2,387 results on '"CHU de Lille"'
Search Results
2. Superiority of Intelligent Video Surveillance + Telealarm Over Telealarm Alone in Elderly People at Risk of Falling (VIGIALARM)
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Hôpital Les Bateliers, CHU de Lille, Hôpital cardiologique, CHU de Lille, Hôpital Saint Philibert, GHICL, Hôpital Côte de Nacre, CHU de Caen, Hopital Charles Nicolle, Hôpital Bois Guillaume, CHU de Rouen, Centre Hospitalier de Saint-Quentin, Centre Hospitalier de Beauvais, and Centre Hospitalier de Valenciennes
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- 2023
3. French Cohort Evaluating the effectiveneSs of Atrioventricular Synchrony by the micRa AV (AV-CESAR)
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CHU de Tours, European Georges Pompidou Hospital, Hôpital privé Clairval - Marseille, Clinique Pasteur Toulouse, University Hospital, Bordeaux, Infirmerie Protestante Lyon, Institut Jacques Cartier - Massy, University Hospital, Grenoble, Hôpital de la Timone, University Hospital, Toulouse, Hopital Prive Saint Martin - Bordeaux, Hospices Civils de Lyon, CHU de Rouen - Accueil, University Hospital, Caen, Médipôle Lyon-Villeurbanne, Hospital Ambroise Paré Paris, Clinique Saint Augustin - Bordeaux, Rennes University Hospital, Clinique de la Sauvegarde - Lyon, University Hospital of Saint-Etienne, Hôpital Privé de Parly II - Le Chesnay, Institut Mutualiste Montsouris, Centre Hospitalier Universitaire, Amiens, University Hospital, Clermont-Ferrand, Centre Hospitalier Régional et Universitaire de Brest, Poitiers University Hospital, Clinique Saint-Gatien - Tours, CHU de Reims, Centre Hospitalier Universitaire de Besancon, Centre Hospitalier Universitaire Dijon, Hôpital Privé de Lille Métropole, University Hospital, Montpellier, University Hospital, Strasbourg, France, Nantes University Hospital, Centre Cardio-Thoracique de Monaco, Hospital St. Joseph, Marseille, France, Centre Hospitalier Régional Metz-Thionville, Centre Hospitalier Annecy Genevois, Clinique du Millenaire, University Hospital, Limoges, Clinique Saint Pierre - Perpignan, Bichat Hospital, Universite de La Reunion, CHU de Lille, Institute Arnault Tzanck, France, Hôpital Privé Les Franciscaines, CHU de Fort de France - Martinique, Henri Mondor University Hospital, University Hospital, Angers, Centre Hospitalier de Lens, and Central Hospital, Nancy, France
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- 2023
4. S-ICD French Cohort Study (HONEST) (HONEST)
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Centre Cardio-Thoracique de Monaco, Centre Cardiologique du Nord, Groupe Hospitalier de la Region de Mulhouse et Sud Alsace, Centre Hospitalier Annecy Genevois, Centre Hospitalier Bretagne Atlantique, Centre Hospitalier William Morey - Chalon sur Saône, Centre Hospitalier du Pays d'Aix, Centre Hospitalier Albi, Centre Hospitalier Antibes - Juan Les Pins, Centre Hospitalier Argenteuil, Centre Hospitalier Henri Duffaut - Avignon, Centre Hospitalier Auxerre, Centre Hospitalier de Bastia, Centre Hospitalier de Bigorre - Tarbes, Boulogne sur Mer Hospital Center, Centre Hospitalier de Carcassonne, Centre hospitalier de Chambéry, Centre Hospitalier of Chartres, Centre Hospitalier de Compiègne, Centre Hospitalier de Haguenau (Est France), Centre hospitalier de la Polynésie française - Papeete, Centre Hospitalier de La Rochelle, Centre Hospitalier de Lens, Ch Mont de Marsan, Centre Hospitalier de Montauban, Centre Hospitalier de Moulins Yzeure, Centre Hospitalier de PAU, Centre Hospitalier de Perigueux, Centre hospitalier de Perpignan, Centre Hospitalier de Roubaix, Centre Hospitalier de Saint-Brieuc, Centre Hospitalier de Troyes, Centre Hospitalier de Valence, Centre Hospitalier de Valenciennes, Centre Hospitalier Departemental Vendee, Centre Hospitalier le Mans, Centre Hospitalier Eure-Seine, Centre Hospitalier Henri Mondor - Aurillac, Centre Hospitalier Intercommunal Castres-Mazamet, Centre Hospitalier Jacques Cœur - Bourges, Centre Hospitalier Libourne, Centre Hospitalier Princesse Grace, Centre Hospitalier Régional d'Orléans, Hôpital NOVO, Centre Hospitalier Rodez, Centre Hospitalier Saint Joseph Saint Luc de Lyon, Central Hospital Saint Quentin, Centre Hospitalier Saintonge - Saintes, Centre Hospitalier Sud Francilien, Centre Hospitalier Territorial- Nouméa, Centre Hospitalier Toulon, Centre Hospitalier Universitaire de Saint Etienne, Poissy-Saint Germain Hospital, CHR Mercy - Metz, Amiens University Hospital, University Hospital, Angers, Centre Hospitalier Universitaire de Besancon, University Hospital, Clermont-Ferrand, University Hospital, Bordeaux, University Hospital, Caen, Centre Hospitalier Universitaire de la Réunion, CHU de Lille, University Hospital, Limoges, University Hospital, Montpellier, CHU de Nancy, Nantes University Hospital, Poitiers University Hospital, CHU de Rouen - Accueil, University Hospital, Strasbourg, France, University Hospital, Toulouse, CHU de Tours, Centre Hospitalier Universitaire Dijon, Centre Hospitalier Felix Guyon, University Hospital, Grenoble, Centre Hospitalier Régional et Universitaire de Brest, Centre Hospitalier Universitaire de Nice, CHU de Reims, CHU Rennes - Hopital Pontchaillou, Clinique Alleray Labrouste, CMC Ambroise Paré, Clinique Belledonne - Grenoble, Clinique Claude Bernard - Metz, Clinique du Millenaire, Clinique du Parc - Castelnau le Lez - Montpellier, Clinique du Tonkin - Lyon - Villeurbane, Clinique Saint-Hilaire, Clinique Les Fontaines - Melun, Clinique Louis Pasteur Essey-lès-Nancy, Clinique Oreliance - Orléans, Clinique Pasteur Toulouse, Clinique Rhône Durance - Avignon, Clinique Saint Augustin - Bordeaux, Clinique Saint Georges - Nice, Clinique Saint Pierre - Perpignan, Clinique Saint Vincent - Besancon, Clinique Saint-Gatien - Tours, Clinique Saint Joseph, Liège, GCS Cardiologie - Bayonne, Groupe Hospitalier de Bretagne Sud, Groupe Hospitalier du Havre, Raincy Montfermeil Hospital Group, European Georges Pompidou Hospital, Hopital Antoine Beclere, Bichat Hospital, Centre Hospitalier Universitaire de Nīmes, Hôpital de la Croix-Rousse, Hôpital de la Timone, Henri Mondor University Hospital, Hôpital Marie Lannelongue - Le Plessis Robinson, Hôpital Necker-Enfants Malades, University Hospital, Marseille, Hopital Nord Franche-Comte, Hôpital Privé Arnault Tzanck - Mougins - Sophia Antipolis, Hôpital privé Bois Bernard - Lens, Hôpital privé Clairval - Marseille, Hôpital privé Claude Galien - Quincy-sous-Sénart, Hôpital Privé de la Loire- Saint Etienne, Hôpital Privé de Parly II - Le Chesnay, Hôpital privé du Confluent - Nantes, Hôpital privé Le Bois - Lille MetropoleHôpital Privé Les Franciscaines - Nîmes, Hôpital Privé Marseille - Beauregard, Hôpital privé Saint-Martin - Caen, Hospital St. Joseph, Marseille, France, Hôpital Saint Philibert - Lille - GHICL, Hospices Civils de Lyon, Institut Jacques Cartier - Massy, Institut Mutualiste Montsouris, Pitié-Salpêtrière Hospital, Pôle Santé République, Pôle Santé Sud - Le Mans, Polyclinique Les Fleurs - Toulon, Polyclinique Lyon-Nord - Rillieux, Polyclinique Reims-Bezannes-Courlancy, Polyclinique Saint Laurent - Rennes, Polyclinique Vauban - Valencienne, and Amiens SAS
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- 2022
5. Coronavirus Disease 2019-Associated Mucormycosis in France: A Rare but Deadly Complication
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Danion, François, Letscher-Bru, Valérie, Guitard, Juliette, Sitbon, Karine, Dellière, Sarah, Angoulvant, Adela, Desoubeaux, Guillaume, Botterel, Francoise, Bellanger, Anne-Pauline, Gargala, Gilles, Uhel, Fabrice, Bougnoux, Marie-Elisabeth, Gerber, Victor, Michel, Justin, Cornu, Marjorie, Bretagne, Stéphane, Lanternier, Fanny, Merdji, Hamid, Delabranche, Xavier, Parrot, Antoine, Voiriot, Guillaume, Urbina, Tomas, Mebazaa, Alexandre, Chousterman, Benjamin, el Kalioubie, Ahmed, Six, Sophie, Coulon, Pauline, Sendid, Boualem, Anguel, Nadia, Damoisel, Charles, Mussini, Charlotte, Villate, Alban, Navellou, Jean-Christophe, Girault, Christophe, Cassagne, Carole, Augereau, Olivier, Dromer, Francoise, Garcia-Hermoso, Dea, Lortholary, Olivier, Alanio, Alexandre, Center of Experimental and Molecular Medicine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], CHU Strasbourg, Dynamique des interactions hôte pathogène (DIHP), 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 Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), COVID-Mucor study group, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de parasitologie, mycologie, médecine tropicale [CHRU Tours], Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor [Créteil], Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire de Biologie Médicale de Référence Pneumopathie d'hypersensibilité, Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Necker - Enfants Malades [AP-HP], Aix Marseille Université (AMU), CHU Lille, Service de Médecine Intensive et Réanimation [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Tenon [AP-HP], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), COVID-Mucor St Group Hamid Merdji (Médecine Intensive et Réanimation, Hôpitaux Universitaires de Strasbourg, Strasbourg, France), Xavier Delabranche (Réanimation Chirugicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France), Antoine Parrot (Service de Pneumologie, Hôpital Tenon, AP-HP, Paris, France), Guillaume Voiriot (Service de Médecine Intensive et Réanimation, Hôpital Tenon, AP-HP, Paris, France), Tomas Urbina (Service de Réanimation Médicale, Hôpital Saint Antoine, AP-HP, Paris, France), Alexandre Mebazaa (Réanimation Chirurgicale, Hôpital Saint-Louis, AP-HP, Paris, France), Benjamin Chousterman (Réanimation, Hôpital Lariboisière, AP-HP, Paris, France), Ahmed El Kalioubie (Réanimation, CHU de Lille), Sophie Six (Réanimation, CHU de Lille, Lille, France), Pauline Coulon and Boualem Sendid (Service de Mycologie, CHU de Lille, France), Nadia Anguel (Réanimation Médicale, Le Kremlin-Bicêtre, AP-HP, Paris, France), Charles Damoisel (Réanimation Polyvalente, Clamart, AP-HP, France), Charlotte Mussini (Service d’Anatomopathologie, Le Kremlin-Bicêtre, AP-HP, Paris, France), Alban Villate (Hématologie, Tours, France), Jean-Christophe Navellou (Réanimation, CHU Besançon, France), Christophe Girault (Médecine Intensive et Réanimation, CHU Rouen, France), Carole Cassagne (Laboratoire de Mycologie, CHU Timone, Marseille, France), Olivier Augereau (Laboratoire de Microbiologie, Colmar, France), Francoise Dromer, Dea Garcia-Hermoso, Olivier Lortholary, Alexandre Alanio (CNRMA, Institut Pasteur, Paris, France)., Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), and Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille)
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medicine.medical_specialty ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,CAM ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Brief Report ,General surgery ,Mucormycosis ,COVID-19 ,CAPA ,medicine.disease ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,mucormycosis ,AcademicSubjects/MED00290 ,Infectious Diseases ,Oncology ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,medicine ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,business ,Complication - Abstract
We studied COVID-19 associated mucormycosis based on 17 cases reported nationwide and assessed the differences with India. They differed by frequencies of diabetes mellitus (47% in France versus up to 95% in India), hematological malignancies (35% versus 1%), anatomical sites (12% versus >80% rhino-orbito-cerebral) and prognosis (88% mortality versus, We reported 17 cases of COVID-19 associated mucormycosis in France. Compared to India, they differed by frequencies of diabetes mellitus (47% versus up to 95% in India), hematological malignancies (35% versus 1%), anatomical sites and mortality (88% versus
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- 2022
6. Total femur replacement in non-oncologic indications: Functional and radiological outcomes from a French survey with a mean 6 years’ follow-up
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Sophie Putman, French Hip, Olivier Méric, Antoine-Guy Hue, Henri Migaud, Fabrice Fiorenza, Dominique Saragaglia, Jean-Yves Jenny, Franck Dujardin, Paul Bonnevialle, Hôpital Salengro, CHU de Lille, Service d'Orthopédie C, CHU de Lille, Hôpital Salengro, Centre Hospitalier Universitaire [Grenoble] (CHU), Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'orthopédie et de traumatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département d'orthopédie et de traumatologie, Hôpital P.P.-Riquet, CHU Toulouse [Toulouse], Chirurgie Orthopédique et Traumatologique, Hôpital Purpan, Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]
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Male ,Knee Joint ,Disarticulation ,Arthroplasty, Replacement, Hip ,[SDV]Life Sciences [q-bio] ,Hip arthroplasty loosening ,Knee arthroplasty loosening ,0302 clinical medicine ,Surveys and Questionnaires ,Hip replacement ,Orthopedics and Sports Medicine ,Femur ,Range of Motion, Articular ,Arthroplasty, Replacement, Knee ,Aged, 80 and over ,Hematoma ,030222 orthopedics ,Prostheses and Implants ,Middle Aged ,Chronic periprosthetic infection ,Leg Length Inequality ,Prosthesis Failure ,3. Good health ,Total femoral replacement ,Female ,France ,Joint Diseases ,Femoral Fractures ,Adult ,Reoperation ,medicine.medical_specialty ,Prosthesis-Related Infections ,03 medical and health sciences ,medicine ,Humans ,Surgical Wound Infection ,Aged ,Retrospective Studies ,Periprosthetic femoral fracture ,Femur fracture ,Trochanter ,business.industry ,Retrospective cohort study ,030229 sport sciences ,medicine.disease ,Dependent Ambulation ,Surgery ,Radiography ,Implant ,Complication ,business ,Follow-Up Studies - Abstract
Introduction There are few published studies on total femur replacement (TFR) because its indications are rare. Other than malignant diseases, the indications extend to revisions and interprosthetic femur fractures; however, the outcomes of these indications have not been well defined. The aim of this retrospective survey was to analyze the complication rate and functional outcomes of these newer indications. Hypothesis The morbidity and outcomes after TFR are comparable to those reported in the literature for non-cancer indications. Material and methods Between 1997 and 2016, 29 TFR procedures were done at 6 French teaching hospitals in 15 women and 14 men, average age 68 ± 14 years [32–85]. The primary indication was degenerative joint disease in the hip and/or knee in 16 cases, mechanical failure of the implant used after tumor resection in 11 cases and femur fracture in 2 cases. The mean number of surgical procedures before TFR was 3.6 (maximum 5) at the hip and 4.5 (maximum 10) at the knee. Six different models were implanted consisting of a rotational hinge knee (except in one case); 20 patients received a dual mobility system and 9 a standard hip replacement bearing. The femoral shaft was partially conserved 21/29 times and the trochanter 25/29 times. Results Five patients suffered a general complication and 12 suffered a local complication (including 4 hematomas and 2 hip dislocations). Eight patients (28.6%) suffered a surgical site infection, although three had a prior infection. Among the 12 patients with a history of infection or progressive infection before the TFR, 9 healed and 3 had the infection continue. At a minimum follow-up of 2 years and mean of 6 years, 23 TFR implants were still in place and not infected; the other 6 had been removed or were infected, including one patient who underwent disarticulation. The median survival of the non-infected TFR was 15 years. At 10 years, 70% of TFR implants were still in place and non-infected. Walking was possible with or without a cane in 15 patients (51.7%), with two canes or a walker in 12 patients (41.3%) and impossible in 2 patients. Active knee flexion averaged 79.4° ± 30.3° [0°–120°]; 17 patients (62.9%) had 90° or more flexion; two patients (7.4%) had no flexion. The extension deficit averaged 3.7° ± 7°[− 20° to 10°] and 20 patients had no flexion deformity. The leg length difference averaged 1.3cm ± 2.3 [0–10]; 19 patients (67.8%) had no difference in leg length. Discussion Our starting hypothesis was confirmed for the complication rate and clinical outcomes. The benefits of dual mobility cups are emphasized. While the indications for TFR are rare, they will likely increase in the coming years. Level of evidence: IV, Retrospective cohort study…
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- 2019
7. Spastic paraplegia due to recessive or dominant mutations in ERLIN2 can convert to ALS
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Jean-Philippe Camdessanché, Emilien Bernard, Jean-Christophe Antoine, Guillaume Banneau, Etienne Allart, Maria-Del-Mar Amador, François Muratet, Elisa Teyssou, Gabrielle Rudolf, Giovanni Stevanin, Christine Tranchant, Véronique Danel-Brunaud, Marie-Céline Fleury, Stéphanie Millecamps, Mathieu Anheim, 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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie et Pathologie du Mouvement, Hôpital Roger Salengro, Centre Hospitalier Universitaire (CHU) de Lille, CHU de Lille, Service de neurologie [CHU de Saint-Étienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service de Neurologie [CHU Strasbourg], Hôpital de Hautepierre [Strasbourg]-Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), 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), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Service de Neurologie [Hospices civils de Lyon - Hôpital Pierre Wertheimer], Hospices Civils de Lyon (HCL)-Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), MILLECAMPS, Stéphanie, 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), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
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Hereditary spastic paraplegia ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,Article ,03 medical and health sciences ,0302 clinical medicine ,C9orf72 ,medicine ,Spasticity ,Amyotrophic lateral sclerosis ,Exome ,Tetraplegia ,Genetics (clinical) ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Bulbar palsy ,Genetics ,0303 health sciences ,business.industry ,[SCCO.NEUR]Cognitive science/Neuroscience ,[SCCO.NEUR] Cognitive science/Neuroscience ,medicine.disease ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Neurology (clinical) ,medicine.symptom ,business ,Trinucleotide repeat expansion ,030217 neurology & neurosurgery - Abstract
ObjectiveThe aim of this study was to evaluate whether mutations in ERLIN2, known to cause SPG18, a recessive hereditary spastic paraplegia (SP) responsible for the degeneration of the upper motor neurons leading to weakness and spasticity restricted to the lower limbs, could contribute to amyotrophic lateral sclerosis (ALS), a distinct and more severe motor neuron disease (MND), in which the lower motor neurons also profusely degenerates, leading to tetraplegia, bulbar palsy, respiratory insufficiency, and ultimately the death of the patients.MethodsWhole-exome sequencing was performed in a large cohort of 200 familial ALS and 60 sporadic ALS after a systematic screening for C9orf72 hexanucleotide repeat expansion. ERLIN2 variants identified by exome analysis were validated using Sanger analysis. Segregation of the identified variant with the disease was checked for all family members with available DNA.ResultsHere, we report the identification of ERLIN2 mutations in patients with a primarily SP evolving to rapid progressive ALS, leading to the death of the patients. These mutations segregated with the disease in a dominant (V168M) or recessive (D300V) manner in these families or were found in apparently sporadic cases (N125S).ConclusionsInheritance of ERLIN2 mutations appears to be, within the MND spectrum, more complex that previously reported. These results expand the clinical phenotype of ERLIN2 mutations to a severe outcome of MND and should be considered before delivering a genetic counseling to ERLIN2-linked families.
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- 2019
8. The dynamics of change: managerial, organizational and social challenges in the hospital setting
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Desplan, Fabrice, Docteur, Fabrice, Groupe Sociétés, Religions, Laïcités (GSRL), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Direction Générale des Soins - CHU de Lille, CHU de Lille, Direction Générale des Soins, and Institut Coeur Poumons - CHU de Lille
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JEL: I - Health, Education, and Welfare/I.I2 - Education and Research Institutions ,[SHS.SOCIO]Humanities and Social Sciences/Sociology ,Sociologie de la santé ,[SHS.GESTION]Humanities and Social Sciences/Business administration ,Management des institutions de santé - Abstract
International audience; In health organizations, especially Hospital a managerial dimension because they impose an evolution of the institutions and agents that make the health care system live, starting with the Hospital. In this contribution we will examine the conditions that allow, within the hospital framework, a successful integration of the change and especially its managerial dimension. More concretely, we propose to consider change as a factor that reinterrogates managerial practices in order to make them a lever for integration and cohesion in order to escape the risks of destabilization and thus become a driving force for beneficial innovations.Starting from reminders of the contributions of sociology and the hospital field, we propose to consider change as an asset in a singular context, the hospital. Here the hospital is approached as a social structure to integrate the individual logics to transform them into a collective dynamic. It is in this particular sense that we restrict the expression collective action.In a practical dimension, the intervention will help to understand the impacts of change for the various managers and those for whom they are responsible, with the focus on the requirements of the public hospital service; Dans les organisations de santé, en particulier les CHU, le changement est inhérent au développement, à l’innovation médicale, ou encore à l’impératif de prise en compte des demandes sociales. Contribuer à la mission de service public passe par une capacité à animer l’organisation du service de soins mais aussi à impulser et s’adapter aux mutations.Quelles soient scientifiques, techniques, communicationnelles, légales… les différentes évolutions impactent, touchent, toutes les dimensions de l’activité hospitalière, sollicitant de plus en plus le dynamisme des acteurs. Elles ont toutes une dimension managériale car elles imposent une évolution des institutions et des agents qui font vivre le système de soin, à commencer par le CHU. Dans cette contribution nous interrogerons les conditions qui permettent, dans le cadre hospitalier, une intégration réussite du changement et surtout sa dimension managériale. Plus concrètement nous proposons de considérer le changement comme un facteur réinterrogeant les pratiques managériales pour faire de ces dernières, un levier de l’intégration, de cohésion, pour échapper aux risques de déstabilisation et ainsi devenir un moteur d’innovations bénéfiques.A partir de rappels des apports de la sociologie et du terrain hospitalier nous proposons de considérer le changement comme un atout dans un contexte singulier, l’hôpital. Ici l’hôpital est abordé comme une structure sociale devant intégrer les logiques individuelles pour les transformer en dynamique collective. C’est en ce sens particulier nous restreignons l’expression d’action collective.Dans une dimension pratique l’intervention participera à comprendre les impacts du changement pour les différents cadres et ceux dont ils ont la responsabilité, avec en ligne de mire les impératifs du service public hospitalier.
