Author: "Christine Binquet" - Searchworks@Jio Institute Digital Library Search Results

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201. Estimation de la survie conditionnelle aux effets non linéaires et dépendants du temps des facteurs pronostiques

Author: M. Abrahamowicz, Willy Wynant, Catherine Quantin, Jean-Pierre Quenot, and Christine Binquet
Subjects: Epidemiology, Public Health, Environmental and Occupational Health
Abstract: Introduction Les etudes pronostiques estiment souvent des courbes de survie qui decrivent comment la probabilite d’un evenement d’interet change avec la duree de suivi, pour des patients avec differents vecteurs de covariables. Cependant, la validite de ces estimations, et des predictions de risque qui en resultent, depend en grande partie de la precision de l’estimation des effets des covariables evaluees. Pour eviter les hypotheses de risques proportionnels et de linearite conventionnelles, des extensions flexibles du modele de Cox a risques proportionnels incorporent des effets non lineaires (NL) et/ou des effets dependants du temps (TD). Cependant, leur impact sur l’estimation des courbes de survie n’est pas clair. Methodes Nous proposons un modele multivarie flexible pour estimer des courbes de survie individuelles, conditionnelles aux effets NL et/ou TD des covariables. Les fonctions TD et NL ainsi que le logarithme de la fonction de risque de base sont representes par des fonctions splines. Nous validons par simulations nos estimations des courbes de survie et les comparons avec les estimations conventionnelles, basees sur le modele de Cox a risques proportionnels combine avec l’estimateur de Breslow. Nous appliquons alors notre methode pour reevaluer les effets de plusieurs facteurs pronostiques sur la mortalite apres un choc septique. La cohorte etudiee inclus tous les adultes avec un diagnostic de choc septique, admis dans 14 unites de soins intensifs dans 10 hopitaux du Nord-Est de la France, entre octobre 2009 et septembre 2011. L’instant initial est defini comme l’initiation de vasopresseurs en reponse au choc septique et l’evenement d’interet est le deces (toute cause confondue) dans les trois premiers mois suivant le choc septique. Les patients toujours vivants trois mois apres le choc septique ont ete censures a trois mois. La duree de suivie mediane est de 63,5 jours et on observe 433 deces parmi les 858 patients ayant des donnees completes. Resultats Les simulations demontrent que la prise en compte des effets TD et NL peut grandement ameliorer les resultats des etudes pronostiques et que nos estimations flexibles des courbes de survie etaient non biaisees et avaient des erreurs quadratiques moyennes beaucoup plus faibles que les estimations conventionnelles. Dans les analyses appliquees a la mortalite apres un choc septique, notre modele a tres significativement ameliore la deviance (LRT = 84,8, df = 20, p Conclusion La prise en compte des effets non lineaires et/ou dependants du temps des facteurs pronostiques peut considerablement ameliorer la precision des etudes pronostiques.
Published: 2015

202. Rapid Change in the Use of Antiretroviral Agents and Improvement in a Population of HIV-Infected Patients: France, 1995 to 1997

Author: François Dabis, Rosemary Spira, Christine Binquet, Catherine Marimoutou, and Denis Lacoste
Subjects: medicine.medical_specialty, education.field_of_study, biology, business.industry, Mortality rate, Incidence (epidemiology), Immunology, Population, biology.organism_classification, medicine.disease, Pharmacotherapy, Acquired immunodeficiency syndrome (AIDS), Virology, Internal medicine, Epidemiology, medicine, Immunology and Allergy, Medical prescription, Sida, education, business
Abstract: PURPOSE To describe the recent evolution of antiretroviral prescriptions and to look for clinical and biological changes among a population of HIV-infected patients. SUBJECTS Patients received follow-up in the hospital-based information system of the Groupe d'Epidemiologie Clinique du SIDA en Aquitaine (GECSA), Southwestern France, from 1995 to 1997. METHODS Quarterly evolution of the prescriptions of antiretroviral treatments and of the population clinical and biological indicators were studied in this observational survey of computerized records obtained after each hospital contact. RESULTS Overall numbers of patients who received follow-up and of hospital contacts remained stable. The proportion of untreated patients decreased from 38.5% to 10.5%. Monotherapies were progressively abandoned. Double combination therapies with two nucleoside analogues were used for 55% of the patients by early 1996 and then decreased, whereas triple combination therapies with one protease inhibitor (PI) rapidly increased to comprise up to 40% of the prescriptions in 1997. PIs were prescribed earlier and earlier in the course of HIV infection. Overall incidence of AIDS diagnoses and mortality rate decreased by 18% and 22%, respectively, in the first 9 months of use of PIs compared with the preceding 9 months, and by 47% and 56%, respectively, in the following 9 months (p
Published: 1998

203. Profile of the risk of death after septic shock in the present era: an epidemiologic study

Author: Arnaud, Pavon, Christine, Binquet, Fady, Kara, Olivier, Martinet, Frederique, Ganster, Jean-Christophe, Navellou, Vincent, Castelain, Damien, Barraud, Joel, Cousson, Guillaume, Louis, Pierre, Perez, Khaldoun, Kuteifan, Alain, Noirot, Julio, Badie, Chaouki, Mezher, Henry, Lessire, Catherine, Quantin, Michal, Abrahamowicz, Jean-Pierre, Quenot, and J F, Poussel
Subjects: Male, medicine.medical_specialty, Organ Dysfunction Scores, Comorbidity, Critical Care and Intensive Care Medicine, Risk Assessment, Body Mass Index, Sepsis, Sex Factors, Intensive care, Epidemiology, Medicine, Humans, Hospital Mortality, Prospective Studies, Risk factor, Intensive care medicine, APACHE, Aged, Proportional Hazards Models, Cross Infection, business.industry, Septic shock, Age Factors, Middle Aged, medicine.disease, Shock, Septic, Intensive Care Units, Bacteremia, Cohort, Observational study, Female, business
Abstract: To investigate mortality of ICU patients over a 3-month period after an initial episode of septic shock and to identify factors associated with mortality.Prospective multicenter observational cohort study.Fourteen ICUs from 10 French nonacademic and university teaching hospitals.All consecutive adult patients with septic shock admitted between October 2009 and September 2011 were eligible.None.Multivariable analyses were performed using a Cox proportional hazard model and a flexible extension of the Cox model. In total, 1,495 of 10,941 patients (13.7%) had septic shock and 1,488 patients (99.5%) were included. Median age was 68 years (range, 58-78 yr). The majority of admissions (84%) were medical. Median (interquartile range) Simplified Acute Physiological Score II and Sequential Organ Failure Assessment were, respectively, 56 (45-70) and 11 (9-14). ICU and hospital mortality were, respectively, 39.4% and 48.6%. At 3 months, 776 patients (52.2%) had died. Factors significantly associated with increased risk of death in the multivariable Cox model were older age, male sex, comorbidities (immune deficiency, cirrhosis), Knaus C/D score, and high Sequential Organ Failure Assessment score. Flexible analyses indicated that the impact of Sequential Organ Failure Assessment score was greatest early after septic shock, while the onset of the effect of age, nosocomial infection, and cirrhosis was later.This is the most recent large-scale epidemiological study to investigate medium-term mortality in nonselected patients hospitalized in the ICU for septic shock. Advances in early management have improved survival at the initial phase, but risk of death persists in the medium term. Flexible modeling techniques yield insights into the profile of the risk of death in the first 3 months.
Published: 2013

204. Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: a Groupe d'etude des Tumeurs Endocrines (GTE) cohort study

Author: Bruno Vergès, Albert Beckers, Brigitte Delemer, Vincent Rohmer, Arnaud Murat, Jean-Marc Kuhn, Philippe Ruszniewski, Christine Binquet, Julien Thevenon, Philippe Caron, Georges Weryha, Michel Rodier, Sophie Giraud, F. Archambeaud, I. Guilhem, Morgane Le Bras, Philippe Chanson, Béatrice Parfait, Jean-Louis Sadoul, Lionel Groussin, Patricia Niccoli, Catherine Cardot-Bauters, Philippe Bouchard, Eric Baudin, Françoise Duron, Michel Renard, Hélène Bihan, Véronique Kerlan, P. Lecomte, Catherine Lombard-Bohas, Abderrahmane Bourredjem, Anne Barlier, Emilie Castermans, Françoise Borson-Chazot, Bernard Goichot, Olivier Chabre, Antoine Tabarin, Alain Calender, Laurence Faivre, Hélène Du Boullay, Pierre Goudet, Eric Clauser, Alfred Penfornis, Marie-Françoise Odou, Université Joseph Fourier - Grenoble 1 ( UJF ), Immunovirologie et polymorphisme génétique, Université de Nantes ( UN ), 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 ), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ), 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 ), Centre de médecine nucléaire, Fédération d'endocrinologie-Groupement hospitalier Lyon-Est, Centre de recherche en neurobiologie - neurophysiologie de Marseille ( CRN2M ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Service d'Endocrinologie ( BORDEAUX - Endocrino ), CHU Bordeaux [Bordeaux], Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux ( Inserm U745 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Biologie du Cancer et de l'Infection ( BCI - UMR S1036 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Grenoble Alpes ( UGA ), Service d'Endocrinologie ( LIEGE - Endocrino ), Université de Liège, Department of Gastroenterology, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Beaujon, Pathologie et virologie moléculaire ( PVM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'Endocrinologie - Diabète - Nutrition [Reims], Université de Reims Champagne-Ardenne ( URCA ) -Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims ( CHU Reims ), Laboratoire Microorganismes : Génome et Environnement ( LMGE ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire [Rennes], Service d'Endocrinologie ( ANGERS - Endocrino ), CHU Angers, Département de Médecine Interne et Nutrition, CHU Strasbourg, Service d'Endocrinologie ( TOULOUSE - Endocrino ), CHU Toulouse [Toulouse], Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Gustave Roussy ( IGR ), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Service d'Endocrinologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service d'Endocrinologie ( TOURS - Endocrino ), CHRU Tours, Service de diabétologie - endocrinologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( PCVP / CARDIO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Conservatoire National des Arts et Métiers - Paris ( CNAM Paris ), Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Unité de Recherche en Epidémiologie Nutritionnelle ( UREN ), Institut National de la Recherche Agronomique ( INRA ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Médecine interne B, Endocrinologie, Diabète, Maladies métaboliques [CHU Limoges], CHU Limoges, Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), Service d'Endocrinologie ( CHRU - Endocrino ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Service de Diabétologie, Service des maladies métaboliques et endocriniennes, Hôpital Universitaire Carémeau [Nîmes], Service d'Endocrinologie ( NICE - Endocrino ), CHU Nice, Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) ( PCVP / CARDIO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ), Université Joseph Fourier - Grenoble 1 (UJF), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), 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), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), 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-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Service d'Endocrinologie (BORDEAUX - Endocrino), Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux (Inserm U745), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie du Cancer et de l'Infection (BCI ), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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)-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)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Endocrinologie (LIEGE - Endocrino), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pathologie et virologie moléculaire (PVM (UMR_7151)), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université de Reims Champagne-Ardenne (URCA)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Service d'Endocrinologie (ANGERS - Endocrino), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'Endocrinologie (TOULOUSE - Endocrino), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Endocrinologie (TOURS - Endocrino), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Diabétologie - Endocrinologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), 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), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Service d'Endocrinologie (CHRU - Endocrino), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service d'Endocrinologie (NICE - Endocrino), Centre Hospitalier Universitaire de Nice (CHU Nice), Université de Nantes (UN), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-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)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Beaujon, Pathologie et virologie moléculaire (PVM), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Brest (UBO), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Fédération d'endocrinologie, Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO)
Subjects: Oncology, Male, endocrine system diseases, Proto-Oncogene Proteins c-jun, [SDV]Life Sciences [q-bio], Disease, medicine.disease_cause, MESH: Protein Structure, Tertiary, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, MESH : Female, Genetics (clinical), Mutation, General Medicine, MESH: Follow-Up Studies, MESH : Risk Factors, 3. Good health, 030220 oncology & carcinogenesis, Cohort, MESH : Proto-Oncogene Proteins, Female, MESH : Mutation, MESH : Protein Structure, Tertiary, MESH : Proto-Oncogene Proteins c-jun, MESH : Multiple Endocrine Neoplasia Type 1, Cohort study, medicine.medical_specialty, endocrine system, MESH: Mutation, Genetic counseling, MESH : Male, MESH: Multiple Endocrine Neoplasia Type 1, 030209 endocrinology & metabolism, Biology, 03 medical and health sciences, Internal medicine, Proto-Oncogene Proteins, Genetics, medicine, Multiple Endocrine Neoplasia Type 1, Humans, MEN1, Family, Molecular Biology, MESH: Family, MESH: Humans, MESH: Proto-Oncogene Proteins c-jun, [ SDV ] Life Sciences [q-bio], Proportional hazards model, MESH : Humans, Cancer, MESH : Follow-Up Studies, medicine.disease, MESH: Male, Protein Structure, Tertiary, MESH: Proto-Oncogene Proteins, Cancer research, MESH : Family, MESH: Female, Follow-Up Studies
Abstract: International audience; Multiple endocrine neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Although genotype-phenotype studies have so far failed to identify any statistical correlations, some families harbor recurrent tumor patterns. The function of MENIN is unclear, but has been described through the discovery of its interacting partners. Mutations in the interacting domains of MENIN functional partners have been shown to directly alter its regulation abilities. We report on a cohort of MEN1 patients from the Groupe d'étude des Tumeurs Endocrines. Patients with a molecular diagnosis and a clinical follow-up, totaling 262 families and 806 patients, were included. Associations between mutation type, location or interacting factors of the MENIN protein and death as well as the occurrence of MEN1-related tumors were tested using a frailty Cox model to adjust for potential heterogeneity across families. Accounting for the heterogeneity across families, the overall risk of death was significantly higher when mutations affected the JunD interacting domain (adjusted HR = 1.88: 95%-CI = 1.15-3.07). Patients had a higher risk of death from cancers of the MEN1 spectrum (HR = 2.34; 95%-CI = 1.23-4.43). This genotype-phenotype correlation study confirmed the lack of direct genotype-phenotype correlations. However, patients with mutations affecting the JunD interacting domain had a higher risk of death secondary to a MEN1 tumor and should thus be considered for surgical indications, genetic counseling and follow-up.
Published: 2013

205. Prevalence of dry eye disease in elderly individuals of the French population (the MONTRACHET Study)

Author: Muselier-Mathieu, Aurore, Meillon, Cyril, Fiet, Caroline, Vinault, Sandrine, Christine Binquet, Mathieu, Benigne, Tzourio, Christophe, Bron, Alain, Garcher, Catherine, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), U708, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Bordeaux, 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 ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], 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), 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), and ProdInra, Archive Ouverte
Subjects: retina, étude épidémiologique, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, œil, 486 cornea: tears/tear film/dry eye, drought, clinical study, eye diseases, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, [ SDV.MHEP.OS ] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 463 clinical (human) or epidemiologic studies: prevalence/incidence, incidence, étude clinique, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, sécheresse
Abstract: Purpose To report the prevalence of dry eye in a large population-based sample of French individuals older than 75 years. Methods About 9000 individuals 65 years and older were included in the 3C cohort study since 1999 in 3 French cities (Bordeaux, Dijon and Montpellier). In Dijon, an additional ophthalmic examination was performed 10 years after the initial inclusions to assess the relation between systemic age-related diseases and eye diseases in the MONTRACHET Study (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases). Dry eye symptoms were collected with self reported history of dry eye symptoms, use of topical medications and evaluated by the Ocular Surface Disease Index (OSDI) questionnaire. Every patient underwent ophthalmic evaluation which included Schirmer I test without anesthesia, tear film break up time measurement and fluorescein cornea1 staining evaluation. Prevalence of dry eye was evaluated with subjective criteria (history and OSDI questionnaire) and objective criteria. Results One thousand and twenty four subjects were included in the study. Mean age was 83.7 ± 3.8 years old. 62.9% of the patients were women (644). Prevalence of dry eye is reported in Tables 1 and 2. (Δ : Variable; BUT : Break-Up-Time; Fluo : Fluorescein staining; - : Négative; + : Positive) Conclusions As reported in the literature, this study shows wide variations in dry eye prevalence depending on the sign or symptoms considered.
Published: 2013

206. [Prostate cancer: how do patients choose their treatment?]

