to 12-week in UMSARS Part II (exploratory outcome: -1.41 units [95% CI, -2.84; 0.03]; p = 0.05) and in MSA-QoL emotional/social dimension (secondary outcome: -6.99 units [95% CI, -13.40; -0.56]; p < 0.03). A total of 5 deaths occurred (3 on fluoxetine and 2 on placebo). Conclusion: The MSA-FLUO failed to demonstrate fluoxetine superiority over placebo on the total UMSARS score, whereas trends in motor and emotional secondary/exploratory outcomes deserve further investigation.
Published: 2021
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43. French Pharmacovigilance Public System and COVID-19 Pandemic

Author: Aurélie Grandvuillemin, Joëlle Micallef, Milou-Daniel Drici, Annie Pierre Jonville-Béra, Jean Louis Montastruc, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Côte d'Azur (UCA), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Otten, Lisa, and 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]
Subjects: medicine.medical_specialty, MEDLINE, Toxicology, 030226 pharmacology & pharmacy, Decentralization, 03 medical and health sciences, Pharmacovigilance, 0302 clinical medicine, Epidemiology, Pandemic, Agency (sociology), Health care, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Pharmacology, Vaccines, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Thrombosis, medicine.disease, Current Opinion, Medical emergency, business, Adverse drug reaction
Abstract: International audience; 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
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44. Impact of previous exposure to systemic corticosteroids on unfavorable outcome in patients hospitalized for COVID-19

Author: Margaux Lafaurie, Guillaume Martin-Blondel, Pierre Delobel, Nassim Kamar, Sandrine Charpentier, Agnès Sommet, Guillaume Moulis, and the Covid-Clinic-Toul investigators, 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 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)-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), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Pistre, Karine
Subjects: Male, MESH: COVID-19 / drug therapy, [SDV]Life Sciences [q-bio], MESH: Comorbidity, MESH: Adrenal Cortex Hormones / therapeutic use*, MESH: Hospitalization, Comorbidity, law.invention, Cohort Studies, 0302 clinical medicine, Adrenal Cortex Hormones, law, Pharmacology (medical), 030212 general & internal medicine, MESH: Cohort Studies, MESH: Treatment Outcome, MESH: Aged, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Middle Aged, MESH: Inflammation / drug therapy, Middle Aged, Intensive care unit, MESH: Respiration, Artificial / statistics & numerical data, [SDV] Life Sciences [q-bio], Hospitalization, Treatment Outcome, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cohort, Female, Research Article, Cohort study, medicine.medical_specialty, Critical Care, MESH: COVID-19 / mortality, SARS-COV-2, 03 medical and health sciences, MESH: Inflammation / etiology, lcsh:RA1190-1270, Internal medicine, medicine, Humans, Mortality, Propensity Score, Aged, lcsh:Toxicology. Poisons, Inflammation, 030203 arthritis & rheumatology, Pharmacology, MESH: Humans, business.industry, Pharmacoepidemiology, lcsh:RM1-950, COVID-19, Odds ratio, MESH: Propensity Score, medicine.disease, Respiration, Artificial, MESH: Male, Confidence interval, MESH: Critical Care / statistics & numerical data, COVID-19 Drug Treatment, Pneumonia, lcsh:Therapeutics. Pharmacology, Propensity score matching, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Systemic corticosteroids, business, MESH: Female
Abstract: Background The impact of prior exposure to systemic corticosteroids on COVID-19 severity in patients hospitalized for a SARS-CoV-2 pneumonia is not known. The present study was designed to answer to this question. Methods The population study was the Covid-Clinic-Toul cohort which records data about all hospitalized patients with a positive reverse transcriptase polymerase chain reaction for a SARS-CoV-2 infection at Toulouse University hospital, France. Exposure to systemic corticosteroids was assessed at hospital admission. A propensity score (PS) according to corticosteroid exposure was calculated including comorbidities, clinical, radiological and biological variables that impact COVID-19 severity. The primary outcome was composite, including admission to intensive care unit, need of mechanical ventilation and death occurring during the 14 days after hospital admission. Logistic regression models adjusted for the PS (overlap weighting) provided odds ratios (ORs) and their 95% confidence intervals (95% CIs). Results Overall, 253 patients were included in the study. Median age was 64 years, 140 patients (59.6%) were men and 218 (86.2%) had at least one comorbidity. Seventeen patients (6.7%) were exposed to corticosteroids before hospital admission. Chronic inflammatory disease (n = 8) was the most frequent indication. One hundred and twenty patients (47.4%) met the composite outcome. In the crude model, the OR of previous exposure to systemic corticosteroids was 1.64; 95% CI: 0.60–4.44. In the adjusted model, it was 1.09 (95% CI: 0.65–1.83). Conclusion Overall, this study provide some evidences for an absence of an increased risk of unfavorable outcome with previous exposure to corticosteroids in the general setting of patients hospitalized for COVID-19.
Published: 2021
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45. Chest physiotherapy enhances detection of Pseudomonas aeruginosa in nonexpectorating children with cystic fibrosis