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- 2019
9. First-line Screening of OXPHOS Deficiencies Using Microscale Oxygraphy in Human Skin Fibroblasts: A Preliminary Study
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Salim Dekiouk, Jean-Claude Vienne, Jerome Kluza, Karine Mention, Nicolas Germain, Philippe Marchetti, Anne-Frédérique Dessein, Marie Joncquel, William Laine, Dries Dobbelaere, Germain, Nicolas, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Banque de tissus, Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Universitaire de Lille (CHU de Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de référence des maladies métaboliques héréditaires, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre Hospitalier Universitaire de Lille (CHU de Lille)-Centre de Biologie Pathologie et Génétique [CHU Lille], and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
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Male ,Adolescent ,Cellular respiration ,Mitochondrial disease ,Biopsy ,Cell Culture Techniques ,Oxidative phosphorylation ,Computational biology ,Mitochondrion ,Oxidative Phosphorylation ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Oxygen Consumption ,oxidative metabolism ,Respiration ,reserve capacity ,Medicine ,Humans ,Respiratory system ,Retrospective Studies ,Skin ,[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,mitochondrial diseases ,business.industry ,Genetic heterogeneity ,Respiratory chain complex ,Infant, Newborn ,Infant ,Reproducibility of Results ,General Medicine ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,Fibroblasts ,medicine.disease ,respiratory chain complex ,3. Good health ,Mitochondria ,Oxygen ,Feasibility Studies ,030211 gastroenterology & hepatology ,Female ,business ,Research Paper - Abstract
International audience; The diagnosis of mitochondrial diseases is a real challenge because of the vast clinical and genetic heterogeneity. Classically, the clinical examination and genetic analysis must be completed by several biochemical assays to confirm the diagnosis of mitochondrial disease. Here, we tested the validity of microscale XF technology in measuring oxygen consumption in human skin fibroblasts isolated from 5 pediatric patients with heterogeneous mitochondrial disorders. We first set up the protocol conditions to allow the determination of respiratory parameters including respiration associated with ATP production, proton leak, maximal respiration, and spare respiratory capacity with reproducibility and repeatability. Maximum respiration and spare capacity were the only parameters decreased in patients irrespective of the type of OXPHOS deficiency. These results were confirmed by high-resolution oxygraphy, the reference method to measure cellular respiration. Given the fact that microscale XF technology allows fast, automated and standardized measurements, we propose to use microscale oxygraphy among the first-line methods to screen OXPHOS deficiencies.
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- 2018
10. Neurodevelopmental outcome at 2 years for preterm children born at 22 to 34 weeks’ gestation in France in 2011: EPIPAGE-2 cohort study
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Pierrat, Véronique, Marchand-Martin, Laetitia, Arnaud, Catherine, Kaminski, Monique, Resche-Rigon, Matthieu, Lebeaux, Cécile, Bodeau-Livinec, Florence, Morgan, Andrei S., Goffinet, François, Marret, Stéphane, Ancel, Pierre-Yves, Rozé, Jean-Christophe, Flamant, Cyril, 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)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Centre Hospitalier Universitaire de Lille (CHU de Lille), 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), Département de l'information médicale et de la biostatistique [AP-HP Hôpital Saint-Louis], AP-HP Hôpital Saint-Louis, Département Méthodes quantitatives en santé publique (METIS), École des Hautes Études en Santé Publique [EHESP] (EHESP), DHU Risques Et Grossesse, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de pédiatrie néonatale et réanimation - neuropédiatrie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), CIC - Mère Enfant Necker Cochin Paris Centre (CIC 1419), CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), This project has been funded with support from the following organisations: The French Institute of Public Health Research/Institute of Public Health and its partners: the French Health Ministry, the National Institute of Health and Medical Research (INSERM), the National Institute of Cancer, and the National Solidarity Fund for Autonomy (CNSA), The National Research Agency through the French EQUIPEX program of investments in the future (reference ANR-11-EQPX-0038), the PREMUP Foundation, Fondation de France (reference 00050329), and Fondation pour la Recherche Médicale (reference SPF20160936356)., ANR-11-EQPX-0038/11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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 pédiatrie néonatale et réanimation - neuropédiatrie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011), pierrat, veronique, Equipements d'excellence - Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance - - RE-CO-NAI2011 - ANR-11-EQPX-0038 - EQPX - VALID, Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique ( CRESS - U1153 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Lille ( CHU de Lille ), Épidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps, Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département Méthodes quantitatives en santé publique ( METIS ), École des Hautes Études en Santé Publique [EHESP] ( EHESP ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Assistance publique - Hôpitaux de Paris (AP-HP), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Hôpital Charles Nicolle [Rouen], Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques ( GPMCND ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institute for Research and Innovation in Biomedicine ( IRIB ), CIC - Mère Enfant Necker Cochin Paris Centre ( CIC 1419 ), CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), ANR-11-EQPX-0038/11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance ( 2011 ), CHU Lille, Université de Lille, Hôpital Jeanne de Flandre [Lille], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité [CRESS (U1153 / UMR_A_1125 / UMR_S_1153)], Université Toulouse III - Paul Sabatier [UT3], and Hôpital Saint-Louis
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Male ,Pediatrics ,Developmental Disabilities ,[ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Infant, Premature, Diseases ,Blindness ,Population based cohort ,Corrected Age ,0302 clinical medicine ,030202 anesthesiology ,Outcome Assessment, Health Care ,MESH: Blindness/epidemiology ,Blindness/etiology ,Cerebral Palsy/epidemiology ,Cerebral Palsy/etiology ,Child, Preschool ,Developmental Disabilities/epidemiology ,Developmental Disabilities/etiology ,Female ,Follow-Up Studies ,France/epidemiology ,Gestational Age ,Hearing Loss/epidemiology ,Hearing Loss/etiology ,Humans ,Infant, Extremely Premature ,Infant, Premature, Diseases/epidemiology ,Infant, Premature, Diseases/mortality ,Infant, Premature, Diseases/physiopathology ,Outcome Assessment (Health Care) ,Prospective Studies ,Survivors ,030212 general & internal medicine ,Prospective cohort study ,education.field_of_study ,030219 obstetrics & reproductive medicine ,Gestational age ,Gross Motor Function Classification System ,[ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie ,General Medicine ,3. Good health ,Gestation ,France ,Cohort study ,medicine.medical_specialty ,Pédiatrie ,Population ,Cerebral palsy ,03 medical and health sciences ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,030225 pediatrics ,medicine ,education ,Hearing Loss ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,business.industry ,Cerebral Palsy ,Research ,medicine.disease ,Confidence interval ,MESH : Blindness/epidemiology ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business - Abstract
International audience; Objectives To describe neurodevelopmental outcomes at 2 years corrected age for children born alive at 22-26, 27-31, and 32-34 weeks' gestation in 2011, and to evaluate changes since 1997.Design Population based cohort studies, EPIPAGE and EPIPAGE-2.Setting France.Participants 5567 neonates born alive in 2011 at 22-34 completed weeks' gestation, with 4199 survivors at 2 years corrected age included in follow-up. Comparison of outcomes reported for 3334 (1997) and 2418 (2011) neonates born alive in the nine regions participating in both studies.Main outcome measures Survival; cerebral palsy (2000 European consensus definition); scores below threshold on the neurodevelopmental Ages and Stages Questionnaire (ASQ; at least one of five domains below threshold) if completed between 22 and 26 months corrected age, in children without cerebral palsy, blindness, or deafness; and survival without severe or moderate neuromotor or sensory disabilities (cerebral palsy with Gross Motor Function Classification System levels 2-5, unilateral or bilateral blindness or deafness). Results are given as percentage of outcome measures with 95% confidence intervals.Results Among 5170 liveborn neonates with parental consent, survival at 2 years corrected age was 51.7% (95% confidence interval 48.6% to 54.7%) at 22-26 weeks' gestation, 93.1% (92.1% to 94.0%) at 27-31 weeks' gestation, and 98.6% (97.8% to 99.2%) at 32-34 weeks' gestation. Only one infant born at 22-23 weeks survived. Data on cerebral palsy were available for 3599 infants (81.0% of the eligible population). The overall rate of cerebral palsy at 24-26, 27-31, and 32-34 weeks' gestation was 6.9% (4.7% to 9.6%), 4.3% (3.5% to 5.2%), and 1.0% (0.5% to 1.9%), respectively. Responses to the ASQ were analysed for 2506 children (56.4% of the eligible population). The proportion of children with an ASQ result below threshold at 24-26, 27-31, and 32-34 weeks' gestation were 50.2% (44.5% to 55.8%), 40.7% (38.3% to 43.2%), and 36.2% (32.4% to 40.1%), respectively. Survival without severe or moderate neuromotor or sensory disabilities among live births increased between 1997 and 2011, from 45.5% (39.2% to 51.8%) to 62.3% (57.1% to 67.5%) at 25-26 weeks' gestation, but no change was observed at 22-24 weeks' gestation. At 32-34 weeks' gestation, there was a non-statistically significant increase in survival without severe or moderate neuromotor or sensory disabilities (P=0.61), but the proportion of survivors with cerebral palsy declined (P=0.01).Conclusions In this large cohort of preterm infants, rates of survival and survival without severe or moderate neuromotor or sensory disabilities have increased during the past two decades, but these children remain at high risk of developmental delay.
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- 2017
11. Characteristics and Management of IgA Vasculitis (Henoch-Schonlein) in Adults Data From 260 Patients Included in a French Multicenter Retrospective Survey
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Audemard-Verger, Alexandra, Terrier, Benjamin, Dechartres, Agnès, Chanal, Johan, Amoura, Zahir, Le Gouellec, Noémie, Cacoub, Patrice, Jourde-Chiche, Noemie, Urbanski, Geoffrey, Augusto, François, Moulis, Guillaume, Raffray, Loïc, Deroux, Alban, Hummel, Aurélie, Lioger, Bertrand, Catroux, Melanie, Faguer, Stanislas, Goutte, Julie, Martis, Nihal, Maurier, François, Rivière, Etienne, Sanges, Sébastien, Baldolli, Aurélie, Costedoat-Chalumeau, Nathalie, Roriz, Mélanie, Puéchal, Xavier, André, Marc, Lavigne, Christian, Bienvenu, Boris, Mekinian, Arsene, Zagdoun, Elie, Girard, Charlotte, Bérezné, Alice, Guillevin, Loïc, Thervet, Eric, Pillebout, Evangeline, CHU Cochin [AP-HP], Immunologie - Immunopathologie - Immunothérapeutique ( I3 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Epidémiologie Clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 ( UPD5 ) -PRES Sorbonne Paris Cité-French Cochrane Centre, Institut Cochin ( 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 d'immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], CH Valenciennes, Immunologie - Immunopathologie - Immunothérapie ( I3 ), Aix Marseille Université ( AMU ), Vascular research center of Marseille ( VRCM ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Angers, CHU Toulouse [Toulouse], Processus Infectieux en Milieu Insulaire Tropical ( PIMIT ), Centre National de la Recherche Scientifique ( CNRS ) -IRD-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de la Réunion ( UR ), Clinique de médecine interne, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, CHU Necker - Enfants Malades [AP-HP], Service de Médecine Interne, Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), CHU de Poitiers, Département de Néphrologie et Transplantation d'organes, CHU Toulouse [Toulouse]-Hôpital de Rangueil, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Université Nice Sophia Antipolis - Faculté de Médecine ( UNS UFR Médecine ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), Service de médecine interne, Hôpital Sainte-Blandine-Centre hospitalier régional Metz-Thionville ( CHR Metz-Thionville ), Université de Neuchâtel, Centre Hospitalier Universitaire de Lille ( CHU de Lille ), CHU Caen, Nutrition, obésité et risque thrombotique ( NORT ), Institut National de la Recherche Agronomique ( INRA ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Caen, Service de rhumatologie, inflammation-immunopathologie- biothérapie [CHU Saint-Antoine] ( DHU i2B ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], UFR des Sciences et Technologies, Université de la Réunion ( UR ), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de rhumatologie, CHU Bordeaux [Bordeaux], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie - Immunopathologie - Immunothérapeutique (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-French Cochrane Centre, 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 d'Immunologie [CHU Pitié-Salpétrière], 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), Immunologie - Immunopathologie - Immunothérapie (I3), Aix Marseille Université (AMU), Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), 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), Hôpital Sainte-Blandine-Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Université de Neuchâtel (UNINE), Centre Hospitalier Universitaire de Lille (CHU de Lille), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Université de La Réunion (UR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], DIGNAT-GEORGE, Françoise, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-French Cochrane Centre, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie, inflammation-immunopathologie- biothérapie [CHU Saint-Antoine] (DHU i2B ), CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS)-IRD-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville)-Hôpital Sainte-Blandine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
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Adult ,Male ,Gastrointestinal Diseases ,characteristics ,[ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,IgA vasculitis ,Adrenal Cortex Hormones ,Surveys and Questionnaires ,Humans ,Propensity Score ,Cyclophosphamide ,Aged ,Retrospective Studies ,[SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,treatment ,Glomerulonephritis, IGA ,[ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie ,Middle Aged ,Arthralgia ,Henoch-Schönlein purpura ,Logistic Models ,Treatment Outcome ,[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Antirheumatic Agents ,Multivariate Analysis ,Drug Therapy, Combination ,Female ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,France ,prognosis ,Colchicine - Abstract
Data on adult IgA vasculitis (Henoch-Schönlein) (IgAV) are scarce. This survey was designed to better define the clinical spectrum of IgAV and efficacy of treatments in a French patient population.Data on clinical characteristics, histologic features, and treatment response from 260 patients with IgAV included in a French multicenter retrospective survey were analyzed. Efficacy data were compared using different statistical models.The mean ± SD age of the patients with IgAV at diagnosis was 50.1 ± 18 years, and 63% of patients were male. Baseline manifestations included purpura (100%), arthralgias/arthritis/myalgia (61%), glomerulonephritis (70%), and/or gastrointestinal involvement (53%). Thirty percent of patients showed renal failure at baseline. In univariate analysis, the response to therapy was 80% (64 of 80) in patients treated with corticosteroids (CS) alone, compared to 77% (23 of 30) in patients treated with CS plus cyclophosphamide (CYC) and 59% (10 of 17) in patients treated with colchicine (P = 0.17). Multivariable analysis showed that treatment with CS or CS plus CYC was more effective than colchicine in achieving a response. Efficacy differences were demonstrated using different statistical models: in the multivariable logistic regression model, odds ratio (OR) 3.68, 95% confidence interval (95% CI) 1.10-12.33 (P = 0.03); in the inverse probability weighting on propensity score model, OR 3.75, 95% CI 1.28-10.99 (P = 0.02). The efficacy of CS plus CYC as compared to CS alone was discordant according to the analytic method used. Analysis with the multivariable logistic regression model did not demonstrate a difference between CS plus CYC and CS alone (OR 0.88, 95% CI 0.29-2.67; P = 0.82). In contrast, inverse probability weighting on propensity score showed that CS plus CYC was more effective than CS alone (OR 1.79, 95% CI 1.00-3.20; P = 0.049).This series constitutes the largest series of adults with IgAV reported in the literature so far. It provides data on clinical and histologic presentation and therapeutic efficacy, suggesting that CS alone appears to be a reasonable first-line therapy in patients with IgAV, while the benefit of adding CYC to CS remains uncertain.
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- 2017
12. Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis
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Steven Gazal, Hilario Nunes, Jean Sibilia, Christelle Ménard, Aurélien Justet, Philippe Dieudé, Isabelle Callebaut, Amélie Bonnefond, Martin Soubrier, Patrick Revy, Catherine Boileau, Pierre-Antoine Juge, Thierry Schaeverbeke, Aline Frazier, Nathalie Saidenberg, Sébastien Ottaviani, Nadia Nathan, Bruno Crestani, Christophe Béroud, Baptiste Coustet, Vincent Cottin, Lidwine Wemeau-Stervinou, Jean-Pierre Desvignes, Marie-Christophe Boissier, Florence Dastot-Le Moal, Serge Amselem, Philippe Froguel, Yannick Allanore, Annick Clement, Olivier Sand, Gabriel Thabut, Marie-Pierre Debray, Pascal Richette, Caroline Kannengiesser, Benoit Wallaert, Christophe Richez, Dominique Valeyre, Sylvain Marchand-Adam, Huguette Lioté, Nicolas Leulliot, René-Marc Flipo, Raphael Borie, Claire Dromer, David Salgado, Service de Rhumathologie, Hôpital Bichat - Claude Bernard, Assistance Publique - Hôpitaux de Paris (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), Service de Pneumologie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), UMR 1152, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), UMR 1149, Centre de Recherches sur l'Inflammation, Ecologie et Ecophysiologie Forestières [devient SILVA en 2018] (EEF), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Plateforme de génomique constitutionnelle, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-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), Service de Pneumologie et Immuno-Allergologie [CHU LIlle], Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Service de Radiologie, Hospices Civils de Lyon (HCL), UMR 1100, Université Francois Rabelais [Tours], Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Rhumatologie, CH Belfort-Montbéliard, UMR 5164, Immuno ConcEpT Lab, Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Sorbonne Université (SU), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD [France-Ouest]), Muséum national d'Histoire naturelle (MNHN), Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Université de Lille, Droit et Santé, Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), 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 National de la Recherche Scientifique (CNRS), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UMR 1132, Service de Rhumatologie, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Department of Genomics of Common Diseases, Imperial College London, Service Rhumatologie A, Hôpital Cochin [AP-HP], 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 Imagerie, service de Rhumatologie, Centre Hospitalier Universitaire de Lille (CHU de Lille), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service Rhumatologie, Hôpital La Rabta [Tunis], FMTS, CRHI, Laboratoire Immunologie Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA), Fédération Hospitalo-Universitaire OMICARE, Rétrovirus et Pathologie Comparée (RPC), Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL), Maladie Pulmonaires Rares, Hôpital Louis Pradel [CHU - HCL], UMR U1125 Service rhumatologie, service de rhumatologie, CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Hôpital Avicenne [AP-HP], service de génétique, Societe Francaise de Rhumatologie, Club Rhumatismes Inflammation, la Chancellerie des Universites de Paris (legs Poix), Sorbonne Paris Cite (FPI-SPC Program), Agence Nationale de la Recherche ANR-10-LABX-46 ANR-10-EQPX-07-01 ANR-14-CE10-0006 ANR-10-INBS-09, France Genomique National Infrastructure, Pfizer, Chugai, Centre de Resources Biologiques Hopital Bichat Paris France, ANR-14-CE10-0006,GENEXGERTEL,Rôles génomiques et extragénomiques de RTEL1(2014), Hôpital Bichat - Claude Bernard, Assistance Publique - Hôpitaux de Paris ( AP-HP ), Université Paris Diderot (Paris 7), Université Sorbonne Paris Cité ( USPC ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Saint-Etienne, UMR 1137, Fac Sci, Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), 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 Pneumologie et Immuno-Allergologie, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hospices Civils de Lyon ( HCL ), Service de Pneumologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie (Paris 6), Centre National de la Recherche Scientifique ( CNRS ), Université de Bordeaux ( UB ), Sorbonne Universités, Institut de minéralogie, de physique des matériaux et de cosmochimie ( IMPMC ), Muséum National d'Histoire Naturelle ( MNHN ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche pour le Développement ( IRD [France-Ouest] ), Muséum National d’Histoire Naturelle ( MNHN ), Laboratoire de cristallographie et RMN biologiques ( LCRB - UMR 8015 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Droit et Santé (Lille 2) ( UDSL ), European Genomic Institute for Diabetes ( EGID ), Génétique Médicale et Génomique Fonctionnelle ( GMGF ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Lariboisière, Génomique Intégrative et Modélisation des Maladies Métaboliques ( EGID ), Université de Lille-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), CHU Cochin [AP-HP], Institut Cochin ( UM3 (UMR 8104 / U1016) ), Centre Hospitalier Universitaire de Lille ( CHU de Lille ), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques, Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Hôpital La Rabta [Tunis), Université de Strasbourg ( UNISTRA ), Rétrovirus et Pathologie Comparée ( RPC ), Institut National de la Recherche Agronomique ( INRA ) -École pratique des hautes études ( EPHE ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon ( ENVL ), Département Génétique, Institut de l'Elevage, Centre Reference Maladies Respiratoires Rares, Hôpital Armand Trousseau, Assistance Publique - Hôpitaux de Paris ( AP-HP ), Centre Hospitalier Universitaire de Clermont-Ferrand, Unité de Nutrition Humaine - Clermont Auvergne ( UNH ), Université Clermont Auvergne ( UCA ) -Institut national de la recherche agronomique [Auvergne/Rhône-Alpes] ( INRA Auvergne/Rhône-Alpes ), Centre de Recherche en Nutrition Humaine d'Auvergne ( CRNH d'Auvergne ), Hôpital Avicenne, Assistance Publique - Hôpitaux de Paris ( AP-HP ), European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Institut de l'élevage (IDELE), ProdInra, Archive Ouverte, Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], 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)-CHU Trousseau [APHP], 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 génétique et embryologie médicales [CHU Trousseau], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), European Genomic Institute for Diabetes [Lille] (EGID), Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Hôpital Armand Trousseau, Assistance Publique - Hôpitaux de Paris (AP-HP), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Hôpital Avicenne, Assistance Publique - Hôpitaux de Paris (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)
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Male ,Pathology ,medicine.disease_cause ,Arthritis, Rheumatoid ,0302 clinical medicine ,Risk Factors ,Pulmonary fibrosis ,Exome ,Telomerase ,Exome sequencing ,Mutation ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Interstitial lung disease ,Middle Aged ,3. Good health ,Europe ,Polyarthrite rhumatoïde ,maladie pulmonaire ,Phenotype ,Rheumatoid arthritis ,Female ,Pulmonary and Respiratory Medicine ,Adult ,medicine.medical_specialty ,Heterozygote ,fibrose pulmonaire ,03 medical and health sciences ,[ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology ,medicine ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,respiratory system diseases ,Genetic Association Studies ,Aged ,030203 arthritis & rheumatology ,pulmonary fibrosis ,business.industry ,Case-control study ,DNA Helicases ,Sequence Analysis, DNA ,medicine.disease ,030228 respiratory system ,Case-Control Studies ,Immunology ,business ,Lung Diseases, Interstitial ,Software ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53–6.12; p=9.45×10−4). Telomeres were shorter in RA-ILD patients with a TERT, RTEL1 or PARN mutation than in controls (p=2.87×10−2).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility.
