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1. Effects of rabeprazole on the antiplatelet effects and pharmacokinetics of clopidogrel in healthy volunteers

Author

Funck-Brentano, Christian, Szymezak, Jean, Steichen, Olivier, Ducint, Dominique, Molimard, Mathieu, Remones, Véronique, Azizi, Michel, Gaussem, Pascale, CIC Saint-Antoine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), CIC AP-HP (hegp Ex-Broussais)/inserm, Laboratoire de pharmacologie, CHU Bordeaux [Bordeaux], Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine vasculaire et hypertension artérielle [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Risque Thrombotique et Mecanismes de l'Hemostase (U765), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), 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), Janssen-Cilag, and Funck-Brentano, Christian

Subjects
CYP2C19 protein, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Cytochrome P-450 Enzyme System, Vasodilator-stimulated Phosphoprotein, Proton Pump Inhibitors, Drug Interactions, cardiovascular diseases, human, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, circulatory and respiratory physiology, Clopidogrel
Abstract

International audience; BACKGROUND: Several studies have suggested that proton-pump inhibitors (PPIs), mostly omeprazole, interact with clopidogrel efficacy by inhibiting the formation of its active metabolite via CYP2C19 inhibition. Whether this occurs with all PPIs is a matter of debate. As rabeprazole is a less potent CYP2C19 inhibitor than other PPIs, we studied the interaction between rabeprazole and the antiplatelet actions and pharmacokinetics of clopidogrel. AIM: To demonstrate the non-inferiority of rabeprazole over placebo using change in platelet reactivity index (PRI; vasodilator-stimulated phosphoprotein [VASP] assay) in a predefined population of good clopidogrel responders. Omeprazole was used as the positive control. METHODS: In this randomized three-period crossover study in healthy volunteers, 36 healthy men received clopidogrel (75mg/day for 7 days) with placebo, omeprazole (20mg/day) or rabeprazole (20mg/day). Clopidogrel antiplatelet effects and disposition kinetics were assessed on day 7 of combination therapy. Non-inferiority threshold was predefined as an upper limit of the 90% confidence interval for the difference in change in PRI between placebo and rabeprazole of30%), the clopidogrel antiplatelet effect remained non-inferior to placebo during rabeprazole (difference 3.4% [-1.7; 8.5]) but not omeprazole (difference 7.5% [2.5; 12.6]) co-administration. The AUC0-24 and Cmax of active clopidogrel metabolite decreased with both omeprazole and rabeprazole, and conditions of bioequivalence were not met, except for AUC0-24 with rabeprazole. CONCLUSIONS: Rabeprazole does not interact with clopidogrel to the same extent as omeprazole. However, under our experimental conditions and proton-pump inhibitor doses, there was no significant pharmacodynamic interaction between rabeprazole or omeprazole and clopidogrel, despite a significant decrease in the formation of clopidogrel active metabolite.

Published
2013
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2. Effects of rabeprazole on the antiplatelet effects and pharmacokinetics of clopidogrel in healthy volunteers. : PK/PD interaction between rabeprazole and clopidogrel

Author

Funck-Brentano, Christian, Szymezak, Jean, Steichen, Olivier, Ducint, Dominique, Molimard, Mathieu, Remones, Véronique, Azizi, Michel, Gaussem, Pascale, CIC Saint-Antoine, Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Saint-Antoine [APHP], Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de pharmacologie biologique [CHU Pitié-Salpâtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ), CIC AP-HP (hegp Ex-Broussais)/inserm, Laboratoire de pharmacologie, CHU Bordeaux [Bordeaux], Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de médecine vasculaire et hypertension artérielle [CHU HEGP], Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Assistance publique - Hôpitaux de Paris (AP-HP), Risque Thrombotique et Mecanismes de l'Hemostase ( U765 ), 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 ), Janssen-Cilag, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Risque Thrombotique et Mécanismes de l'Hémostase (U765), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), 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), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Risque Thrombotique et Mecanismes de l'Hemostase (U765), 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), and 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)

Subjects
CYP2C19 protein, [ SDV.SP ] Life Sciences [q-bio]/Pharmaceutical sciences, Cytochrome P-450 Enzyme System, Vasodilator-stimulated Phosphoprotein, Proton Pump Inhibitors, Drug Interactions, cardiovascular diseases, human, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, circulatory and respiratory physiology, Clopidogrel
Abstract