Author: Nathalie Wizla-Derambure, Marie Mittaine, E. Deneuville, Michael Fayon, Christophe Marguet, Ludovic Lemée, Véronique Houdouin, Michel Abely, Philippe Reix, S. Ramel, Laure Couderc, Marie-Laure Dalphin, Muriel Le Bourgeois, Evelyne Leroux, Isabelle Pin, F. Huet, Harriet Corvol, Tiphaine Bihouée, Muriel Laurans, Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-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), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Service de pédiatrie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU de Bordeaux Pellegrin [Bordeaux], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Pneumologie et d'Allergologie Pédiatriques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Mucoviscidose: physiopathologie et phénogénomique [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Vaincre la Mucoviscidose, Association de lutte contre la Mucoviscidose, Normandie Université (NU)-Normandie Université (NU), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), HAL-SU, Gestionnaire, 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 Service de Pneumologie pédiatrique [CHU Trousseau]
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, lcsh:Medicine, Chest physiotherapy, medicine.disease_cause, Cystic fibrosis, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Haemophilus influenzae, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, 030212 general & internal medicine, Respiratory infections and tuberculosis, CF and non-CF bronchiectasis, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Lung, Paediatric pulmonology, Pseudomonas aeruginosa, business.industry, lcsh:R, medicine.disease, 3. Good health, medicine.anatomical_structure, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Staphylococcus aureus, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Sputum, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business, Airway
Abstract: Lung damage in cystic fibrosis (CF) is strongly associated with lower airway infections. Early treatment of Pseudomonas aeruginosa is recommended. Pathogen detection requires sampling of lower airway secretions, which remains a challenge in nonexpectorating patients. Our hypothesis was that chest physiotherapy would improve the quality of airway secretion samples and increase the rates of pathogens detected in nonexpectorating patients.This prospective multicentre study compared three successive methods for sampling airway secretions applied through the same session: 1) an oropharyngeal swab (OP), 2) a chest physiotherapy session followed by a provoked cough to obtain sputum (CP-SP) and 3) a second oropharyngeal swab collected after chest physiotherapy (CP-OP). Haemophilus influenzae, Staphylococcus aureus and P. aeruginosa growth cultures were assessed. Accuracy tests and an equivalence test were performed to compare the three successive methods of collection.300 nonexpectorating children with CF were included. P. aeruginosa was detected cumulatively in 56 (18.9%) children, and according to the different collection methods in 28 (9.8%), 37 (12.4%) and 44 (14.7%) children by using OP, CP-OP and CP-SP, respectively. Compared with OP, the increased detection rate was +22% for CP-OP (p=0.029) and +57% for CP-SP (p=0.003). CP-SP had the best positive predictive value (86.3%) and negative predictive value (96.0%) for P. aeruginosa compared with the overall detection.The results of this adequately powered study show differences in the rates of pathogens detected according to the sampling method used. Chest physiotherapy enhanced detection of P. aeruginosa in nonexpectorating children with CF.
Published: 2021
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46. 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
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47. First-Line Biologic Therapy and Obesity in Moderate-to-Severe Psoriasis: Results from the Prospective Multicenter Cohort Psobioteq