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- 2017
13. Long-term evolution of neuroendocrine cell hyperplasia of infancy: the FRENCHI findings
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Dervaux, Morgane, Thumerelle, Caroline, Fabre, Candice, Abou-Taam, Rola, Bihouee, Tiphaine, Brouard, Jacques, Clement, Annick, Delacourt, Christophe, Delestrain, Céline, Epaud, Ralph, Ghdifan, Sofiane, Hadchouel, Alice, Houdouin, Véronique, Labouret, Géraldine, Perisson, Caroline, Reix, Philippe, Renoux, Marie-Catherine, Troussier, Françoise, Weiss, Laurence, Mazenq, Julie, Nathan, Nadia, Dubus, Jean-Christophe, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Centre Hospitalier Intercommunal de Créteil (CHIC), Département de pneumologie pédiatrique [CHU Créteil] (RespiRare), Centre Hospitalier Universitaire de Lille (CHU de Lille), Centre de ressources et de compétences pour la mucoviscidose [Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Sud Saint Pierre [Ile de la Réunion], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital de Hautepierre [Strasbourg], Maladies génétiques d'expression pédiatrique (U933), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM]
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Neuroendocrine cell hyperplasia of infancy ,Follow-up ,[SDV]Life Sciences [q-bio] ,Childhood interstitial lung disease ,Pediatrics, Perinatology and Child Health ,Cohort - Abstract
Only few studies report long-term evolution of patients with neuroendocrine cell hyperplasia of infancy (NEHI). We report data from a 54-patient cohort followed up in the French network for rare respiratory diseases (RespiRare). Demographic characteristics and respiratory and nutritional evolution were collected at the time of the patient's last scheduled visit. The mean duration of follow-up was 68 months (5 months to 18 years). Fifteen patients (27.8%) were considered clinically cured. During follow-up, hospitalizations for wheezy exacerbations were reported in 35 patients (55%), and asthma diagnosed in 20 (37%). Chest CT scan improvement was noted in 25/44 (56.8%). Spirometry showed a persistent obstructive syndrome in 8/27 (29.6%). A sleep disorder was rare (2/36, 5.5%). Oxygen weaning occurred in 28 of the 45 patients initially treated (62.2%) and was age-dependent (35.7% under 2 years, 70.5% between 2 and 6 years, and 100% after 7 years). Oxygen duration was linked to a biopsy-proven diagnosis (p = 0.02) and to the use of a nutritional support (p = 0.003). Corticosteroids were largely prescribed at diagnosis, with no evident respiratory or nutritional effect during follow-up. Among 23 patients with an initial failure to thrive, 12 (52.2%) had no weight recovery. Initial enteral feeding (17/54, 31.5%) was stopped at a mean age of 43 months (3 to 120), with no effect on cure and oxygen liberation at the last visit. Conclusion: Our results show that NEHI has a globally positive, but unequal, improvement over time. Further prospective studies are needed to better clarify the different trajectories of patients with NEHI. What is Known: • Neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease whose long-term outcome is considered positive from very few studies including heterogeneous populations. What is New: • The 68-month follow-up of our 54-patient cohort showed respiratory/nutritional symptom persistence in 72.2%, oxygen requiring in 34%, and asthma in 37%. When controlled, radiological or functional improvement was noted in 56.8 and 40.7%. Further prospective studies are needed to better clarify the different trajectories of patients with NEHI.
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- 2022
14. Clinical Characteristics and Risk Factors of Extensive Macular Atrophy with Pseudodrusen: The EMAP Case-Control National Clinical Trial
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Douillard, Aymeric, Picot, Marie-Christine, Delcourt, Cecile, Lacroux, Annie, Zanlonghi, Xavier, Puech, Bernard, Defoort-Dhelemmes, Sabine, Drumare, Isabelle, Jozefowicz, Elsa, Bocquet, Beatrice, Baudoin, Corinne, Marzouka, Nour Al-Dain, Perez-Roustit, Sarah, Arsene, Sophie, Gissot, Valerie, Devin, Francois, Arndt, Carl, Wolff, Benjamin, Mauget-Faysse, Martine, Quaranta, Maddalena, Mura, Thibault, Deplanque, Dominique, Oubraham, Hassiba, Cohen, Salomon Yves, Gastaud, Pierre, Zambrowsky, Olivia, Creuzot Garcher, Catherine, Said, Saddek Mohand, Garavito, Rocio Blanco, Souied, Eric, Sahel, José-Alain, Audo, Isabelle, Hamel, Christian, Meunier, Isabelle, Clinical Investigation Center - Clinical Research and Epidemiology Unit, Centre Hospitalier Universitaire de Montpellier ( CHU Montpellier ), CIC 1411 Clinical Investigation Center, Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHRU Montpellier, Clin Invest Ctr, Montpellier, France, INSERM, CIC 1411, Montpellier, France, CHRU Montpellier, Clin Res & Epidemiol Unit, Montpellier, France, Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université de Bordeaux ( UB ), U1219 Bordeaux Population Health Research Center, Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Université de Montpellier ( UM ), Eye Clinic, Clinique Sourdille, Centre Ophtalmologique de la Clinique Jules Verne, Service d’Exploration de la Vision et Neuro-ophtalmologie, Hôpital Robert Salengro, Centre Hospitalier Régional Universitaire de Lille ( CHRU de Lille ), Centre Hospitalier Universitaire de Lille ( CHU de Lille ), CIC 1403 Centre d’Investigation Clinique, Université de Lille, Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), CIC 1415 Centre d’Investigation Clinique, Centre Monticelli Paradis d'Ophtalmologie, Hôpital Robert Debré - Eye Clinic, Centre Hospitalier Universitaire de Reims ( CHU de Reims ), Fondation Ophtalmologique Adolphe de Rothschild, Centre d'Imagerie Médicale La Maison Rouge, Centre Ophtalmologique Rabelais, Clinical Investigation Center and Clinical Research and Epidemiology Unit, Centre Hospitalier Intercommunal de Créteil, Centre Ophtalmologique d'Imagerie et de Laser, Centre Hospitalier Universitaire de Nice ( CHU de Nice ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Université Bourgogne Franche-Comté ( UBFC ), Eye Clinic - Eye Nutrition and Signaling Group, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CIC 1423 DHU Sight Restore, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Institut de la Vision, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie (Paris 6), Sorbonne Universités, Académie des Sciences, Academie des Sciences, Institute of Ophthalmology, University of Messina, CIC 1423 CIC des Quinze-Vingts - DHU Sight Restor, Laboratoires Thea, Bayer, Novartis, Roche, Ophthotech, Allergan, PHRC, PHRC National, Thea, Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Hôpital Gui de Chauliac [Montpellier], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Lille (CHU de Lille), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Hospitalier Universitaire de Nice (CHU de Nice), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), 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), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre Hospitalier Universitaire de Nice (CHU Nice), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU), Académie des Sciences [Paris], Institut de France, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)
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Adult ,Male ,genetic structures ,[SDV]Life Sciences [q-bio] ,Visual Acuity ,Retinal Drusen ,Diagnostic Techniques, Ophthalmological ,Blindness ,Macular Degeneration ,Risk Factors ,Geographic Atrophy ,Odds Ratio ,Photography ,Humans ,Sex Distribution ,Aged ,Aged, 80 and over ,[ SDV ] Life Sciences [q-bio] ,Middle Aged ,eye diseases ,Choroidal Neovascularization ,Case-Control Studies ,Disease Progression ,Female ,France ,Tomography, Optical Coherence - Abstract
Purpose: To assess the association of clinical and biological factors with extensive macular atrophy with pseudodrusen (EMAP) characterized by bilateral macular atrophy occurring in patients aged 50 to 60 years and a rapid progression to legal blindness within 5 to 10 years. Design: A national matched case-control study. Participants: Participants were recruited in 10 French Departments of Ophthalmology and their associated clinical investigation centers. All 115 patients with EMAP had symptoms before the age of 55 years due to bilateral extensive macular atrophy with a larger vertical axis and diffuse pseudodrusen. Three controls without age-related macular degeneration (AMD) or retinal disease at fundus examination were matched for each patient with EMAP by gender, age, and geographic area (in total 415). Methods: Subjects and controls underwent an eye examination including color, red-free autofluorescent fundus photographs and spectral-domain optical coherence tomography with macular analysis. The interviews collected demographic, lifestyle, family and personal medical history, medications, and biological data. Associations of risk factors were estimated using conditional logistic regression. Main Outcome Measures: Extensive macular atrophy with pseudodrusen status (cases vs. controls). Results: Extensive macular atrophy with pseudodrusen most frequently affected women (70 women, 45 men). After multivariate adjustment, family history of glaucoma or AMD was strongly associated with EMAP (odds ratio [OR], 2.3, P = 0.008 and OR, 1.5, P = 0.01, respectively). No association was found with cardiac diseases or their risk factors. Mild and moderate kidney disease and higher neutrophil rate were associated with a reduced risk of EMAP (OR, 0.58, P = 0.04; OR, 0.34, P = 0.01; and OR, 0.59, P = 0.003, respectively). On the contrary, eosinophilia (OR, 1.6; P = 0.0002), lymphocytosis (OR, 1.84; P = 0.0002), increased erythrocyte sedimentation rate (OR, 6.5; P = 0.0005), decreased CH50 (P = 0.001), and high plasma C3 level (P = 0.023) were significantly associated with a higher risk of EMAP. Conclusions: This study documents an association between EMAP and family history of AMD and glaucoma, a clear female predominance, and a systemic inflammatory profile. The reduced CH50 and increased C3 plasma values could reflect a more severe complement pathway dysfunction than in AMD, leading to early pseudodrusen and rapid development of geographic atrophy. There is no association of EMAP with AMD cardiac diseases or cardiac risks, including cigarette smoking.
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- 2016
15. The level of blast CD33 expression positively impacts the effect of gemtuzumab ozogamicin in patients with acute myeloid leukemia
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Adrienne de Labarthe, Florent Dumezy, Edouard Cornet, Sylvie Castaigne, Hervé Dombret, Cécile Pautas, Orianne Wagner-Ballon, Estelle Guérin, Jean-Noël Bastie, Xavier Thomas, Emmanuel Raffoux, Guillaume Olombel, Jean Feuillard, Sylvain Chantepie, Julien Guy, Ollivier Legrand, Claude Preudhomme, Adriana Plesa, Jean-Yves Perrot, Véronique Salaun, Pascal Turlure, Cheval, Christelle, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie biologique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hématologie Biologique (HEGP - Hématologie Biologique), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Lille (CHU de Lille), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Laboratoire d'hématologie [AP-HP Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire d'Hématologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie Biologique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Centre Hospitalier de Versailles André Mignot (CHV), Service d'Hémato-oncologie [CHU Saint-Louis], 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), Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'Hématologie Biologique ( HEGP - Hématologie Biologique ), Assistance publique - Hôpitaux de Paris (AP-HP), Centre Hospitalier Universitaire de Lille ( CHU de Lille ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Centre Hospitalier de Versailles (CHV), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,Myeloid ,Patients ,Gemtuzumab ozogamicin ,Immunology ,CD33 ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biochemistry ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,hemic and lymphatic diseases ,Calicheamicin ,medicine ,ComputingMilieux_MISCELLANEOUS ,Leukemia ,business.industry ,Myeloid leukemia ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Cell Biology ,Hematology ,[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy ,medicine.disease ,3. Good health ,Immunoconjugate ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Monoclonal ,Cancer research ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,France ,[SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy ,business ,030215 immunology ,medicine.drug - Abstract
International audience; Gemtuzumab ozogamicin (GO) is an immunoconjugate, combining an anti-CD33 monoclonal antibody to calicheamicin, a highly cytotoxic antibiotic. First developed as single agent in adults with relapsed acute myeloid leukemia (AML), it was then evaluated in combination with chemotherapy in newly diagnosed patients. In the randomized Acute Leukemia French Association (ALFA)–0701 study, we reported that sequential administration of a lower dose of GO allowed the safe delivery of a high cumulative dose associated with a substantial improvement in patient outcome. A recent meta-analysis has confirmed that adding GO to chemotherapy may provide a survival advantage in patients without adverse cytogenetic characteristics. However, these results were obtained regardless of the level of blast CD33 expression. In vitro, a clear relationship between CD33 expression and GO efficacy has nevertheless been shown. In vivo, contradictory results have been reported so far. No impact was found when CD33 expression was evaluated as a continuous covariable or using a 20% cutoff. Higher response rates were nevertheless reported for patients with CD33+ expression ≥98% in 1 phase 2 study or when showing CD33 expression as mean fluorescence intensity (MFI) using an isotype antibody as control. To further evaluate the impact of CD33 expression on GO treatment effect, we retrospectively analyzed the results of the ALFA-0701 study.
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- 2016
16. Prenatal diagnosis by trio exome sequencing in fetuses with ultrasound anomalies: A powerful diagnostic tool
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Tran Mau-Them, Frédéric, Delanne, Julian, Denommé-Pichon, Anne-Sophie, Safraou, Hana, Bruel, Ange-Line, Vitobello, Antonio, Garde, Aurore, Nambot, Sophie, Bourgon, Nicolas, Racine, Caroline, Sorlin, Arthur, Moutton, Sébastien, Marle, Nathalie, Rousseau, Thierry, Sagot, Paul, Simon, Emmanuel, Vincent-Delorme, Catherine, Boute, Odile, Colson, Cindy, Petit, Florence, Legendre, Marine, Naudion, Sophie, Rooryck, Caroline, Prouteau, Clément, Colin, Estelle, Guichet, Agnès, Ziegler, Alban, Bonneau, Dominique, Morel, Godelieve, Fradin, Mélanie, Lavillaureix, Alinoé, Quelin, Chloé, Pasquier, Laurent, Odent, Sylvie, Vera, Gabriella, Goldenberg, Alice, Guerrot, Anne-Marie, Brehin, Anne-Claire, Putoux, Audrey, Attia, Jocelyne, Abel, Carine, Blanchet, Patricia, Wells, Constance F., Deiller, Caroline, Nizon, Mathilde, Mercier, Sandra, Vincent, Marie, Isidor, Bertrand, Amiel, Jeanne, Dard, Rodolphe, Godin, Manon, Gruchy, Nicolas, Jeanne, Médéric, Schaeffer, Elise, Maillard, Pierre-Yves, Payet, Frédérique, Jacquemont, Marie-Line, Francannet, Christine, Sigaudy, Sabine, Bergot, Marine, Tisserant, Emilie, Ascencio, Marie-Laure, Binquet, Christine, Duffourd, Yannis, Philippe, Christophe, Faivre, Laurence, Thauvin-Robinet, Christel, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Unité fonctionnelle d' Innovation en Diagnostic Génomique des Maladies Rares (CHU Dijon) (UF6254), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FHU TRANSLAD (CHU de Dijon), Laboratoire de Génétique Chromosomique et Moléculaire [CHU Dijon], Service de Gynécologie Obstétrique, Médecine Foetale et Stérilité Conjugale - Chirurgie Gynécologie et Oncologique [CHU de Dijon], Centre de Référence Maladies Rares Anomalies du Développement et Syndromes Malformatifs Nord, Centre Hospitalier Universitaire de Lille (CHU de Lille), Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département de Biochimie et Génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de référence Maladies Rares CLAD-Ouest [Rennes], Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Génétique Clinique, Hôpital Femme Mère Enfant, Centre Hospitalier Universitaire de Lyon, Service de Gynécologie et Obstétrique [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Génétique et Centre de Diagnostic Anténatal, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Equipe Maladies Génétiques de L'Enfant et de L'Adulte, Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée [Montpellier], Centre de Référence Anomalies du Développement et Syndromes Malformatifs [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Centre de Référence Anomalies du Développement et Syndromes Malformatifs [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut du Thorax [Nantes], Embryology and genetics of human malformation, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Génétique Médicale et Clinique, Hôpital Necker-Enfants Malades, Unité Fonctionnelle de Génétique Médicale, Cytogénétique, Génétique Médicale et Biologie de La Reproduction, Centre Hospitalier Intercommunal Poissy-Saint-Germain-en-Laye, Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, UMR 1253 IBrain Imagerie & Cerveau Equipe 2 : 'Neurogénomique & Physiopathologie neuronale' (NPN), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Génétique Médicale, Pôle Femme, Mère, Enfants CHU de La Réunion-GH Sud Réunion-Saint-Pierre, Pôle Femme, Mère, Enfants, CHU de La Réunion-GH Sud Réunion-Saint-Pierre-CHU de La Réunion-GH Sud Réunion-Saint-Pierre, Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Unité de Génétique Clinique Prénatale, Département de Génétique Médicale, Hôpital de la Timone [CHU - APHM] (TIMONE)- Hôpital de la Timone [CHU - APHM] (TIMONE), 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), and This work was supported by grants from Dijon University Hospital, the ISITE-BFC (PIA ANR), the European Union through the FEDER programs, and the AnDDI-Rares network for ES performed in this study.
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prenatal ,[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health ,chromosomal microarray ,exome sequencing (ES) ,diagnostic yield ,Genetics ,Molecular Medicine ,fetal ,Genetics (clinical) - Abstract
Introduction: Prenatal ultrasound (US) anomalies are detected in around 5%–10% of pregnancies. In prenatal diagnosis, exome sequencing (ES) diagnostic yield ranges from 6% to 80% depending on the inclusion criteria. We describe the first French national multicenter pilot study aiming to implement ES in prenatal diagnosis following the detection of anomalies on US.Patients and methods: We prospectively performed prenatal trio-ES in 150 fetuses with at least two US anomalies or one US anomaly known to be frequently linked to a genetic disorder. Trio-ES was only performed if the results could influence pregnancy management. Chromosomal microarray (CMA) was performed before or in parallel.Results: A causal diagnosis was identified in 52/150 fetuses (34%) with a median time to diagnosis of 28 days, which rose to 56/150 fetuses (37%) after additional investigation. Sporadic occurrences were identified in 34/56 (60%) fetuses and unfavorable vital and/or neurodevelopmental prognosis was made in 13/56 (24%) fetuses. The overall diagnostic yield was 41% (37/89) with first-line trio-ES versus 31% (19/61) after normal CMA. Trio-ES and CMA were systematically concordant for identification of pathogenic CNV.Conclusion: Trio-ES provided a substantial prenatal diagnostic yield, similar to postnatal diagnosis with a median turnaround of approximately 1 month, supporting its routine implementation during the detection of prenatal US anomalies.
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- 2023
17. Safety and efficacy of low-dose PI3K inhibitor taselisib in adult patients with CLOVES and Klippel–Trenaunay syndrome (KTS): the TOTEM trial, a phase 1/2 multicenter, open-label, single-arm study
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Marc Bardou, Pierre Vabres, Laurence Faivre, Annabel Maruani, Victoria E R Parker, A. Phan, Christine Chiaverini, L. Martin, Jill Clayton-Smith, C. Fleck, Maxime Luu, Tristan Mirault, Fanny Morice-Picard, M. Carpentier, Marie-Line Jacquemont, Hervé Devilliers, Marjolaine Willems, A. Maurer, Romaric Loffroy, Didier Bessis, Florence Petit, Robert K. Semple, M. Yousfi, 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), FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Référence des Maladies Génétiques à Expression Cutanée (MAGEC), Service de médecine interne et maladies systémiques (SOC 2) [CHU de Dijon], Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Institute of Applied Physics [Bern] (IAP), University of Bern, CHU Bordeaux [Bordeaux], Centre de Référence Maladies Rares Anomalies du Développement et Syndromes Malformatifs Nord, Centre Hospitalier Universitaire de Lille (CHU de Lille), Hôpital Lapeyronie [Montpellier] (CHU), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre national de référence des maladies vasculaires rares, 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Manchester [Manchester], CHU Dijon, AstraZeneca [Cambridge, UK], University of Edinburgh, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
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Adult ,Klippel-Trenaunay-Weber Syndrome ,medicine.medical_specialty ,Klippel-Trenaunay syndrome ,Syzygium ,[SDV]Life Sciences [q-bio] ,Population ,Overgrowth syndrome ,Article ,Phosphatidylinositol 3-Kinases ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Internal medicine ,taselisib ,medicine ,Humans ,education ,Adverse effect ,Genetics (clinical) ,education.field_of_study ,business.industry ,Imidazoles ,clinical trial ,PIK3CA ,medicine.disease ,3. Good health ,Clinical trial ,Oxazepines ,Tolerability ,030220 oncology & carcinogenesis ,Mutation ,Cohort ,Quality of Life ,mosaic ,business ,PROS treatment - Abstract
International audience; ABSTRACT Purpose PIK3CA pathogenic variants in the PIK3CA-related overgrowth spectrum (PROS) activate phosphoinositide 3-kinase signaling, providing a rationale for targeted therapy, but no drug has proven efficacy and safety in this population. Our aim was to establish the six-month tolerability and efficacy of low-dose taselisib, a selective class I PI3K inhibitor, in PROS patients. Methods Patients over 16 years with PROS and PIK3CA pathogenic variants were included in a phase IB/IIA multicenter, open-label single-arm trial (six patients at 1 mg/day of taselisib, then 24 at 2 mg/day). The primary outcome was the occurrence of dose limiting toxicity (DLT). Efficacy outcomes were the relative changes after treatment of (1) tissue volume at affected and unaffected sites, both clinically and on imaging; (2) cutaneous vascular outcomes when relevant; (3) biologic parameters; (4) quality of life; and (5) patient-reported outcomes. Results Among 19 enrolled patients, 2 experienced a DLT (enteritis and pachymeningitis) leading to early trial termination (17 treated, 10 completed the study). No serious adverse reaction occurred in the 1 mg cohort ( n = 6). No significant reduction in affected tissue volume was observed (mean −4.2%; p = 0.81; SD 14.01). Thirteen (76.4%) participants reported clinical improvement (pain reduction, chronic bleeding resolution, functional improvement). Conclusion Despite functional improvement, the safety profile of low-dose taselisib precludes its long-term use.