International audience; BACKGROUND: Several studies have suggested that proton-pump inhibitors (PPIs), mostly omeprazole, interact with clopidogrel efficacy by inhibiting the formation of its active metabolite via CYP2C19 inhibition. Whether this occurs with all PPIs is a matter of debate. As rabeprazole is a less potent CYP2C19 inhibitor than other PPIs, we studied the interaction between rabeprazole and the antiplatelet actions and pharmacokinetics of clopidogrel. AIM: To demonstrate the non-inferiority of rabeprazole over placebo using change in platelet reactivity index (PRI; vasodilator-stimulated phosphoprotein [VASP] assay) in a predefined population of good clopidogrel responders. Omeprazole was used as the positive control. METHODS: In this randomized three-period crossover study in healthy volunteers, 36 healthy men received clopidogrel (75mg/day for 7 days) with placebo, omeprazole (20mg/day) or rabeprazole (20mg/day). Clopidogrel antiplatelet effects and disposition kinetics were assessed on day 7 of combination therapy. Non-inferiority threshold was predefined as an upper limit of the 90% confidence interval for the difference in change in PRI between placebo and rabeprazole of30%), the clopidogrel antiplatelet effect remained non-inferior to placebo during rabeprazole (difference 3.4% [-1.7; 8.5]) but not omeprazole (difference 7.5% [2.5; 12.6]) co-administration. The AUC0-24 and Cmax of active clopidogrel metabolite decreased with both omeprazole and rabeprazole, and conditions of bioequivalence were not met, except for AUC0-24 with rabeprazole. CONCLUSIONS: Rabeprazole does not interact with clopidogrel to the same extent as omeprazole. However, under our experimental conditions and proton-pump inhibitor doses, there was no significant pharmacodynamic interaction between rabeprazole or omeprazole and clopidogrel, despite a significant decrease in the formation of clopidogrel active metabolite.

Published
2013
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3. Clonal architecture of chronic myelomonocytic leukemias

Author

Olivier A. Bernard, François Delhommeau, Lionel Ades, Uwe Platzbecker, Michaela Fontenay, Aline Renneville, Guillaume Meurice, Nathalie Droin, Philippe Rameau, Claude Preudhomme, Pierre Fenaux, Raphael Itzykson, Cedric Orear, Céline Berthon, Olivier Kosmider, Eric Solary, Olivier Gagey, William Vainchenker, Margot Morabito, Hématopoïèse normale et pathologique, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie biologique, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Hématologie Biologique, Centre de biologie Pathologie PM Degand, Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de recherche sur le cancer, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Universitätsklinikum Carl Gustav Carus, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Institut Gustave Roussy (IGR), CIC Saint-Antoine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Génétique des hémopathies humaines (EMI 210), 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 Cochin (UMR_S567 / UMR 8104), Service d'hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Paris 5 (UPD5), 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 National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Gustave Roussy ( IGR ) -Université Paris-Sud - Paris 11 ( UP11 ), CHU Cochin [AP-HP], Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Complexité, Innovation, Activités Motrices et Sportives ( CIAMS ), Université Paris-Sud - Paris 11 ( UP11 ) -Université d'Orléans ( UO ), Plateforme de Génomique, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse ( AMMICa ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -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)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Saint-Antoine [APHP], Génétique des hémopathies humaines ( EMI 210 ), 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 Cochin ( UMR_S567 / UMR 8104 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Paris 5 ( UPD5 ), 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 National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), 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, Complexité, Innovation, Activités Motrices et Sportives (CIAMS), Université Paris-Sud - Paris 11 (UP11)-Université d'Orléans (UO), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, Mutation rate, Myeloid, Immunology, Loss of Heterozygosity, [ SCCO.PSYC ] Cognitive science/Psychology, Gene mutation, Biology, Biochemistry, Somatic evolution in cancer, Clonal Evolution, Cohort Studies, Loss of heterozygosity, 03 medical and health sciences, 0302 clinical medicine, Mutation Rate, hemic and lymphatic diseases, medicine, Humans, Myeloid Cells, Aged, 030304 developmental biology, Dominance (genetics), Aged, 80 and over, Genetics, 0303 health sciences, Myelodysplastic syndromes, [SCCO.NEUR]Cognitive science/Neuroscience, Cell Differentiation, Leukemia, Myelomonocytic, Chronic, Cell Biology, Hematology, Middle Aged, medicine.disease, Hematopoiesis, Leukemia, medicine.anatomical_structure, Case-Control Studies, 030220 oncology & carcinogenesis, Mutation, [ SCCO.NEUR ] Cognitive science/Neuroscience, [SCCO.PSYC]Cognitive science/Psychology, Female
Abstract