Author: Carle Paul, Alain Dupuy, Pascal Joly, Caroline Giboin, Denis Jullien, Manuelle Viguier, Emilie Sbidian, Hervé Bachelez, Florence Assan, Hugo Arlegui, Olivier Chosidow, Emmanuel Mahé, Marie Beylot-Barry, Nathalie Beneton, and Psobioteq, Florence Tubach, Marie-Aleth Richard, Hôpital Henri Mondor, 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), Hôpital Robert Debré, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre Hospitalier Le Mans (CH Le Mans), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Victor Dupouy, Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Marseille, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Hopital Saint-Louis [AP-HP] (AP-HP), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), French Ministry of Health [PHRC AOM 09 195], French National Agency for the Safety of Medicines and Health Products (ANSM), Abbvie, MSD France, Janssen Johnson and Johnson USA Janssen Biotech Inc, Pfizer Pfizer, Departement a la Recherche Clinique et au Developpement (DRCD - Department for Clinical Research and Development), Assistance Publique - Hopitaux de Paris (Paris Hospitals), French Society of Dermatology, Psoriasis Research Group, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), 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], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Dermatology, Antibodies, Monoclonal, Humanized, Body Mass Index, Etanercept, Cohort Studies, Interquartile range, Drug survival, Internal medicine, Psoriasis, Ustekinumab, Adalimumab, medicine, Humans, Cumulative incidence, Obesity, Psobioteq, 2. Zero hunger, business.industry, Patient Selection, Middle Aged, medicine.disease, Infliximab, 3. Good health, Discontinuation, Biological Therapy, Methotrexate, Female, Dermatologic Agents, France, business, Body mass index, medicine.drug, Biologic therapy
Abstract: Background: Obesity is associated with an increased risk of psoriasis. Objective: In this study, we examined whether body mass index (BMI) is taken into account when choosing first-line biologic therapy for psoriasis. Methods: In this cohort study, we compared obese (BMI ≥30 kg/m2) and non-obese patients for the first-line biologic therapy prescribed, its survival, reasons for discontinuation, therapy optimization, co-prescription of methotrexate and factors associated with long drug survival. Results: A total of 931 patients were included: 594 (64%) were male, median age was 46 years (interquartile range 36–56). The most-prescribed biologic agents as first-line treatment were adalimumab (ADA; 42.7%), ustekinumab (UST; 29.9%) and etanercept (ETA; 22.9%); only frequency of infliximab (IFX) prescription differed between groups. Drug survival was significantly shorter for obese than non-obese patients ( p < 2.10–4) and was worse for obese than non-obese patients for UST ( p = 0.009) and ETA ( p = 0.02), with no difference for ADA ( p = 0.11). The main reason for discontinuation was primary inefficacy (62%), which was more frequent in obese than non-obese patients. The cumulative incidence of optimization did not significantly differ between the groups, except for ADA (SHR 1.91, 95% CI [1.23–2.96], p = 0.005). On multivariate analysis, risk of discontinuation was associated with only ETA as first-line biologic therapy (HR 1.51, 95% CI 1.04–2.19). Conclusion: This study highlighted the lack of difference in prescription of first-line biologic treatment, except for IFX, between obese and non-obese patients presenting moderate-to-severe psoriasis. Drug survival in obese patients is shorter, mainly because of inefficacy, than in non-obese patients. This highlights the need for targeted pharmacological studies in obese individuals to find optimal administration schemes.
Published: 2021
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48. Perinatal outcome after planned vaginal delivery in monochorionic compared with dichorionic twin pregnancy