Author: Catherine, Enel, Alexandre, Matte, Célia, Berchi, Christine, Binquet, Luc, Cormier, and Catherine, Lejeune
Subjects: Male, Prostatectomy, Physician-Patient Relations, Radiotherapy, Decision Making, Biomedical Technology, Prostatic Neoplasms, Robotics, Middle Aged, Choice Behavior, Treatment Refusal, Reproductive Health, Humans, Patient Participation, Qualitative Research, Aged
Abstract: Prostate cancer remains a public health concern in France for men between 50 and 70 years old. Low-risk or intermediate-risk localised prostate cancer can be treated by a number of therapeutic options.Identify, in patients' discourse, the mechanisms and the logic involved in therapeutic decision-making.Qualitative study involving 15 men aged between 53 and 70 years, treated for early-stage prostate cancer, via interviews examining diagnosis pathway, how patients perceive and cope with the illness, and how they choose a treatment.The men made their choices using their own initiative during a multiple-stage process. The determining factors were: quality of relationship with physicians, wish to benefit from the available technological advances in medical care, and minimum impairment to their sexual and reproductive identity. Chances of survival did not appear to be their primary concern.This qualitative study reveals that men make their own decisions in terms of choice of therapy, whether encouraged by their physicians to participate or not.
Published: 2013

207. Impact of time to initiation of appropriate antibiotic therapy on early mortality of patients with septic shock

Author: Sandrine Vinault, Arnaud Pavon, Christine Binquet, and Jean-Pierre Quenot
Subjects: medicine.medical_specialty, Septic shock, medicine.drug_class, business.industry, Antibiotics, Critical Care and Intensive Care Medicine, medicine.disease, Antibiotic therapy, Poster Presentation, Emergency medicine, medicine, In patient, Intensive care medicine, business
Abstract: The impact of appropriate antibiotic therapy on prognosis of patients with septic shock is well established. However, the prognostic influence of time to initiation of antibiotics remains debated. We evaluated the effect on 7-day mortality of time to initiation of appropriate antibiotic therapy in patients hospitalised in critical care for septic shock.
Published: 2013

208. [Public clinical trials: which kind of monitoring should be used?]

Author: Catherine, Cornu, Christine, Binquet, Claire, Thalamas, Céline, Vigouroux, Ségolène, Gaillard, Tiphanie, Ginhoux, Bernadette, Vaz, Claire, Jossan, Alexandra, Félin, Annabelle, Sailly, François, Gueyffier, Valérie, Journot, and Behrouz, Kassaï
Subjects: Quality Control, Clinical Trials as Topic, Risk Management, Endpoint Determination, Research Design, Data Interpretation, Statistical, Humans, Clinical Trials Data Monitoring Committees, Quality Indicators, Health Care
Abstract: Sponsors must take responsibility for the quality of trials at the best possible cost. Our objective was to describe the most frequent quality failures, how they impact trial results, and identify the most efficient monitoring strategies using published articles and reports.Errors affecting clinical trials include conception, procedures, data management, and data analysis. The consequences are usually an overestimation of the treatment effect. No study shows that monitoring reduces the risk of errors, and there is no comparison of monitoring methods. Many research organisations advocate for monitoring based on risk analysis and recommend an extensive use of centralised monitoring.Trial quality depends on trial conception and design. Study conduct should guarantee a maximum level of quality level. This should be done using risk management and extensive centralised monitoring.
Published: 2013

209. CFTR p.Arg117His associated with CBAVD and other CFTR-related disorders

Author: Christel, Thauvin-Robinet, Anne, Munck, Frédéric, Huet, Alix, de Becdelièvre, Clément, Jimenez, Guy, Lalau, Elodie, Gautier, Jacques, Rollet, Jean, Flori, Raphaëlle, Nové-Josserand, Jean-Claude, Soufir, Alain, Haloun, Dominique, Hubert, Elise, Houssin, Gil, Bellis, Gilles, Rault, Albert, David, Laurent, Janny, Raphaël, Chiron, Nathalie, Rives, Dominique, Hairion, Patrick, Collignon, Antoine, Valeri, Gilles, Karsenty, Annick, Rossi, Marie-Pierre, Audrézet, Claude, Férec, Julie, Leclerc, Marie des, Georges, Mireille, Claustres, Thierry, Bienvenu, Bénédicte, Gérard, Pierre, Boisseau, Faïza, Cabet-Bey, David, Cheillan, Delphine, Feldmann, Christine, Clavel, Eric, Bieth, Albert, Iron, Brigitte, Simon-Bouy, Vincent, Izard, Julie, Steffann, Stéphane, Viville, Catherine, Costa, Véronique, Drouineaud, Patricia, Fauque, Christine, Binquet, Claire, Bonithon-Kopp, Mike A, Morris, Laurence, Faivre, Michel, Goossens, Michel, Roussey, Emmanuelle, Girodon, L, Weiss, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de pédiatrie (CHU de Dijon), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre de Biologie Pathologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Centre hospitalier universitaire de Nantes (CHU Nantes), CIC Cochin Pasteur (CIC 1417), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe hospitalier Broca-Université Paris Descartes - Paris 5 (UPD5)-Hôtel-Dieu-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut national d'études démographiques (INED), Centre de Ressources et de Compétences de la Mucoviscidose (CRCM), Centre de Perharidy-Cellule de Coordination du Réseau Mucoviscidose (CECOREM), MLab, Dauphine Recherches en Management (DRM), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Gamétogenèse et Qualité du Gamète - ULR 4308 (GQG), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Lille, Département de génétique médicale [Hôpital de la Timone - APHM], 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), CHRU de Brest, service de chirurgie urologique et de la transplantation reinale (CHU - BREST - Urologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Chirurgie urologique et transplantation rénale [Hôpital de la Conception - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, 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), Biochimie et biologie moléculaire, Hôpital Cochin [AP-HP], Service d'hématologie et immunologie, Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de génétique médicale [CHU Nantes], Service d'Endocrinologie Moléculaire et Maladies rares, Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biochimie et de Biologie Moléculaire [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), Plasticité de l'épithélium respiratoire dans les conditions normales et pathologiques - UMR-S 903 (PERPMP), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Reims Champagne-Ardenne (URCA), CHU Toulouse [Toulouse], Laboratoire de Génétique Humaine, Développement et Cancer, Université Bordeaux Segalen - Bordeaux 2, Centre Hospitalier de Versailles André Mignot (CHV), Université Paris Descartes - Paris 5 (UPD5), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-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), Laboratoire de Biologie de la reproduction CECOS - [CHU de Dijon], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), 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, Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Service de Pédiatrie, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5)-Groupe hospitalier Broca-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), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5)-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Dauphine-PSL-Centre National de la Recherche Scientifique (CNRS)-Université Paris Dauphine-PSL, Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Gamétogenèse et Qualité du Gamète (GQG), Normandie Université (NU)-Normandie Université (NU)-Université de Lille, Droit et Santé-Université de Lille, Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U1172 Inserm), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Service de biochimie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], and Centre Hospitalier de Versailles (CHV)
Subjects: Infertility, Male, medicine.medical_specialty, Heterozygote, Cystic Fibrosis, Offspring, [SDV]Life Sciences [q-bio], Cystic Fibrosis Transmembrane Conductance Regulator, Gene mutation, Compound heterozygosity, Asymptomatic, Cystic fibrosis, 03 medical and health sciences, 0302 clinical medicine, Vas Deferens, Male Urogenital Diseases, Mutation Rate, Internal medicine, Prenatal Diagnosis, Genotype, Genetics, medicine, Humans, Family history, Child, Sweat, Genetics (clinical), Infertility, Male, 030304 developmental biology, 0303 health sciences, business.industry, Infant, Newborn, Infant, medicine.disease, 3. Good health, Phenotype, 030228 respiratory system, Child, Preschool, Immunology, Mutation, Female, medicine.symptom, business
Abstract: International audience; BACKGROUND:The high frequency of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene mutation p.Arg117His in patients with congenital bilateral absence of the vas deferens (CBAVD) and in newborns screened for CF has created a dilemma.METHODS:Phenotypic and genotypic data were retrospectively collected in 179 non-newborn French individuals carrying p.Arg117His and a second CFTR mutation referred for symptoms or family history, by all French molecular genetics laboratories, referring physicians, CF care centres and infertility clinics.RESULTS:97% of the patients had the intronic T7 normal variant in cis with p.Arg117His. 89% patients were male, with CBAVD being the reason for referral in 76%. In 166/179 patients with available detailed clinical features, final diagnoses were: four late-onset marked pulmonary disease, 83 isolated CBAVD, 67 other CFTR-related phenotypes, including 44 CBAVD with pulmonary and/or pancreatic symptoms and 12 asymptomatic cases. Respiratory symptoms were observed in 30% of the patients, but the overall phenotype was mild. No correlation was observed between sweat chloride concentrations and disease severity. Five couples at risk of CF offspring were identified and four benefited from prenatal or preimplantation genetic diagnoses (PND or PGD). Eight children were born, including four who were compound heterozygous for p.Arg117His and one with a severe CF mutation.CONCLUSIONS:Patients with CBAVD carrying p.Arg117His and a severe CF mutation should benefit from a clinical evaluation and follow-up. Depending on the CBAVD patients' genotype, a CFTR analysis should be considered in their partners in order to identify CF carrier couples and offer PND or PGD
Published: 2013

210. Stroke impact scale version 2: validation of the French version

Author: Charles Benaim, Thierry Moulin, Yannick Béjot, Pierre Decavel, Marc Puyraveau, Morgane Chotard, Mariette Mercier, Bernard Parratte, Christine Binquet, and Sylvia Caël
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Psychometrics, Physical Therapy, Sports Therapy and Rehabilitation, Anxiety, Hospital Anxiety and Depression Scale, Cronbach's alpha, Surveys and Questionnaires, Activities of Daily Living, Medicine, Humans, Stroke, Aged, Aged, 80 and over, business.industry, Depression, Discriminant validity, Construct validity, Reproducibility of Results, Middle Aged, medicine.disease, Convergent validity, Scale (social sciences), Physical therapy, Quality of Life, Ceiling effect, Female, France, business
Abstract: Background Almost 1 person in 1,000 experiences a stroke annually in France. Health-related quality-of-life (HRQoL) measurement with specific questionnaires is useful to study the consequences of stroke on patients' daily lives. Objective The purpose of this study was to validate the French version of the Stroke Impact Scale (SIS) questionnaire, as no disease-specific questionnaire was validated in French heretofore. Methods Two hundred eighty-eight patients with stroke were classified into 2 groups (158 acute, 130 chronic). Rate of item completion, test-retest reliability, sensitivity to change, and construct validity, convergent validity, and discriminant validity of the questionnaire were assessed. Acute group patients were recruited during the first month poststroke and followed for 3 months. Chronic group patients (stroke dating from 1 year) were recruited from outpatient consultations. The first 100 patients in the chronic group were called back 15 days after inclusion for test-retest measurements. The Barthel Index, Hospital Anxiety and Depression Scale (HADS), and Duke Health Profile questionnaires were administered. Results The French version of the SIS was well accepted by all participants. It had good reproducibility. Cronbach alpha was 89% for all scales. A ceiling effect was noted in the majority of scales. Physical domains were significantly correlated to other measures of physical capacity (Barthel Index and Duke Health Profile; Spearman coefficients were between .5 and .73), and the emotional and social domains were significantly correlated to almost all domains of the Duke Health Profile. Psychometric properties were similar to those of the US version. Responsiveness was good for physical and emotional domains. Limitations Validation was conducted only on people who were able to answer the questionnaire. Conclusions The French SIS version presents good psychometric properties, except for ceiling effect. This is the first stroke-specific questionnaire evaluating perceived health after stroke to be validated in France and could be useful for further investigations of HRQoL after stroke.
Published: 2013

211. Total plasma protein in very preterm babies: prognostic value and comparison with illness severity scores

Author: Francesco Bonsante, Pierre-Yves Robillard, Christine Binquet, Catherine Quantin, Jean-Bernard Gouyon, Silvia Iacobelli, Centre d'Études Périnatales de l'Océan Indien (CEPOI), Université de La Réunion (UR)-Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Études Périnatales de l'Océan Indien ( CEPOI ), Université de la Réunion ( UR ) -Centre Hospitalier Universitaire de La Réunion ( CHU La Réunion ), Service Biostatistiques et Informatique Médicale (CHU de Dijon) ( DIM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques ( CIC-EC ), and 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 )
Subjects: Pediatrics, Multivariate analysis, Critical Care and Emergency Medicine, Epidemiology, [ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics, lcsh:Medicine, law.invention, Cohort Studies, 0302 clinical medicine, law, Infant, Very Low Birth Weight, 030212 general & internal medicine, Prospective Studies, Pediatric Epidemiology, lcsh:Science, Multidisciplinary, Area under the curve, Blood Proteins, Intensive care unit, 3. Good health, Cohort, Medicine, Infant, Premature, Research Article, medicine.medical_specialty, Pediatric Critical Care, Clinical Research Design, Birth weight, Fluid Management, 03 medical and health sciences, Hypoproteinemia, 030225 pediatrics, Internal medicine, medicine, Humans, Premature, Retrospective Studies, Nutrition, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Receiver operating characteristic, business.industry, Very Low Birth Weight, lcsh:R, Infant, Newborn, Infant, medicine.disease, Newborn, Confidence interval, lcsh:Q, Neonatology, business
Abstract: International audience; OBJECTIVE: We aimed to investigate the predictive value for severe adverse outcome of plasma protein measurements on day one of life in very preterm infants and to compare total plasma protein levels with the validated illness severity scores CRIB, CRIB-II, SNAP-II and SNAPPE-II, regarding their predictive ability for severe adverse outcome. METHODS: We analyzed a cohort of infants born at 24-31 weeks gestation, admitted to the tertiary intensive care unit of a university hospital over 10.5 years. The outcome measure was "severe adverse outcome" defined as death before discharge or severe neurological injury on cranial ultrasound. The adjusted odd ratio (aOR) and 95% confidence interval (95% CI) of severe adverse outcome for hypoproteinemia (total plasma protein level \textless40 g/L) was calculated by univariate and multivariate analyses. Calibration (Hosmer-Lemeshow goodness-of-fit) was performed and the predictive ability for severe adverse outcome was assessed for total plasma protein and compared with CRIB, CRIB-II, SNAP-II and SNAPPE-II, by calculating receiver operating characteristic (ROC) curves and their associated area under the curve (AUC). RESULTS: 761 infants were studied: 14.4% died and 4.1% survived with severe cerebral ultrasound findings. The aOR of severe adverse outcome for hypoproteinemia was 6.1 (95% CI 3.8-9.9). The rank order for variables, as assessed by AUCs and 95% CIs, in predicting outcome was: total plasma protein [0.849 (0.821-0.873)], SNAPPE-II [0.822 (0.792-0.848)], CRIB [0.821 (0.792-0.848)], SNAP-II [0.810 (0.780-0.837)] and CRIB-II [0.803 (0.772-0.830)]. Total plasma protein predicted severe adverse outcome significantly better than CRIB-II and SNAP-II (both p\textless0.05). Calibration for total plasma protein was very good. CONCLUSIONS: Early hypoproteinemia has prognostic value for severe adverse outcome in very preterm, sick infants. Total plasma protein has a predictive performance comparable with CRIB and SNAPPE-II and greater than other validated severity scores.
Published: 2013

212. Congenital \textittoxoplasma infection: monthly prenatal screening decreases transmission rate and improves clinical outcome at age 3 years

Author: François Peyron, C. Bonithon Kopp, Michal Abrahamowicz, Christine Binquet, Catherine Cornu, S. Vinault, Martine Wallon, Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and 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)
Subjects: Microbiology (medical), Adult, Male, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Prenatal diagnosis, Prenatal care, Toxoplasmosis, Congenital, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Pregnancy, Prenatal Diagnosis, medicine, Humans, Young adult, Pregnancy Complications, Infectious, 0303 health sciences, 030306 microbiology, business.industry, Obstetrics, Infant, Newborn, Gestational age, Infant, Middle Aged, medicine.disease, Toxoplasmosis, Infectious Disease Transmission, Vertical, 3. Good health, Infectious Diseases, Child, Preschool, Gestation, Female, France, business, Cohort study
Abstract: Background. Toxoplasma infection during pregnancy exposes the fetus to risks of congenital infection and sequelae that depend heavily on gestational age (GA) at time of infection. Accurate risk estimates by GA are necessary to counsel parents and improve clinical decisions. Methods. We analyzed data from pregnant women diagnosed with acute Toxoplasma infection in Lyon (France) from 1987 to 2008 and assessed how the risks of congenital toxoplasmosis and of clinical signs at age 3 years vary depending on GA at the time of maternal infection. Results. Among 2048 mother-infant pairs, 93.2% of mothers received prenatal treatment and 513 (24.7%) fetuses were infected. Because of a significant reduction in risk since 1992 when monthly screening was introduced (59.4% vs 46.6% at 26 GA weeks; P= .038), probabilities of infection were estimated on the basis of maternal infections diagnosed after mid-1992 (n = 1624). Probabilities of congenital infection were
Published: 2013