International audience; Genomic studies in chronic myeloid malignancies, including myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), and MPN/MDS, have identified common mutations in genes encoding signaling, epigenetic, transcription, and splicing factors. In the present study, we interrogated the clonal architecture by mutation-specific discrimination analysis of single-cell-derived colonies in 28 patients with chronic myelomonocytic leukemias (CMML), the most frequent MPN/MDS. This analysis reveals a linear acquisition of the studied mutations with limited branching through loss of heterozygosity. Serial analysis of untreated and treated samples demonstrates a dynamic architecture on which most current therapeutic approaches have limited effects. The main disease characteristics are early clonal dominance, arising at the CD34(+)/CD38(-) stage of hematopoiesis, and granulomonocytic differentiation skewing of multipotent and common myeloid progenitors. Comparison of clonal expansions of TET2 mutations in MDS, MPN, and CMML, together with functional invalidation of TET2 in sorted progenitors, suggests a causative link between early clonal dominance and skewed granulomonocytic differentiation. Altogether, early clonal dominance may distinguish CMML from other chronic myeloid neoplasms with similar gene mutations.

Published
2013
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4. Applying ecological and evolutionary theory to cancer : a long and winding road

Author

Frédérique Billy, Annabelle Ballesta, Philippe Fort, Benoît Perthame, Serge Koscielny, Helene Trauchessec, Daniel Fisher, Céline Cosseau, Guillaume Mitta, Ruoping Tang, Patrice Lassus, W. Vainchenker, Christoph Grunau, Damien Grégoire, Corinne Quittau-Prévostel, Vjekoslav Dulic, Vitali Volpert, Eric Assenat, Michael E. Hochberg, Alexander Lorz, Philippe Blache, Thomas Lepoutre, François Delhommeau, Jean-Pierre Marie, Urszula Hibner, Peggy Raynaud, Frédéric Thomas, Jean Clairambault, Dorothée Missé, Fanny Fava, Eric Solary, Benjamin Roche, François Rousset, Emmanuel Vignal, Liliana Krasinska, Raphael Itzykson, Stephen Baghdiguian, Simon P. Daoust, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Biologie Cellulaire (CRBM), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche sur l'Education, les apprentissages et la didactique (CREAD), Institut universitaire de formation des maîtres - Bretagne (IUFM Bretagne), Université de Brest (UBO)-Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Rennes 2 (UR2), Ecologie et évolution des interactions [2011-2014] (2EI), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Service Médico-Chirurgical des Maladies de l'Appareil Digestif et de Transplantation Hépatique, Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire Jacques-Louis Lions (LJLL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Nonlinear Analysis for Biology and Geophysical flows (BANG), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Paris Descartes - Paris 5 (UPD5), CIC Saint-Antoine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hématopoïèse normale et pathologique, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Mathématiques et Applications - ENS Paris (DMA), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Multi-scale modelling of cell dynamics : application to hematopoiesis (DRACULA), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Institut Camille Jordan (ICJ), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-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), National Center for Ecological Analysis and Synthesis (NCEAS), Santa Fe Institute, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle ( MIVEGEC ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD [France-Sud] ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ), Centre de recherches de biochimie macromoléculaire ( CRBM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -IFR122-Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre de Recherche sur l'Education, les apprentissages et la didactique ( CREAD ), Institut universitaire de formation des maîtres - Bretagne ( IUFM Bretagne ), Université de Brest ( UBO ) -Université de Brest ( UBO ) -Université européenne de Bretagne ( UEB ) -Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Ecologie et évolution des interactions ( 2EI ), Université de Perpignan Via Domitia ( UPVD ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences de l'Evolution de Montpellier ( ISEM ), Université de Montpellier ( UM ) -Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique ( CNRS ), CHU Saint-Eloi, Laboratoire Jacques-Louis Lions ( LJLL ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Nonlinear Analysis for Biology and Geophysical flows ( BANG ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ) -Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ), Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Saint-Antoine [APHP], Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Gustave Roussy ( IGR ) -Université Paris-Sud - Paris 11 ( UP11 ), Département de Mathématiques et Applications - ENS Paris ( DMA ), École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Multi-scale modelling of cell dynamics : application to hematopoiesis ( DRACULA ), Institut Camille Jordan [Villeurbanne] ( ICJ ), Centre National de la Recherche Scientifique ( CNRS ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -École Centrale de Lyon ( ECL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -École Centrale de Lyon ( ECL ), Université de Lyon-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre de génétique et de physiologie moléculaire et cellulaire ( CGPhiMC ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lyon, Laboratoire Parole et Langage ( LPL ), Centre National de la Recherche Scientifique ( CNRS ) -Aix Marseille Université ( AMU ), 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 ), National Center for Ecological Analysis and Synthesis ( NCEAS ), National Center for Ecological Analysis and Synthesis, Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), École normale supérieure - Paris (ENS Paris), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan [Villeurbanne] (ICJ), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Institut Camille Jordan [Villeurbanne] (ICJ), 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 National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre de recherches de biochimie macromoléculaire (CRBM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-IFR122-Centre National de la Recherche Scientifique (CNRS), Ecologie et évolution des interactions (2EI), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-École Centrale de Lyon (ECL), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Laboratoire d'Ingénierie dirigée par les modèles pour les Systèmes Embarqués (LISE), Département Ingénierie Logiciels et Systèmes (DILS), Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Université Paris-Saclay-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (CIRAD)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire d'Etudes Aérodynamiques (LEA), Centre National de la Recherche Scientifique (CNRS)-ENSMA-Université de Poitiers, Hématopoïèse normale et pathologique (U1170 Inserm), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Multi-Models and Numerical Methods (M3N), Inria Paris-Rocquencourt, Génétique et évolution des maladies infectieuses (GEMI), and Modat, Anne