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- 2021
18. Functional genomics uncovers the transcription factor BNC2 as required for myofibroblastic activation in fibrosis
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Marie Bobowski-Gerard, Clémence Boulet, Francesco P. Zummo, Julie Dubois-Chevalier, Céline Gheeraert, Mohamed Bou Saleh, Jean-Marc Strub, Amaury Farce, Maheul Ploton, Loïc Guille, Jimmy Vandel, Antonino Bongiovanni, Ninon Very, Eloïse Woitrain, Audrey Deprince, Fanny Lalloyer, Eric Bauge, Lise Ferri, Line-Carolle Ntandja-Wandji, Alexia K. Cotte, Corinne Grangette, Emmanuelle Vallez, Sarah Cianférani, Violeta Raverdy, Robert Caiazzo, Viviane Gnemmi, Emmanuelle Leteurtre, Benoit Pourcet, Réjane Paumelle, Kim Ravnskjaer, Guillaume Lassailly, Joel T. Haas, Philippe Mathurin, François Pattou, Laurent Dubuquoy, Bart Staels, Philippe Lefebvre, Jérôme Eeckhoute, Université de Lille, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Lille (CHU de Lille), ANR-16-RHUS-0006,PreciNASH,PreciNASH(2016), ANR-16-IDEX-0004,ULNE,ULNE(2016), ANR-21-CE14-0032,HSCreg,Identification et caractérisation d'un nouveau facteur de transcription controlant l'activation des cellules stellaires et la fibrose hépatique(2021), ANR-20-CE14-0034,DeCodeNASH,L'activation métabolique des cellules dendritiques dans la steatopathie métabolique(2020), and ANR-21-CE17-0016,MEdicAL,Cibler les MEcanismes cellulaires du défaut de régénération pour le développement d'une médecine de précision pour l'hépatite ALcoolique.(2021)
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DNA-Binding Proteins ,Liver Cirrhosis ,Mice ,Multidisciplinary ,[SDV]Life Sciences [q-bio] ,General Physics and Astronomy ,Animals ,Humans ,General Chemistry ,Genomics ,Myofibroblasts ,General Biochemistry, Genetics and Molecular Biology ,Transcription Factors - Abstract
Tissue injury triggers activation of mesenchymal lineage cells into wound-repairing myofibroblasts, whose unrestrained activity leads to fibrosis. Although this process is largely controlled at the transcriptional level, whether the main transcription factors involved have all been identified has remained elusive. Here, we report multi-omics analyses unraveling Basonuclin 2 (BNC2) as a myofibroblast identity transcription factor. Using liver fibrosis as a model for in-depth investigations, we first show that BNC2 expression is induced in both mouse and human fibrotic livers from different etiologies and decreases upon human liver fibrosis regression. Importantly, we found that BNC2 transcriptional induction is a specific feature of myofibroblastic activation in fibrotic tissues. Mechanistically, BNC2 expression and activities allow to integrate pro-fibrotic stimuli, including TGFβ and Hippo/YAP1 signaling, towards induction of matrisome genes such as those encoding type I collagen. As a consequence, Bnc2 deficiency blunts collagen deposition in livers of mice fed a fibrogenic diet. Additionally, our work establishes BNC2 as potentially druggable since we identified the thalidomide derivative CC-885 as a BNC2 inhibitor. Altogether, we propose that BNC2 is a transcription factor involved in canonical pathways driving myofibroblastic activation in fibrosis.
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- 2022
19. Impact of the COVID-19 pandemic and associated lockdown measures on the management, health, and behavior of the cystic fibrosis population in France during 2020 (MUCONFIN)
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Nadia Oubaya, Thibaud Pombet, Celine Delestrain, Natascha Remus, Benoit Douvry, Dominique Grenet, Harriet Corvol, Guillaume Thouvenin, Virginie Prulière-Escabasse, Hakima Mounir, Dominique Argoud, Cédric Fretigne, Laurence Costes, Marie-Pierre Mackiewicz, Camille Jung, Laitissia Ahamada, Sophie Lanone, Bernard Maitre, Anne-Cécile Bégot, Ralph Epaud, Hôpital Henri Mondor, 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), Laboratoire Interdisciplinaire de Recherche sur les Transformations des pratiques Éducatives et des pratiques Sociales (LIRTES), Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Catholique de Paris (ICP), Centre Hospitalier Intercommunal de Créteil (CHIC), Département de pneumologie pédiatrique [CHU Créteil] (RespiRare), Centre Hospitalier Universitaire de Lille (CHU de Lille), Hôpital Foch [Suresnes], 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), Service de Pneumologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], 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 - Faculté de Médecine (SU FM), Sorbonne Université (SU), IMRB - GEIC2O/'Genetic and Environmental Interactions in COPD, Cystic fibrosis and Other (rare) respiratory diseases' [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), and Lanone, Sophie
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Adult ,Cystic Fibrosis ,SARS-CoV-2 ,Public Health, Environmental and Occupational Health ,healthcare ,COVID-19 ,anxiety ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,lockdown ,Young Adult ,Communicable Disease Control ,[SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Humans ,France ,Pandemics - Abstract
BackgroundMost of the studies on cystic fibrosis (CF) focused on SARS-CoV-2 prevalence and suggested a low incidence of infection in this population. We aimed to assess the impact of the pandemic and related lockdown measures implemented in May 2020 in response to the first wave of SARS-CoV-2 infection on healthcare access, health, and behavior in CF patients.MethodsA national questionnaire opened online from May 15th, 2020 to June 11th, 2020 was completed by 751 CF-patients, aged 14 years and over. It comprised questions about access to healthcare, anxiety and depression, smoking, alcohol, drug and psychotropic drug consumption, adherence to CF treatment, and constraints. A semi-structured comprehensive interview was performed no later than 1 month after the end of the lockdown in 16 CF-patients.ResultsThe mean age of the population was 28.0 [interquartile range (IQR) 20.0–37.0] years old. More than 75% of in-person consultations scheduled during the lockdown were canceled. Alternatively, 27% were postponed, and telehealth consultations were proposed and accepted in almost 40% of cases. More than 75% of the scheduled physiotherapy sessions were canceled and replaced mainly by self-drainage. Annual follow-up clinic visits were consistently postponed whereas required hospitalizations at CF centers for exacerbation were maintained in most cases. While 43.2% CF-patients had signs of anxiety, 51.0% presented symptoms of depression, both associated with increased use of psychotic medications and inversely correlated to COVID-19 prevalence. Among the lower and lower middle classes, very little medical information was obtained or requested by the patient, participation to sports or other activities was low, while excessive home confinement and isolation were more frequent. In contrast, in the upper middle and upper classes, individuals solicitated help to their CF centre, had more physical activities, and maintained contact with friends or families.ConclusionThe first lockdown in France had only minimal impact on the management care of CF-patients but was associated with increased symptoms of anxiety and depression, together with behavioral changes that varied with social class.Trial registrationNCT04463628.
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- 2022
20. Atlas électronique de la santé, de la planification et du développement durable pour le développement de la société de l'information
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Anne QUESNEL-BARBET, Centre Hospitalier Universitaire de Lille (CHU de Lille), Centre Hospitalier Régional et Universitaire (CHU) de Lille, employée sur des fonctions de recherche en géographie, géomatique en santé, Sarah Curtis, and QUESNEL-BARBET, Anne
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[SDV] Life Sciences [q-bio] ,[SPI]Engineering Sciences [physics] ,Computer-Assisted ,Decision-Making ,[SPI] Engineering Sciences [physics] ,Geographic Information System ,[SDV]Life Sciences [q-bio] ,Atlases ,[SHS] Humanities and Social Sciences ,Medical Informatics ,[SHS]Humanities and Social Sciences - Abstract
copie de l'abstract, sans pagination, ni mise en forme finale Accompagnée de la présentation orale non publiée en pdf; International audience; our aim is to propose a new decision-support tool through an e-Atlas for health caremanagement to answer to specific problems in epidemiology and territory management.This e-Atlas is the second tool of our medical informatics proiect named 'POLESAT,and completes our health geomatics platform in Public Health. This e-Atlas prototype willimprove and provide information to health responsible authorities, healthcareprofessionals (medical staff, physician and health decision-makers) and the public withgeographical information, new knowledge discovery, analysis and scientificcommunications. At this time, this e-Atlas prototype only covers the North - Pas-de-Calais region of France.Method: Database contains hospital stay activity in 2006 in the university Hospital ofLille. This application is developed using SAS software for the automation of dataprocessing (input) and maps (ouput). For mapping, we used base maps of the PostalPMSI Zones and Health Proximity Zones. The setting webpage of map results is mainlycarried out with the Jalbum software. To obtain interactive mapping, we added tooltipwith a iava script function in the html page. Then, additional statistical information frommap database appears when the mouse moves over postal code areas. Maps can bedownloaded or saved from the web server in several formats. The prototype is accessibleby both login and password from a secured web server by simple authentification(Htaccess), and strong authentification (certificate). The Secure Hypertext TransferProtocol (HTTPS) allows a secure transport of HTTP queries and responses withencrypted passwords.Results: e-Atlas provides mapping information about territorial supply and consumptionof hospital care (needs), and displays maps of catchment hospital areas by department.Our e-Adas allows doing an activity background inventory on the state of hospital activity(supply and demand), It has multiple uses and will answer users' needs.Conclusion: e-Atlas should be enlarged to all public, private hospital stay activity of ourregion and become our second tool after the modeling process planning tool.
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- 2009
21. POLESAT : e-Atlas de Santé, Planification et Développement Durable
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Julien Soula, Régis Beuscart, Anne Quesnel, Karine Wyndels, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Lille (CHU de Lille), CHU de Lille, Beuscart Régis et al, and QUESNEL-BARBET, Anne
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0206 medical engineering ,Biomedical Engineering ,Biophysics ,Decision Support Systems ,Library science ,02 engineering and technology ,[INFO] Computer Science [cs] ,Health Services Accessibility ,030218 nuclear medicine & medical imaging ,[SHS]Humanities and Social Sciences ,Database ,03 medical and health sciences ,0302 clinical medicine ,Humans ,[INFO]Computer Science [cs] ,Diagnosis-Related Groups ,Health Education/methods ,Spatial knowledge representation ,Knwoledge acquisition ,020601 biomedical engineering ,Access to information ,Geography ,Geographic Cartography ,Clinical/organization & administration ,[SHS] Humanities and Social Sciences ,Geomatics/GIS ,Medical Informatics - Abstract
Resume De nouvelles connaissances relevent de l’activite hospitaliere PMSI. Elles permettent la realisation d’etudes en geographie de la sante : geo-epidemiologie, planification sanitaire et usage des soins de sante. Nos objectifs a travers la realisation de notre plate-forme geomatique 1 sont de fournir aupres des etablissements de soins, des tutelles et du grand public des nouvelles connaissances objectives et bases de reflexion a partir des informations et analyses geographiques a l’echelle de la region Nord – Pas-de-Calais et a differents niveaux d’analyse territoriale (bureau postal PMSI, zone de proximite etc.). Pour atteindre nos buts et permettre d’ameliorer l’information et l’aide a la decision aupres des usagers et au rythme de chacun, nous allons fournir, a l’aide de notre plate-forme, les acces, transmissions, communications et informations des etudes geographiques realisees.
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- 2009
22. POLESAT: e-Atlas of Health, Planning and Sustainable Development
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Anne QUESNEL-BARBET, Soula, Julien, Wyndels, Karine, Beuscart, Régis, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Centre Hospitalier Universitaire de Lille (CHU de Lille), CHU de Lille, and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
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Geographic Cartography ,Database ,User-Computer Interface ,Diagnosis related group ,Decision Support Systems ,Computer-assisted ,[INFO]Computer Science [cs] ,Geographic Information Systems/organization & administration ,Access to information ,Medical Informatics ,Decision-making ,[SHS]Humanities and Social Sciences - Abstract
International audience; New knowledge come from detailed hospital activity of the French Medical Information System (PMSI). They allow doing health geography studies in geo-epidemiology, planning and healthcare uses to answer specific Public Health problems. Through our geomatics platform, we aim to give new scientific knowledge and reflection to healthcare professionals and the public thanks to geographical information and geographical analysis. The geographical studies are carried out at several division levels (postal-PMSI zones, proximity zones etc.) in the French Nord-Pas-de-Calais region of four million of inhabitants. In order to improve information, decision-making, and in tandem with each user's rhythm, we will provide access, transmission, communication and information of the geographical studies through our first tool of Health e-Atlas.; De nouvelles connaissances relèvent de l'activité hospitalière PMSI. Elles permettent la réalisation d'études en géographie de la santé : géo-épidémiologie, planification sanitaire et usage des soins de santé. Nos objectifs à travers la réalisation de notre plate-forme géomatique 1 sont de fournir auprès des établissements de soins, des tutelles et du grand public des nouvelles connaissances objectives et bases de réflexion à partir des informations et analyses géographiques à l'échelle de la région Nord-Pas-de-Calais et à différents niveaux d'analyse territoriale (bureau postal PMSI, zone de proximité etc.). Pour atteindre nos buts et permettre d'améliorer l'information et l'aide à la décision auprès des usagers et au rythme de chacun, nous allons fournir, à l'aide de notre plate-forme, les accès, transmissions, communications et informations des études géographiques réalisées.
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- 2009
23. Proposal for a standardized discharge letter after hospital stay for acute myocardial infarction
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Francois Schiele, Gilles Lemesle, Denis Angoulvant, Michel Krempf, Serge Kownator, Saida Cheggour, Loic Belle, Jean Ferrières, Christophe Bauters, Cyrille Bergerot, Farzin Beygui, Franck Boccara, Eric Bonnefoy, Eric Bruckert, Guillaume Cayla, Jean-Philippe Collet, Pierre Coste, Vincent Descotes-Genon, Gregory Ducrocq, Meyer Elbaz, Michel Farnier, Emile Ferrari, Dominique Guedj, Laszlo Levai, Jacques Mansourati, Nicolas Mansencal, Nicolas Meneveau, Christophe Meune, Olivier Morel, Patrick Ohlmann, Francois Paillard, Christophe Piot, Etienne Puymirat, Gilles Rioufol, François Roubille, Pierre Sabouret, Emmanuel Teiger, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Lille (CHU de Lille), Université Francois Rabelais [Tours], Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Centre Cardiologique et Vasculaire, Partenaires INRAE, Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier d'Annecy Genevois, Hôpital de Rangueil, and CHU Toulouse [Toulouse]
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medicine.medical_specialty ,Consensus ,Primary care ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Antithrombotic ,Humans ,Medicine ,030212 general & internal medicine ,Myocardial infarction ,Risk management ,communication ,business.industry ,discharge ,primary care ,General Medicine ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,medicine.disease ,Patient Discharge ,3. Good health ,Residual risk ,Regimen ,Emergency medicine ,Cardiology and Cardiovascular Medicine ,business ,Risk assessment ,Fibrinolytic agent - Abstract
In patients admitted for acute myocardial infarction, the communication and transition from specialists to primary care physicians is often delayed, and the information imparted to subsequent healthcare providers (HCPs) may be sub-optimal. A French group of cardiologists, lipidologists and diabetologists decided to establish a consensus to optimize the discharge letter after hospitalization for acute myocardial infarction. The aim is to improve both the timeframe and the quality of the content transmitted to subsequent HCPs, including information regarding baseline assessment, procedures during hospitalization, residual risk, discharge treatments, therapeutic targets and follow-up recommendations in compliance with European Society of Cardiology guidelines. A consensus was obtained regarding a template discharge letter, to be released within two days after patient’s discharge, and containing the description of the patient’s history, risk factors, acute management, risk assessment, discharge treatments and follow-up pathway. Specifically for post acute MI patients, tailored details are necessary regarding the antithrombotic regimen, lipid-lowering and anti-diabetic treatments, including therapeutic targets. Lastly, the follow-up pathway needs to be precisely mentioned in the discharge letter. Additional information such as technical descriptions, imaging, and quality indicators may be provided separately. A template for a standardized discharge letter based on 8 major headings could be useful for implementation in routine practice and help to improve the quality and timing of information transmission between HCPs after acute MI.
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- 2020
24. Avis de l'Anses relatif à la Pertinence de la ré-évaluation de la VTR chronique par voie orale pour les ions perchlorate
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Chevalier, Nicolas, Bodin, Laurent, Fini, Jean Baptiste, Garnier, Robert, Joyeux, Michel, Laurentie, Michel, Mortamais, Marion, Oliver Petit, Isabelle, Roudot, Alain-Claude, Viguié, Catherine, Wemeau, Jean-Louis, Angeli, Karine, Farion, Nicolas, CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Physiologie moléculaire et adaptation (PhyMA), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre antipoison et de toxicovigilance (Paris) (CAPTV Paris), Université Paris Diderot - Paris 7 (UPD7)-Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Retraité, Laboratoire de Fougères - ANSES, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Institut National de la Santé et de la Recherche Médicale (INSERM), Service Cardiologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Bretagne Occidentale - UFR Médecine et Sciences de la Santé (UBO UFR MSS), Université de Brest (UBO), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Lille - Direction de la recherche et de l’innovation, Centre Hospitalier Universitaire de Lille (CHU de Lille), Direction de l'Evaluation des Risques (DER), and Anses
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Perchlorates ,Toxicological reference values ,Benchmark doses ,[SDV]Life Sciences [q-bio] ,ions ,valeur toxicologique de référence - Abstract
Since 2011, ANSES has been asked on several occasions to examine the health risks associated with perchlorate (ClO4-) in DW following the identification of situations in which resources used for DW production were contaminated. In 2011, the Agency had recommended a guideline value (GV) for perchlorate in DW of 15 µg.L-1 for adult consumers, derived from the TRV of 0.7 µg.kg bw-1.d-1(ANSES, 2011), based on the inhibition of iodine uptake by the thyroid gland. ANSES had also advised against using water contaminated by perchlorate when preparing feeding bottles for infants aged up to 6 months, pending a national survey on perchlorate contamination of food, in particular to clarify the concentrations found in the powdered infant formula used for bottle preparation.In 2012, in its opinion concerning epidemiological studies on associations between exposure to perchlorate in DW and thyroid function in specific populations, the Agency had concluded that: "the results from the evaluated epidemiological studies do not enable conclusions to be drawn concerning the possible association between thyroid-stimulating hormone (TSH) levels and perchlorate concentrations in drinking water in pregnant women and newborns [...]. The absence of information concerning the iodine status of the studied populations makes it difficult to interpret the published epidemiological data." (ANSES, 2012).In its opinion of 8 April 2014 on the presence of perchlorate in infant formula and in DW, the Agency had noted the same limitations relating to the available epidemiological studies and insisted on the need to take account of the iodine status of the study population for assessing the health impact of human exposure to perchlorate and for interpreting the published epidemiological data.In its opinion of 26 December 2018, the Agency had concluded that recent epidemiological studies, including the one by the French Institute for Public Health Surveillance1(InVS) published in 2016, did not provide any additional conclusive evidence on the biological or clinical effects of perchlorate versus those taken into account in the previous ANSES opinions (ANSES 2011, 2012, 2014). The data examined in this opinion did not call into question the conclusions of the previous ANSES opinions concerning the hazard characterisation and the RV proposed by the Agency in 2011.However, with regard to the assessment of exposure to perchlorate, new data made it possible to estimate the average oral exposure of the adult population to perchlorate. This estimate was based firstly on data on perchlorate contamination of food collected by the Directorate General for Competition Policy, Consumer Affairs and Fraud Control (DGCCRF) as part of its national surveys, and secondly on data on DW contamination for the period 2014-2017 produced by the Regional Health Agencies (ARSs) and available in the SISE-Eaux database. On this basis, ANSES estimated that exposure via DW consumption accounted for about 25% of ingestion exposure. As this estimate was in line with the data in the literature and was close to the 20% default percentage defined by the World Health Organization (WHO) in 2016, the Agency felt it necessary to lower to 20% the share of exposure via water (which had previously been set at 60%) used for calculating the GV of perchlorate in DW for adults. As a result, the proposed GV was lowered to 5 µg.L-1 for the adult population.ANSES also emphasised that the existing data on food contamination were too incomplete to characterise the distribution of the general population's exposure to perchlorate by the oral route and to assess the health risk. It therefore recommended that perchlorate be included in the third French Total Diet Study (TDS3).In the absence of new data on the contamination of infant formula with perchlorate since the 2014 expert appraisal, the Agency also reiterated the conclusions of this earlier expert appraisal: "daily intakes of perchlorate, calculated on the basis of perchlorate levels in infant formulas available on the French market, do not exceed the TRV of 0.7 µg.kg bw-1.d-1for 95% of the population of children aged under 6 months consuming infant formula based on an average concentration of perchlorate of 1 µg.L-1in DW for reconstituting infant bottles" (ANSES, 2018).Lastly, ANSES indicated in this same 2018 opinion, in Section 3.2.8 concerning the conclusions on the choice of the TRV, that the Working Group on "Assessment of the health risks associated with chemical parameters in drinking water" (ERS EDCH) and the Expert Committee (CES) on "Water" considered that in any future assessment of the health risks associated with the ingestion of perchlorate, following publication of the work under way by the US EPA, it would be necessary to re-examine the method for determining the critical dose and establishing the TRV for perchlorate."All the agencies establishing chronic oral TRVs for perchlorate have chosen inhibition of iodine uptake by the thyroid as the critical effect (Table 1 on page 8).In 2019, the US EPA adopted a different approach based on toxicokinetic-toxicodynamic modelling to assess the impact of perchlorate exposure on thyroid hormone (TH) production and the effect of a reduction in maternal plasma free thyroxine (fT4) concentrations during the first trimester of pregnancy on the child's neurodevelopment, as measured by a decrease in intelligence quotient. The US EPA suggested adopting a TRV of 2.2 µg.kg bw-1.d-1, resulting in a maximum contaminant level of 56 µg.L-1 perchlorate in DW.As mentioned previously, and in view of the management difficulties encountered, the DGS had formally asked ANSES to analyse the US EPA's work on assessing the health risks associated with the presence of perchlorate in DW, in order to provide the ARSs with appropriate and proportionate guidance on the health risk.In view of this, ANSES was asked to re-examine the assessment of the health risks associated with the ingestion of perchlorate, in light of the US EPA's work. The first deliverable of this formal request therefore had the ultimate objective of determining whether the ANSES TRV of 0.7 µg.kg bw1.d-1 should be maintained. This first deliverable concluded that this TRV should not be called into question in light of the US EPA's work, mainly because of major uncertainties about the predictive ability of the model used. The Agency therefore decided to retain its chronic oral TRV established in 2011, based on the no-effect level observed in the study by Greer et al. (2002). However, all the TRVs established since that date are based on a Benchmark Dose (BMD) approach, so the Agency therefore issued an internal request to assess the relevance of this approach, based in particular on recent publications (Weterings et al. 2016, Bruce et al. 2018, Haber et al. 2021).; Depuis 2011, l’Anses a été saisie à plusieurs reprises sur les risques sanitaires liés aux ions perchlorate (ClO4-) dans les eaux destinées à la consommation humaine (EDCH), suite à la mise en évidence de situations de contamination de ressources utilisées pour la production d’EDCH. En 2011, l’Agence avait préconisé une valeur guide (VG) pour les ions perchlorate dans les EDCH de 15 µg.L-1 pour le consommateur adulte, définie à partir de la VTR de 0,7 µg.kg p.c.