Author: François Goffinet, M. V. Senat, Loïc Sentilhes, Norbert Winer, Charles Garabedian, Patrick Rozenberg, Elie Azria, Christophe Vayssière, Diane Korb, Thomas Schmitz, Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Maternité Port-Royal [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), DHU Risques Et Grossesse, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), AOM2012 Ministère des Affaires Sociales et de la Santé, The authors thank URC-CIC Paris Descartes Necker/Cochin (Laurence Lecomte) for the study implementation, monitoring and data management. This work was funded by a grant from the French Ministry of Health (PHRC, AOM2012). L.S. carried out consultancy work and was a lecturer for Ferring Laboratories in the previous 3 years., and The authors thank URC‐CIC Paris Descartes Necker/Cochin (Laurence Lecomte) for the study implementation, monitoring and data management. This work was funded by a grant from the French Ministry of Health (PHRC, AOM2012).
Subjects: Adult, medicine.medical_specialty, Population, Twins, Reproductive technology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Labor Presentation, 03 medical and health sciences, 0302 clinical medicine, Obstetrics and gynaecology, dichorionic twins, Pregnancy, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Prospective Studies, 030212 general & internal medicine, education, Perinatal Mortality, Twin Pregnancy, education.field_of_study, 030219 obstetrics & reproductive medicine, Radiological and Ultrasound Technology, business.industry, Vaginal delivery, Obstetrics, Cephalic presentation, Infant, Newborn, Pregnancy Outcome, Obstetrics and Gynecology, Gestational age, Chorion, General Medicine, neonatal morbidity, twin pregnancy, Delivery, Obstetric, Obstetric Labor Complications, 3. Good health, Reproductive Medicine, Vagina, monochorionic twins, Pregnancy, Twin, Female, planned vaginal delivery, France, Monochorionic twins, business
Abstract: OBJECTIVE To assess, according to chorionicity, the perinatal outcome of twin pregnancy in which vaginal delivery is planned. METHODS JUMODA (JUmeaux MODe d'Accouchement) was a national prospective population-based cohort study of twin pregnancies, delivered in 176 maternity units in France, from February 2014 to March 2015. In this planned secondary analysis, we assessed, according to chorionicity, the perinatal outcome of twin pregnancies, in which vaginal delivery was planned, that delivered at or after 32 weeks of gestation with the first twin in cephalic presentation. In order to select a population with well-recognized indications for planned vaginal delivery, we applied the same exclusion criteria as those in the Twin Birth Study, an international randomized trial. Monochorionic twin pregnancies with twin-to-twin transfusion syndrome or twin anemia-polycythemia sequence were defined as complicated and were excluded. The primary outcome was a composite of intrapartum mortality and neonatal morbidity and mortality. Multivariable logistic regression models were used to control for potential confounders. Subgroup analyses were conducted according to birth order (first or second twin) and gestational age at delivery (
Published: 2021
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49. ESSAI RANDOMISÉ POUR ÉVALUER L’EFFICACITÉ ET LA SÉCURITÉ DE TRAITEMENTS CHEZ DES PATIENTS AMBULATOIRES ATTEINTS DE COVID-19 AYANT DES FACTEURS DE RISQUE ESSAI COVERAGE FRANCE : PRÉSENTATION DU PROTOCOLE