213. Spatial Distribution of Macular Pigment in an Elderly French Population: The Montrachet Study

Author: Niyazi Acar, Catherine Creuzot-Garcher, Louis Arnould, Cécile Delcourt, Christine Binquet, Lionel Bretillon, Seydou Alassane, Olivier Fleck, Alain M. Bron, 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 ), 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 ), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), PHRC regional Council of Burgundy INRA CNRS Universite de Bourgogne Regional Council of Burgundy France (PARI) FEDER (European Funding for Regional Economic Development), ANR : Labex,LipSTIC,ANR-11-LABX-0021-01-LipSTIC, 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), 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), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR: 11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011), 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), and ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011)
Subjects: Male, iris color, Lutein, genetic structures, degeneration, 01 natural sciences, Photometry, Macular Degeneration, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Medicine, Macula Lutea, macular pigment optical density, Aged, 80 and over, retinal thickness, education.field_of_study, medicine.diagnostic_test, Incidence, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Age Factors, Zeaxanthin, zeaxanthin, age-related maculopathy, population-based study, Population Surveillance, Female, France, sunlight, Tomography, Optical Coherence, medicine.medical_specialty, Population, [ SDV.MHEP.GEG ] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, elderly, 010309 optics, 03 medical and health sciences, Optical coherence tomography, Ophthalmology, 0103 physical sciences, ring-like structure, Humans, education, omega-3-fatty-acids, Aged, lutein, business.industry, association, Retinal, Odds ratio, medicine.disease, eye diseases, Confidence interval, Cross-Sectional Studies, chemistry, optical-density, 030221 ophthalmology & optometry, Maculopathy, Optometry, Macular Pigment, sense organs, business
Abstract: International audience; PURPOSE. We describe the spatial distribution and cross-sectional associations with physical and lifestyle attributes. METHODS. The participants of the Montrachet (Maculopathy Optic Nerve, nuTRition neurovAsCular and HEarT) study underwent an exhaustive ophthalmologic examination, including optical coherence tomography, to measure retinal thickness. The spatial distribution of macular pigment optical density (MPOD) defined as a ring-like, intermediate or no-ring pattern, was assessed by means of the two-wavelength autofluorescence technique. Blood samples were taken to measure plasma lutein and zeaxanthin using high performance liquid chromatography (HPLC). RESULTS. We studied 635 subjects with good-quality MPOD measurements. The mean age was 82.0 +/- 3.4 years. A ring-like structure was found in 109 (17.2%) participants. Participants with a ring-like spatial distribution had a thinner macula in the central subfield (P < 0.001). In multivariate analysis, individuals never protecting themselves from sunlight and with dark iris color were less likely to present a ring-like than a no-ring spatial distribution (P = 0.033 and P = 0.013, respectively). Only in males were lutein plasma levels higher in ring-like and intermediate MPOD profiles than in no-ring structures (odds ratio [OR] = 1.59 for 100 additional mu g; 95% confidence interval [CI] = 1.16-2.18 and OR = 1.64; 95% CI, 1.17-2.28). CONCLUSIONS. In this population-based study, individuals never protecting themselves from sunlight, and with dark iris color and a thinner macula were less prone to displaying a ring-like MPOD spatial distribution.
Published: 2016

214. Relationships of Macular Pigment Optical Density With Plasma Lutein, Zeaxanthin, and Diet in an Elderly Population: The Montrachet Study

Author: Olivier Fleck, Christine Binquet, Cécile Delcourt, Vanessa Cottet, Sandrine Daniel, Lionel Bretillon, Alain M. Bron, Seydou Alassane, Catherine Creuzot-Garcher, Niyazi Acar, Creuzot Garcher, Catherine, 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 ), 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 ), Lipides - Nutrition - Cancer (U866) ( LNC ), 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), PHRC regional Council of Burgundy INRA CNRS Universite de Bourgogne Regional Council of Burgundy France (PARI) FEDER (European Funding for Regional Economic Development), ANR : Labex,LipSTIC,ANR-11-LABX-0021-01-LipSTIC, 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), 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), Lipides - Nutrition - Cancer (U866) (LNC), 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR: 11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011), 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), and ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011)
Subjects: Male, Aging, Lutein, Urban Population, Organes des sens, Visual Acuity, degeneration, eye disease, chemistry.chemical_compound, 0302 clinical medicine, Macular Pigment, Macula Lutea, 030212 general & internal medicine, macular pigment optical density, risk-factors, Carotenoid, Chromatography, High Pressure Liquid, Aged, 80 and over, chemistry.chemical_classification, education.field_of_study, Confounding, carotenoids, food and beverages, Middle Aged, Healthy Volunteers, supplemental lutein, lutein, zeaxanthin, diet, elderly, population-based, study, Zeaxanthin, age-related maculopathy, population-based study, Population Surveillance, Alimentation et Nutrition, Female, France, Adult, medicine.medical_specialty, prevalence, Sensory Organs, Population, 03 medical and health sciences, Zeaxanthins, Internal medicine, medicine, Humans, Food and Nutrition, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, serum concentrations, education, omega-3-fatty-acids, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Aged, Retrospective Studies, business.industry, Feeding Behavior, medicine.disease, sample, eye diseases, Age-related maculopathy, Endocrinology, chemistry, 030221 ophthalmology & optometry, Maculopathy, business, Follow-Up Studies
Abstract: International audience; PURPOSE. To investigate the association of macular pigment optical density (MPOD) with plasma lutein, zeaxanthin, and diet in an elderly population.METHODS. We conducted a population-based study, the Montrachet (Maculopathy Optic Nerve, nuTRition neurovAsCular, and HEarT disease) study, in subjects older than 75 years. The MPOD was measured by means of the two-wavelength autofluorescence technique. Plasma lutein and zeaxanthin were measured in fasting blood samples using HPLC. Food frequency consumption was assessed with self-reported food frequency questionnaires.RESULTS. Overall, 433 healthy participants (62.1% females) were included. Mean age was 82.0 +/- 3.6 years. Mean MPOD at 0.5 degrees eccentricity was 0.57 +/- 0.25 density units (DU) and was higher in women than in men (0.59 +/- 0.25 vs. 0.53 +/- 0.25, P = 0.017). The MPOD was lower in alcohol consumers than in non-alcohol consumers (0.55 +/- 0.25 vs. 0.61 +/- 0.25, P = 0.016). Median plasma lutein and zeaxanthin levels were 281.4 mu g/L and 20.0 mu g/L, respectively, and were higher in women (P = 0.010 and P = 0.003, respectively). The MPOD was positively correlated with plasma lutein and zeaxanthin (r = 0.10, P = 0.030 and r = 0.11, P = 0.027, respectively). A higher consumption of squash was associated with higher plasma lutein and zeaxanthin. Adjusting for confounders and diet revealed that MPOD was weakly associated with plasma lutein in nonsmokers (beta = 0.11, P = 0.021).CONCLUSIONS. This study suggests that plasma lutein is associated with MPOD after taking into account potential confounding factors in an elderly population.
Published: 2016

215. The epidemiology of septic shock in French intensive care units: the prospective multicenter cohort EPISS study

Author: Alain Noirot, Jean-Christophe Navellou, Frédérique Ganster, Khaldoun Kuteifan, Arnaud Pavon, Damien Barraud, F Kara, Olivier Martinet, Vincent Castelain, Jean-Pierre Quenot, Guillaume Louis, Joel Cousson, Christine Binquet, Henry Lessire, Chaouki Mezher, Pierre Perez, Julio Badie, 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 ), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de réanimation polyvalente, Centre hospitalier de Haguenau, Service de réanimation Médicale, CHU Strasbourg, Service de réanimation médicale, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre hospitalier régional Metz-Thionville ( CHR Metz-Thionville ), Centre Hospitalier Emile Muller [Mulhouse] ( CH E.Muller Mulhouse ), Groupe Hospitalier de Territoire Haute Alsace ( GHTHA ) -Groupe Hospitalier de Territoire Haute Alsace ( GHTHA ), CH de Vesoul, CH Belfort-Montbéliard, CH Montbéliard, CH Colmar, 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), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Réanimation médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), and BMC, Ed.
Subjects: Male, medicine.medical_specialty, Pediatrics, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Critical Care and Intensive Care Medicine, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Intensive care, Severity of illness, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, 030212 general & internal medicine, Prospective Studies, Mortality, 10. No inequality, Prospective cohort study, Aged, Aged, 80 and over, Septic shock, business.industry, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Research, Hazard ratio, 030208 emergency & critical care medicine, Middle Aged, medicine.disease, Shock, Septic, 3. Good health, Intensive Care Units, Shock (circulatory), Emergency medicine, Cohort, Female, France, medicine.symptom, business, Cohort study, Follow-Up Studies
Abstract: International audience; INTRODUCTION: To provide up-to-date information on the prognostic factors associated with 28-day mortality in a cohort of septic shock patients in intensive care units (ICUs). METHODS: Prospective, multicenter, observational cohort study in ICUs from 14 French general (non-academic) and university teaching hospitals. All consecutive patients with septic shock admitted between November 2009 and March 2011 were eligible for inclusion. We prospectively recorded data regarding patient characteristics, infection, severity of illness, life support therapy and discharge. RESULTS: Among 10,941 patients admitted to participating ICUs between October 2009 and September 2011, 1495 (13.7%) patients presented inclusion criteria for septic shock and were included. Invasive mechanical ventilation was needed in 83.9% (n=1248), inotropes in 27.7% (n=412), continuous renal replacement therapy in 32.5% (n=484) and hemodialysis in 19.6% (n=291). Mortality at 28 days was 42% (n=625). Variables associated with time to mortality, right-censored at day 28: age (for each additional 10 yrs) (hazard ratio, HR=1.29; 95% confidence interval [CI]: 1.20-1.38), immunosuppression (HR=1.63; 95%CI: 1.37-1.96), Knaus class C/D score versus class A/B score (HR=1.36; 95%CI:1.14-1.62) and Sepsis-related Organ Failure Assessment (SOFA) score (HR=1.24 for each additional point; 95%CI: 1.21-1.27). Patients with septic shock and renal/urinary tract infection had a significantly longer time to mortality (HR=0.56; 95%CI: 0.42-0.75). CONCLUSION: Our observational data of consecutive patients from real-life practice confirm that septic shock is common and carries high mortality in general intensive care unit populations. Our results are in contrast with the clinical trial setting, and could be useful for healthcare planning and clinical study design.
Published: 2012

216. Clinical and molecular spectrum of renal malformations in Kabuki syndrome

Author: Christine Binquet, Jean-Benoît Courcet, Valérie Cormier-Daire, Marjolaine Willems, Sylvain Poisson, Brigitte Gilbert-Dussardier, Elodie Sanchez, Rémi Salomon, Marie Ange Delrue, Sylvie Odent, Eudeline Alix, Annick Toutain, Aurélia Jaquette, Clarisse Baumann, Le Quan Sang Kim-Han, Damien Sanlaville, Anna Pelet, Honorine Kayirangwa, Laurence Faivre, Martine Le Merrer, Christiane Mousson, Alice Goldenberg, Marie-Pierre Cordier, Marie-Line Jacquemont, Anne Moncla, Stéphanie Perez-Martin, Caroline Michot, Sandrine Vinault, Joelle Roume, Frédéric Huet, Didier Lacombe, Lucille Pinson, Catherine Vincent-Delorme, Stanislas Lyonnet, Marianne Till, David Geneviève, Pierre Sarda, Antoine Burguet, Nicole Philip, Jeanne Amiel, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital d'Enfants [CHU Dijon], Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, Service de génétique clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Génétique Médicale, Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre de Référence Anomalies du Développement Ouest, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Cellules souches mésenchymateuses, environnement articulaire et immunothérapies de la polyarthrite rhumatoide, Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire de Génétique Chromosomique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Référence ' Anomalies du Développement et Syndromes Malformatifs Sud - Est PACA ', 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), Département de Génétique Médicale, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Génétique, Hôpital Poissy-saint Germain, Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Maladies Rares, Anomalies du Développement Nord de France-CH Arras - CHRU Lille, Service de néphrologie (CHU de Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, CHU de Montpellier, Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Génétique Médicale [CHU Necker], Service de Cytogénétique (HFME), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants ( UMR_S 953 ), Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service Pédiatrique, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Hospices Civils de Lyon ( HCL ) -CHU de Lyon-Centre Neuroscience et Recherche, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, CHU de Poitiers-Centre de Référence Anomalies du Développement Ouest, CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Bretonneau-CHRU Tours, Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), 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 ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), 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 ), 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 ), Génétique des Anomalies du Développement ( GAD ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC, CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Hopital Necker-Enfants Malades-Assistance publique - Hôpitaux de Paris (AP-HP), Service de Cytogénétique ( HFME ), Hôpital Femme Mère Enfant [CHU - HCL] ( HFME ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Hôpital du Bocage, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris-Sud - Paris 11 ( UP11 ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Hôpital du Bocage, Centre hospitalier universitaire de Poitiers ( CHU Poitiers ) -Centre de Référence Anomalies du Développement Ouest, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hospices Civils de Lyon ( HCL ) -Hôpital Femme Mère Enfant [CHU - HCL] ( HFME ), Hospices Civils de Lyon ( HCL ), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL)-Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), 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), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), and IFR100 - Structure fédérative de recherche Santé-STIC-Université de Bourgogne (UB)
Subjects: Male, Pathology, Genotyping Techniques, urologic and male genital diseases, Kidney, Cohort Studies, chemistry.chemical_compound, Child, Ultrasonography, Histone Demethylases, 0303 health sciences, 030305 genetics & heredity, Nuclear Proteins, Hypoplasia, 3. Good health, Neoplasm Proteins, DNA-Binding Proteins, medicine.anatomical_structure, Vestibular Diseases, Child, Preschool, Creatinine, Biological Markers, Female, France, Abnormalities, Multiple, Cohort study, Glomerular Filtration Rate, Adult, Genetic Markers, medicine.medical_specialty, Adolescent, Urinary system, Urology, Renal function, 03 medical and health sciences, Young Adult, medicine, Humans, Abnormalities, Multiple, Preschool, Genetic Association Studies, 030304 developmental biology, Retrospective Studies, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Infant, Retrospective cohort study, medicine.disease, Hematologic Diseases, chemistry, Face, Pediatrics, Perinatology and Child Health, business, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Kabuki syndrome, Biomarkers
Abstract: International audience; OBJECTIVE: To determine the frequency and types of renal malformations, and to evaluate renal function in a cohort of patients with Kabuki syndrome (KS). STUDY DESIGN: Renal ultrasound scans and plasma creatinine measurements were collected from a French cohort of 94 patients with genotyped KS. Renal function was evaluated based on the estimated glomerular filtration rate. A genotype-phenotype study was conducted for renal and urinary tract malformations. RESULTS: Renal malformations were present in 22% of cases, and urinary tract anomalies were present in 15%. Renal malformations were observed in 28% of the MLL2 mutation-positive group and in 0% of the MLL2 mutation-negative group (P = .015). No correlation was found between the presence or absence of renal or urinary tract malformations and the location or type of MLL2 mutation. Renal function was normal except for 1 patient with a MLL2 mutation diagnosed in the first days of life and severe renal disease due to unilateral renal agenesia and controlateral severe hypoplasia that progressed to the terminal stage at age 2 years. CONCLUSION: Our study emphasizes the need for ultrasound and renal function screening in children diagnosed with KS.
Published: 2012

217. LupusQoL-FR is valid to assess quality of life in patients with systemic lupus erythematosus

Author: Jean-François Besancenot, Jean-Loup Pennaforte, Jean-Louis Pasquali, Pierre Kaminsky, Laurent Arnaud, Zahir Amoura, Francis Guillemin, Denis Wahl, Nadine Magy-Bertrand, Christine Binquet, Hervé Devilliers, Bernard Bonnotte, François Maurier, 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 ), Service de Médecine Interne (SOC 1 et SOC 2) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre National de Référence du Lupus et Syndrome des Antiphospholipides, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Service d'Immunologie Clinique, CHU Strasbourg, Immunologie et chimie thérapeutiques ( ICT ), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique ( CNRS ), Service de Médecine Interne et Vasculaire [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Risque cardiovasculaire, rigidité-fibrose et hypercoagulabilité ( RCV ), Université Henri Poincaré - Nancy 1 ( UHP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de médecine interne, Hôpital Sainte-Blandine-Centre hospitalier régional Metz-Thionville ( CHR Metz-Thionville ), Service de Médecine Interne et Maladies Orphelines [CHRU Nancy], Service de Médecine Interne, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Ecole de santé publique, Université Paris Descartes - Paris 5 ( UPD5 ) -Nancy Université, 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), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Risque cardiovasculaire, rigidité-fibrose et hypercoagulabilité (RCV), Université Henri Poincaré - Nancy 1 (UHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville)-Hôpital Sainte-Blandine, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Médecine interne [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Nancy Université, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), 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), Hôpital Sainte-Blandine-Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Saas, Philippe, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC)
Subjects: Male, Psychometrics, MESH: Self Report, MESH : Prospective Studies, MESH : Self Report, Severity of Illness Index, 0302 clinical medicine, Surveys and Questionnaires, Medicine, Lupus Erythematosus, Systemic, MESH : Lupus Erythematosus, Systemic, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Pharmacology (medical), MESH : Female, 030212 general & internal medicine, Prospective Studies, MESH: Translations, MESH: Middle Aged, MESH : Psychometrics, MESH : Questionnaires, Middle Aged, MESH : Adult, MESH: Reproducibility of Results, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Severity of Illness Index, Adult, medicine.medical_specialty, SF-36, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Male, MESH : Translations, External validity, 03 medical and health sciences, Rheumatology, Cronbach's alpha, MESH: Psychometrics, MESH: Severity of Illness Index, Humans, Translations, MESH: Lupus Erythematosus, Systemic, MESH : Middle Aged, 030203 arthritis & rheumatology, Rasch model, MESH: Humans, business.industry, MESH: Questionnaires, MESH : Reproducibility of Results, MESH : Humans, Discriminant validity, Construct validity, Reproducibility of Results, MESH: Quality of Life, MESH: Adult, MESH : Quality of Life, MESH: Male, MESH: Prospective Studies, Mann–Whitney U test, Physical therapy, Quality of Life, Self Report, business, MESH: Female
Abstract: International audience; OBJECTIVE: To cross-culturally adapt the LupusQoL into French, to test its measurement properties and to further investigate its domain structure. METHODS: The cultural adaptation process according to guidelines and pre-testing resulted in the LupusQoL-FR. SLE patients completed the LupusQoL-FR at baseline, 15 days, 3 months and 6 months. Validity was studied through content and construct validity (factorial and Rasch analysis for structural validity, Spearman's correlation and Mann-Whitney tests for external validity). Cronbach's α and intra-class correlation coefficients were computed for reliability. The standardized response mean was computed to evaluate responsiveness. RESULTS: In all, 182 patients, age 39.6 (10.6) years, mostly outpatients [mean SELENA-SLEDAI 2.6 (3.5)] were recruited. Factor analysis with eight imposed factors was very close to the original LupusQoL. A screeplot with parallel analysis showed that LupusQoL domains could be aggregated in two physical and mental scales. Both eight- and two-factor structures showed a good Rasch fit, internal consistency (Cronbach's α: 0.85-0.95), and test-retest reliability (intra-class correlation coefficient 0.79-0.95). External convergent (correlation with SF-36, r=0.59-0.78) and divergent validity (according to SELENA-SLEDAI) were also satisfactory. CONCLUSION: The LupusQoL-FR is valid to assess quality of life in SLE patients. A two-factor structure of physical and mental aggregated scales is a valid alternative to the original eight-domain structure.
Published: 2012