-1.j-1(Anses, 2011), fondée sur l’inhibition du captage de l’iode par la thyroïde. L’Anses avait également conseillé de ne pas utiliser une eau contaminée par les ions perchlorate pour la préparation des biberons des nourrissons jusqu’à 6 mois, dans l'attente de la réalisation d’une enquête nationale sur la contamination des aliments en perchlorates, en particulier pour préciser les concentrations retrouvées dans les formulations de lait maternisé en poudre utilisées pour la préparation des biberons.En 2012, dans son avis relatif aux études épidémiologiques portant sur les associations entre une exposition aux ions perchlorate dans les EDCH et la fonction thyroïdienne dans des populations spécifiques, l’Agence concluait : « les résultats des études épidémiologiques examinées par les experts ne permettent pas de conclure quant à l’existence ou à l’absence d’une association chez les femmes enceintes ou les nouveau-nés entre les niveaux de thyréostimuline (TSH, thyroid stimulating hormone) et des concentrations en ions perchlorate dans les eaux de boisson […]. L’absence d’information concernant le statut en iode des populations étudiées rend difficile l’interprétation des données épidémiologiques publiées. »(Anses, 2012).Dans son avis du 8 avril 2014 relatif à la présence d’ions perchlorate dans le lait infantile et dans les EDCH, l’Agence relevait les mêmes limites relatives aux études épidémiologiques disponibles et insistait sur la nécessité de prendre en compte le statut en iode de la population étudiée pour l’évaluation de l’impact sanitaire de l’exposition aux ions perchlorate chez l’Homme et pour l’interprétation des données épidémiologiques publiées.Dans son avis du 26 décembre 2018, l’Agence concluait que les études épidémiologiques récentes, y compris celle de de l’Institut de veille sanitaire1(InVS) publiée en 2016, n’apportaient pas d’éléments conclusifs supplémentaires sur les effets biologiques ou cliniques des ions perchlorate par rapport à celles prises en compte dans les précédents avis de l’Anses (Anses 2011, 2012, 2014). Les données examinées dans cet avis n’étaient pas de nature à remettre en cause les conclusions des avis précédents de l’Anses, concernant la caractérisation des dangers et la VTR proposée en 2011 par l’Agence.Cependant, s’agissant de l’évaluation de l’exposition aux ions perchlorate, de nouvelles données ont permis d’estimer l’exposition moyenne de la population adulte aux ions perchlorate par voie orale. Cette estimation se fondait d’une part sur les données de contamination des aliments par les ions perchlorate, recueillies par la Direction générale de la concurrence, de la consommation et de la répression des fraudes (DGCCRF) dans le cadre de ses enquêtes nationales et d’autre part sur les données de contamination des EDCH pour la période 2014-2017, produites par les Agences régionales de santé (ARS) et disponibles dans la base de données SISE-Eaux. Sur cette base, l’Anses estimait que la contribution de ’exposition liée à la consommation d’EDCH représente environ 25% de l’exposition par ingestion. Cette estimation concordant avec les données de la littérature et se rapprochant du pourcentage de 20% défini par défaut par l’Organisation Mondiale de la Santé (OMS) en 2016, l’Agence considérait nécessaire d’abaisser à 20% la part de l’exposition hydrique pour le calcul de la VG des ions perchlorate dans les EDCH pour les adultes, antérieurement fixée à 60%. En conséquence, la VG proposée avait été abaissée à 5 µg.L-1 pour la population adulte. L’Anses soulignait, par ailleurs, que les données existantes de contamination des aliments étaient trop parcellaires pour caractériser la distribution de l’exposition de la population générale aux ions perchlorate par voie orale et évaluer le risque sanitaire. En conséquence, elle recommandait de prendre en compte les ions perchlorate lors de l’étude de l’alimentation totale (EAT) 3.En l’absence de nouvelles données de contamination des laits infantiles par les ions perchlorate depuis l’expertise de 2014, l’Agence rappelait également les conclusions de ce précédent avis : « les apports journaliers en ions perchlorate, calculés sur la base des teneurs en ions perchlorate des laits infantiles disponibles sur le marché français, ne dépassent pas la VTR de 0,7 µg.kg p.c.-1.j-1 pour 95% de la population des enfants âgés de moins de 6 mois consommateurs de laits infantiles sur la base d’une concentration moyenne en ions perchlorate dans l’EDCH de 1 µg.L-1 pour la reconstitution des biberons » (Anses, 2018).Enfin, l’Anses indiquait dans ce même avis publié en 2018, au paragraphe 3.2.8 relatif aux conclusions sur le choix de la VTR : « le groupe de travail « Évaluation des risques sanitaires associés aux paramètres chimiques des eaux destinées à la consommation humaine) » (ERS EDCH) et le comité d’experts spécialisés (CES) « Eaux » estiment qu’en cas de future évaluation des risques sanitaires liés à l’ingestion d’ions perchlorate postérieure à la publication des travaux en cours de l’US EPA, il sera nécessaire de réexaminer le mode de détermination de la dose critique et de construction de la VTR des ions perchlorate. »L’ensemble des organismes établissant une VTR chronique par voie orale pour les ions perchlorate ont retenu comme effet critique l'inhibition du captage de l'iode au niveau thyroïdien (Tableau 1 en page 8). En 2019, l'US EPA a adopté une approche différente reposant d'une part sur une modélisation toxicocinétique-toxicodynamique permettant d'évaluer l'impact d'une exposition aux ions perchlorate sur la production d'hormones thyroïdiennes (HT) et d'autre part d'évaluer l'effet d’une diminution des concentrations plasmatiques de thyroxine libre (fT4) maternelles lors du premier trimestre de grossesse sur le neurodéveloppement de l’enfant, objectivé par une baisse du quotient intellectuel. L’US EPA suggérait de retenir une VTR de 2,2 µg.kg p.c.-1.j-1, aboutissant à une valeur de gestion de 56 µg.L-1 en ions perchlorate dans les EDCH.Comme mentionné précédemment et au regard des difficultés de gestion rencontrées, la DGS avait saisi l’Anses pour analyser les travaux de l’US EPA relatifs à l’évaluation des risques sanitaires liés à la présence d’ions perchlorate dans l’EDCH, afin de donner aux ARS des orientations adaptées et proportionnées au risque sanitaire.Compte tenu de ces éléments, l’Anses avait donc été sollicitée pour examiner à nouveau l’évaluation des risques sanitaires liés à l’ingestion d’ions perchlorate, à la lumière des travaux de l’US EPA. Le premier livrable de cette saisine a eu, par conséquent, pour objectif final de déterminer si la VTR de l’Anses à 0,7 µg.kg p.c.-1.j-1 devait être maintenue. La conclusion de ce premier livrable fut de ne pas remettre en cause cette VTR à la lumière des travaux de l’US EPA, du fait notamment d’incertitudes majeures sur la capacité prédictive du modèle utilisé.L’Agence a donc décidé de conserver sa VTR chronique par voie orale établie en 2011, fondée sur la dose sans effet observée dans l’étude de Greer et al. (2002). Cependant, toutes les VTR établies depuis cette date s’appuient sur une approche Benchmark Dose (BMD), de sorte que l’Agence s’est auto-saisie pour évaluer la pertinence de cette approche, en s’appuyant notamment sur les publications récentes (Weterings et al. 2016, Bruce et al. 2018, Haber et al. 2021).[Saisines liées : 1-SA-0336 ; 2012-SA-0119 ; 2016-SA-0155 et 2017-SA-0170]
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- 2022
25. Primary plasma cell leukemias displaying t(11;14) have specific genomic, transcriptional, and clinical features
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Titouan Cazaubiel, Xavier Leleu, Aurore Perrot, Salomon Manier, Laure Buisson, Sabrina Maheo, Laura Do Souto Ferreira, Romain Lannes, Luka Pavageau, Cyrille Hulin, Jean-Pierre Marolleau, Laurent Voillat, Karim Belhadj, Marion Divoux, Borhane Slama, Sabine Brechignac, Margaret Macro, Anne-Marie Stoppa, Laurence Sanhes, Frédérique Orsini-Piocelle, Jean Fontan, Marie-Lorraine Chretien, Hélène Demarquette, Mohamad Mohty, Anais Schavgoulidze, Herve Avet-Loiseau, Jill Corre, Service d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), 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)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de Lille, Service des maladies du sang, Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), 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 Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Chalon-sur-Saône William Morey, Hôpital Henri Mondor, Université de Lorraine (UL), Avignon Université (AU), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Saint Jean de Perpignan, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Claude Huriez [Lille], CHU Lille, CHU Saint-Antoine [AP-HP], 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), Centre Hospitalier Universitaire de Purpan (CHU Purpan), and CHU Toulouse [Toulouse]
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Chromosome Aberrations ,[SDV]Life Sciences [q-bio] ,Immunology ,Humans ,Cell Biology ,Hematology ,Genomics ,Multiple Myeloma ,Prognosis ,Transcriptome ,Biochemistry ,Leukemia, Plasma Cell - Abstract
Primary plasma cell leukemia (pPCL) is an aggressive form of multiple myeloma (MM) that has not benefited from recent therapeutic advances in the field. Because it is very rare and heterogeneous, it remains poorly understood at the molecular level. To address this issue, we performed DNA and RNA sequencing of sorted plasma cells from a large cohort of 90 newly diagnosed pPCL and compared with MM. We observed that pPCL presents a specific genomic landscape with a high prevalence of t(11;14) (about half) and high-risk genomic features such as del(17p), gain 1q, and del(1p32). In addition, pPCL displays a specific transcriptome when compared with MM. We then wanted to characterize specifically pPCL with t(11;14). We observed that this subentity displayed significantly fewer adverse cytogenetic abnormalities. This translated into better overall survival when compared with pPCL without t(11;14) (39.2 months vs 17.9 months, P = .002). Finally, pPCL with t(11;14) displayed a specific transcriptome, including differential expression of BCL2 family members. This study is the largest series of patients with pPCL reported so far.
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- 2022
26. All-oral triplet combination with ixazomib, lenalidomide, and dexamethasone in newly diagnosed transplant-eligible myeloma patients: final results of the phase 2 IFM study 2013-06
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Touzeau, Cyrille, Perrot, Aurore, Roussel, Murielle, Karlin, Lionel, Benboubker, Lotfi, Jacquet, Caroline, Mohty, Mohamad, Facon, Thierry, Manier, Salomon, Chretien, Marie-Lorraine, Tiab, Mourad, Hulin, Cyrille, Leleu, Xavier, Loiseau, Hervé, Dejoie, Thomas, Planche, Lucie, Attal, Michel, Moreau, Philippe, Service d'Hématologie Hôtel Dieu Nantes, Hôtel Dieu, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), SIRIC ILIAD [Angers, Nantes], Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, CHU Lyon Sud, Pierre Benite, France, Partenaires INRAE, Service de cancérologie et d'hématologie thérapie cellulaire [CHU Bretonneau], CHU Bretonneau, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-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), CHU de Lille, Service des maladies du sang, Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hématologie clinique [CH La Roche-sur-Yon], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Département d'Hématologie [CHU Haut Lévèque, Pessac], Hôpital Haut-Lévêque [CHU de Bordeaux], Service d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de biochimie [Hôtel-Dieu], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu, Département de la Recherche Clinique et du Développement [AP-HP Hôtel Dieu] (DRCD-URC Eco), Unité de Recherche Clinique en Economie de la Santé d'Ile-de-France, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Gestionnaire, Hal Sorbonne Université
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[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2022
27. Modelling a regional reorganization of cardiovascular surgery provision
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Bruno Aublet-Cuvellier, Henri Warembourg, Régis Beuscart, Anne Quesnel-Barbet, Marie Christine Nuttens, Pierre Jean Thumerelle, Alain Prat, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Lille (CHU de Lille), CHU Clermont-Ferrand, Département Génie Biologique, Université de Lille, Sciences et Technologies, CHU de Lille, Université de Lille, and QUESNEL-BARBET, Anne
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Male ,spatial modelling ,Health (social science) ,[SDV]Life Sciences [q-bio] ,Geography, Planning and Development ,Distribution (economics) ,Medically Underserved Area ,Health Services Accessibility ,[SHS]Humanities and Social Sciences ,0302 clinical medicine ,PMSI database ,Health care ,Epidemiology ,030212 general & internal medicine ,Child ,Aged, 80 and over ,education.field_of_study ,cardiovascular surgery ,regional health planning ,Public sector ,Middle Aged ,3. Good health ,accessibility ,[SDV] Life Sciences [q-bio] ,MESH: Cardiovascular Diseases, epidemiologic methods, geography ,Cardiovascular Diseases ,Child, Preschool ,Female ,[SHS] Humanities and Social Sciences ,France ,0305 other medical science ,Adult ,medicine.medical_specialty ,Adolescent ,Population ,Service use ,Waiting list mortality ,Unit (housing) ,03 medical and health sciences ,medicine ,Humans ,Operations management ,education ,Aged ,030505 public health ,business.industry ,Public Health, Environmental and Occupational Health ,Infant, Newborn ,Infant ,geographical and epidemiological methods ,Surgery ,Epidemiologic Studies ,business - Abstract
International audience; The Nord - Pas-de-Calais region of France is under-served in terms of access to cardiovascular surgery services, as illustrated by relatively high levels of waiting list mortality. This prompted the decision to create a new surgical unit (notably with facilities for extracorporeal circulatory support) in the region's densely populated, former industrial heartland called the “Mining Basin". Geographical and epidemiological modelling was used prospectively to estimate the likely future level of activity of the existing public sector cardiovascular surgery units. Furthermore, information on the regional population distribution and the likely pattern of service use enabled us to estimate the new unit's potential activity. Our simulations produced nine scenarios which describe variations in the existing public units' activity ranging from –54% to +95%. This type of approach should enable policy makers to improve the organization of healthcare provision.
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- 2005
28. What is the Nature of the Reach-and-Grasp Deficit in Glaucoma?
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Xavier Corveleyn, Quentin Lenoble, Jean-François Rouland, Muriel Boucart, Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Laboratoire d'Anthropologie et de Psychologie Cliniques, Cognitives et Sociales (LAPCOS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université Lille 2 - Faculté de Médecine, Centre Hospitalier Universitaire de Lille (CHU de Lille), and Centre National de la Recherche Scientifique (CNRS)
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Adult ,Male ,Motor disorder ,medicine.medical_specialty ,Reach and grasp ,genetic structures ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,Motor Disorders ,Glaucoma ,Task (project management) ,[SCCO]Cognitive science ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,medicine ,Humans ,Intraocular Pressure ,Aged ,Rehabilitation ,business.industry ,Middle Aged ,medicine.disease ,eye diseases ,Biomechanical Phenomena ,Ophthalmology ,Peak velocity ,030221 ophthalmology & optometry ,Visual Field Tests ,Female ,Visual Fields ,business ,Glaucoma, Open-Angle ,Psychomotor Performance ,psychological phenomena and processes ,030217 neurology & neurosurgery - Abstract
PReCIS:: In a reach-and-grasp task, patients with glaucoma exhibited a motor disorder, even when they had time to explore their environment. The motor performance of glaucoma patients should be taken into account in rehabilitation. PURPOSE Vision plays an important role in planning and executing manual prehension (reaching and grasping). We assess the impact of glaucoma on motor production, as a function of the visual exploration time available to the patients. METHODS We compared performance in 2 reach-and-grasp tasks determined by whether or not the participants (16 glaucoma patients, 14 age-matched and 18 young controls) had time to explore the objects before reaching and grasping a target object defined by its color. RESULTS Differences were observed between glaucoma patients and age-matched controls on movement duration and peak velocity (reaching phase) only when participants were not provided time to look at the objects before the movement (immediate condition). CONCLUSIONS Glaucoma patients exhibited a motor disorder (grasping phase) only when they had no time to explore their environment before performing the reach-and-grasp task. The motor abnormalities in reaching phase observed in glaucoma patients in previous studies seem to result from difficulties in target identification rather than from visuomotor deficits. From a clinical point of view, motor performances of glaucoma patients could be modulated by task, especially by temporal constraints of task.
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- 2020
29. Burden of Migraine in Patients With Preventive Treatment Failure Attending European Headache Specialist Centers: Real-World Evidence From the BECOME Study
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David P. B. Watson, Paolo Martelletti, Josefin Snellman, Charly Gaul, Shannon Ritter, Emma Ramsden, Christian Lucas, Patricia Pozo-Rosich, Institut Català de la Salut, [Pozo-Rosich P] Unitat de Cefalees, Servei de Neurologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Cefalees i Dolors Neurològics, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Lucas C] Pain Clinic, Service de Neurochirurgie, Hôpital Salengro, CHU de Lille, 59037 Lille Cedex, France. [Watson DPB] Hamilton Medical Group, Aberdeen AB15 4ZT, Scotland. [Gaul C] Migraine and Headache Clinic Königstein, 61462 Königstein im Taunus, Germany. [Ramsden E] Novartis Pharma AG, 4033 Basel, Switzerland. [Ritter S] Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, USA, and Vall d'Hebron Barcelona Hospital Campus
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Pediatrics ,medicine.medical_specialty ,Work productivity ,diagnóstico::pronóstico::resultado del tratamiento::fracaso del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Activities of daily living ,Diagnosis::Prognosis::Treatment Outcome::Treatment Failure [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos con cefaleas::cefaleas primarias::trastornos migrañosos [ENFERMEDADES] ,burden ,healthcare resource ,migraine ,patient-reported outcomes ,treatment failure ,work productivity ,Population ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Migranya - Tractament ,Burden ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Quality of life ,Healthcare resource ,Health care ,medicine ,education ,Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Headache Disorders::Headache Disorders, Primary::Migraine Disorders [DISEASES] ,Depression (differential diagnoses) ,Migraine ,Original Research ,education.field_of_study ,Patient-reported outcomes ,business.industry ,Emergency department ,medicine.disease ,Anesthesiology and Pain Medicine ,Treatment failure ,Avaluació de resultats (Assistència sanitària) ,Anxiety ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Migraña; Fracaso del tratamiento; Productividad laboral Migraine; Treatment failure; Work productivity Migranya; Fracàs del tractament; Productivitat laboral Introduction Migraine is consistently ranked as one of the most disabling neurological conditions in the world, often causing a substantial impairment of daily activities and quality of life. It also carries a high economic burden of direct and indirect healthcare costs. Patients with difficult-to-treat migraine often cycle through different preventive therapies, but real-world prospective evidence describing the burden of migraine in patients with prior preventive treatment failure (PPTF) in Europe is limited. In BECOME, we aimed to characterize and assess the prevalence and burden of migraine in patients with PPTF attending specialist headache centers in Europe and Israel. Furthermore, we assessed this burden in pre-specified subgroups based on the frequency of monthly migraine days (MMD) and number of PPTFs. Methods BECOME was a prospective, non-interventional study conducted in two concurrent parts across 17 countries in Europe and Israel. In part 1, patients visiting the centers over a 3-month period were screened for frequency of PPTF, MMD, and other characteristics. In part 2, patients from part 1 with ≥ 1 PPTF and ≥ 4 MMD were enrolled, and impact of migraine on patient-reported outcomes, and healthcare resource utilization (HRU) were examined. Results In part 1 (n = 20,837), 62.2% of patients reported ≥ 1 PPTF. In part 2 (n = 2419), 15.3% of patients reported ≥ 4 PPTF. In part 2, the migraine burden measured by the EuroQoL 5 dimensions 5 level (EQ-5D-5L) questionnaire indicated an impact of at least moderate severity in performing usual activities in 26.5% of patients, pain/discomfort in 51.2%, and 26.1% reported being at least moderately anxious/depressed. Most patients reported a severe impact on daily activities and disability due to migraine. Abnormal Hospital Anxiety and Depression subscale scores of ≥ 11 were observed in 29% (anxiety) and 19.8% (depression) of the population. In part 2, analysis of HRU showed 21.2% patients visited an emergency department and 8.4% were hospitalized for headache/migraine in the past year. Conclusions This study provides real-world evidence of the high personal, social, and HRU burden of migraine in Europe and Israel. This study was funded by Novartis Pharma AG, Basel, Switzerland. The study sponsor participated in the study design, data collection, data review, data analysis and writing of the report. The Rapid Service Fee was funded by Novartis Pharma AG, Basel, Switzerland.
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- 2021
30. Friends and enemies agents collaboration protocol to optimize multi-skills patient scheduling in emergency department
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Ajmi, Faiza, Ajmi, Faten, Othman, Sarah, Zgaya, Hayfa, Renard, Jean-Marie, Smith, Gregoire, Hammadi, Slim, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), CHU Lille - Direction de la recherche et de l’innovation, and Centre Hospitalier Universitaire de Lille (CHU de Lille)
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[INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation - Abstract
International audience; This paper focuses on scheduling patients in emergency department (ED) according to the priority of patients' treatments, determined by the triage process. This multiskills patient scheduling problem is modeled through four dimensional (hypercube) solutions search space whose axes are: Medical staff, Patients, ED structure and Time and it can be formulated as a flexible job shop scheduling problem. We have then to solve a NP-hard combinatorial optimization problem (COP) in the emergency department (ED). The objective is to minimize a score integrating the total waiting time of patients in the (ED) with emphasis on patients with severe conditions. The Friends and Enemies collaboration protocol between agents is developed for solving the problem where each agent integrate a complete metaheuristic scheme in its behavior. Each agent act autonomously in the solution environment and interacts cooperatively with it and with the other agents. The interaction between agents allows the metaheuristic hybridization including the tuning of its parameters. The simulation results show that the scenarios with 2 or more agents were significantly higher in performance than the scenarios with 1 single agent. Thus, it is confirmed that the collaboration protocol between agents influences the quality of the solutions and the scalability of our approach, with the addition of new agents, there is an improvement in the results. Our approach is tested on a set of real (ED) data and the simulation results show that the proposed friends end enemies collaboration protocol can significantly improve the efficiency of the (ED) by reducing the score and especially the total waiting time of multi-skills patient scheduling problem.
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- 2021
31. Recommendations on the management of pudendal nerve entrapment syndrome: A formalised expert consensus
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B. Rioult, Virginie Quistrebert, Michel Cosson, Claire Garreau, Marie-Aimée Perrouin-Verbe, Anne-Marie Leroi, Bertrand Quinio, Frédérique Mohy, Jean-Jacques Labat, Katleen Jottard, Pascale Picard, Rebecca Haddad, Christine Levêque, Roger Robert, Eric Bautrant, Guy Valancogne, Gérard Amarenco, Luc Bruyninx, Thibault Riant, Lara Quintas, Amandine Guinet-Lacoste, Xavier Deffieux, Thierry G. Vancaillie, Marc Beer Gabel, Stéphane Ploteau, Amélie Levesque, Centre hospitalier universitaire de Nantes (CHU Nantes), Pelvi-Perineal Surgery and Rehabilitation Department, Private Medical Centre 'l'Avancée-Clinique Axium', Aix en Provence, France., Tête d'or' Reeducation Centre, Lyon, France., Maurice Bensignor Multidisciplinary Pain Center, Centre Catherine de Sienne, Nantes, France., Neurogastroenterology and Pelvic Floor Unit, Sheba Medical Center, Tel Hashomer, Israel., Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Department of Surgery, Brugmann Hospital, Brussels, Belgium., CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Gynecology, Clinical Institute of Gynecology, Obstetrics, and Neonatology, Faculty of Medicine, Barcelona, Spain., CHU Clermont-Ferrand, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Hospices Civils de Lyon (HCL), Plate-forme Mouvement et handicap [Hôpital Henry Gabrielle - Lyon], Hôpital Henry Gabrielle [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Department of Gynecologic Surgery, Jeanne de Flandre Hospital, CHU de Lille, Lille, France., AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and General Practitioner's Office, Le Bono, France.