Author: Onaisi, Racha, Duvignaud, Alexandre, Nguyen Binh, Antoine, Dupouy, Julie, Chastang, Julie, Le Bel, Josselin, Landman, Roland, Naccache, Jean Marc, Lefèvre, Benjamin, Piroth, Lionel, Binquet, C, Makinson, Alain, Darnaud, Thomas, Begue, Cyril, Weiss, Laurence, Richert, Laura, Anglaret, Xavier, Denis, Malvy, Joseph, Jean Philippe, Druais, Pierre Louis, Darmon, David, Ral, Cedric, Lhomme, Edouard, Saint-Lary, Olivier, Université de Bordeaux (UB), 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), Groupe hospitalier Pellegrin, Global Health in the Global South (GHiGS), Institut de Recherche pour le Développement (IRD)- 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)-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), Sorbonne Université (SU), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), 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), Centre d'investigation clinique de Toulouse (CIC 1436), 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier Saint-Joseph [Paris], Centre Hospitalier Universitaire de Nancy (CHU Nancy), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Bastia (CHB), 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 ), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Haute Autorité de Santé [Saint-Denis La Plaine] (HAS), Université Côte d'Azur (UCA), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes (UN), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), 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, and Dupuis, Christine
Subjects: treatment, [SDV]Life Sciences [q-bio], protocols, trial, Internal, controlled, clinical, [SDV] Life Sciences [q-bio], early, randomized, outpatient, Medicine, General, Covid-19
Abstract: Context. The Covid-19 pandemic is of unprecedented magnitude and has had major social and health consequences. Primary care professionals, mainly general practitioners, ensure the care of most patients with Covid-19. An early-stage treatment administered to patients with risk factors for developing a severe disease could reduce hospitalization and death rates. No treatment is currently validated in this indication. Objectives. To evaluate the safety and efficacy of experimental candidate agents delivered in outpatient settings to reduce the risk of hospitalization or death in at-risk patients with early-stage proven Covid-19 and no indication for hospital admission. Methods. Multicentric, open-label, multi-arm, multi-stage (MAMS) randomized controlled trial with a pilot tolerability and safety phase, and a clinical efficacy phase. Efficacy will be determined by the proportion of participants who have an indication for hospital admission, administration of acute oxygen therapy (because of Covid-19) or who decease between D0 and D14 in the experimental treatment group compared to the control group. Expected results. This trial will assess the tolerance and efficacy of diverse treatments administered at an early stage of Covid-19, in patients with risk factors of developing a severe disease. It will also provide information that can contribute to increase primary care actors' ability to conduct clinical trials at the national level., Contexte. La pandémie de Covid-19 a eu d’importantes répercussions sanitaires et sociales. Les acteurs de soins primaires, en particulier les spécialistes de médecine générale, prennent en charge la majorité des patients atteints de Covid-19. Un traitement précoce initié en première ligne, notamment chez les patients à risque d’aggravation, pourrait réduire les taux d’hospitalisation et de décès. Aucun traitement n’est actuellement validé dans cette indication.Objectif. Évaluer l’efficacité et la tolérance de traitements expérimentaux administrés à un stade précoce, en ambulatoire, dans le but de diminuer le risque de développer une forme sévère de la maladie chez des patients atteints de Covid-19 ayant des facteurs de risque d’aggravation et qui n’ont pas de critères d’hospitalisation.Méthodes. Essai thérapeutique contrôlé randomisé multicentrique, en ouvert, multi-bras, multi-étapes (MAMS) comprenant une phase pilote d’évaluation de la tolérance et une phase d’évaluation de l’efficacité. L’efficacité sera évaluée par la proportion de participants ayant eu une indication d’hospitalisation, une indication d’oxygénothérapie aiguë (en raison de la Covid-19), ou décédés entre J0 et J14 dans le groupe traitement expérimental par rapport au groupe témoin. Résultats attendus. Cet essai permettra d’évaluer la tolérance et l’efficacité de l’administration précoce de divers traitements dans le cadre de la Covid-19 chez des patients à risque de développer des formes graves. Il fournira également des informations susceptibles d’améliorer la recherche clinique interventionnelle impliquant la personne humaine en soins primaires et sa structuration.
Published: 2021

50. Personality dimensions could be predictive of quality-of-life outcome after deep brain stimulation of the sub-thalamic nucleus in Parkinson's

Author: Boussac, M., Danaila, T., Eusebio, A., Hainque, E., Corvol, J. C., Rascol, O., Moreau, C., Rolland, A. S., Devos, D., Ansquer, S., Boukbiza, O. L., Marques, A. R., Maltete, D., Drapier, S., Jarraya, B., Belamri, L., Burbaud, P., Meyer, M., Rouaud, T., Giordana, B., Tir, Mélissa, Brefel-Courbon, C., Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Assistance Publique - Hôpitaux de Marseille (APHM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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), Environnement, Ville, Société (EVS), École normale supérieure de Lyon (ENS de Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT), Laboratoire d'interaction du rayonnement X avec la matière (LIXAM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

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