218. Prognostic factors of septic shock

Author: Khaldoun Kuteifan, JF Poussel, F Kara, Damien Barraud, Vincent Castelain, Arnaud Pavon, Christine Binquet, Jean-Pierre Quenot, Joel Cousson, Jean-Christophe Navellou, Pierre Perez, Olivier Martinet, and Frédérique Ganster
Subjects: medicine.medical_specialty, business.industry, Septic shock, Intensive care, Incidence (epidemiology), Poster Presentation, Emergency medicine, medicine, Critical Care and Intensive Care Medicine, business, medicine.disease, Intensive care medicine, Optimal management
Abstract: The incidence of septic shock in intensive care (ICU) in France is around 8 to 10%, with in-hospital mortality ranging from 55 to 60% [1]. The identification of prognostic factors is essential to guarantee optimal management.
Published: 2012

219. Hypoproteinemia on the first day of life and adverse outcome in very preterm infants admitted to the neonatal intensive care unit

Author: Jean-Bernard Gouyon, Catherine Quantin, Cyril Ferdynus, Jonathan Cottenet, Silvia Iacobelli, Francesco Bonsante, C. Lacoutière, Christine Binquet, Centre d'Études Périnatales de l'Océan Indien (CEPOI), Université de La Réunion (UR)-Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, 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), Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre d'Études Périnatales de l'Océan Indien ( CEPOI ), Université de la Réunion ( UR ) -Centre Hospitalier Universitaire de La Réunion ( CHU La Réunion ), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), 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 ), Service Biostatistiques et Informatique Médicale (CHU de Dijon) ( DIM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer (U866) ( LNC ), 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA )
Subjects: Male, Pediatrics, medicine.medical_specialty, Neonatal intensive care unit, Adverse outcomes, Leukomalacia, Periventricular, Birth weight, Day of life, MEDLINE, [ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Diseases, Infant, Premature, Diseases, 03 medical and health sciences, Hypoproteinemia, 0302 clinical medicine, Intensive Care Units, Neonatal, 030225 pediatrics, Neonatal, Medicine, Birth Weight, Humans, 030212 general & internal medicine, Premature, Cerebral Hemorrhage, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Periventricular, business.industry, Infant, Newborn, Obstetrics and Gynecology, Infant, Blood Proteins, medicine.disease, Newborn, Infant newborn, 3. Good health, Very preterm, Intensive Care Units, Pediatrics, Perinatology and Child Health, Female, business, Infant, Premature, Leukomalacia
Abstract: International audience; OBJECTIVE: We aimed to investigate the relationship between day-1 hypoproteinemia and severe adverse outcome (SAO) in very preterm infants admitted to the neonatal intensive care unit (NICU). STUDY DESIGN: Retrospective study of all patients born from 24 to 31 weeks gestation and cared for in our NICU over an 8-year period. Infants were excluded if the serum protein value on the first day of life was not available. RESULT: A total of 913 patients were included. In all, 14.6% presented with SAO (death or severe neurological injury on cranial ultrasound). Hypoproteinemia (total protein level \textless40 g l(-1)) on day 1 of life occurred in 19.5 % of all patients. The rate of SAO was 33.7% in patients with hypoproteinemia and 9.9% in those with normoproteinemia (P\textless0.0001). Logistic and multiple regression analysis confirmed that the association hypoproteinemia-SAO remained significant after adjustment for the other major predictors of outcome present at baseline (odds ratio 3.4; 95% confidence interval 2.1-5.4; P\textless0.0001). CONCLUSION: Hypoproteinemia was highly associated with SAO in this cohort of critically ill preterm infants. We are unable to explain the link between hypoproteinemia and adverse outcome in our population. This investigation serves as a hypothesis-generating report of a large preterm infants sample, and suggests the need to assess the predictive accuracy for adverse outcome of hypoproteinemia in future prospective studies.
Published: 2012

220. Impact of whole-body computed tomography on mortality and surgical management of severe blunt trauma

Author: Delphine Garrigue, Marc Freysz, Jean-Michel Yeguiayan, Claire Bonithon-Kopp, Anabelle Yap, Claude Jacquot, Christine Binquet, Bruno Riou, Claude Martin, Département de médecine d'urgence / SAMU - SMUR - CESU 21 (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Fédération des Urgences - SAMU 59, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Pôle Anesthésie Réanimation, CHU Grenoble, Centre de Traumatologie et Département d'Anesthésie Réanimation, Université de la Méditerranée - Aix-Marseille 2-Centre Hospitalier Universitaire Nord, Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, 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), Service d'Accueil des Urgences [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC), This study was supported by the Programme Hospitalier de Recherche Clinique 2003 of the French Ministry of Health (National PHRC), the Société Française d'Anesthésie Réanimation (SFAR), and the Centre Hospitalier Universitaire of Dijon., 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Lipides - Nutrition - Cancer (U866) ( LNC ), 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), 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 ), Service d'Accueil des Urgences, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], BMC, Ed., Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SHS.INFO]Humanities and Social Sciences/Library and information sciences, Critical Care and Intensive Care Medicine, Wounds, Nonpenetrating, [SHS.INFO] Humanities and Social Sciences/Library and information sciences, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Intensive care, [ SHS.INFO ] Humanities and Social Sciences/Library and information sciences, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Young adult, Mortality, Prospective cohort study, Trauma Severity Indices, blunt trauma, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], business.industry, Mortality rate, Research, Disease Management, 030208 emergency & critical care medicine, Middle Aged, 3. Good health, Surgery, Blunt trauma, Propensity score matching, Injury Severity Score, Female, business, Tomography, X-Ray Computed, Cohort study
Abstract: International audience; IntroductionThe mortality benefit of whole-body computed tomography (CT) in early trauma management remains controversial and poorly understood. The objective of this study was to assess the impact of whole-body CT compared with selective CT on mortality and management of patients with severe blunt trauma.MethodsThe FIRST (French Intensive care Recorded in Severe Trauma) study is a multicenter cohort study on consecutive patients with severe blunt trauma requiring admission to intensive care units from university hospital trauma centers within the first 72 hours. Initial data were combined to construct a propensity score to receive whole-body CT and selective CT used in multivariable logistic regression models, and to calculate the probability of survival according to the Trauma and Injury Severity Score (TRISS) for 1,950 patients. The main endpoint was 30-day mortality.ResultsIn total, 1,696 patients out of 1,950 (87%) were given whole-body CT. The crude 30-day mortality rates were 16% among whole-body CT patients and 22% among selective CT patients (p = 0.02). A significant reduction in the mortality risk was observed among whole-body CT patients whatever the adjustment method (OR = 0.58, 95% CI: 0.34-0.99 after adjustment for baseline characteristics and post-CT treatment). Compared to the TRISS predicted survival, survival significantly improved for whole-body CT patients but not for selective CT patients. The pattern of early surgical and medical procedures significantly differed between the two groups.ConclusionsDiagnostic whole-body CT was associated with a significant reduction in 30-day mortality among patients with severe blunt trauma. Its use may be a global indicator of better management.
Published: 2012

221. Prior transient ischemic attack and dementia after subsequent ischemic stroke

Author: Yannick Béjot, Maurice Giroud, Agnès Jacquin, Thibault Moreau, Olivier Rouaud, Christine Binquet, Claire Bonithon-Kopp, Jérôme Durier, Corine Aboa-Eboulé, and Guy-Victor Osseby
Subjects: Male, medicine.medical_specialty, Multivariate analysis, Population, Logistic regression, Risk Factors, Internal medicine, parasitic diseases, medicine, Odds Ratio, Dementia, Humans, cardiovascular diseases, education, Stroke, Aged, Aged, 80 and over, education.field_of_study, business.industry, Odds ratio, Middle Aged, medicine.disease, Confidence interval, nervous system diseases, Psychiatry and Mental health, Clinical Psychology, Ischemic Attack, Transient, Ischemic stroke, Multivariate Analysis, Female, Geriatrics and Gerontology, business, Gerontology
Abstract: Although functional recovery and survival after ischemic stroke seem to improve in patients with prior transient ischemic attack (TIA), little is known about the effect of prior TIA on poststroke cognition. To evaluate the impact of prior TIA on dementia, 1697 nonaphasic patients who survived the first month after their first-ever ischemic stroke were identified from the population-based registry of Dijon, France, from 1985 to 2007 and divided into 3 groups according to the time interval between prior TIA and stroke (
Published: 2011

222. [Not Available]

Author: Catherine, Cornu, Clémence, Camberlein, Christine, Binquet, Carine, Robert, Céline, Vigouroux, Caroline, Bouyssou, Alexandra, Felin, Marie-Françoise, Dupont-Mordelet, Annabelle, Sailly, Christine, Kubiak, Géraldine, Poli, Sonia, Gueguen, Charlène, Duchesne, Stéphanie, Ploix, and Claire, Thalamas
Abstract: Clinical Investigation Centres (CICs) are academic organisations for performing clinical studies. They are a part of a national network which is co-ordinated by French national institute for health and medical research (Inserm), and the head office of healthcare provision (DGOS). There are working groups and specialised networks within the overall CIC network. The Harmonisation of CIC Procedures (HPCIC) group wrote a manual of good professional practices for clinical research. This manual is described here. This manual was written by consensus. It was approved by the coordinators of all CICs, external experts, and validated by representatives of both Inserm and the General directorate of healthcare provision (DGOS). The CIC Good Professional Practices manual is a guide divided into two sections. The first section covers the general management of a CIC (common to all CICs). The second section covers the core activities of CICs, running clinical studies (clinical study coordination, clinical investigation, data management, statistical analysis, valorisation). This manual is available for all CICs and any other clinical research organisations. It will serve as a basis for CIC self-quality evaluation, audits between CICs, and external audits. This manual shows how much the CICs want to standardise practices and procedures nationwide to offer their partners the best quality in performing clinical studies.
Published: 2011

223. The new Ghent criteria for Marfan syndrome: what do they change?

Author: Eloisa Arbustini, Karin Mayer, Laurence Faivre, Lesley C. Adès, J. De Backer, Christine Binquet, Elodie Gautier, Jean-Eric Wolf, Bart Loeys, O Bouchot, Peter N. Robinson, Guillaume Jondeau, Bert Callewaert, Paul Coucke, Christophe Béroud, Anne H. Child, Dalil Hamroun, Gwenaëlle Collod-Béroud, Chantal Stheneur, Catherine Boileau, H. Plauchu, A. De Paepe, Nadine Hanna, Delphine Detaint, Mine Arslan-Kirchner, Uta Francke, Claire Bonithon-Kopp, Maurizia Grasso, Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut für Physik, Humboldt-Universität zu Berlin, Newtonstr. 15, D-12489 Berlin, Germany, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), Center for Medical Genetics [Ghent], Ghent University Hospital, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, COLLOD-BEROUD, Gwenaëlle, Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Humboldt University Of Berlin, 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 ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Groupe Appl. Phys. ( GAP ), GAP, Institut de génétique humaine ( IGH ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), 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 ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bichat
Subjects: Marfan syndrome, Nosology, Proband, musculoskeletal diseases, Adult, Male, Pediatrics, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, Fibrillin-1, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 030204 cardiovascular system & hematology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Fibrillins, Marfan Syndrome, 03 medical and health sciences, Young Adult, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Mitral valve, medicine.artery, Genetics, medicine, Mitral valve prolapse, Humans, cardiovascular diseases, Ectopia lentis, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Child, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Aorta, business.industry, Microfilament Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine.disease, Weill–Marchesani syndrome, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine.anatomical_structure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Human medicine, business, Follow-Up Studies
Abstract: International audience; The diagnosis of Marfan syndrome (MFS) is challenging and international criteria have been proposed. The 1996 Ghent criteria were adopted worldwide, but new diagnostic criteria for MFS were released in 2010, giving more weight to aortic root aneurysm and ectopia lentis. We aimed to compare the diagnosis reached by applying this new nosology vs the Ghent nosology in a well-known series of 1009 probands defined by the presence of an FBN1 mutation. A total of 842 patients could be classified as MFS according to the new nosology (83%) as compared to 894 (89%) according to the 1996 Ghent criteria. The remaining 17% would be classified as ectopia lentis syndrome (ELS), mitral valve prolapse syndrome or mitral valve, aorta, skeleton and skin (MASS) syndrome, or potential MFS in patients aged less than 20 years. Taking into account the median age at last follow-up (29 years), the possibility has to be considered that these patients would go on to develop classic MFS with time. Although the number of patients for a given diagnosis differed only slightly, the new nosology led to a different diagnosis in 15% of cases. Indeed, 10% of MFS patients were reclassified as ELS or MASS in the absence of aortic dilatation; conversely, 5% were reclassified as MFS in the presence of aortic dilatation. The nosology is easier to apply because the systemic score is helpful to reach the diagnosis of MFS only in a minority of patients. Diagnostic criteria should be a flexible and dynamic tool so that reclassification of patients with alternative diagnosis is possible, requiring regular clinical and aortic follow-up.
Published: 2011

224. Septic shock in a cohort of patients from the northeast of France: a preliminary epidemiological study, EPISS group

Author: Damien Barraud, Jean-Pierre Quenot, Jean-Christophe Navellou, Arnaud Pavon, Joel Cousson, JF Poussel, Christine Binquet, F Kara, and Olivier Martinet
Subjects: medicine.medical_specialty, Surviving Sepsis Campaign, business.industry, Septic shock, Incidence (epidemiology), Critical Care and Intensive Care Medicine, medicine.disease, Intensive care, Poster Presentation, Epidemiology, Cohort, Emergency medicine, medicine, business
Abstract: Incidence of septic shock in France ranges from 8 to 10% among patients admitted to intensive care. Mortality at 28 days is 55 to 60% [1]. We aimed to investigate epidemiology, treatment and mortality of patients with septic shock further to the Surviving Sepsis Campaign international guidelines [2].
Published: 2011

225. A decision tree to help determine the best timing and antiretroviral strategy in HIV-infected patients

Author: S. Mahy, M. Fardeheb, Catherine Quantin, Lionel Piroth, Christian Rabaud, Bruno Hoen, Isabelle Fournel, Jean-Pierre Faller, Yazdan Yazdanpanah, D. Rey, Christine Binquet, Pascal Chavanet, Département d'infectiologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Entente Interdépartementale pour la Démoustication, Région Rhône-Alpes, Laboratoire Chrono-environnement - CNRS - UBFC (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), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Laboratoire Chrono-environnement ( LCE ), and Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC )
Subjects: Adult, Male, medicine.medical_specialty, [ INFO ] Computer Science [cs], Epidemiology, Anti-HIV Agents, Decision tree, HIV Infections, Drug Administration Schedule, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Life Expectancy, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Antiretroviral Therapy, Highly Active, Hiv infected patients, Medicine, Humans, Protease inhibitor (pharmacology), In patient, [INFO]Computer Science [cs], Computer Simulation, 030212 general & internal medicine, Cd4 cell count, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, 030306 microbiology, business.industry, Decision Trees, Middle Aged, Viral Load, medicine.disease, Antiretroviral therapy, Markov Chains, 3. Good health, CD4 Lymphocyte Count, Infectious Diseases, Treatment Outcome, Immunology, Disease Progression, Female, business, Viral load, Follow-Up Studies
Abstract: SUMMARYOptimal antiretroviral strategies for HIV-infected patients still need to be established. To this end a decision tree including different antiretroviral strategies that could be adopted for HIV-infected patients was built. A 10-year follow-up was simulated by using transitional probabilities estimated from a large cohort using a time-homogeneous Markov model. The desired outcome was for patients to maintain a CD4 cell count of >500 cells/mm3without experiencing AIDS or death. For patients with a baseline HIV viral load ⩾5 log10copies/ml, boosted protease inhibitor-based immediate highly active antiretroviral therapy (HAART) allowed them to spend 12% more time with CD4 ⩾500/mm3than did delayed HAART (6·40vs. 5·69 and 5·57vs. 4·90 years for baseline CD4 ⩾500 and 350–499/mm3, respectively). In patients with a baseline HIV viral load ⩽3·5 log10copies/ml, delayed HAART performed better than immediate HAART (6·43vs. 6·26 and 5·95vs. 5·18 for baseline CD4 ⩾500 and 350–499/mm3, respectively). Immediate HAART is beneficial in patients with a baseline HIV viral load ⩾5 log10copies/ml, whereas deferred HAART appears to be the best option for patients with CD4 ⩾350/mm3and baseline HIV viral load 10copies/ml.
Published: 2011