Subjects
Process (engineering), cancer, disease biology, [SDV.CAN]Life Sciences [q-bio]/Cancer, disease biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Synthesis, 03 medical and health sciences, 0302 clinical medicine, Genetics, Neoplastic progression, medicine, cancer, evolutionary theory, ComputingMilieux_MISCELLANEOUS, Ecology, Evolution, Behavior and Systematics, Evolutionary theory, 030304 developmental biology, 0303 health sciences, [ SDE.BE ] Environmental Sciences/Biodiversity and Ecology, Ecology, Cancer, Evolutionary medicine, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Evasion (ethics), medicine.disease, 3. Good health, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, evolutionary medicine, 030220 oncology & carcinogenesis, Darwinism, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, General Agricultural and Biological Sciences
Abstract

International audience; Since the mid 1970s, cancer has been described as a process of Darwinian evolution, with somatic cellular selection and evolution being the fundamental processes leading to malignancy and its many manifestations (neoangiogenesis, evasion of the immune system, metastasis, and resistance to therapies). Historically, little attention has been placed on applications of evolutionary biology to understanding and controlling neoplastic progression and to prevent therapeutic failures. This is now beginning to change, and there is a growing international interest in the interface between cancer and evolutionary biology. The objective of this introduction is first to describe the basic ideas and concepts linking evolutionary biology to cancer. We then present four major fronts where the evolutionary perspective is most developed, namely laboratory and clinical models, mathematical models, databases, and techniques and assays. Finally, we discuss several of the most promising challenges and future prospects in this interdisciplinary research direction in the war against cancer.

Published
2013
Full Text
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5. ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC)

Author

Tendera, M., Aboyans, V., Bartelink, M. l., Baumgartner, I., Clement, D., Collet, J. p., Cremonesi, A., De Carlo, M., Erbel, R., Fowkes, F. g. r., Heras, M., Kownator, S., Minar, E., Ostergren, J., Poldermans, D., Riambau, V., Roffi, M., Rother, J., Sievert, H., Van Sambeek, M., Zeller, T., Bax, J., Auricchio, A., Baumgartner, H., Ceconi, C., Dean, V., Deaton, C., Fagard, R., Funck Brentano, C., Hasdai, D., Hoes, A., Knuuti, J., Kolh, P., Mcdonagh, T., Moulin, C., Popescu, B., Reiner, Z., Sechtem, U., Sirnes, P. a., Torbicki, A., Vahanian, A., Windecker, S., Agewall, S., Blinc, A., Bulvas, M., Cosentino, Francesco, De Backer, T., Gottsater, A., Gulba, D., Guzik, T. j., Jonsson, B., Késmárky, G., Kitsiou, A., Kuczmik, W., Larsen, M. l., Madaric, J., Mas, J. l., Mcmurray, J. j., Micari, A., Mosseri, M., Muller, C., Naylor, R., Norrving, B., Oto, O., Pasierski, T., Plouin, P. f., Ribichini, F., Ricco, J. b., Ruilope, L., Schmid, J. p., Schwehr, U., Sol, B. g., Sprynger, M., Tiefenbacher, C., Tsioufis, C., Van Damme, H., Endorsed By: The European Stroke Organisation, Authors/task Force Members, Committee For Practice Guidelines, E. s. c., Reviewers, Document, Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale et Comparée (NETEC), Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Université de Limoges (UNILIM), Julius Centre for Health Sciences and Primary Health Care, Department of cardiology, Universität Duisburg-Essen [Essen], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Institut Clinic de Tòrax, Department of Vascular Surgery, Erasmus Medical Centre, Department of Neurology, Asklepios Klinik Altona, Albert-Ludwigs-Universität Freiburg, Service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], CIC Saint-Antoine, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [APHP], Turku PET Centre, University of Turku, Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS), University Hospital Center Zagreb, Service de cardiologie, Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Karolinska Institute, karolinska institute, 1st Department of Internal Medicine, University of Pécs, Medical School, Cooltech Applications, Cooltech, Department of Neurology Lunds University Hospital Lund, Service de médecine vasculaire et hypertension artérielle [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Cardiology, Università degli Studi di Verona, Université de Limoges (UNILIM)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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), University of Pécs Medical School (UP MS), University of Pecs-University of Pecs, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and University of Verona (UNIVR)