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medicine.medical_specialty ,Consensus ,Pudendal nerve ,030232 urology & nephrology ,Primary care ,03 medical and health sciences ,0302 clinical medicine ,medicine ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Effective treatment ,Humans ,Intensive care medicine ,Good practice ,ComputingMilieux_MISCELLANEOUS ,Pain Measurement ,Pudendal Neuralgia ,030219 obstetrics & reproductive medicine ,Pudendal Nerve Entrapment Syndrome ,Pulsed radiofrequency ,business.industry ,Expert consensus ,United States ,3. Good health ,Anesthesiology and Pain Medicine ,Homogeneous ,business - Abstract
BACKGROUND Since the development and publication of diagnostic criteria for pudendal nerve entrapment (PNE) syndrome in 2008, no comprehensive work has been published on the clinical knowledge in the management of this condition. The aim of this work was to develop recommendations on the diagnosis and the management of PNE. METHODS The methodology of this study was based on French High Authority for Health Method for the development of good practice and the literature review was based on the PRISMA method. The selected articles have all been evaluated according to the American Society of Interventional Pain Physicians assessment grid. RESULTS The results of the literature review and expert consensus are incorporated into 10 sections to describe diagnosis and management of PNE: (1) diagnosis of PNE, (2) patients advice and precautions, (3) drugs treatments, (4) physiotherapy, (5) transcutaneous electrostimulations (TENS), (6) psychotherapy, (7) injections, (8) surgery, (9) pulsed radiofrequency, and (10) Neuromodulation. The following major points should be noted: (i) the relevance of 4+1 Nantes criteria for diagnosis; (ii) the preference for initial monotherapy with tri-tetracyclics or gabapentinoids; (iii) the lack of effect of opiates, (iv) the likely relevance (pending more controlled studies) of physiotherapy, TENS and cognitive behavioural therapy; (v) the incertitudes (lack of data) regarding corticoid injections, (vi) surgery is a long term effective treatment and (vii) radiofrequency needs a longer follow-up to be currently proposed in this indication. CONCLUSION These recommendations should allow rational and homogeneous management of patients suffering from PNE. They should also allow to shorten the delays of management by directing the primary care. SIGNIFICANCE Pudendal nerve entrapment (PNE) has only been known for about 20 years and its management is heterogeneous from one practitioner to another. This work offers a synthesis of the literature and international experts' opinions on the diagnosis and management of PNE.
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- 2021
32. Impact of the automation of inpatient bed management to reduce the emergency service waiting time
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Faiza Ajmi, Faten Ajmi, Sarah Ben Othman, Hayfa Zgaya, Gregoire Smith, Jean-Marie Renard, Slim Hammadi, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), CHU Lille - Direction de la recherche et de l’innovation, and Centre Hospitalier Universitaire de Lille (CHU de Lille)
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InformationSystems_GENERAL ,Inpatient bed management ,patient pathway optimization ,artificial intelligent for healthcare ,hospital management ,[INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation - Abstract
International audience; The patient waiting time to be transferred for hospitalization is the time that the patient waits between the decision to hospitalize and the actual admission to an inpatient hospital bed. One of the difficulties encountered in qualifying waiting time for inpatient bed is the inability of hospital information systems to measure it. Hospitals in France have a specialized bed allocation team. This team must manage the bed allocation problem between different hospital departments using phone communication to assign patients to the adapted service. This kind of communication represents a lengthy additional workload in which effectiveness is uncertain. This paper presents a new approach to automate bed management in downstream service. For that, we have implemented algorithms based on artificial intelligent integrated in an inpatient web platform using IoT-Beacons, which is implemented to improve and facilitate the exchange of availability information of downstream beds within the Lille university hospital center (LUHC).
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- 2021
33. La géographie de la santé et la planification sanitaire avec le système d'informations médicales
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Quesnel-Barbet, Anne, Quesnel, Bruno, Bauters, Francis, Vigneron, Emmanuel, Beuscart, Régis, QUESNEL-BARBET, Anne, P Degoulet, M Fieschi, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, CHU de Lille, Service des maladies du sang, Université Paul-Valéry - Montpellier 3 (UPVM), CHU de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), and Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille
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Diagnosis-Related Groups DATABASE ,Knowledge ,health planning ,health geography ,[INFO]Computer Science [cs] ,[SHS] Humanities and Social Sciences ,[INFO] Computer Science [cs] ,Medical Informatics ,[SHS]Humanities and Social Sciences - Abstract
International audience; This paper outlines the combined use of the PMSI information system and geographical data for regional planning of hematology department activities in the Nord-Pas-de-Calais Region (France). The PMSI information system is comparable to the DRG approach used in other countries. Data extracted from hospitals PMSIs are transferred to specific databases where quantitative geographical methods are applied. Thus, potential information becomes available, in particular in the context of the evolution of the Healthier Regional Policy. The study also provides evidence that the PMSI pertains interesting regional information about morbidity of specific kinds of diseases
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- 1998
34. Loss of hepatocyte identity following aberrant YAP activation: a key mechanism in alcoholic hepatitis
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Julie Dubois-Chevalier, Guillaume Lassailly, François Maggiotto, Line Carolle Ntandja-Wandji, Massih Ningarhari, Philippe Mathurin, Sébastien Dharancy, Pau Sancho-Bru, Laurent Dubuquoy, Emmanuel Boleslawski, Anne Corlu, Josepmaria Argemi, Florent Artru, Alexandre Louvet, Jérôme Eeckhoute, Emilie Anglo, Mohamed Bou Saleh, Stéphanie Truant, Viviane Gnemmi, Ramon Bataller, 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), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), 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)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Nutrition, Métabolismes et Cancer (NuMeCan), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), 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), Sequencing was performed by the GenomEast platform, a member of the 'France Génomique' consortium (ANR-10-INBS-0009)., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), The authors acknowledge funding from the National Institute on Alcohol Abuse and Alcoholism (NIAAA-->/NIH, grant 1U01AA021908), Association Française pour l'Etude du Foie, Institut national de la santé et de la recherche médicale (INSERM), CHU de Lille and Région Haut de France. Work at INSERM U1011 was supported by grants from the Fondation pour la Recherche Médicale (Equipe labellisée, DEQ20150331724), 'European Genomic Institute for Diabetes' (E.G.I.D., ANR-10-LABX-46) and European Commission. PS-B was supported by Fondo de Investigación Sanitaria Carlos III (FIS), co-financed by Fondo Europeo de Desarrollo Regional, Unión Europea, 'Una manera de hacer Europa' (FIS PI17/00673, and from the NIAAA grant 1U01AA021908-01-33490., Institute for Translational Research in Inflammation - U 1286 [INFINITE (Ex-Liric)], Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 [ONCO-THAI], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Nutrition, Métabolismes et Cancer [NuMeCan], University of Pittsburgh [PITT], Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD], Université de Lille, Inserm, CHU Lille, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER], Université de Lille, LillOA, and Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID
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0301 basic medicine ,MST1 ,Alcoholic hepatitis ,Hepatocyte ,Hippo/YAP ,Regeneration ,Transdifferentiation ,03 medical and health sciences ,Mice ,[SCCO]Cognitive science ,0302 clinical medicine ,Downregulation and upregulation ,medicine ,Animals ,Hepatocyte differentiation ,Hippo signaling pathway ,Hepatology ,Chemistry ,Hepatitis, Alcoholic ,YAP-Signaling Proteins ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,[SCCO] Cognitive science ,medicine.disease ,Liver regeneration ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,3. Good health ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Cancer research ,Hepatocytes ,030211 gastroenterology & hepatology ,Female ,France - Abstract
International audience; Background & AimsAlcoholic hepatitis (AH) is a life-threatening disease with limited therapeutic options, because understanding of the molecular drivers leading to death are not well understood. This study evaluates the Hippo/Yes-associated protein (YAP) pathway which has been shown to play a role in liver regeneration.MethodThe Hippo/YAP pathway was dissected in explants of patients transplanted for AH or alcoholic cirrhosis and in control livers, using RNA-Seq, real-time PCR, Western blot, immunohistochemistry (IHC) and transcriptome analysis after laser microdissection. We transfected primary human hepatocytes with constitutively active YAP (YAPS127A) and treated HepaRG cells and primary hepatocytes isolated from AH livers with a YAP inhibitor. We also used mouse models of ethanol exposure (Lieber de Carli) and liver regeneration (CCl4) after hepatocyte transduction of YAPS127A.ResultsIn AH samples RNA-Seq analysis and IHC of total liver and microdissected hepatocytes revealed marked down-regulation of Hippo shown by lower MST1 kinase and abnormal activation of YAP in hepatocytes. Overactivation of YAP in hepatocytes in vitro and in vivo led to biliary differentiation and loss of key biological functions such as regeneration capacity. Conversely, treatment of abnormal hepatocytes from AH patients with a YAP inhibitor restored the mature hepatocyte phenotype. In ethanol-fed mice, YAP activation using YAPS127A resulted in a loss of hepatocyte differentiation. Hepatocyte proliferation was hampered using YAPS127A after CCl4 intoxication.ConclusionAberrant activation of YAP plays an important role in hepatocyte transdifferentiation in AH, through a loss of hepatocyte identity and impaired regeneration. Thus, targeting YAP is a promising strategy for the treatment of patients with AH.Lay summaryAlcoholic hepatitis (AH) is characterized by inflammation and a life-threatening alteration of liver regeneration by mechanisms that have not been identified. We show that AH livers are characterized by profound deregulation of the Hippo/YAP pathway with uncontrolled activation of the transcription co-factor YAP in hepatocytes. YAP activation in hepatocytes leads to their transdifferentiation towards a biliary phenotype associated with inflammation as well as a regeneration defect. YAP inhibition reverts this hepatocyte defect and appears to be an original therapeutic strategy of regenerative treatment for AH.
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- 2021
35. Evaluation of a new Histoplasma spp. reverse transcriptase quantitative PCR assay
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Alanio, Alexandre, Gits-Muselli, Maud, Lanternier, Fanny, Sturny-Leclère, Aude, Benazra, Marion, Hamane, Samia, Rodrigues, Anderson Messias, Garcia-Hermoso, Dea, Lortholary, Olivier, Dromer, Françoise, Bretagne, Stéphane, French Mycoses Study Group, The, Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Federal University of Sao Paulo (Unifesp), The authors report no funding for this study., The French mycoses study group is composed of: Marine Gosset Woimant, Geneviève blanchard (Centre Hospitaler de Pontoise, Pontoise), Souad Silhadi (Centre Hospitalier de Chambéry, Chambéry), Nicolas Vignier, Aurelia Pitsch, Kaoutar Jidar (Centre Hospitalier de Melun, Melun), Nicolas Traversier (Centre Hospitalier Felix Guyon, La Réunion), Didier Poisson, Claire Lecointre (Centre Hospitalier Régional d'Orléans, Orléans), Françoise Foulet, Françoise Botterel, Nawel Ait Ammar, Amsellem (CHU Henri Mondor, Créteil), Frederic Gabriel (CHU de Bordeau-GH Pellegrin, Bordeaux), Philipe Poirier (CHU de Clermont Ferrand, Clermont-Ferrand), Marjorie Cornu, Severine Loridant (CHU de Lille, Lille), Florent Morio, David Boutoille, Fakhri Jeddi (CHU de Nantes, Nantes), Lilia Hasseine (CHU de Nice, Nice), Rachida Ouissa (CHU de Pointe à Pitre, Guadeloupe), Dominique Toubas (CHU de Reims, Reims), Eric Bailly, Guillaume Désoubeaux (CHU deTours), Emily Ronez (Hôpital Ambroise Paré, Boulogne), Guillaume Foulon, Sebastien Lefrançois (Hôpital Américain, Neuilly), Christine Bonnal (Hôpital Bichat, Paris), André Paugam, Maxime Dougados (Hôpital Cochin, Paris), Marine Desroches (Hôpital d'Instruction des Armées Percy, Clamart), Hélène Barazzutti, Nicolas Paleiron (Hôpital d'Instruction des Armées, Toulon), Meja rabodonirina (Hôpital de la Croix Rousse, Lyon), Emilie Catherinot, Emilie Cardot-Martin, Chrisian Hiesse, Hélène Salvator (Hôpital Foch, Suresnes), Claire Aguilar, Anne Gigandon, Thomas de Montpreville (Hôpital Marie Lannelongue, Le Plessis-Robinson), Marie-Elisabeth Bougnoux, Emilie Sitterlé (Hôpital Necker Enfants Malades, Paris), Arnaud Fekkar, Sébastien Imbert, Alexandre Bleibtreu (Hôpital Pité Salpétrière), Yaye Senghor (Hôpital Saint Joseph, Paris), Blandine Denis, Jean-Michel Molina, Geoffroy Liegeon, Anne-Lise Munnier, Marion Malphettes (Hôpital Saint Louis, Paris), Julie Denis (Hôpitaux Civils de Strasbourg, Strasbourg), Alain Berlioz-Arthaud (Institut Pasteur de Bangui, Bangui, République centrafricaine), Franciska Lange (Centre Hospitalier Sallanches-Chamonix, Sallanches), Myriam Chiaruzzi, Loic Epelboin (Centre Hospitalier Andrée Rosemon, Cayenne, Guyane Française), The authors are grateful to the technical staff of the mycology-parasitology laboratory at Hospital Saint Louis, Paris, France for handling specimens and performing this assay routinely, in particular, Elodie Da Silva, Thierry Pautet, Dieyenaba Siby-Diakite, Sarah seng and Julie Bui, who performed optimization experiments., Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université de Paris (UP), Institut Pasteur [Paris], and Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP]
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Whole blood ,qPCR ,quantification cycle ,whole nucleic acids ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,reverse transcriptase ,bacterial infections and mycoses ,[SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy ,Histoplasmosis ,fungal load ,[SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology - Abstract
International audience; Laboratory diagnosis of histoplasmosis is based on various methods including microscopy, culture, antigen and DNA detection of Histoplasma capsulatum var. capsulatum (Hcc) or H. capsulatum var. duboisii (Hcd). To improve sensitivity of existing quantitative PCR assays, we developed a new reverse transcriptase qPCR (RTqPCR) assay allowing amplification of whole nucleic acids of Histoplasma spp.. and validated on suspected cases.The limit of detection was 20 copies and the specificity against 114 fungal isolates/species was restricted to Histoplasma spp.. Whole nucleic acids of 1,319 prospectively collected consecutive samples from 907 patients suspected of histoplasmosis were tested routinely between May 2015 and May 2019 in parallel with standard diagnostic procedures performed in parallel. 44 had proven histoplasmosis due to Hcc (n=40) or Hcd (n=4) infections. RTqPCR was positive in 43/44 patients (97.7% sensitivity), in at least one specimen. Nine out of 863 cases (99% specificity) were RTqPCR positive and therefore classified as possible cases. RTqPCR was positive in 13/30 (43.3%) blood tested in proven cases. A positive RTqPCR in blood was significantly associated with Hcc progressive disseminated histoplasmosis with a positive RTqPCR in 92.3% of the immunocompromised patients with disseminated disease. This new Histoplasma RTqPCR assay enabling amplification of hcc and hcd is highly sensitive and allows the diagnosis of histoplasmosis advantageously from blood and BAL.
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- 2021
36. Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies
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Mélanie Fradin, Nicolas Sadoul, Xavier Waintraub, Didier Klug, Albert Hagège, Pascal Sabouraud, Arnaud Isapof, Julien Durigneux, Olivier Lascols, Pascal Laforêt, Armelle Magot, Ivana Dabaj, Eloi Marijon, Camille Vatier, Pascal Cintas, Emmanuelle Salort, Bénédicte Gaborit, Antoine Muchir, Xavier Ferrer, Pascale Richard, Corinne Metay, Stéphane Boulé, Sarah Leonard-Louis, Philippe Mabo, V. Tiffreau, Caroline Stalens, Jitendra K. Vohra, Stéphane Schaeffer, Khadija Chikhaoui, Eric Bieth, Sandra Mercier, Pierre Ambrosi, Aleksandra Nadaj-Pakleza, Michèle Mayer, Katja Zeppenfeld, Gisèle Bonne, Véronique Manel, Jean-Marc Davy, Guilhem Sole, Ghassan Moubarak, Nicolas Lamblin, Klaus Dieterich, Christophe Meune, Abdallah Fayssoil, Arnaud Lazarus, Philippe Maury, Karim Wahbi, Philippe Petiot, Isabelle Jéru, Annick Toutain, Corinne Vigouroux, Ana Ferreiro, Maud Michaud, H.M. Bécane, Bruno Eymard, Thomas D. Gossios, Marie-Christine Vantyghem, Saurabh Kumar, Estelle Gandjbakhch, Yann Péréon, T. Thompson, Marie-Christine Minot-Myhié, Anthony Behin, Frédéric Sacher, Philippe Charron, Nicolas Combes, Julien Praline, Dominique Babuty, Emmanuelle Lagrue, Usha B. Tedrow, Jean-Marc Sellal, Florence Petit, Perry M. Elliott, Frédéric Anselme, Philippe Chevalier, Frederic Taithe, Christine Barnerias, Vincent Laugel, Andoni Echaniz-Laguna, Raphaël P. Martins, Alexander F.A. Androulakis, Rabah Ben Yaou, Franck Boccara, Ulrike Walther-Louvier, Tanya Stojkovic, Françoise Bouhour, Annachiara De Sandre-Giovannoli, Susana Quijano-Roy, Françoise Chapon, Jean-Noël Trochu, Céline Tard, Anne Rollin, Jean-Marie Cuisset, Denis Duboc, Raphaël Porcher, Catherine Sarret, Jonathan M. Kalman, Florence Demurger, Damien Bonnet, Christine Francannet, Neal K. Lakdawala, Romain Eschalier, Fabien Labombarda, Kostantinos Savvatis, Raul Juntas Morales, Isabelle Desguerre, Nicolas Lévy, Anne-Claire Brehin, Service de Cardiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Rouen, Normandie Université (NU), St Bartholomew's Hospital (London), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Association française contre les myopathies (AFM-Téléthon), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Service de Cardiologie B, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Unité de recherche de l'institut du thorax (ITX-lab), 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), Hôpital Ambroise Paré [AP-HP], William Harvey Research Institute, Barts and the London Medical School, Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Filière Neuromusculaire (FILNEMUS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université de Caen Normandie (UNICAEN), Laboratoire d'Informatique Scientifique et Industrielle (LISI), Université de Poitiers-Ecole Nationale Supérieure de Mécanique et d'Aérotechnique [Poitiers] (ISAE-ENSMA), Hôpital Raymond Poincaré [AP-HP], CHU Lille, Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), 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 National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Aix Marseille Université (AMU), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique Pasteur [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The Royal Melbourne Hospital, Leiden University Medical Center (LUMC), Universiteit Leiden, Service de neurologie pédiatrique [CHU Necker], Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], 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), CHU Necker - Enfants Malades [AP-HP], Hôpital Privé Le Bois Ramsay Santé [Lille], Service de génétique [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Roger Salengro [Lille], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM] (CRB TAC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Clermont-Ferrand, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Bordeaux], Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie cadiovasculaire et thoracique [Rouen], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Trousseau [APHP], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), 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), CHU Strasbourg, Clinique Ambroise Paré [Centres Médico-Chirurgicaux Ambroise Pré, Pierre Cherest, Hartmann], Hôpital Cochin [AP-HP], Hospices Civils de Lyon (HCL), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Lorraine (UL), Service de neurologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [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), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Laboratoire d'étude de la motricité humaine - EA 3608 (LEMH), Université de Lille, Droit et Santé, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montréal (UdeM), Laboratoire Génie des procédés papetiers (LGP2 ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), The Heart Hospital [London], University College of London [London] (UCL), This study was funded by grants from the AFM-Téléthon (French Alliance against Myopathies), which was not involved in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. Some of this work was undertaken at University College London (United Kingdom) and St. Bartholomew’s Hospital (London, United Kingdom), which received a portion of funding from the United Kingdom Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie et maladies vasculaires, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Unit of Neuromuscular Morphology [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP]-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des maladies rares neuromusculaires Aquitaine-Grand Sud Ouest, CHU Bordeaux [Bordeaux], Laboratoire d'Informatique Scientifique et Industrielle (LISI / ENSMA), LISI-ENSMA, Service de Biochimie-Génétique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Thérapie des maladies du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Cardiologie A, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Endocrinologie et Métabolisme, Unité de Cardiologie et Soins Intensifs, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Service de Génétique [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre de Référence M3C Malformations Cardiaques Congénitales Complexes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Hôpital neurologique, Centre Hospitalier Universitaire de Lille (CHU de Lille), Service Neurologie Pédiatrique, Service de Neuropédiatrie, INSERM U836, équipe 4, Muscles et pathologies, Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Département de Neurologie, Hôpital Civil de Strasbourg, Groupe Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-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), Service de génétique médicale, CHU - HÔTEL-DIEU Clermont-Ferrand, CLAD Ouest, Centre Hospitalier Universitaire [Rennes], Centre recherche en CardioVasculaire et Nutrition (C2VN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Clinique Ambroise Paré, CHU Cochin [AP-HP], Epilepsie, sommeil et explorations fonctionnelles neuropédiatriques, Hospices Civils de Lyon (HCL)-Hopital Neurologique-Hôpital Femme Mère Enfant, Department of Medicine, Columbia University [New York]-College of Physicians and Surgeons, Service de neurologie, Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Hôpital de Rangueil, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), laboratoire d'étude de la motricité humaine (LEMH EA3608), Université de Montréal - UdeM (CANADA), Laboratoire Génie des procédés papetiers (LGP2), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Myologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Genomic Institute for Diabetes - FR 3508 (EGID), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, 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 Purpan [Toulouse], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut de Myologie, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
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Adult ,Male ,Tachycardia ,medicine.medical_specialty ,implantable ,Accurate estimation ,Ventricular Tachyarrhythmias ,Validation Studies as Topic ,030204 cardiovascular system & hematology ,tachycardia ,Sudden death ,LMNA ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,death ,Physiology (medical) ,Internal medicine ,defibrillators ,medicine ,Humans ,In patient ,030212 general & internal medicine ,sudden ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Prediction score ,business.industry ,Defibrillators, Implantable ,ventricular ,Tachycardia, Ventricular ,Cardiology ,Female ,medicine.symptom ,Cardiomyopathies ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator–treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0–7.2] and 5.1 [2.0–9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711–0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642–0.959), and the calibration slope was 1.082 (95% CI, 0.643–1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03058185.