226. 'Influence of prior transient ischaemic attack on stroke prognosis'

Author: Olivier Rouaud, Claire Bonithon-Kopp, Christine Binquet, Yves Cottin, Yannick Béjot, Guy-Victor Osseby, Christine Marie, Corine Aboa-Eboulé, Maurice Giroud, Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Laboratoire de génie des procédés - environnement - agroalimentaire (GEPEA), Institut Universitaire de Technologie - Nantes (IUT Nantes), Université de Nantes (UN)-Université de Nantes (UN)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut Universitaire de Technologie Saint-Nazaire (IUT Saint-Nazaire), Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Universitaire de Technologie - La Roche-sur-Yon (IUT La Roche-sur-Yon), Université de Nantes (UN), 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), Motricité - Plasticité, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire RICO (ObseRvatoire des Infarctus de Côte d’Or) [Dijon], Observatoire des Infarctus de Côte-d'Or (RICO) [Dijon], Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Laboratoire de génie des procédés - environnement - agroalimentaire ( GEPEA ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Nantes ( UN ) -IMT Atlantique Bretagne-Pays de la Loire ( IMT Atlantique ) -Université Bretagne Loire ( UBL ) -Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique ( ONIRIS ), 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 ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon )
Subjects: Male, Stroke registry, Multivariate analysis, CEREBRAL INFARCTION, Survival, 030204 cardiovascular system & hematology, Disability Evaluation, 0302 clinical medicine, RELEVANCE, DIJON, Medicine, ''RISK-FACTORS, Registries, RECOVERY'', Stroke, Ischaemic strokes, POPULATION, Neurologic Examination, education.field_of_study, NEUROPROTECTION, medicine.diagnostic_test, Cerebral infarction, Middle Aged, RECOVERY, Prognosis, HUMAN BRAIN, Magnetic Resonance Imaging, 3. Good health, Psychiatry and Mental health, Treatment Outcome, Ischemic Attack, Transient, [ SCCO.NEUR ] Cognitive science/Neuroscience, Cardiology, Regression Analysis, Female, Adult, medicine.medical_specialty, Population, FRANCE, 03 medical and health sciences, Internal medicine, parasitic diseases, Hospital discharge, Humans, cardiovascular diseases, TOLERANCE, education, Aged, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Magnetic resonance imaging, medicine.disease, nervous system diseases, Linear Models, Physical therapy, RISK-FACTORS, Surgery, Neurology (clinical), Tomography, X-Ray Computed, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: International audience; ''Background To evaluate potential neuroprotection afforded by prior transient ischaemic attack (TIA) on functional and survival outcomes after ischaemic stroke. Methods All cases of first-ever ischaemic strokes, diagnosed between 1985 and 2008, were identified from the Dijon Stroke Registry. Patients were analysed in three groups according to the time interval between prior TIA and stroke (= 4 weeks, no TIA) or the duration of TIA ( 30 min, no TIA). Outcomes were severe functional handicap (unable to walk, bedridden or death) at hospital discharge or at outpatient consultation, and 1-month and 1-year any-cause mortality. Stratified analyses were performed by stroke subtypes (non-lacunar, lacunar). Generalised linear mixed models and Cox proportional hazard models with a sandwich covariance matrix accounting for the treatment centre as a random effect were used for multivariate analyses. Results Among the 3015 patients with first-ever ischaemic stroke, 389 had had a prestroke TIA = 4 weeks. Patients with TIAs had better ambulatory status (adjusted OR 0.61, 95% CI 0.45 to 0.81; p=0.008) and better survival at 1 month (adjusted HR 0.76, 95% CI 0.65 to 0.89; p=0.0006) and at 1 year (adjusted HR 0.72, 95% CI 0.67 to 0.76; p
Published: 2011

227. Toxoplasmose congénitale : comparaison randomisée de stratégies de prévention des rétinochoroïdites

Author: Alexandrin Félin, François Kieffer, François Peyron, Claire Bonithon-Kopp, Patricia Garcia-Méric, Catherine Cornu, Alain Bonnin, Jean-Bernard Gouyon, Isabelle Villena, Pascal Dureau, Philippe Thulliez, Christine Binquet, Martine Wallon, Sandrine Masson, Jacqueline Franck, Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and 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)
Subjects: Gynecology, medicine.medical_specialty, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], business.industry, Treatment outcome, Follow up studies, Congenital toxoplasmosis, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, medicine, Pharmacology (medical), 030212 general & internal medicine, business, Therapeutic strategy
Abstract: Resume En France, les enfants atteints d’une toxoplasmose congenitale confirmee recoivent un traitement de 12 a 24 mois. Ce traitement prolonge peut engendrer des risques potentiellement severes, notamment hematologiques et cutanes. Notre objectif est de comparer l’efficacite de deux strategies therapeutiques sur la prevention de retinochoroidites grâce a un essai randomise de non-inferiorite ouvert a deux groupes paralleles sur 486 enfants âges de 3 a 6 mois atteints d’une forme non severe de toxoplasmose congenitale Apres randomisation, un traitement par pyrimethamine-sulfamides de 3 mois est initie, suivi d’un traitement par Fansidarr® pendant 9 mois, ou d’une abstention therapeutique. Les visites de suivi sur deux ans comporteront un examen de fond de l’oeil, une prise de sang et des questionnaires pour evaluer la qualite de vie des enfants et l’anxiete des parents. La confirmation de la non-inferiorite de l’efficacite d’un traitement court ameliorera la qualite de vie des parents et des enfants.
Published: 2011

228. [Congenital toxoplasmosis: randomised comparison of strategies for retinochoroiditis prevention]

Author: Martine, Wallon, François, Kieffer, Christine, Binquet, Philippe, Thulliez, Patricia, Garcia-Méric, Pascal, Dureau, Jacqueline, Franck, François, Peyron, Alain, Bonnin, Isabelle, Villena, Claire, Bonithon-Kopp, Jean-Bernard, Gouyon, Sandrine, Masson, Alexandrin, Félin, and Catherine, Cornu
Subjects: Male, Antimalarials, Sulfonamides, Choroiditis, Pyrimethamine, Treatment Outcome, Anti-Infective Agents, Quality of Life, Humans, Infant, Female, Toxoplasmosis, Congenital, Follow-Up Studies
Abstract: In France, children with confirmed congenital toxoplasmosis receive a treatment for a period of 12 to 24 months. Such prolonged treatment may generate potentially severe risks, in particular hematologic and cutaneous. Our objective is to compare the effectiveness of two therapeutic strategies on the prevention of retinochoroiditis by a randomized, non-inferiority, open-label, parallel study including 486 children, 3 to 6 months of age with a non-severe form of congenital toxoplasmosis. Following randomization, pyrimethamine-sulphonamide treatment is initiated for a period of three months, followed by a treatment with Fansidar(®) for 9 months, or therapeutic abstention. Follow-up visits during a two-year period will include an examination of the eye, a blood test, and questionnaires to evaluate the children's quality of life and their parents' anxiety. Confirming the non-inferiority of the effectiveness of a short-term treatment will improve the quality of life of parents and children.
Published: 2010

229. Cardiovascular manifestations in men and women carrying a FBN1 mutation

Author: Eloisa Arbustini, Laurence Faivre, Mine Arslan-Kirchner, Anatoli Kiotsekoglou, Christine Binquet, Claire Bonithon-Kopp, Dorothy Halliday, Christophe Béroud, Henri Plauchu, Lesley C. Adès, Julie De Backer, Bart Loeys, Catherine Boileau, Elodie Gautier, Anne H. Child, Uta Francke, Gwenaëlle Collod-Béroud, Mireille Claustres, Delphine Detaint, Peter N. Robinson, Anne De Paepe, Chantal Stheneur, Guillaume Jondeau, Karin Mayer, Service de cardiologie, Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiac & Vascular Sciences, St Georges, University of London, Center for Medical Genetics [Ghent], Ghent University Hospital, Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut cellule souche et cerveau (U846 Inserm - UCBL1), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), IRCCS - Pavia, Center for Human Genetics and Laboratory Medicine, Center of Human Genetics and Laboratory Medicine, Institut für Humagenetik, Hannover Medical School [Hannover] (MHH)-Institut für Humagenetik, Service de pédiatrie, urgences enfants [CHU Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], The Oxford Radcliffe Hospitals NHS Trust, Département de médecine d'urgence / SAMU - SMUR - CESU 21 (CHU de Dijon), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique, Hôpital de l'Hôtel Dieu [CHU-HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Sonalee Laboratory for Marfan syndrome and related disorders, Department of Cardiological Sciences, St. George's Hospital Medical School, Department of medical genetics, Royal Alexandra Children's Hospital, Department of Genetics [Stanford], Stanford Medicine, Stanford University-Stanford University, Center for Medical Genetics, Universiteit Gent = Ghent University [Belgium] (UGENT), COLLOD-BEROUD, Gwenaëlle, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Universiteit Gent = Ghent University (UGENT), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), 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 ), Lipides - Nutrition - Cancer (U866) ( LNC ), 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute ( SBRI ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hannover Medical School [Hannover] ( MHH ) -Institut für Humagenetik, Service de pédiatrie, urgences enfants, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Institut de génétique humaine ( IGH ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lyon-Université de Lyon-Hôtel Dieu, Department of Genetics and Pediatrics, Stanford University [Stanford], and Ghent University [Belgium] ( UGENT )
Subjects: Male, Marfan syndrome, Fibrillin-1, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Gene mutation, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Gastroenterology, Marfan Syndrome, 0302 clinical medicine, Mitral valve prolapse, Child, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Aortic dissection, 0303 health sciences, Mitral Valve Prolapse, Microfilament Proteins, Middle Aged, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Connective tissue disease, Aortic Aneurysm, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Phenotype, Female, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, Adolescent, Genotype, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Fibrillins, Young Adult, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine.artery, Internal medicine, medicine, Humans, Risk factor, 030304 developmental biology, Aorta, Vascular disease, business.industry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, Surgery, Aortic Dissection, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, business
Abstract: International audience; Aims In patients with Marfan syndrome and other type-1 fibrillinopathies, genetic testing is becoming more easily available, leading to the identification of mutations early in the course of the disease. This study evaluates the cardiovascular (CV) risk associated with the discovery of a fibrillin-1 (FBN1) mutation. Methods and results A total of 1013 probands with pathogenic FBN1 mutations were included, among whom 965 patients [median age: 22 years (11– 34), male gender 53%] had data suitable for analysis. The percentage of patients with an ascending aortic (AA) dilatation increased steadily with increasing age and reached 96% (95% CI: 94 –97%) by 60 years. The presence of aortic events (dissection or prophylactic surgery) was rare before 20 years and then increased progressively, reaching 74% (95% CI: 67–81%) by 60 years. Compared with women, men were at higher risk for AA dilatation [≤30 years: 57% (95% CI: 52– 63) vs. 50% (95% CI: 45– 55), P ¼ 0.0076] and aortic events [≤30 years: 21% (95% CI: 17–26) vs. 11% (95% CI: 8–16), P , 0.0001; adjusted HR: 1.4 (1.1 –1.8), P ¼ 0.005]. The prevalence of mitral valve (MV) prolapse [≤60 years: 77% (95% CI: 72– 82)] and MV regurgitation [≤60 years: 61% (95% CI: 53–69)] also increased steadily with age, but surgery limited to the MV remained rare [≤60 years: 13% (95% CI: 8– 21)]. No difference between genders was observed (for all P. 0.20). From 1985 to 2005 the prevalence of AA dilatation remained stable (P for trend ¼ 0.88), whereas the percentage of patients with AA dissection significantly decreased (P for trend ¼ 0.01). Conclusion The CV risk remains important in patients with an FBN1 gene mutation and is present throughout life, justifying regular aortic monitoring. Aortic dilatation or dissection should always trigger suspicion of a genetic background leading to thorough examination for extra-aortic features and comprehensive pedigree investigation.
Published: 2010

230. Newborn screening programmes including genetic analyses: limits and risks of negative consequences?

Author: Christel Thauvin-Robinet, Anne Munck, Christine Binquet, Frédéric Huet, Emmanuelle Girodon, and Michel Roussey
Subjects: Male, Pediatrics, medicine.medical_specialty, Cystic Fibrosis, Epidemiology, Cystic Fibrosis Transmembrane Conductance Regulator, Disease, medicine.disease_cause, Global Health, Cystic fibrosis, Neonatal Screening, Risk Factors, Medicine, Humans, Genetic Testing, Caucasian population, Mutation, Newborn screening, biology, business.industry, Public Health, Environmental and Occupational Health, Genetic Diseases, Inborn, Infant, Newborn, medicine.disease, Cystic fibrosis transmembrane conductance regulator, Europe, Respiratory failure, Clinical diagnosis, biology.protein, Female, business, Program Evaluation
Abstract: Newborn screening for inherited disorders enables early identification of affected children and intervention to prevent or mitigate morbidity and mortality associated with these conditions. Since 1962, most areas throughout the world have developed newborn screening (NBS) programmes including for more than 50 serious disorders.1 2 While most diseases are screened by biochemical techniques only, the NBS programme for cystic fibrosis (CF), which is being implemented in an increasing number of countries (USA, UK, Spain, France, Italy, Australia, Czech Republic, Poland …),3 4 relies on determination of immunoreactive trypsinemia (IRT) and subsequent screening for 30 common mutations of the cystic fibrosis transmembrane conductance regulator ( CFTR) gene when IRT is above 65 μg/l. Such programmes require careful attention on mutations to be included in the screening panel. CF is usually defined as the most frequent life-shortening autosomal recessive hereditary disease in the Caucasian population affecting from 1/2250 to 10 500 live births in Europe (median 1/3500). Children with classical CF present with chronic pulmonary obstruction and infections, leading to respiratory failure and pancreatic insufficiency (PI).5 The clinical diagnosis is usually confirmed by elevated sweat chloride values (≥60 mmol/l) and/or the identification of two CF-causing mutations. Apart from F508del, the most frequent severe CF-causing mutation, over 1600 mutations have been identified with …
Published: 2010

231. Geographic variations of multiple sclerosis in France

Author: Marc Debouverie, Erik Sauleau, Agnès Fromont, Laurence Clerc, Sandra Vukusic, Johan Adnet, Alain Weill, Christian Confavreux, Christine Binquet, Thibault Moreau, Isabelle Fournel, Audrey Bellisario, and Claire Bonithon-Kopp
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Adolescent, National Health Programs, Cross-sectional study, Population, Health insurance system, Young Adult, Epidemiology, medicine, Humans, education, Child, education.field_of_study, High prevalence, Multiple sclerosis, Incidence (epidemiology), Infant, Bayes Theorem, Middle Aged, medicine.disease, Geography, Cross-Sectional Studies, Child, Preschool, Lower prevalence, Female, Neurology (clinical), France, Demography
Abstract: France is located in an area with a medium to high prevalence of multiple sclerosis, where its epidemiology is not well known. We estimated the national and regional prevalence of multiple sclerosis in France on 31 October 2004 and the incidence between 31 October 2003 and 31 October 2004 based on data from the main French health insurance system: the Caisse Nationale d'Assurance Maladie des Travailleurs Salaries. The Caisse Nationale d'Assurance Maladie des Travailleurs Salaries insures 87% of the French population. We analysed geographic variations in the prevalence and incidence of multiple sclerosis in France using the Bayesian approach. On the 31 October 2004, 49 417 people were registered with multiple sclerosis out of the 52 359 912 insured with the Caisse Nationale d'Assurance Maladie des Travailleurs Salaries. Among these, 4497 were new multiple sclerosis cases declared between 31 October 2003 and 31 October 2004. After standardization for age, total multiple sclerosis prevalence in France was 94.7 per 100,000 (94.3-95.1); 130.5 (129.8-131.2) in females and 54.8 (54.4-55.3) in males. The national incidence of multiple sclerosis between 31 October 2003 and 31 October 2004 was 7.5 per 100,000 (7.3-7.6); 10.4 (10.2-10.6) in females and 4.2 (4.0-4.3) in males. The prevalence and incidence of multiple sclerosis were higher in North-Eastern France, but there was no obvious North-South gradient. This study is the first performed among a representative population of France (87%) using the same method throughout. The Bayesian approach, which takes into account spatial heterogeneity among geographical units and spatial autocorrelation, did not confirm the existence of a prevalence gradient but only a higher prevalence of multiple sclerosis in North-Eastern France and a lower prevalence of multiple sclerosis in the Paris area and on the Mediterranean coast.
Published: 2010