Subjects
Male, medicine.medical_treatment, Carotid endarterectomy, 030204 cardiovascular system & hematology, Renal artery stenosis, MESH: Risk Assessment, Coronary artery disease, Coronary artery bypass surgery, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Risk Factors, Risk Factors, MESH: Peripheral Arterial Disease, 80 and over, 030212 general & internal medicine, Medical History Taking, ComputingMilieux_MISCELLANEOUS, Endarterectomy, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, Endovascular Procedures, Middle Aged, Prognosis, 3. Good health, Exercise Therapy, Cardiology, Female, Radiology, medicine.symptom, MESH: Cardiovascular Agents, Cardiology and Cardiovascular Medicine, Vascular Surgical Procedures, Adult, Diagnostic Imaging, medicine.medical_specialty, MESH: Endovascular Procedures, Risk Assessment, MESH: Prognosis, methods, 03 medical and health sciences, MESH: Physical Examination, Peripheral Arterial Disease, Angioplasty, Internal medicine, medicine, MESH: Exercise Therapy, Humans, cardiovascular diseases, MESH: Vascular Surgical Procedures, Physical Examination, Aged, MESH: Humans, business.industry, MESH: Diagnostic Imaging, MESH: Medical History Taking, MESH: Adult, Cardiovascular Agents, medicine.disease, Intermittent claudication, MESH: Male, MESH: Reperfusion, Adult, Aged, Aged, 80 and over, Cardiovascular Agents, therapeutic use, Diagnostic Imaging, Endovascular Procedures, methods, Exercise Therapy, Female, Humans, Male, Medical History Taking, Middle Aged, Peripheral Arterial Disease, diagnosis/therapy, Physical Examination, Prognosis, Reperfusion, methods, Risk Assessment, Risk Factors, Vascular Surgical Procedures, diagnosis/therapy, therapeutic use, Reperfusion, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Carotid stenting, business, MESH: Female
Abstract