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- 2019
37. How to improve donor skin availability: Pragmatic procedures to minimize the discard rate of cryopreserved allografts in skin banking
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Louise Pasquesoone, Nicolas Germain, Boualem Sendid, Anne-Sophie Hatzfeld, Olivier Gaillot, Pierre Marie Danze, Philippe Marchetti, Pierre Guerreschi, Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), 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)-Centre National de la Recherche Scientifique (CNRS), Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, This study was supported by the CHU de Lille., and 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)
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medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,Human skin ,Critical Care and Intensive Care Medicine ,Cryopreservation ,03 medical and health sciences ,0302 clinical medicine ,Bacterial and fungal contamination ,Humans ,Transplantation, Homologous ,Medicine ,Skin allograft ,Retrospective Studies ,business.industry ,030208 emergency & critical care medicine ,General Medicine ,Tissue banking ,Contamination ,Allografts ,Anti-Bacterial Agents ,3. Good health ,Surgery ,Contamination rate ,Tissue bank ,030221 ophthalmology & optometry ,Emergency Medicine ,Clinical safety ,Burns ,business ,Skin allografts ,Donor skin - Abstract
International audience; BackgroundMicrobial contamination of human skin allografts is a frequent cause of allograft discard. Our purpose was to evaluate the discard rate of skin bank contaminated allografts and specific procedures used to reduce allograft contamination without affecting safety.MethodsWe conducted at the Lille Tissue Bank a retrospective study of all deceased donors (n = 104) harvested from January 2018 to December 2018. Skin procurement was split into 3 zones: the back of the body and the two legs that were processed separately. It represented 433 cryopreserved skin allograft pouches of approximatively 500 cm² each. Donors were almost equally split between brain-dead (53%, 55/104) and cadaveric (47%, 49/104) donors.ResultsOut of all donors, 42 (40.5%) had at least one sampling zone with a positive microbiological test resulting in 106 (24%) contaminated skin pouches. The contamination rate did not vary according to the harvested zone or type of donor. Traumatic deaths showed significantly less contamination rates than other death types (p < 0.05). Contamination rate decreased with time spent in the antibiotic solution. The risk of having contaminated allografts was five-fold higher when the skin spent less than 96 h in the antibiotic cocktail (p < 0.05). According to our validation protocol, most donors (32/42, 76%) had skin allografts contaminated with bacteria (mainly Staphylococcus spp) compatible with clinical use. No recipient infection was recorded as a result of skin graft contaminated with saprophytic or non-pathogenic germs. By harvesting 3 separate zones per donor, the total surface area for clinical use increased by 53% for contaminated donors. Overall, the proportion of contamination-related discarded allografts was 3.2% (14/433 of pouches).ConclusionFew simple pragmatic measures (including skin incubation in the antibiotic bath for at least 96 h at 4 °C, splitting the skin harvesting areas to minimize the risk of cross-infection and clinical use of allografts contaminated with saprophytic and non-pathogenic germs) can reduce the discard rate of contaminated allografts without affecting clinical safety.
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- 2021
38. Sensitivity to central crowding for faces in patients with glaucoma
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Carole Peyrin, Aude Warniez, Jean François Rouland, Aymeric Stievenard, Muriel Boucart, Peyrin, Carole, Centre Hospitalier Universitaire de Lille (CHU de Lille), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC))
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Intraocular pressure ,medicine.medical_specialty ,genetic structures ,media_common.quotation_subject ,Nerve fiber layer ,Glaucoma ,Audiology ,Contrast Sensitivity ,03 medical and health sciences ,0302 clinical medicine ,Face perception ,Perception ,medicine ,Humans ,Contrast (vision) ,Intraocular Pressure ,ComputingMilieux_MISCELLANEOUS ,media_common ,Mouth ,business.industry ,[SCCO.NEUR]Cognitive science/Neuroscience ,[SCCO.NEUR] Cognitive science/Neuroscience ,Cognition ,masking ,medicine.disease ,Crowding ,crowding ,Ophthalmology ,medicine.anatomical_structure ,glaucoma ,[SCCO.PSYC] Cognitive science/Psychology ,[SCCO.PSYC]Cognitive science/Psychology ,030221 ophthalmology & optometry ,face perception ,Visual Fields ,business ,Tomography, Optical Coherence ,030217 neurology & neurosurgery - Abstract
Precis Some patients with glaucoma report difficulties to recognize faces when they are far away. We show that this deficit could result from a higher sensitivity to crowding in central vision. Purpose The aim of the study is to investigate whether face recognition difficulties reported by some patients with glaucoma result from a greater sensitivity to inner crowding in central vision. Methods Seventeen patients with glaucoma and 17 age-matched normally sighted controls participated in the study. An isolated mouth (uncrowded condition) or a mouth within a face (crowded condition) was randomly displayed centrally for 200 ms. For each condition, participants were asked to decide whether the mouth was closed or open. The stimuli were presented at 3 angular sizes (0.6×0.4, 1×0.72, and 1.5×1.08 degrees). Accuracy was measured. Results Crowding affected performance differentially for patients and controls. Consistent with previous studies controls exhibited a "face superiority effect," with a better accuracy when the mouth was located within the face than when it was isolated. Sensitivity to crowding, reflected in a better accuracy with the isolated mouth, was observed in 10 of 17 patients only for small images. Crowding disappeared for larger faces, as the facial features were spaced out. Five patients were not sensitive to crowding. Importantly, no difference was found between the 2 subgroups of patients (sensitive vs. nonsensitive) in terms of mean deviation, contrast sensitivity, acuity, thickness of the retinal nerve fiber layer, or macular ganglion cell-inner plexiform layer. Conclusions An excessive sensitivity to central crowding might explain the difficulties in face perception and reading reported by some patients with glaucoma. The sensory or cognitive processes underlying this excessive sensitivity must be elucidated to improve central perception in glaucoma.
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- 2021
39. New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation
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Cécile Croix, Pascal Berthelot, Bruno Oyallon, Jean Guillon, Cédric Logé, Stéphane Bach, Marie-Claude Viaud-Massuard, Caroline Denevault-Sabourin, Fabrice Gouilleux, Marie Brachet-Botineau, Thomas Robert, Sajida Ibrahim, William Raoul, Noël Pinaud, Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), GICC EA 7501, IMT (Innovation moléculaire et thérapeutique) (IMT), Université de Tours (UT)-Université de Tours (UT), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), 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)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de Biologie Intégrative des Modèles Marins (LBI2M), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Fédération de recherche de Roscoff (FR2424), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), North-West University [South Aftrica] (NWU), GICC EA 7501, PATCH (Pharmacologie des anticorps thérapeutiques chez l'Homme) (PATCH), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1 (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Université de Tours, Université de Tours-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Université de Tours, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), GICC EA 7501, LNOx (Niche leucémique et métabolisme redOx) (LNOx), Université de Tours-Université de Tours-Centre National de la Recherche Scientifique (CNRS), IICiMed - EA 1155, Université de Nantes (UN)-UFR Sciences et Techniques [Université de Nantes], Université de Nantes (UN)-UFR des Sciences Pharmaceutiques [Université de Nantes], Université de Nantes (UN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, INSERM U12132-UMR CNRS 5320, Univ. Bordeaux, ISM, UMR-5255, F-33405 Talence, France, CNRS, ISM, UMR5255, (CNRS, ISM, UMR5255, ), Raoul, William, University of Tours, F-37200 Tours, Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), CHU de Lille, Régulations Naturelles et Artificielles (ARNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Université de Bordeaux (UB), and Université Bordeaux Segalen - Bordeaux 2
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Protein Conformation ,[SDV]Life Sciences [q-bio] ,Pharmaceutical Science ,Chemistry Techniques, Synthetic ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,Analytical Chemistry ,Metastasis ,chemistry.chemical_compound ,0302 clinical medicine ,hemic and lymphatic diseases ,Drug Discovery ,Murine leukemia virus ,0303 health sciences ,Pim kinases ,anticancer targeted therapy ,biology ,Kinase ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,Myeloid leukemia ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,3. Good health ,Molecular Docking Simulation ,[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences ,Chemistry (miscellaneous) ,030220 oncology & carcinogenesis ,Molecular Medicine ,kinase inhibitor ,PIM1 ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Protein Serine-Threonine Kinases ,Article ,lcsh:QD241-441 ,03 medical and health sciences ,Quinoxaline ,Proto-Oncogene Proteins c-pim-1 ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,lcsh:Organic chemistry ,Proto-Oncogene Proteins ,Quinoxalines ,quinoxaline ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,medicine ,Humans ,[CHIM]Chemical Sciences ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Physical and Theoretical Chemistry ,Protein Kinase Inhibitors ,030304 developmental biology ,Organic Chemistry ,Cancer ,medicine.disease ,biology.organism_classification ,In vitro ,chemistry ,Cancer research - Abstract
International audience; Proviral integration site for Moloney murine leukemia virus (Pim)-1/2 kinase overexpression has been identified in a variety of hematologic (e.g., multiple myeloma or acute myeloid leukemia (AML)) and solid (e.g., colorectal carcinoma) tumors, playing a key role in cancer progression, metastasis, and drug resistance, and is linked to poor prognosis. These kinases are thus considered interesting targets in oncology. We report herein the design, synthesis, structure–activity relationships (SAR) and in vitro evaluations of new quinoxaline derivatives, acting as dual Pim1/2 inhibitors. Two lead compounds (5c and 5e) were then identified, as potent submicromolar Pim-1 and Pim-2 inhibitors. These molecules were also able to inhibit the growth of the two human cell lines, MV4-11 (AML) and HCT-116 (colorectal carcinoma), expressing high endogenous levels of Pim-1/2 kinases.
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- 2021
40. Preoperative REM sleep behavior disorder and subthalamic nucleus deep brain stimulation outcome in Parkinson disease 1 year after surgery
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Isabelle Benatru, Dominique Guehl, Philippe Derost, Stéphane Thobois, David Devos, Franck Durif, Elodie Durand, Mélissa Tir, Ouhaid Lagha-Boukbiza, Elodie Hainque, Elsa Besse-Pinot, Caroline Giordana, Jean-Christophe Corvol, B. Debilly, David Maltête, Tiphaine Rouaud, Sophie Drapier, Lucie Hopes, Bruno Pereira, Ana Marques, Cécile Hubsch, Maria Livia Fantini, Olivier Rascol, Alexandre Eusebio, Caroline Moreau, Anne-Sophie Rolland, Béchir Jarraya, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Lille, 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), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Neurologie [CHU Rennes], CHU Pontchaillou [Rennes], 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-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Excellence en Maladies Neurodégénératives (NeuroToul), CHU Toulouse [Toulouse], Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Hôpital Foch [Suresnes], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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), Ministère des Affaires Sociales et de la Santé, The study was funded by the France Parkinson charity and French Ministry of Health (PHRC National 2012) and promoted by CHU Lille (coordinated by Pr Devos and Pr Corvol) with the support of the French network NS-PARK and supported by NS-PARK/F-CRIN and the Fédération de la Recherche Clinique du CHU de Lille., Marques, Ana, CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Clermont-Ferrand, École d’Orthoptie - Clermont-Ferrand (EO - UdA), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Service de neurologie et pathologie du mouvement, Hôpital Roger Salengro [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), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Hôpital de la Timone [CHU - APHM] (TIMONE), 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 d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Toulouse Neuro Imaging Center (ToNIC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-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, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Lille Neurosciences & Cognition - U 1172 (LilNCog), 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), 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), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes (UN)
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medicine.medical_specialty ,Activities of daily living ,Deep Brain Stimulation ,REM Sleep Behavior Disorder ,Disease ,Risk Assessment ,REM sleep behavior disorder ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Subthalamic Nucleus ,Rating scale ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Prospective cohort study ,business.industry ,Subthalamic nucleus deep brain stimulation ,Parkinson Disease ,medicine.disease ,3. Good health ,Surgery ,Treatment Outcome ,Preoperative Period ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Neurology (clinical) ,Neurosurgery ,business ,030217 neurology & neurosurgery ,Research Article - Abstract
Background and ObjectivesTo determine whether patients with Parkinson disease (PD) eligible for subthalamic nucleus deep brain stimulation (STN-DBS) with probable REM sleep behavior disorder (RBD) preoperatively could be more at risk of poorer motor, nonmotor, and quality of life outcomes 12 months after surgery compared to those without RBD.MethodsWe analyzed the preoperative clinical profile of 448 patients with PD from a French multicentric prospective study (PREDISTIM) according to the presence or absence of probable RBD based on the RBD Single Question and RBD Screening Questionnaire. Among the 215 patients with PD with 12 months of follow-up after STN-DBS, we compared motor, cognitive, psycho-behavioral profile, and quality of life outcomes in patients with (pre-opRBD+) or without (pre-opRBD–) probable RBD preoperatively.ResultsAt preoperative evaluation, pre-opRBD+ patients were older (61 ± 7.2 vs 59.5 ± 7.7 years; p = 0.02), had less motor impairment (Movement Disorder Society–sponsored version of the Unified Parkinson’s Disease Rating Scale [MDS-UPDRS] III “off”: 38.7 ± 16.2 vs 43.4 ± 7.1; p = 0.03) but more nonmotor symptoms on daily living activities (MDS-UPDRS I: 12.6 ± 5.5 vs 10.7 ± 5.3; p < 0.001), had more psychobehavioral manifestations (Ardouin Scale of Behavior in Parkinson's Disease total: 7.7 ± 5.1 vs 5.1 ± 0.4; p = 0.003), and had worse quality of life (Parkinson's Disease Questionnaire–39: 33 ± 12 vs 29 ± 12; p = 0.03), as compared to pre-opRBD– patients. Both pre-opRBD+ and pre-opRBD– patients had significant MDS-UPDRS IV score decrease (−37% and −33%, respectively), MDS-UPDRS III “med ‘off’/stim ‘on’” score decrease (−52% and −54%), and dopaminergic treatment decrease (−52% and −49%) after surgery, with no between-group difference. There was no between-group difference for cognitive and global quality of life outcomes.ConclusionsIn patients with PD eligible for STN-DBS, the presence of probable RBD preoperatively is not associated with a different clinical outcome 1 year after neurosurgery.Trial Registration InformationNCT02360683.Classification of EvidenceThis study provides Class II evidence that in patients with PD eligible for STN-DBS, the presence of probable RBD preoperatively is not associated with poorer outcomes 1 year post surgery.
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- 2021
41. PCSK9 post-transcriptional regulation: Role of a 3′UTR microRNA-binding site variant in linkage disequilibrium with c.1420G
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Claire Bardel, O. Marmontel, Manon Muntaner, Eléonore Divry, Philippe Moulin, Mathilde Di Filippo, Séverine Nony, Bertrand Cariou, Nicolas Chatron, Sybil Charrière, Charlotte Decourt, Alexandre Janin, Marine Moindrot, Luc Dauchet, Sabrina Dumont, Aline Meirhaeghe, Hospices Civils de Lyon (HCL), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), 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), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), 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), Unité de recherche de l'institut du thorax (ITX-lab), 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), Lille University Hospital (CHU de Lille, Lille, France) Region Hauts-de-France European Regional Development Fund (ERDF-FEDER Presage) as part of the CPER Institut de Recherche en ENvironnement Industriel (IRENI) program 36,034CLIMIBIO CPER research project Pfizer, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), 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), CCSD, Accord Elsevier, Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
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0301 basic medicine ,Untranslated region ,Linkage disequilibrium ,Luciferase assay ,Hypercholesterolemia ,MiRNA binding ,030204 cardiovascular system & hematology ,Biology ,Linkage Disequilibrium ,PCSK9 ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Humans ,Allele ,Post-transcriptional regulation ,3' Untranslated Regions ,miRNA ,Genetics ,Binding Sites ,rs562556 ,Proprotein convertase ,Loss of function ,[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,MicroRNAs ,030104 developmental biology ,Kexin ,Proprotein Convertase 9 ,Cardiology and Cardiovascular Medicine - Abstract
International audience; Background and aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in cholesterol homeostasis. A common variant, the G allele in position c.1420 (c.1420G), has been associated with a decrease of both plasma PCSK9 and LDL-cholesterol concentrations. However, the functional effect of this variant is currently not well understood. We hypothesized that it could be explained by functional variants in linkage disequilibrium (LD), more specifically, by variants located in the PCSK9 3' UTR as targets for miR regulation of PCSK9 expression.Methods: Variations in LD with c.1420G were studied in 1029 patients followed for dyslipidaemia. In silico studies identified potential miRNA binding sites induced by PCSK9 3'UTR variants in LD with c.1420G. Their functionality was studied with a luciferase reporter assay in HuH-7 cells and confirmed by cotransfection of anti-miRNAs.Results: The c.*571C and c.*234T variants located in the PCSK9 3'UTR were found in tight LD with c.1420G (D' = 0.962; LOD = 163.06). The haplotype carrying c.*571C showed a 6.7% decrease in luciferase activity (p = 0.003). Inhibition of hsa-miR-1228-3p and hsa-miR-143-5p counteracted their effect on the haplotype carrying c.*571C allele, suggesting that PCSK9 expression was decreased by the endogenous binding of hsa-miR-1228-3p and hsa-miR-143-5p on its 3'UTR.Conclusions: This post-transcriptional regulation might contribute towards the association between plasma PCSK9 levels and c.1420G. Such regulation of PCSK9 expression may open new perspectives for the treatment of hypercholesterolemia and atherosclerosis cardiovascular diseases.
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- 2020
42. Impact of gastric electrical stimulation on economic burden of refractory vomiting: a French nationwide multicentre study
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Guillaume Gourcerol, Benoit Coffin, Bruno Bonaz, Hélène Hanaire, Stanislas Bruley Des Varannes, Frank Zerbib, Robert Caiazzo, Jean Charles Grimaud, François Mion, Samy Hadjadj, Paul Valensi, Lucine Vuitton, Guillaume Charpentier, Alain Ropert, Romain Altwegg, Philippe Pouderoux, Etienne Dorval, Michel Dapoigny, Henri Duboc, Pierre Yves Benhamou, Aurélie Schmidt, Nathalie Donnadieu, Philippe Ducrotte, Bruno Guerci, Helene Hanaire, Stanislas Bruley des Varannes, Francois Mion, Aurelie Schmidt, Nathalie Donadieu, Philippe Ducrotté, Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], CHU Rouen, Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Toulouse [Toulouse], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Lille (CHU de Lille), Centre d'Investigation Clinique [Hôpital de la Conception - APHM] (CIC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), CHU de Lyon, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Sud Francilien [Corbeil-Essonnes] (CH Sud Francilien), Centre Hospitalier Universitaire de Rennes (CHU Rennes), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Clermont-Ferrand, STEVE CONSULTANTS 69600 OULLINS., Service d'Hépato-Gastroentérologie [CHU Rouen], Normandie Université (NU), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Enterra Research Group, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Hôpital Charles Nicolle [Rouen], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
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Gastric electrical stimulation ,medicine.medical_specialty ,Gastroparesis ,Cost effectiveness ,Nausea ,Vomiting ,Electric Stimulation Therapy ,Financial Stress ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Internal medicine ,Medicine ,Humans ,Adverse effect ,ComputingMilieux_MISCELLANEOUS ,2. Zero hunger ,Hepatology ,business.industry ,Gastroenterology ,Nutritional status ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Electric Stimulation ,3. Good health ,Treatment Outcome ,Gastric Emptying ,030220 oncology & carcinogenesis ,Quality of Life ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Body mass index - Abstract
Medico-economic data of patients suffering from chronic nausea and vomiting are lacking. In these patients, gastric electrical stimulation (GES) is an effective, but costly treatment. The aim of this study was to assess the efficacy, safety and medico-economic impact of Enterra therapy in patients with chronic medically refractory nausea and vomiting.Data were collected prospectively from patients with medically refractory nausea and/or vomiting, implanted with an Enterra device and followed for two years. Gastrointestinal quality of life index (GIQLI) score, vomiting frequency, nutritional status and safety were evaluated. Direct and indirect expenditure data were prospectively collected in diaries.Complete clinical data were available for142 patients (60 diabetic, 82 non-diabetic) and medico-economic data were available for 96 patients (36 diabetic, 60 non-diabetic), 24 months after implantation. GIQLI score increased by 12.1 ± 25.0 points (p.001), with a more significant improvement in non-diabetic than in diabetic patients (+15.8 ± 25.0 points, p.001 versus 7.3 ± 24.5 points, p = .027, respectively). The proportion of patients vomiting less than once per month increased by 25.5% (p.001). Hospitalisations, time off work and transport were the main sources of costs. Enterra therapy decreased mean overall healthcare costs from 8873 US$ to 5525 US$ /patient/year (p = .001), representing a saving of 3348 US$ per patient and per year. Savings were greater for diabetic patients (4096 US$ /patient/year) than for non-diabetic patients (2900 US$ /patient/year).Enterra therapy is an effective, safe and cost-effective option for patients with refractory nausea and vomiting.gov Identifier: NCT00903799.