232. Flexible modeling of the effects of continuous prognostic factors in relative survival

Author: Claire Bonithon-Kopp, Roch Giorgi, Catherine Quantin, Michal Abrahamowicz, Christine Binquet, and Amel Mahboubi
Subjects: Statistics and Probability, Polynomial regression, Hazard (logic), Multivariate adaptive regression splines, Relative survival, Logarithm, Epidemiology, Multivariable calculus, Hazard ratio, Survival Analysis, Data Interpretation, Statistical, Statistics, Covariate, Econometrics, Humans, Computer Simulation, Colorectal Neoplasms, Mathematics, Proportional Hazards Models
Abstract: Relative survival methods permit separating the effects of prognostic factors on disease-related 'excess mortality' from their effects on other-causes 'natural mortality', even when individual causes of death are unknown. As in conventional 'crude' survival, accurate assessment of prognostic factors requires testing and possibly modeling of non-proportional effects and, for continuous covariates, of non-linear relationships with the hazard. We propose a flexible extension of the additive-hazards relative survival model, in which the observed all-causes mortality hazard is represented by a sum of disease-related 'excess' and natural mortality hazards. In our flexible model, the three functions representing (i) the baseline hazard for 'excess' mortality, (ii) the time-dependent effects, and (iii) for continuous covariates, non-linear effects, on the logarithm of this hazard, are all modeled by low-dimension cubic regression splines. Non-parametric likelihood ratio tests are proposed to test the time-dependent and non-linear effects. The accuracy of the estimated functions is evaluated in multivariable simulations. To illustrate the new insights offered by the proposed model, we apply it to re-assess the effects of patient age and of secular trends on disease-related mortality in colon cancer.
Published: 2010

233. Risk factors and causes of death in MEN1 disease. A GTE (Groupe d'Etude des Tumeurs Endocrines) cohort study among 758 patients

Author: Philippe Ruszniewski, Alfred Beckers, Fabrice Menegaux, Annie Costa, Antoine Tabarin, Brigitte Delemer, Pierre Goudet, Christine Cardot-Bauters, Claire Bonithon-Kopp, Patricia Niccoli, Françoise Borson-Chazot, Arnaud Murat, Christine Binquet, Philippe Bouchard, and Georges Chabrier
Subjects: Oncology, Adult, Diagnostic Imaging, Male, medicine.medical_specialty, endocrine system diseases, Lower risk, Belgium, Risk Factors, Internal medicine, Cause of Death, medicine, Multiple Endocrine Neoplasia Type 1, Humans, Family history, Risk factor, Multiple endocrine neoplasia, Survival analysis, Cause of death, Proportional Hazards Models, Chi-Square Distribution, business.industry, Hazard ratio, Pituitary tumors, Middle Aged, medicine.disease, Prognosis, Survival Analysis, Surgery, Female, France, business, Follow-Up Studies
Abstract: The natural history of multiple endocrine neoplasia type 1 (MEN1) is known through single-institution or single-family studies. We aimed to analyze the risk factors and causes of death in a large cohort of MEN1 patients. Overall, 758 symptomatic MEN1 patients were identified through the GTE network (Groupe d’etude des Tumeurs Endocrines), which involves French and Belgian genetics laboratories responsible for MEN1 diagnosis and 80 clinical reference centers. The causes of death were analyzed. A frailty model, including time-dependent variables, was used to assess the impact of each clinical lesion, except for hyperparathyroidism, on survival. The median follow-up was 6.3 years. Female gender, family history of MEN1, and recent diagnosis were associated with a lower risk of death. Compared with nonaffected patients, those with thymic tumors (hazard ratio [HR] = 4.64, 95% CI = 1.73-12.41), glucagonomas–vipomas–somatostatinomas (HR = 4.29, 95% CI = 1.54-11.93), nonfunctioning pancreatic tumors (HR = 3.43, 95% CI = 1.71-6.88), and gastrinoma (HR = 1.89, 95% CI = 1.09-3.25) had a higher risk of death after adjustment for age, gender, and diagnosis period. The increased risk of death among patients with adrenal tumors was not significant, but three patients died from aggressive adrenal tumors. Pituitary tumors, insulinomas, and bronchial tumors did not increase the risk of death. The proportion of MEN1-related deaths decreased from 76.8 to 71.4% after 1990. The prognosis of MEN1 disease has improved since 1980. Thymic tumors and duodenopancreatic tumors, including nonsecreting pancreatic tumors, increased the risk of death. Rare but aggressive adrenal tumors may also cause death. Most deaths were related to MEN1. New recommendations on abdominal and thoracic imaging are required.
Published: 2009

234. The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening

Author: Brigitte Simon-Bouy, Georges, Bénédicte Gérard, Harriet Corvol, Emmanuelle Girodon, Raphaele Nove-Josserand, Catherine Costa, Michael A. Morris, Delphine Feldmann, Annick Clement, G. Bellis, Sylvie Leroy, Christine Binquet, J. Leclerc, A Iron, Laurence Faivre, M Roussey, Anne Munck, Mireille Claustres, F. Huet, Elodie Gautier, Claire Bonithon-Kopp, E. Houssin, Emmanuelle Génin, Isabelle Sermet-Gaudelus, S. Perez-Martin, Eric Bieth, Pierre Boisseau, Cabet-Bey F, Christine Clavel, J. Flori, Dominique Hubert, N. Wizla, Marie-Pierre Audrézet, Gabriel Bellon, A. Haloun, Guy Lalau, d'Acremont G, T Bienvenu, Christel Thauvin-Robinet, Gilles Rault, C. Alberti-Boulmé, Claude Férec, Michel Goossens, and R. Medina
Subjects: medicine.medical_specialty, Heterozygote, Cystic Fibrosis, Genetic counseling, Population, FRANCE, Cystic Fibrosis Transmembrane Conductance Regulator, Genetic Counseling, Penetrance, Kaplan-Meier Estimate, Compound heterozygosity, Cystic fibrosis, Gastroenterology, Neonatal Screening, Internal medicine, CYSTIC_FIBROSIS, Genotype, Genetics, Medicine, Humans, Allele, education, Genetics (clinical), Newborn screening, education.field_of_study, business.industry, Infant, Newborn, medicine.disease, SCREENING, Cross-Sectional Studies, Phenotype, Mutation, business
Abstract: Background: Cystic fibrosis (CF) is caused by compound heterozygosity or homozygosity of CF transmembrane conductance regulator gene (CFTR) mutations. Phenotypic variability associated with certain mutations makes genetic counselling difficult, notably for R117H, whose disease phenotype varies from asymptomatic to classical CF. The high frequency of R117H observed in CF newborn screening has also introduced diagnostic dilemmas. The aim of this study was to evaluate the disease penetrance for R117H in order to improve clinical practice. Methods: The phenotypes in all individuals identified in France as compound heterozygous for R117H and F508del, the most frequent CF mutation, were described. The allelic prevalences of R117H (p R117H), on either intron 8 T5 or T7 background, and F508del (p F508del) were determined in the French population, to permit an evaluation of the penetrance of CF for the [R117H]+[F508del] genotype. Results: Clinical details were documented for 184 [R117H]+[F508del] individuals, including 72 newborns. The disease phenotype was predominantly mild; one child had classical CF, and three adults' severe pulmonary symptoms. In 5245 healthy adults, p F508del was 1.06%, p R117H;T7 0.27% and p R117H;T5 ,0.01%. The theoretical number of [R117H;T7]+[F508del] individuals in the French population was estimated at 3650, whereas only 112 were known with CF related symptoms (3.1%). The penetrance of classical CF for [R117H;T7]+[F508del] was estimated at 0.03% and that of severe CF in adulthood at 0.06%. Conclusions: These results suggest that R117H should be withdrawn from CF mutation panels used for screening programmes. The real impact of so-called disease mutations should be assessed before including them in newborn or preconceptional carrier screening programmes .
Published: 2009

235. Estimating the cost related to surveillance of colorectal cancer in a French population

Author: Christine Binquet, Maria Raikou, Thierry Moreau, Michal Abrahamowicz, Franck Bonnetain, Claire Bonithon-Kopp, Amel Mahboubi, Catherine Lejeune, Laurent Bedenne, Catherine Quantin, Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Department of Epidemiology, Biostatistics and Occupational Health [Montréal], McGill University = Université McGill [Montréal, Canada], Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), London School of Economics and Political Science (LSE), This work has been funded by a SNFGE grants (Société Nationale Française de Gastroentérologie)., Lipides - Nutrition - Cancer (U866) ( LNC ), 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Department of Epidemiology and Biostatistics, McGill University, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), London School of Economics and Political Science ( LSE ), 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), and Autard, Delphine
Subjects: Male, economic evaluation, MESH: Registries, Colorectal cancer, Economics, Econometrics and Finance (miscellaneous), MESH : Aged, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH : Costs and Cost Analysis, MESH : Population Surveillance, Mass Screening, MESH : Female, Registries, health care economics and organizations, MESH: Aged, education.field_of_study, MESH: Middle Aged, Health Policy, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Population Surveillance, Costs and Cost Analysis, surveillance, 030211 gastroenterology & hepatology, Female, MESH : Colorectal Neoplasms, France, Colorectal Neoplasms, medicine.medical_specialty, recurrence, Abdominal ultrasound, MESH : Male, cost prediction, Population, colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Costs and Cost Analysis, Article, MESH: Population Surveillance, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, MESH : Middle Aged, MESH: Mass Screening, MESH : France, education, Mass screening, Aged, MESH : Mass Screening, Estimation, Health economics, MESH: Humans, business.industry, Public health, MESH : Humans, medicine.disease, MESH: Male, Surgery, MESH: France, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Economic evaluation, Emergency medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, MESH : Registries, MESH: Colorectal Neoplasms
Abstract: International audience; Little is known about costs related to the surveillance of patients that have undergone curative resection of colorectal cancer. The aim of this study was to calculate the observed surveillance costs for 385 patients followed-up over a 3-year period, to estimate surveillance costs if French guidelines are respected, and to identify the determinants related to surveillance costs to derive a global estimation for France, using a linear mixed model. The observed mean surveillance cost was 713. If French recommendations were strictly applied, the estimated mean cost would vary between 680 and 1,069 according to the frequency of abdominal ultrasound. The predicted determinants of cost were: age, recurrence, duration of surveillance since diagnosis, and adjuvant treatments. For France, the surveillance cost represented 4.4% of the cost of colorectal cancer management. The cost of surveillance should now be balanced with its effectiveness and compared with surveillance alternatives.
Published: 2009

236. Contribution of record linkage to vital status determination in cancer patients

Author: Isabelle, Fournel, Michaël, Schwarzinger, Christine, Binquet, Eric, Benzenine, Catherine, Hill, and Catherine, Quantin
Subjects: Information Management, Health Status, Neoplasms, Humans, France, Medical Record Linkage
Abstract: To assess the performance of vital status determination by record linkage between a hospital database and the French national mortality database with anonymised data in order to adhere to French legislation. Hospital database of the Institut Gustave Roussy (IGR), the largest cancer centre in France, and the French mortality databases from 1998-2004 were used for this record linkage. A phonetic code adapted to French language was first applied to identifiers. The last name, maiden name, all first names and the date of birth were then each rendered anonymous using irreversible hash coding. Record linkage, using the probabilistic method developed by Jaro, was based on four fields: the last name, first given name, date of birth and code of birth place. Other variables were used for further automatic and manual validation. Linkage results were very satisfactory for the 10,089 patients included: sensitivity was 94.8% and specificity 99.5%. The positive and negative likelihood ratios were respectively 190 and 0.05. The main causes of discordances were erroneous or incomplete information such as unrecorded maiden name in the hospital database. Results were improved by adding manual validation to electronic matching: sensitivity rose to 97.2% and specificity to 99.4%. Record linkage using anonymised data applied to large scale hospital data is possible and has good validity. This method offers new prospects for large prognostic studies based on hospital data provided that the diagnosis date is systematically recorded in the hospital database.
Published: 2009

237. Pathogenic FBN1 mutations in 146 adults not meeting clinical diagnostic criteria for Marfan syndrome: further delineation of type 1 fibrillinopathies and focus on patients with an isolated major criterion

Author: Bert Callewaert, A. De Paepe, Mireille Claustres, Laurence Faivre, Lesley C. Adès, Anne H. Child, Eloisa Arbustini, O Bouchot, Uta Francke, P. Comeglio, A. Kiotsekoglou, Maurizia Grasso, Christophe Béroud, Peter N. Robinson, Guillaume Jondeau, Mine Arslan-Kirchner, Claire Bonithon-Kopp, J. De Backer, Gwenaëlle Collod-Béroud, Elodie Gautier, Bart Loeys, Christine Binquet, Catherine Boileau, Paul Coucke, Chantal Stheneur, Kenneth H. Mayer, Jean-Eric Wolf, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Center for Medical Genetics [Ghent], Ghent University Hospital, Department of Cardiological Sciences, St George's Hospital, Institute of Genetic Medicine and the Howard Hugues Medical Institute, Johns Hopkins University School of Medicine, Centre for Inherited Cardiovacular Diseases, Foundation IRCCS Policlinico San Matteo, Center for Human Genetics and Laboratory Medicine, Center of Human Genetics and Laboratory Medicine, Institut für Humagenetik, Hannover Medical School [Hannover] (MHH)-Institut für Humagenetik, Service de pédiatrie, urgences enfants [CHU Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré [AP-HP], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de chirurgie cardio-vasculaire, Institut für Medizinische Genetik, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Discipline of Paediatrics and Child Health, The University of Sydney, Marfan Research Group, Westmead Hospital [Sydney], Department of Clinical Genetics, Department of Genetics and Pediatrics, Stanford University [Stanford], Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bichat, Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], Service de cardiologie, Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), 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 de Montpellier (UM), Service d'Ophtalmologie (CHU de Dijon), Laboratoire de géographie physique : Environnements Quaternaires et Actuels (LGP), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut für Physik, Humboldt-Universität zu Berlin, Newtonstr. 15, D-12489 Berlin, Germany, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital du Bocage, Karlsruhe Institute of Technology (KIT), Apoptose, cancer et immunité (U848), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), 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)-Hôpital Bichat, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), 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 ), Université de Montpellier ( UM ), Laboratoire de géographie physique ( LGP ), Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Centre National de la Recherche Scientifique ( CNRS ), Groupe Appl. Phys. ( GAP ), GAP, Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), 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 ), Institut de génétique humaine ( IGH ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Karlsruhe Institute of Technology ( KIT ), Apoptose, cancer et immunité ( U848 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bichat, Humboldt University Of Berlin, Hannover Medical School [Hannover] ( MHH ) -Institut für Humagenetik, Service de pédiatrie, urgences enfants, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, UFR Paris-Ile-de-France-Ouest (PIFO), Universitätsmedizin Charité, The University of Sydney [Sydney], The Children's Hospital at Westmead, Service de biochimie, d'hormonologie et de génétique moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), and COLLOD-BEROUD, Gwenaëlle
Subjects: Marfan syndrome, Nosology, Adult, Male, Pediatrics, medicine.medical_specialty, Systemic disease, Fibrillin-1, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease_cause, Fibrillins, Ectopia Lentis, Marfan Syndrome, Cohort Studies, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Genetics, medicine, Missense mutation, Humans, Ectopia lentis, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Mutation, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, 030305 genetics & heredity, Microfilament Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine.disease, Connective tissue disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Phenotype, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Cohort, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, business
Abstract: International audience; Mutations in the FBN1 gene cause Marfan syndrome (MFS) and have been associated with a wide range of milder overlapping phenotypes. A proportion of patients carrying a FBN1 mutation does not meet diagnostic criteria for MFS, and are diagnosed with "other type I fibrillinopathy." In order to better describe this entity, we analyzed a subgroup of 146 out of 689 adult propositi with incomplete "clinical" international criteria (Ghent nosology) from a large collaborative international study including 1,009 propositi with a pathogenic FBN1 mutation. We focused on patients with only one major clinical criterion, [including isolated ectopia lentis (EL; 12 patients), isolated ascending aortic dilatation (17 patients), and isolated major skeletal manifestations (1 patient)] or with no major criterion but only minor criteria in 1 or more organ systems (16 patients). At least one component of the Ghent nosology, insufficient alone to make a minor criterion, was found in the majority of patients with isolated ascending aortic dilatation and isolated EL. In patients with isolated EL, missense mutations involving a cysteine were predominant, mutations in exons 24-32 were underrepresented, and no mutations leading to a premature truncation were found. Studies of recurrent mutations and affected family members of propositi with only one major clinical criterion argue for a clinical continuum between such phenotypes and classical MFS. Using strict definitions, we conclude that patients with FBN1 mutation and only one major clinical criterion or with only minor clinical criteria of one or more organ system do exist but represent only 5% of the adult cohort.
Published: 2009

238. Clinical and mutation-type analysis from an international series of 198 probands with a pathogenic FBN1 exons 24-32 mutation

Author: Mine Arslan-Kirchner, Eloisa Arbustini, A. De Paepe, Paul Coucke, Jean-Eric Wolf, O Bouchot, Bart Loeys, P Khau-Van-Kien, Chantal Stheneur, Peter N. Robinson, Elodie Gautier, Nicola Marziliano, Bert Callewaert, Karin Mayer, Christophe Béroud, P Comeglio, Mireille Claustres, A Kiotsekoglou, Claire Bonithon-Kopp, Laurence Faivre, Lesley C. Adès, Guillaume Jondeau, Anne H. Child, Gwenaëlle Collod-Béroud, Catherine Boileau, Uta Francke, J. De Backer, Christine Binquet, 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), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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), Center for Medical Genetics [Ghent], Ghent University Hospital, Department of Cardiological Sciences, St George's Hospital, Institute of Genetic Medicine and the Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Centre for Inherited Cardiovacular Diseases, Foundation IRCCS Policlinico San Matteo, Center for Human Genetics and Laboratory Medicine, Center of Human Genetics and Laboratory Medicine, Institut für Humagenetik, Hannover Medical School [Hannover] (MHH)-Institut für Humagenetik, Service de pédiatrie, urgences enfants [CHU Ambroise-Paré], Hôpital Ambroise Paré [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Service de Cardiologie [CHU de Dijon], Service de chirurgie cardio-vasculaire, Institut für Medizinische Genetik, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Discipline of Paediatrics and Child Health, The University of Sydney, Marfan Research Group, Westmead Hospital [Sydney], Department of Clinical Genetics, Department of Genetics [Stanford], Stanford Medicine, Stanford University-Stanford University, Centre de reference national pour le syndrome de Marfan et apparentés, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), This study was supported by a grant from the French ministry of health (PHRC 2004), GIS maladies rares 2004, Bourse de la Société Francaise de Cardiologie, Fédération Franc¸aise de Cardiologie 2005 and ANR-05-PCOD-014. BC and BL are respectively a research fellow and a senior clinical investigator of the Fund for Scientific Research – Flanders. AC and PC thank the Marfan Trust and the Bluff Field Charitable Fund for support., HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Service de chirurgie cardio-vasculaire et thoracique (CHU Dijon), COLLOD-BEROUD, Gwenaëlle, 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), 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), Centre for Medical Genetics, Hannover Medical School [Hannover] (MHH) - Institut für Humagenetik, Service de pédiatrie, urgences enfants, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Ambroise Paré, Laboratoire Electronique, Informatique et Image (Le2i), Centre National de la Recherche Scientifique (CNRS) - Université de Bourgogne (UB) - AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service de Cardiologie II, Centre Hospitalier Universitaire, Laboratoire de Génétique Moléculaire, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier) - Hôpital Arnaud de Villeneuve, Universitätsmedizin Charité, The University of Sydney [Sydney], The Children's Hospital at Westmead, Department of Genetics and Pediatrics, Stanford University [Stanford], Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bichat - Claude Bernard [Paris], Service de biochimie, d'hormonologie et de génétique moléculaire, Handicaps génétiques de l'enfant, Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), UFR P.I.F.O, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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 ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Hannover Medical School [Hannover] ( MHH ) -Institut für Humagenetik, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Laboratoire Electronique, Informatique et Image ( Le2i ), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Arts et Métiers (ENSAM), and HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Subjects: Proband, Marfan syndrome, clinical and mutation-type analysis, congenital, hereditary, and neonatal diseases and abnormalities, Fibrillin-1, DNA Mutational Analysis, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, Fibrillins, Article, Ectopia Lentis, [SHS.INFO] Humanities and Social Sciences/Library and information sciences, Neonatal Marfan syndrome, 03 medical and health sciences, Exon, Genetics, medicine, Humans, Ectopia lentis, Gene, Genetics (clinical), 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Genetic heterogeneity, 030305 genetics & heredity, Microfilament Proteins, Exons, exons 24–32, medicine.disease, Phenotype, 3. Good health, Codon, Nonsense, Mutation (genetic algorithm), Mutation, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, FBN1 mutations
Abstract: International audience; Mutations in the FBN1 gene cause Marfan syndrome (MFS) and a wide range of overlapping phenotypes. The severe end of the spectrum is represented by neonatal MFS, the vast majority of probands carrying a mutation within exons 24-32. We previously showed that a mutation in exons 24-32 is predictive of a severe cardiovascular phenotype even in non-neonatal cases, and that mutations leading to premature truncation codons are under-represented in this region. To describe patients carrying a mutation in this so-called 'neonatal' region, we studied the clinical and molecular characteristics of 198 probands with a mutation in exons 24-32 from a series of 1013 probands with a FBN1 mutation (20%). When comparing patients with mutations leading to a premature termination codon (PTC) within exons 24-32 to patients with an in-frame mutation within the same region, a significantly higher probability of developing ectopia lentis and mitral insufficiency were found in the second group. Patients with a PTC within exons 24-32 rarely displayed a neonatal or severe MFS presentation. We also found a higher probability of neonatal presentations associated with exon 25 mutations, as well as a higher probability of cardiovascular manifestations. A high phenotypic heterogeneity could be described for recurrent mutations, ranging from neonatal to classical MFS phenotype. In conclusion, even if the exons 24-32 location appears as a major cause of the severity of the phenotype in patients with a mutation in this region, other factors such as the type of mutation or modifier genes might also be relevant.
Published: 2009

239. The FBN2 gene: new mutations, locus-specific database (Universal Mutation Database FBN2), and genotype-phenotype correlations

Author: Christine Binquet, Christine Monino, Laurence Faivre, Gwenaëlle Collod-Béroud, Dalil Hamroun, Guillaume Jondeau, Christophe Béroud, Luitgard M. Neumann, Prateek Gupta, Catherine Boileau, Mireille Claustres, Dianna M. Milewicz, Elodie Gautier, Maurice Godfrey, Christoph Marschall, Hanns Georg Klein, Cheryl L. Maslen, Mélissa Yana Frédéric, 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 ), Center for Human Genetics and Laboratory Medicine, Center of Human Genetics and Laboratory Medicine, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bichat, Hémostase, bio-ingénierie et remodelage cardiovasculaires ( LBPC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Galilée, Charité Campus Virchow-Klinikum (CVK), 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 ), Department of Molecular and Medical Genetics, Oregon Health and Science University, Center for Human Molecular Genetics, University of Nebraska Omaha, Department of Internal Medicine and Neurosurgery, The University of Texas Medical School, Service de biochimie, d'hormonologie et de génétique moléculaire, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, UFR Paris-Ile-de-France-Ouest (PIFO), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Montpellier 1, INSERM, GIS-Institut des Maladies Rares 2004, Contract grant sponsor: Association Française contre les Myopathies (AFM), Grant number: AFM-R07017FF, Contract grant sponsor: Agence Nationale pour la Recherche (ANR), Grant number: ANR-05PCOD-14-02., 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), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Oregon Health and Science University [Portland] (OHSU), University of Nebraska System-University of Nebraska System, Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), COLLOD-BEROUD, Gwenaëlle, 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 Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, and University of Nebraska [Omaha]
Subjects: Fibrillin-2, MESH : Polymorphism, Genetic, Fibrillin-1, DNA Mutational Analysis, MESH : Genotype, [SDV.GEN] Life Sciences [q-bio]/Genetics, computer.software_genre, MESH: Genotype, 0302 clinical medicine, Genotype, Databases, Genetic, Missense mutation, Congenital contractural arachnodactyly, MESH: DNA Mutational Analysis, Genetics (clinical), MESH: Databases, Genetic, Regulation of gene expression, Genetics, 0303 health sciences, Database, MESH : Gene Expression Regulation, Microfilament Proteins, Phenotype, MESH: Gene Expression Regulation, Beals-Hecht syndrome, 3. Good health, INC, MESH : Phenotype, MESH : Mutation, Fibrillin, musculoskeletal diseases, MESH: Mutation, MESH : Microfilament Proteins, database OFFICIAL JOURNAL wwwhgvsorg & 2008 WILEY-LISS, Locus (genetics), fibrillin, MESH : DNA Mutational Analysis, Biology, Fibrillins, MESH: Phenotype, MESH: Sequence Homology, Nucleic Acid, congenital contractural arachnodactyly, 03 medical and health sciences, MESH: Microfilament Proteins, Sequence Homology, Nucleic Acid, MESH: Polymorphism, Genetic, medicine, Humans, MESH : Sequence Homology, Nucleic Acid, FBN2, CCA, MESH : Databases, Genetic, Gene, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Polymorphism, Genetic, MESH: Humans, MESH : Humans, medicine.disease, Gene Expression Regulation, Mutation, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, computer, 030217 neurology & neurosurgery
Abstract: International audience; Congenital contractural arachnodactyly (CCA) is an extremely rare disease, due to mutations in the FBN2 gene encoding fibrillin-2. Another member of the fibrillin family, the FBN1 gene, is involved in a broad phenotypic continuum of connective-tissue disorders including Marfan syndrome. Identifying not only what is in common but also what differentiates these two proteins should enable us to better comprehend their respective functions and better understand the multitude of diseases in which these two genes are involved. In 1995 we created a locus-specific database (LSDB) for FBN1 mutations with the Universal Mutation Database (UMD) tool. To facilitate comparison of identified mutations in these two genes and search for specific functional areas, we created an LSDB for the FBN2 gene: the UMD-FBN2 database. This database lists 26 published and six newly identified mutations that mainly comprise missense and splice-site mutations. Although the number of described FBN2 mutations was low, the frequency of joint dislocation was significantly higher with missense mutations when compared to splice site mutations.
Published: 2009

240. Markov modelling of HIV infection evolution in the HAART era

Author: Yazdan Yazdanpanah, Christine Binquet, Pascal Chavanet, J. Berger, David Rey, Amel Mahboubi, C. Chirouze, G. Le Teuff, J. P. Faller, Catherine Quantin, Lionel Piroth, M. Abrahamovicz, and C. Rabaud
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Adolescent, Epidemiology, HIV Infections, Young Adult, Pharmacotherapy, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Immunopathology, Antiretroviral Therapy, Highly Active, medicine, Humans, Protease inhibitor (pharmacology), Prospective Studies, Sida, Substance Abuse, Intravenous, Reverse-transcriptase inhibitor, biology, business.industry, Middle Aged, Viral Load, medicine.disease, biology.organism_classification, Markov Chains, CD4 Lymphocyte Count, Infectious Diseases, Immunology, Cohort, Disease Progression, Female, business, medicine.drug
Abstract: SUMMARYThe aim was to investigate the impact of the main prognostic factors on HIV evolution. A multi-state Markov model was applied in a cohort of 2126 patients to estimate impact of these factors on patients' clinical and immunological evolutions. Clinical progression and immunological deterioration shared most of their prognostic factors: male gender, intravenous drug use, weight loss, low haemoglobin level (3) and HIV viral load (>5 log10copies/ml). Highly active retroviral therapy reduced the risks of clinical progression and immune deterioration whatever patients' CD4 cell count. Risk reductions were 41–60% for protease inhibitor-based and 27–68% for non-nucleoside reverse transcriptase inhibitor-based regimens. Three-year transition probabilities showed that only patients with a CD4 cell count ⩾350 CD4/mm3could in most cases maintain their immunity. This model provides ‘real life’ transition probabilities from one immunological stage to another, allowing decision analyses that could help determine the beneficial therapeutic strategies for HIV-infected patients.
Published: 2009

241. Clinical and molecular study of 320 children with Marfan syndrome and related type I fibrillinopathies in a series of 1009 probands with pathogenic FBN1 mutations

Author: Frédéric Huet, Peter N. Robinson, Guillaume Jondeau, Karin Mayer, Claire Bonithon-Kopp, Bertrand Chevallier, Uta Francke, Elodie Gautier, Laurence Faivre, Anne H. Child, Anatoli Kiotsekoglou, Christophe Béroud, Mireille Claustres, Bart Loeys, Maurizia Grasso, Gwenaëlle Collod-Béroud, Mine Arslan-Kirchner, Christine Binquet, Alice Masurel-Paulet, Catherine Boileau, Eloisa Arbustini, Julie De Backer, Anne De Paepe, Lesley C. Adès, Bert Callewaert, Dorothy Halliday, P Comeglio, Paul Coucke, Chantal Stheneur, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Medical Genetics [Ghent], Ghent University Hospital, Department of Cardiological Sciences, St George's Hospital, Service de pédiatrie, urgences enfants [CHU Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Howard Hughes Medical Institute (HHMI), Centre for Inherited Cardiovacular Diseases, Foundation IRCCS Policlinico San Matteo, Center for Human Genetics and Laboratory Medicine, Center of Human Genetics and Laboratory Medicine, Institut für Humagenetik, Hannover Medical School [Hannover] (MHH)-Institut für Humagenetik, Department of Biochemistry [Oxford], University of Oxford [Oxford], Institut für Medizinische Genetik, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Discipline of Paediatrics and Child Health, The University of Sydney, Marfan Research Group, Westmead Hospital [Sydney], Department of Clinical Genetics, Department of Genetics [Stanford], Stanford Medicine, Stanford University-Stanford University, Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, Service de cardiologie, Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by a grant from the French Ministry of Health (grant Programme Hospitalier de Recherche Clinique 2004), Groupement d’Intérêt Scientifique Maladies Rares 2004, Bourse de la Société Francaise de Cardiologie, Fédération Franc¸aise de Cardiologie 2005, and ANR-05-PCOD-014. Drs Callewaert and Loeys are a research fellow and a senior clinical investigator, respectively, of the Fund for Scientific ResearchFlanders. Drs Child and Comeglio thank the Marfan Trust and the Bluff Field Charitable Fund for support., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), COLLOD-BEROUD, Gwenaëlle, Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Oxford, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques ( CIC-EC ), Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), 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 ), Service de pédiatrie, urgences enfants, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Institute of Genetic Medicine and the Howard Hugues Medical Institute, Johns Hopkins University School of Medicine, Hannover Medical School [Hannover] ( MHH ) -Institut für Humagenetik, Universitätsmedizin Charité, The University of Sydney [Sydney], The Children's Hospital at Westmead, Department of Genetics and Pediatrics, Stanford University [Stanford], Service de biochimie, d'hormonologie et de génétique moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bichat, and Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 )
Subjects: Male, Proband, Marfan syndrome, Pediatrics, CI— confidence interval, Fibrillin-1, [SDV.GEN] Life Sciences [q-bio]/Genetics, 030204 cardiovascular system & hematology, MESH : Child, Preschool, PTC—premature termination codon, AAD—ascending aortic dilation, 0302 clinical medicine, MESH: Genetic Screening, MESH : Child, MESH: Child, Medicine, MESH : Female, Family history, Child, Ectopia lentis, Aortic dissection, education.field_of_study, Dural ectasia, Microfilament Proteins, MESH: Follow-Up Studies, Connective tissue disease, 3. Good health, MFS—Marfan syndrome, Child, Preschool, Female, MESH : Mutation, musculoskeletal diseases, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, MESH: Mutation, Adolescent, MESH : Microfilament Proteins, Abbreviations, MESH : Male, Population, Fibrillins, MESH: Marfan Syndrome, 03 medical and health sciences, MESH: Microfilament Proteins, MESH : Adolescent, Humans, Genetic Testing, FBN1, education, childhood, MESH : Genetic Screening, MESH: Adolescent, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH : Marfan Syndrome, MESH: Humans, business.industry, MESH : Humans, MESH: Child, Preschool, MESH : Follow-Up Studies, medicine.disease, EL— ectopia lentis, MESH: Male, Surgery, Mutation, Pediatrics, Perinatology and Child Health, international criteria, business, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, MESH: Female, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: From a large series of 1009 probands with pathogenic FBN1 mutations, data for 320 patients
Published: 2009

242. [Follow-up of cancer treatment activities at the University Teaching Hospital in Dijon: the value of data from standardized discharge summaries]

Author: Monique, Titton, Christine, Binquet, Michèle, Vourc'h, Laurent, Martin, François, Girodon, and Catherine, Quantin
Subjects: Adult, Aged, 80 and over, Male, Adolescent, Middle Aged, Patient Discharge, Hospitals, University, Young Adult, Neoplasms, Hospital Information Systems, Humans, Female, France, Algorithms, Aged
Abstract: This work aimed to assess the feasibility of coalescing data sources to follow up on the management and delivery of cancer patient care using both anatomical-pathological data and a medical record information system based on the "Medicalisation of Information Systems Programme" which is administered by an independent source. The study group was comprised of all hospitalised cancer patients in the Dijon university teaching hospital during the first quarter of 2001. Data were obtained from a cross-analysis of medical records with pathological information and standard discharge files. A manual validation was then carried out to ensure a valid synthesis. Overall, 1377 abstracts were created and selected for cancer patients hospitalized for the first time. Among these, 60% were validated by the compatibility and concordance of data between the medical record discharge issued and the pathological record, less than 5% were identified only through looking at the anatomical-pathological data in the medical record, and 24% identified by exploring the patient discharge forms. These results demonstrate the difficulty and challenge as well as the benefits of crossing multiple sources of patient information and combine them to more thoroughly and appropriately assess the hospital's activity for caring for cancer patients.
Published: 2008

243. Dietary fatty acids and recurrence of colorectal adenomas in a European intervention trial

Author: Christine Binquet, Nicolas Methy, Jean Faivre, Marie-Christine Boutron-Ruault, Claire Bonithon-Kopp, and Bernard Paillot
Subjects: Adenoma, Adult, Male, Cancer Research, medicine.medical_specialty, Colorectal cancer, Linoleic acid, Medicine (miscellaneous), Colorectal adenoma, Gastroenterology, Linoleic Acid, chemistry.chemical_compound, Risk Factors, Internal medicine, Surveys and Questionnaires, Epidemiology, medicine, Odds Ratio, Humans, Aged, chemistry.chemical_classification, Nutrition and Dietetics, business.industry, Fatty Acids, Odds ratio, Middle Aged, medicine.disease, Dietary Fats, Diet, Europe, Oleic acid, Oncology, chemistry, Fatty Acids, Unsaturated, Female, Neoplasm Recurrence, Local, business, Colorectal Neoplasms, Polyunsaturated fatty acid
Abstract: Epidemiological studies have provided inconsistent data about the role of dietary fatty acids in colorectal cancer, and few studies have addressed their role in colorectal adenoma. The aim of the study was to assess the risk of overall adenoma recurrence associated with dietary consumption of total fat, subtypes of fat, and specific fatty acids (oleic acid, linoleic acid, alpha-linolenic acid). The study sample was composed of 523 patients with confirmed adenomas at the index colonoscopy, 35 to 75 yr old, who completed the European fiber-calcium intervention trial and had an initial dietary assessment using a qualitative and quantitative food questionnaire. The overall 3-yr recurrence rate was 22.6% (118 out of 523 patients). There were no significant associations between overall adenoma recurrence and either total fat, subtypes of fat, or specific fatty acids. However, polyunsaturated fatty acids and linoleic acid were both moderately but significantly associated with distal and multiple recurrence. No significant associations were observed with recurrence of proximal or advanced adenomas. Our findings do not support the hypothesis of strong associations between dietary fatty acids and recurrence of colorectal adenomas. The hypothesis of a differential role of specific fatty acids according to colorectal subsites deserves further investigation.
Published: 2008