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- 2020
43. Estimation du nombre de problèmes et détermination du nombre de sujets nécessaires dans les études d’utilisabilité : une approche bayésienne
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Vandewalle, Vincent, Caron, Alexandre, Dervaux, Benoît, MOdel for Data Analysis and Learning (MODAL), Laboratoire Paul Painlevé (LPP), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-École polytechnique universitaire de Lille (Polytech Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille - Direction de la recherche et de l’innovation, Centre Hospitalier Universitaire de Lille (CHU de Lille), Vandewalle, Vincent, and Laboratoire Paul Painlevé - UMR 8524 (LPP)
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[MATH.MATH-ST]Mathematics [math]/Statistics [math.ST] ,[QFIN.RM] Quantitative Finance [q-fin]/Risk Management [q-fin.RM] ,[QFIN.RM]Quantitative Finance [q-fin]/Risk Management [q-fin.RM] ,[MATH.MATH-ST] Mathematics [math]/Statistics [math.ST] ,ComputingMilieux_MISCELLANEOUS - Abstract
National audience
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- 2020
44. Prospective and observational study of COVID-19's impact on mental health and training of young surgeons in France
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Xavier Matillon, Dharmesh Ramlugun, Louis Dagneaux, Gabriel Saiydoun, Ève Durbant, Agnès Paasche, Alexandra Hauguel, Océane Pécheux, Anthony Levy-Bohbot, Stessy Kutchukian, Antoine Cayeux, Emmanuelle Verdier, Jean Meyblum, Rani Kassir, Taha Mouhib, Benjamin Pradere, Sylvain Gautier, Maxime Vallée, Ilan Weizman, Clément Baumgarten, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Medizinische Universität Wien = Medical University of Vienna, Centre Hospitalier Universitaire de Reims (CHU Reims), Les Hôpitaux Universitaires de Strasbourg (HUS), Centre hospitalier universitaire de Grenoble (CHU de Grenoble), CHU Grenoble, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Université de La Réunion - UFR Santé (UR UFRS), Université de La Réunion (UR), Centre Hospitalier Universitaire de Lille (CHU de Lille), Centre Hospitalo-Universitaire de Grenoble (CHU de Grenoble), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Amiens-Picardie, Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biomécanique des Interactions et de l'Organisation des Tissus et des Cellules (BIOTIC), Laboratoire de Mécanique et Génie Civil (LMGC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Raymond Poincaré [AP-HP], Hôpitaux Universitaires Henri-Mondor, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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 Univ, Réunion
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Male ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,MEDLINE ,Workload ,030230 surgery ,Anxiety ,03 medical and health sciences ,0302 clinical medicine ,Sleep Initiation and Maintenance Disorders ,Research Letter ,Medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,General ,Pandemics ,ComputingMilieux_MISCELLANEOUS ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Surgeons ,business.industry ,Depression ,SARS-CoV-2 ,COVID-19 ,Mental health ,3. Good health ,Mental Health ,Family medicine ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Surgery ,Observational study ,Female ,France ,business ,Stress, Psychological - Abstract
International audience
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- 2020
45. Estimating the number of usability problems affecting medical devices: modelling the discovery matrix
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Vincent Vandewalle, Alexandre Caron, Coralie Delettrez, Renaud Périchon, Sylvia Pelayo, Alain Duhamel, Benoit Dervaux, MOdel for Data Analysis and Learning (MODAL), Laboratoire Paul Painlevé (LPP), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-École polytechnique universitaire de Lille (Polytech Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille - Direction de la recherche et de l’innovation, Centre Hospitalier Universitaire de Lille (CHU de Lille), Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), This research was funded by the Swiss National Science Foundation (grant number: SNSF-164279) and the French Agence Nationale de la Recherche (grant number: ANR-15-CE36–0007)., ANR-15-CE36-0007,Useval-DM,Evaluation de l'utilisabilité de Technologies de Santé / Dispositifs Médicaux(2015), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Paul Painlevé - UMR 8524 (LPP), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-École polytechnique universitaire de Lille (Polytech Lille)-Université de Lille, Sciences et Technologies, Centre d’Investigation Clinique - Innovation Technologique [Lille] (CIC-IT Lille), Vandewalle, Vincent, and Evaluation de l'utilisabilité de Technologies de Santé / Dispositifs Médicaux - - Useval-DM2015 - ANR-15-CE36-0007 - AAPG2015 - VALID
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[SDV.IB] Life Sciences [q-bio]/Bioengineering ,lcsh:R5-920 ,Missing data ,[QFIN.RM]Quantitative Finance [q-fin]/Risk Management [q-fin.RM] ,Bayesian statistics ,Technical Advance ,Bias ,Usability testing ,Research Design ,[MATH.MATH-ST]Mathematics [math]/Statistics [math.ST] ,Humans ,[QFIN.RM] Quantitative Finance [q-fin]/Risk Management [q-fin.RM] ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,lcsh:Medicine (General) ,[MATH.MATH-ST] Mathematics [math]/Statistics [math.ST] ,Probability ,Medical device ,Maximum likelihood - Abstract
Background. Usability testing of medical devices are mandatory for market access. The testings’ goal is to identify usability problems that could cause harm to the user or limit the device’s effectiveness. In practice, human factor engineers study participants under actual conditions of use and list the problems encountered. This results in a binary discovery matrix in which each row corresponds to a participant, and each column corresponds to a usability problem. One of the main challenges in usability testing is estimating the total number of problems, in order to assess the completeness of the discovery process. Today’s margin-based methods fit the column sums to a binomial model of problem detection. However, the discovery matrix actually observed is truncated because of undiscovered problems, which corresponds to fitting the marginal sums without the zeros. Margin-based methods fail to overcome the bias related to truncation of the matrix. The objective of the present study was to develop and test a matrix-based method for estimating the total number of usability problems.Methods. The matrix-based model was based on the full discovery matrix (including unobserved columns) and not solely on a summary of the data (e.g. the margins). This model also circumvents a drawback of margin-based methods by simultaneously estimating the model’s parameters and the total number of problems. Furthermore, the matrix-based method takes account of a heterogeneous probability of detection, which reflects a real-life setting. As suggested in the usability literature, we assumed that the probability of detection had a logit-normal distribution.Results. We assessed the matrix-based method’s performance in a range of settings reflecting real-life usability testing and with heterogeneous probabilities of problem detection. In our simulations, the matrix-based method improved the estimation of the number of problems (in terms of bias, consistency, and coverage probability) in a wide range of settings. We also applied our method to five real datasets from usability testing.Conclusions. Estimation models (and particularly matrix-based models) are of value in estimating and monitoring the detection process during usability testing. Matrix-based models have a solid mathematical grounding and, with a view to facilitating the decision-making process for both regulators and device manufacturers, should be incorporated into current standards.
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- 2020
46. Raising rare disease awareness using red flags, role play simulation and patient educators: results of a novel educational workshop on Raynaud phenomenon and systemic sclerosis
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M. Assaraf, J. Galland, David Launay, Eric Hachulla, Etienne Rivière, C. Yelnik, M.M. Farhat, Sandrine Morell-Dubois, Hélène Maillard, Marc Lambert, C. Roubille, Guillaume Lefèvre, Vincent Sobanski, S. Sanges, Centre de Simulation PRESAGE, Univ. Lille, UFR Médecine, F-59000, Lille, Département de Médecine Interne et Immunologie Clinique, CHU Lille, F-59037, 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), Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Oust de France (CeRAINO), F-59000, Lille, Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), Lille, Département de Médecine Interne et Immunologie Clinique, CHU Lille, F-59037, Lille Cedex, Service de médecine interne, Hôpital Lariboisière, Assistance Publique - Hôpitaux de Paris, F-75010, Paris, Université de Paris Diderot, F-75010, Paris, Service de médecine interne et maladies infectieuses, CHU de Bordeaux, F-33600, Pessac, Centre de simulation SimBA-S de Bordeaux, CHU de Bordeaux et Université de Bordeaux, F-33000, Bordeaux, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Lille (CHU de Lille), Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and MORNET, Dominique
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Medical education ,Patient educators ,[SDV]Life Sciences [q-bio] ,education ,lcsh:Medicine ,Review ,Simulated patient ,Formative assessment ,Raynaud phenomenon ,Big data ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Medical diagnosis ,Genetics (clinical) ,ComputingMilieux_MISCELLANEOUS ,Scleroderma, Systemic ,Health professionals ,4. Education ,Role play ,lcsh:R ,Raynaud Disease ,General Medicine ,Rare diseases ,[SDV] Life Sciences [q-bio] ,Systemic sclerosis ,Clinical case ,Simulated patients ,Emblems and Insignia ,Psychology ,030217 neurology & neurosurgery ,Simulation ,Rare disease ,Red flags - Abstract
Background As lack of awareness of rare diseases (RDs) among healthcare professionals results in delayed diagnoses, there is a need for a more efficient approach to RD training during academic education. We designed an experimental workshop that used role-play simulation with patient educators and focused on teaching “red flags” that should raise the suspicion of an RD when faced with a patient with frequently encountered symptoms. Our objective was to report our experience, and to assess the improvement in learners’ knowledge and the satisfaction levels of the participants. Results The workshop consisted of 2 simulated consultations that both started with the same frequent symptom (Raynaud phenomenon, RP) but led to different diagnoses: a frequent condition (idiopathic RP) and an RD (systemic sclerosis, SSc). In the second simulated consultation, the role of the patient was played by a patient educator with SSc. By juxtaposing 2 seemingly similar situations, the training particularly highlighted the elements that help differentiate SSc from idiopathic RP. When answering a clinical case exam about RP and SSc, students that had participated in the workshop had a higher mean mark than those who had not (14 ± 3.7 vs 9.6 ± 5.5 points out of 20, p = 0.001). Participants mostly felt “very satisfied” with this training (94%), and “more comfortable” about managing idiopathic RP and SSc (100%). They considered the workshop “not very stressful” and “very formative” (both 71%). When asked about the strengths of this training, they mentioned the benefits of being put in an immersive situation, allowing a better acquisition of practical skills and a more interactive exchange with teachers, as well as the confrontation with a real patient, leading to a better retention of semiological findings and associating a relational component with this experience. Conclusions Through the use of innovative educational methods, such as role-play simulation and patient educators, and by focusing on teaching “red flags”, our workshop successfully improved RP and SSc learning in a way that satisfied students. By modifying the workshop’s scenarios, its template can readily be applied to other clinical situations, making it an interesting tool to teach other RDs.
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- 2020
47. The Profile of Emotional Competence (PEC): A French short version for cancer patients
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Anne-Sophie Baudry, Veronique Christophe, Emilie Constant, Guillaume Piessen, Amelie Anota, FREGAT Working Group, Pôle Cancérologie et Spécialités Médicales [Valenciennes], Centre hospitalier [Valenciennes, Nord], Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), French National Platform Quality of Life and Cancer, Human and Social Sciences Department [Lyon], Centre Léon Bérard [Lyon], Department of Digestive and Oncological Surgery [Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Université de Lille, Unité de Méthodologie et de Qualité de Vie en Cancérologie (UMQVC), Institut Régional Fédératif du Cancer (IRFC)-Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Pôle cancérologie (CHRU Besançon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), This work was supported by the SIRIC ONCOLille (Grant INCa-DGOS Inserm 6041) to VC and the 'Region Hauts-de-France.' FREGAT was funded with support from the French National Cancer Institute (INCa) and the CHU de Lille is the sponsor of the FREGAT study., FREGAT Working Group, Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Plateforme nationale qualité de vie et cancer, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut Régional Fédératif du Cancer (IRFC), and Bodescot, Myriam
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Questionnaires ,Male ,Psychometrics ,Emotions ,[SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,Social Sciences ,050109 social psychology ,Anxiety ,Emotional competence ,Mathematical and Statistical Techniques ,0302 clinical medicine ,Neoplasms ,Item response theory ,Medicine and Health Sciences ,Psychology ,Aged, 80 and over ,Multidisciplinary ,[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,Depression ,Statistics ,05 social sciences ,Middle Aged ,Prognosis ,3. Good health ,Research Design ,030220 oncology & carcinogenesis ,Physical Sciences ,Medicine ,Female ,medicine.symptom ,Factor Analysis ,Research Article ,Clinical psychology ,Intrapersonal communication ,Adult ,Psychological Adjustment ,Science ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Emotional Adjustment ,Research and Analysis Methods ,03 medical and health sciences ,Quality of life (healthcare) ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Mental Health and Psychiatry ,medicine ,Humans ,Interpersonal Relations ,0501 psychology and cognitive sciences ,Statistical Methods ,Aged ,Survey Research ,Mood Disorders ,Biology and Life Sciences ,Polytomous Rasch model ,Confidence interval ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Quality of Life ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Self Report ,Mathematics - Abstract
BackgroundIntrapersonal and interpersonal Emotional Competence (EC) predicts better health and disease adjustment. This study aimed to validate a short version of the Profile of Emotional Competence (PEC) scale for cancer patients.MethodsFive hundred and thirty-five patients with cancer completed a self-reported questionnaire assessing their intra- and interpersonal EC (PEC), their anxiety and depression symptoms (HADS), and their health-related quality of life (QLQ-C30). Confirmatory factor analyses and Item Response Theory models with the Partial Credit Model were performed to validate and reduce the scale.FindingsThe Short-PEC (13 items), composed of 2 sub-scores of intra- (6 items) and interpersonal (7 items) EC, showed an improved factorial structure (Root Mean Square Error of Approximation (RMSEA) = 0.075 (90% confidence interval 0.066-0.085), comparative fit index = 0.915) with good psychometric properties.DiscussionFuture studies should use the Short-PEC to explain and predict the adjustment of cancer patients. The short-PEC could be also used in clinical routine to assess the level of EC of patients and to adapt psychosocial intervention.
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- 2020
48. Galectin-3 modulates epithelial cell adaptation to stress at the ER-mitochondria interface
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Coppin, Lucie, Jannin, Arnaud, Ait Yahya, Emilie, Thuillier, Caroline, Villenet, Céline, TARDIVEL, Meryem, Bongiovanni, Antonino, Gaston, Cécile, De Beco, Simon, Barois, Nicolas, Van Seuningen, Isabelle, Durand, Emmanuelle, Bonnefond, Amélie, Vienne, Jean-Claude, Vamecq, Joseph, Figeac, Martin, Vincent, Audrey, Delacour, Delphine, Porchet, Nicole, Pigny, Pascal, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), 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)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, Université de Lille, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), 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), This work was supported by academic fundings from Inserm, Université de Lille, CHU de Lille and by the Ligue Nationale contre le Cancer, comité de la Somme (grant to PP) and comité du Nord (grant to IVS), by grants from 'Initiatives d’excellence' (Idex ANR-11-IDEX-0005-02) - Labex « Who Am I? » (ANR-11-LABX-0071) (to D.D.), the Groupama Foundation – Research Prize for Rare Diseases (to D.D.), the Human Frontier Science Program (RGP0038/2018), from Contrat de Plan Etat Région (CPER Cancer 2007-2013 (to I.v.S.)). The UMR CNRS 8199 platform, (Lille, France) which belongs to the ‘Federation de Recherche’ 3508 Labex EGID (European Genomics Institute for Diabetes, ANR-10-LABX-46) was supported by the ANR Equipex 2010 session (ANR-10-EQPX-07-01, ‘LIGAN-PM’)., ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-11-LABX-0071,WHO AM I,Determinants de l'Identité : de la molécule à l'individu(2011), ANR-10-LABX-0046,EGID,EGID Diabetes Pole(2010), ANR-10-EQPX-0007,LIGAN PM,Plate forme Lilloise de séquençage du génome humain pour une médecine personnalisée(2010), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER], and Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M))
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lcsh:Cytology ,Galectins ,[SDV]Life Sciences [q-bio] ,Apoptosis ,Epithelial Cells ,Blood Proteins ,Energy metabolism ,Endoplasmic Reticulum ,Endoplasmic Reticulum Stress ,Cancer metabolism ,Article ,Mitochondria ,Mitochondrial Membranes ,Unfolded Protein Response ,otorhinolaryngologic diseases ,Humans ,Thapsigargin ,lcsh:QH573-671 ,Reactive Oxygen Species - Abstract
International audience; Abstract Cellular stress response contributes to epithelial defense in adaptation to environment changes. Galectins play a pivotal role in the regulation of this response in malignant cells. However, precise underlying mechanisms are largely unknown. Here we demonstrate that Galectin-3, a pro and anti-apoptotic lectin, is required for setting up a correct cellular response to stress by orchestrating several effects. First, Galectin-3 constitutes a key post-transcriptional regulator of stress-related mRNA regulons coordinating the cell metabolism, the mTORC1 complex or the unfolded protein response (UPR). Moreover, we demonstrated the presence of Galectin-3 with mitochondria-associated membranes (MAM), and its interaction with proteins located at the ER or mitochondrial membranes. There Galectin-3 prevents the activation and recruitment at the mitochondria of the regulator of mitochondria fission DRP-1. Accordingly, loss of Galectin-3 impairs mitochondrial morphology, with more fragmented and round mitochondria, and dynamics both in normal and cancer epithelial cells in basal conditions. Importantly, Galectin-3 deficient cells also display changes of the activity of the mitochondrial respiratory chain complexes, of the mTORC1/S6RP/4EBP1 translation pathway and reactive oxygen species levels. Regarding the ER, Galectin-3 did not modify the activities of the 3 branches of the UPR in basal conditions. However, Galectin-3 favours an adaptative UPR following ER stress induction by Thapsigargin treatment. Altogether, at the ER-mitochondria interface, Galectin-3 coordinates the functioning of the ER and mitochondria, preserves the integrity of mitochondrial network and modulates the ER stress response.
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- 2020
49. PoleSat_2018: an optimized, automated, geomatics IT tool based on a gravitational model: strategic decision support in hospital catchment area planning
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Anne Quesnel-Barbet, Ismahane Ben Gayed, Mathurin Gamichon, Pierre Bazile, François Dufossez, Julien Soula, Arnaud Hansske, Eric-André Sauleau, Pierre Parrend, CHU of Lille (MRCHU), Risques, Epidémiologie, Territoire, INformations, Education et Santé (RETINES), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Laboratoire d'Informatique Fondamentale de Lille (LIFL), Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), École polytechnique universitaire de Lille (Polytech Lille), Centre hospitalier de Béthune, French Association for Geographic Information, 94160 Saint‑Mandé, France., Département de la santé publique [CHU Strasbourg], CHU Strasbourg, Département Informatique du laboratoire ICUBE (ICUBE-Informatique), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ECAM Strasbourg-Europe, Groupe Hospitalier de l'Institut Catholique Lillois (GHICL), Faculté Libre de Médecine, GHICL, Université de Lille, CHU de Lille, Université de Strasbourg, QUESNEL-BARBET, Anne, École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), and Université catholique de Lille (UCL)
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Computer science ,Process (engineering) ,[SPI] Engineering Sciences [physics] ,General Chemical Engineering ,Gravitation Marketing of health services ,Geomatics ,General Physics and Astronomy ,[MATH] Mathematics [math] ,[INFO] Computer Science [cs] ,Health informatics ,[SHS]Humanities and Social Sciences ,03 medical and health sciences ,[SPI]Engineering Sciences [physics] ,0302 clinical medicine ,General Materials Science ,[INFO]Computer Science [cs] ,030212 general & internal medicine ,[MATH]Mathematics [math] ,Catchment area (health) ,General Environmental Science ,Graphical user interface ,Spatial decision support system ,business.industry ,Heuristic ,Decision support systems (clinical) ,030503 health policy & services ,General Engineering ,Diagnosis-related groups ,Computer simulation ,3. Good health ,Visualization ,Engineering management ,General Earth and Planetary Sciences ,Catchment area ,[SHS] Humanities and Social Sciences ,0305 other medical science ,business - Abstract
In France and elsewhere, decision-makers, healthcare professionals and health planners need to better understand and specify the provision of medical care. To this end, a hospital-based research project on a gravitational health planning modelling process was initiated in 2002. Since then, geomatics has emerged as a major scientific field for facing new challenges in medical informatics and health planning, thanks to the use of attractive interfaces, new methods and user-friendly IT technologies. Our initial 2002 model has recently been enhanced, optimized and automated as part of a spatial decision support system (PoleSat_2018). These decisive improvements and optimizations were mainly based on Delaunay triangulation, the replacement of human expertise with a heuristic dominance rule that provides a complete automated algorithm, and an online graphical user interface. Rapid, easy planning scenarios (by grouping and/or closing hospitals) give a quasi-instantaneous, strategic visualization of hospital catchment areas for decision-makers who are not experts in geomatics via ready-to-use maps and spreadsheets. This new implementation achieves our main objective, since the proposed deterministic method provides a completely automated, stable algorithm. A custom version of this tool is now being used by the French Ministry of Health for real planning issues. Consequently, PoleSat could be easily generalized as a prospective, strategic decision support tool for various health planning issues.
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- 2020
50. Evaluation of the impact of a nurse-led program of patient self-assessment and self-management in axial spondyloarthritis: results of a prospective, multicentre, randomized, controlled trial (COMEDSPA)
- Author
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Emmanuelle Dernis, Martin Soubrier, Jean Sibilia, Xavier Mariette, Pascal Claudepierre, Catherine Beauvais, Thierry Schaeverbeke, Laure Gossec, Maxime Dougados, Pascal Richette, Sandrine Guis, René-Marc Flipo, Anna Molto, Bernard Combe, Adeline Ruyssen-Witrand, Sophie Pouplin, Isabelle Chary-Valckenaere, Daniel Wendling, Philippe Gaudin, Françoise Fayet, Gérard Chalès, Serge Poiraudeau, Alain Saraux, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), APHP, Rheumatology B Department, Université Paris Descartes - Paris 5 (UPD5), Department of Rehabilitation, Medical University of Warsaw - Poland, Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Department of Rheumatology, University Teaching Hospital, CHRU Besançon, and University of Franche-Comté, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre Hospitalier Le Mans (CH Le Mans), CHU de Marseille, CHU Marseille, Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre de Rhumatologie toulouse [CHU Toulouse], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, Université de Montpelier, Centre Hospitalier Universitaire de Lille (CHU de Lille), Hôpital Lariboisière-APHP, Service de Rhumatologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Rhumatologie Bordeaux (SERVICE DE RHUMATOLOGIE), CHU Bordeaux [Bordeaux], CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de Rhumatologie [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
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Self-assessment ,Male ,medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,education ,Population ,nurse ,law.invention ,03 medical and health sciences ,Diagnostic Self Evaluation ,0302 clinical medicine ,Rheumatology ,Randomized controlled trial ,law ,Statistical significance ,medicine ,Humans ,Pharmacology (medical) ,Spondylitis, Ankylosing ,030212 general & internal medicine ,Spondylitis ,BASDAI ,health care economics and organizations ,030203 arthritis & rheumatology ,education.field_of_study ,Ankylosing spondylitis ,Self-management ,Practice Patterns, Nurses' ,business.industry ,Self-Management ,Patient Acuity ,spondyloarthritis ,Middle Aged ,self-assessment ,medicine.disease ,Home Care Services ,Exercise Therapy ,Outcome and Process Assessment, Health Care ,Nursing Evaluation Research ,Physical therapy ,Quality of Life ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,business - Abstract
Objective To evaluate the impact of a nurse-led program of self-management and self-assessment of disease activity in axial spondyloarthritis. Methods Prospective, randomized, controlled, open, 12-month trial (NCT02374749). Participants were consecutive axial spondyloarthritis patients (according to the rheumatologist) and nurses having participated in a 1-day training meeting. The program included self-management: educational video and specific video of graduated, home-based exercises for patients; and self-assessment: video presenting the rationale of tight monitoring of disease activity with composite scores (Ankylosing Spondylitis Disease activity Score, ASDAS/Bath Ankyslosing Spondylitis Disease Activity Index, BASDAI). The nurse trained patients to collect, calculate and report (monthly) ASDAS/BASDAI. Treatment allocation was by random allocation to this program or a comorbidities assessment (not presented here and considered here as the control group). Results A total of 502 patients (250 and 252 in the active and control groups, respectively) were enrolled (age: 46.7 (12.2) years, male gender: 62.7%, disease duration: 13.7 (11.0) years). After the one-year follow-up period, the adherence to the self-assessment program was considered good (i.e. 79% reported scores >6 times). Despite a lack of statistical significance in the primary outcome (e.g. coping) there was a statistically significant difference in favor of this program for the following variables: change in BASDAI, number and duration of the home exercises in the active group, and physical activity (international physical activity score, IPAQ). Conclusion This study suggests a short-term benefit of a nurse-led program on self-management and self-assessment for disease activity in a young axial spondyloarthritis population in terms of disease activity, exercises and physical activity.
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- 2020
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