244. Occult hepatitis B in HIV-HCV coinfected patients

Author: Lionel Piroth, Marie-Edith Lafon, Christine Binquet, Pascale Bertillon, Anne Gervais, Enguerrand Lootvoet, Jean-Marie Lang, Jean Pierre De Jaureguiberry, Geneviève Chene, Catherine Leport, and null The Anrs Co8 Aproco-Copilote Study
Subjects: Microbiology (medical), Adult, Male, Hepatitis B virus, Hepacivirus, Hepatitis C virus, HIV Infections, medicine.disease_cause, Polymerase Chain Reaction, Statistics, Nonparametric, Cohort Studies, Flaviviridae, Medicine, Humans, Hepatitis B Antibodies, General Immunology and Microbiology, biology, business.industry, virus diseases, Lamivudine, General Medicine, Hepatitis B, Hepatitis C Antibodies, biology.organism_classification, medicine.disease, Virology, Hepatitis C, digestive system diseases, CD4 Lymphocyte Count, Infectious Diseases, DNA, Viral, biology.protein, Female, Viral disease, Antibody, business, Viral load, medicine.drug
Abstract: The prevalence of occult hepatitis B infection in HIV infected patients is controversial, varying from less than 1% to 62% in different studies. Blood samples of 111 HIV-infected patients, HCV-positive, HBs antigen negative, followed in the APROCO-ANRS EP11 cohort, were used to detect HBV DNA by using 2 different validated assays (Cobas Amplicor HBV Monitor Test and INSERM U271 qualitative ultra-sensitive PCR), completed when positive by HBV real-time PCR. HBV DNA was found in 6 (5.4%, 95% CI 1.2%-9.6%) patients by at least 1 of these assays, but none tested positive in all 3 assays. All 6 patients had anti-HBc without anti-HBs antibodies; 5 were not on lamivudine. Their median CD4 and CD8 counts were significantly lower and their HIV viral load higher than in the other 105 patients. In conclusion, the prevalence of occult hepatitis B may vary significantly according to the molecular assay used, even though these assays are validated with high specificity and quite high sensitivity. Occult hepatitis B may be encountered in HIV-HCV coinfected patients without anti-HBV treatment, with anti-HBc but without anti-HBs antibodies, and relatively low immunity, suggesting a potential risk of further reactivation, as already sporadically reported.
Published: 2008

245. Contribution of molecular analyses in diagnosing Marfan syndrome and type I fibrillinopathies: an international study of 1009 probands

Author: Guillaume Jondeau, Mine Arslan-Kirchner, Christophe Béroud, Peter N. Robinson, Christine Binquet, Anne H. Child, J. De Backer, Paul Coucke, Eloisa Arbustini, Gwenaëlle Collod-Béroud, Elodie Gautier, Chantal Stheneur, Laurence Faivre, Mireille Claustres, Karin Mayer, Claire Bonithon-Kopp, H. Plauchu, Uta Francke, Catherine Boileau, A De Paepe, A Kiotsekoglou, Lesley C. Adès, Bart Loeys, Nicola Marziliano, Bert Callewaert, P Comeglio, Dorothy Halliday, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Department of Cardiological Sciences, St George's Hospital, Center for Medical Genetics [Ghent], Ghent University Hospital, Institute of Genetic Medicine and the Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Centre for Inherited Cardiovacular Diseases, Foundation IRCCS Policlinico San Matteo, Center for Human Genetics and Laboratory Medicine, Center of Human Genetics and Laboratory Medicine, Institut für Humagenetik, Hannover Medical School [Hannover] (MHH)-Institut für Humagenetik, Service de pédiatrie, urgences enfants [CHU Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, Department of Biochemistry [Oxford], University of Oxford [Oxford], Service de Génétique, Hôtel Dieu, Institut für Medizinische Genetik, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Marfan Research Group, Westmead Hospital [Sydney], Department of Clinical Genetics, Discipline of Paediatrics and Child Health, The University of Sydney, Department of Genetics [Stanford], Stanford Medicine, Stanford University-Stanford University, Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], This work was supported by a grant from the French ministry of health (PHRC 2004), GIS maladies rares 2004, Bourse de la Socie´te´ Francaise de Cardiologie, Fédération Franc¸aise de Cardiologie 2005, and ANR-05-PCOD-014. BC and BL are respectively a research fellow and a senior clinical investigator of the Fund for Scientific Research – Flanders. AC and PC thank the Marfan Trust, and the Bluff Field Charitable Fund for support., COLLOD-BEROUD, Gwenaëlle, University of Oxford, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques ( CIC-EC ), Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), 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 ), Hannover Medical School [Hannover] ( MHH ) -Institut für Humagenetik, Service de pédiatrie, urgences enfants, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bichat, Universitätsmedizin Charité, The Children's Hospital at Westmead, The University of Sydney [Sydney], Department of Genetics and Pediatrics, Stanford University [Stanford], and Service de biochimie, d'hormonologie et de génétique moléculaire
Subjects: Proband, Nosology, Marfan syndrome, Male, Pediatrics, Systemic disease, MESH : International Cooperation, Fibrillin-1, International Cooperation, MESH : Aged, [SDV.GEN] Life Sciences [q-bio]/Genetics, Marfan Syndrome, MESH : Child, MESH: Child, Epidemiology, MESH : Female, Ectopia lentis, Child, Genetics (clinical), Aorta, Aortic dissection, MESH: Aged, 0303 health sciences, 030305 genetics & heredity, Microfilament Proteins, MESH: Aorta, MESH : Adult, Connective tissue disease, 3. Good health, Female, MESH : Mutation, musculoskeletal diseases, Adult, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, MESH: Mutation, MESH : Microfilament Proteins, Adolescent, MESH : Male, Fibrillins, MESH: Marfan Syndrome, 03 medical and health sciences, MESH: Microfilament Proteins, MESH : Adolescent, Genetics, medicine, Humans, 030304 developmental biology, Aged, MESH: Adolescent, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH : Marfan Syndrome, MESH: Humans, business.industry, MESH : Humans, MESH : Aorta, MESH: Adult, medicine.disease, MESH: Male, MESH: International Cooperation, Mutation, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, business, MESH: Female
Abstract: International audience; BACKGROUND: The diagnosis of Marfan syndrome (MFS) is usually initially based on clinical criteria according to the number of major and minor systems affected following international nosology. The number of FBN1 mutation carriers, at risk of aortic complications who would not be properly diagnosed based only on clinical grounds, is of growing importance owing to the increased availability of molecular screening. The aim of the study was to identify patients who should be considered for FBN1 mutation screening. METHODS: Our international series included 1009 probands with a known FBN1 mutation. Patients were classified as either fulfilling or not fulfilling "clinical" criteria. In patients with unfulfilled "clinical" criteria, we evaluated the percentage of additional patients who became positive for international criteria when the FBN1 mutation was considered. The aortic risk was evaluated and compared in patients fulfilling or not fulfilling the "clinical" international criteria. RESULTS: Diagnosis of MFS was possible on clinical grounds in 79% of the adults, whereas 90% fulfilled the international criteria when including the FBN1 mutation. Corresponding figures for children were 56% and 85%, respectively. Aortic dilatation occurred later in adults with unfulfilled "clinical criteria" when compared to the Marfan syndrome group (44% vs 73% at 40 years, p
Published: 2008

246. Flexible statistical models provided new insights into the role of quantitative prognostic factors for mortality in gastric cancer

Author: Claire Bonithon-Kopp, Jean Faivre, Christine Binquet, Michal Abrahamowicz, Catherine Quantin, and K. Astruc
Subjects: Oncology, Male, medicine.medical_specialty, Epidemiology, Population, Stomach Neoplasms, Internal medicine, medicine, Humans, Prospective Studies, education, Stomach cancer, Prospective cohort study, Survival analysis, Aged, Neoplasm Staging, Proportional Hazards Models, education.field_of_study, Models, Statistical, business.industry, Proportional hazards model, Age Factors, Cancer, Middle Aged, medicine.disease, Prognosis, Survival Analysis, Cohort, Female, France, business, Demography
Abstract: Objectives To reassess the effects of prognostic factors on mortality in gastric cancers, and to illustrate the advantages of flexible modeling. Study Design and Setting A prospective population-based cohort of persons diagnosed with gastric cancers in 1976 to 1995 in Burgundy, France, was followed for 5 years since diagnosis. Multivariable survival analyses, stratified by cancer stage, involved both conventional Cox's model and its flexible generalization, which permitted testing the underlying assumptions and accounting for changes over time in the effects of prognostic factors. Results Conventional assumptions of proportional hazards (PH) (P = 0.003) and linear increase in risk with increasing age (P = 0.003) were rejected for age at cancer diagnosis in patients with less advanced (stage I/II) gastric cancers. Flexible modeling revealed that: (1) the effect of age was important mostly in the first year after diagnosis; and (2) mortality increased both for the youngest and the oldest patients. In conventional analyses, calendar year of diagnosis had no association with mortality in stage I/II cancers (P = 0.37). In contrast, flexible analyses indicated a statistically significant reduction in early, mostly postsurgical, mortality between early 1970s and 1980s. Conclusion Flexible modeling and testing conventional assumptions may yield new insights in prognostic studies of cancer mortality.
Published: 2007

247. Diagnostic accuracy of inflammatory markers as early predictors of infection after elective colorectal surgery: results from the IMACORS study

Author: Patrick Rat, Olivier Facy, Christine Binquet, Brice Paquette, David Orry, and Pablo Ortega-Deballon
Subjects: medicine.medical_specialty, business.industry, General surgery, medicine, Surgery, Diagnostic accuracy, business, Colorectal surgery
Published: 2015

248. Utilité de la procalcitonine et de la protéine C-réactive sériques pour le diagnostic des infections intra-abdominales après chirurgie colorectale programmée : une méta-analyse

Author: Valentina Giaccaglia, Abderrahmane Bourredjem, F. Cousin, Isabelle Fournel, Christine Binquet, and P. Ortega-Deballon
Subjects: Epidemiology, Public Health, Environmental and Occupational Health
Abstract: Introduction Les infections intra-abdominales representent les complications les plus frequentes et les plus graves en termes de morbi-mortalite apres chirurgie colorectale programmee, en raison notamment d’un diagnostic souvent trop tardif. Plusieurs marqueurs ont ete etudies dans la litterature pour predire leur apparition, en particulier la proteine C-reactive (CRP) et la procalcitonine (PCT), mais avec des resultats contradictoires. L’objectif de cette meta-analyse etait de comparer les capacites predictives de la CRP et de la PCT dans la survenue des infections intra-abdominales apres chirurgie colorectale programmee en tenant compte de l’ensemble des donnees publiees et de leur heterogeneite. Methodes Les bases de donnees bibliographiques Medline et Cochrane ont ete consultees afin d’identifier les etudes portant sur le dosage de la CRP et/ou PCT a j2 et/ou j3 et/ou j4 et/ou j5. Seules les etudes ayant comme critere de jugement les infections intra-abdominales apres chirurgie colorectale programmee ont ete retenues. La qualite methodologique a ete evaluee par l’outil QUADAS2. Pour chaque biomarqueur et a chaque temps, les estimations de la sensibilite et specificite obtenues dans les differentes etudes ont ete utilisees pour estimer la courbe ROC resumee (SROC) et l’aire sous la courbe (AUC) correspondante. Le modele bivarie a effet aleatoire de DerSimonian and Laird a ete applique pour tenir compte de l’heterogeneite des estimations. L’analyse principale portait sur les valeurs de CRP et PCT obtenues a j4. Resultats Au total, 11 articles rassemblant 2692 patients ont ete inclus dans la meta-analyse. Sur l’ensemble des etudes, la frequence d’infections intra-abdominales etait de 9,6 %. A j4, la sensibilite variait entre 75 et 100 % et la specificite entre 60 et 76 % pour la CRP suivant les seuils choisis par les auteurs. Pour la PCT, la sensibilite variait entre 69 et 82 %, et la specificite entre 40 et 71 %. Il n’existait pas de difference significative entre CRP (AUC : 0,79 (IC 95 % [0,75–0,83]) et PCT (0,72 (IC 95 % [0,66–0,77]) a j4. Il n’existait pas non plus de differences significatives pour j2, j3 et j5. Conclusion Les resultats preliminaires suggerent que la PCT n’a pas une capacite predictive significativement superieure a la CRP pour les infections intra-abdominales apres chirurgie colorectale programmee. Avec un cout inferieur a la PCT, le dosage de la CRP a j4 pourrait etre privilegie pour predire les infections intra-abdominales.
Published: 2015

249. Are the recommendations of the French consensus conference on the management of colon cancer followed up?

Author: Vincent Dancourt, Olivier Coatmeur, Anne-Marie Bouvier, Jean Faivre, Christine Binquet, and Côme Lepage
Subjects: Male, Cancer Research, medicine.medical_specialty, Multivariate analysis, Health Planning Guidelines, Epidemiology, Colorectal cancer, Consensus Development Conferences as Topic, Population, Colonoscopy, Context (language use), Antineoplastic Agents, Medicine, Humans, Neoplasm Metastasis, education, Aged, Neoplasm Staging, Aged, 80 and over, education.field_of_study, Tumour node metastasis, medicine.diagnostic_test, business.industry, General surgery, Public Health, Environmental and Occupational Health, Consensus conference, Guideline, medicine.disease, Surgery, Oncology, Colonic Neoplasms, Female, France, Guideline Adherence, business, Follow-Up Studies
Abstract: The aim of this study was to determine how the guidelines published after this conference have spread. Pretherapeutic evaluation and treatment were assessed for all colon cancers diagnosed in a well-defined French population in 2000. Patients were classified either as managed according to the recommendations, or as undermanaged or overmanaged. Outside the emergency context, pretherapeutic work-up was classified as in conformity with the consensus in 48.0% of the cases, as undervalued in 21.9% and as overvalued in 30.1%. The resection rate at 90% was not far from the optimum. Pathological data allowed us to classify nearly all cases according to the tumour node metastasis classification; however, the number of examined nodes was below the recommendations in 30.8% of cases. Chemotherapy was performed according to the recommendations in 71.4% of cases, 23.1% were undertreated and 5.5% were overtreated. The multivariate analysis indicates that patients aged 75 years or more were less likely to receive chemotherapy than was recommended (P
Published: 2006

250. A population-based assessment of the prognostic value of the CD19 positive lymphocyte count in B-cell chronic lymphocytic leukemia using Cox and Markov models

Author: Valérie Jooste, Catherine Quantin, Christine Binquet, P.M. Carli, R. Cailliod, M. Maynadie, and G. Le Teuff
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Epidemiology, Lymphocyte, Chronic lymphocytic leukemia, Population, Antigens, CD19, Immunophenotyping, Stable Disease, Internal medicine, medicine, Humans, Lymphocyte Count, Stage (cooking), education, Aged, Proportional Hazards Models, Aged, 80 and over, education.field_of_study, business.industry, Regression analysis, Middle Aged, medicine.disease, Prognosis, Leukemia, Lymphocytic, Chronic, B-Cell, Survival Analysis, Markov Chains, medicine.anatomical_structure, Immunology, Disease Progression, Population study, Female, business
Abstract: No population-based study has assessed the prognostic impact on survival of the CD19 positive lymphocyte count, evaluated by immunophenotyping at diagnosis, in B-cell chronic lymphocytic leukemia (B-CLL). Aiming at addressing this issue, we investigated the clinical outcome of a well-defined population of B-CLL patients. Survival of B-CLL patients, diagnosed between 1990 and 1999 and recorded by the Registry of Hematological Malignancies of the Côte d'Or, was analysed applying Cox's regression model to the 237 included cases and to the 195 Binet stage A patients. To assess simultaneously the predictive value of each parameter on the risk of disease progression and on the risk of death, we completed this analysis by applying a three-states homogeneous Markov model to the whole study population. Analysis of the entire population showed that age (p0.001), Binet stage (p = 0.008) and CD19 positive lymphocyte count (p = 0.038) were three independent prognostic factors. However, in stage A patients, only progression into a more advanced stage, analysed as a time-dependent variable, and age had a clear impact on survival (p0.001 for both). Markov model revealed that an increased CD19 positive lymphocyte count increased the risk of disease progression in stage A patients (p = 0.002) but did not have direct impact on survival of either stage A patients with stable disease or stage B or C patients. An increased CD19 positive lymphocyte count at diagnosis is a marker of an increased risk of disease progression in stage A patients. Thus, it can be a useful tool for the clinical management of these patients.
Published: 2005

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