2D : two-dimensional 3D : three-dimensional ABI : ankle–brachial index ACAS : Asymptomatic Carotid Atherosclerosis Study ACCF : American College of Cardiology Foundation ACE : angiotensin-converting enzyme ACS : acute coronary syndrome ACST : Asymptomatic Carotid Surgery Trial ALI : acute limb ischaemia ASTRAL : Angioplasty and Stenting for Renal Artery Lesions trial BASIL : Bypass versus Angioplasty in Severe Ischaemia of the Leg BOA : Dutch Bypass Oral Anticoagulants or Aspirin CABG : coronary artery bypass grafting CAD : coronary artery disease CAPRIE : Clopidogrel versus Aspirin in Patients at Risk for Ischaemic Events CAPTURE : Carotid ACCULINK/ACCUNET Post Approval Trial to Uncover Rare Events CARP : Coronary Artery Revascularization Prophylaxis CAS : carotid artery stenting CASPAR : Clopidogrel and Acetylsalicylic Acid in Bypass Surgery for Peripheral Arterial Disease CASS : Coronary Artery Surgery Study CAVATAS : CArotid and Vertebral Artery Transluminal Angioplasty Study CEA : carotid endarterectomy CHARISMA : Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilization, Management and Avoidance CI : confidence interval CLEVER : Claudication: Exercise Versus Endoluminal Revascularization CLI : critical limb ischaemia CORAL : Cardiovascular Outcomes in Renal Atherosclerotic Lesions COURAGE : Clinical Outcomes Utilization Revascularization and Aggressive Drug Evaluation CPG : Committee for Practice Guidelines CREST : Carotid Revascularization Endarterectomy vs. Stenting Trial CT : computed tomography CTA : computed tomography angiography CVD : cardiovascular disease DECREASE-V : Dutch Echocardiographic Cardiac Risk Evaluation DRASTIC : Dutch Renal Artery Stenosis Intervention Cooperative Study DSA : digital subtraction angiography DUS : duplex ultrasound/duplex ultrasonography EACTS : European Association for Cardio-Thoracic Surgery EAS : European Atherosclerosis Society ECST : European Carotid Surgery Trial EPD : embolic protection device ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EUROSCORE : European System for Cardiac Operative Risk Evaluation EVA-3S : Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis EXACT : Emboshield and Xact Post Approval Carotid Stent Trial GALA : General Anaesthesia versus Local Anaesthesia for Carotid Surgery GFR : glomerular filtration rate GRACE : Global Registry of Acute Coronary Events HbA1c : glycated haemoglobin HDL : high-density lipoprotein HOPE : Heart Outcomes Prevention Evaluation HR : hazard ratio IC : intermittent claudication ICSS : International Carotid Stenting Study IMT : intima–media thickness ITT : intention to treat LDL : low-density lipoprotein LEAD : lower extremity artery disease MACCEs : major adverse cardiac and cerebrovascular events MDCT : multidetector computed tomography MONICA : Monitoring of Trends and Determinants in Cardiovascular Disease MRA : magnetic resonance angiography MRI : magnetic resonance imaging NASCET : North American Symptomatic Carotid Endarterectomy Trial ONTARGET : Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial OR : odds ratio PAD : peripheral artery diseases PARTNERS : Peripheral Arterial Disease Awareness, Risk, and Treatment: New Resources for Survival PCI : percutaneous coronary intervention PET : positron emission tomography PRO-CAS : Predictors of Death and Stroke in CAS PTA : percutaneous transluminal angioplasty RAAS : renin–angiotensin–aldosterone system RADAR : Randomized, Multicentre, Prospective Study Comparing Best Medical Treatment Versus Best Medical Treatment Plus Renal Artery Stenting in Patients With Haemodynamically Relevant Atherosclerotic Renal Artery Stenosis RAS : renal artery stenosis RCT : randomized controlled trial REACH : Reduction of Atherothrombosis for Continued Health RR : risk ratio SAPPHIRE : Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy SCAI : Society for Cardiovascular Angiography and Interventions SIR : Society of Interventional Radiology SPACE : Stent-Protected Angioplasty versus Carotid Endarterectomy SPARCL : Stroke Prevention by Aggressive Reduction in Cholesterol Levels Study STAR : Stent Placement in Patients With Atherosclerotic Renal Artery Stenosis and Impaired Renal Function SSYLVIA : Stenting of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial Arteries SVMB : Society for Vascular Medicine and Biology TASC : TransAtlantic Inter-Society Consensus TIA : transient ischaemic attack UEAD : upper extremity artery disease VA : vertebral artery Guidelines summarize and evaluate all available evidence, at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes but are complements for textbooks and cover the ESC Core Curriculum topics. Guidelines and recommendations should help the physicians to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible physician(s). A large number of Guidelines have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines can be found on the ESC website (http://www.escardio.org/guidelines-surveys/esc-guidelines/about/Pages/rules-writing.aspx). ESC Guidelines represent the official position of the ESC on a given topic and are regularly updated. Members of this Task Force were selected by the ESC to represent professionals involved with the medical care of patients with this pathology. Selected experts in the field undertook a comprehensive review of the published evidence for diagnosis, management, and/or prevention of a given condition according to ESC Committee for Practice Guidelines (CPG) policy. A critical evaluation of diagnostic and therapeutic procedures was performed including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger populations were included, where data exist. The level of evidence and the strength of recommendation of particular treatment options were weighed and graded according to pre-defined scales, as outlined in Tables 1 and 2 . …

Published
2011
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6. From array-based hybridization of Helicobacter pylori isolates to the complete genome sequence of an isolate associated with MALT lymphoma

Author

Francis Mégraud, Christiane Bouchier, Anne Ruskoné-Foumestraux, Zoé Rouy, Ivo G. Boneca, Sophie Creno, Dominique Lamarque, Marie-Agnès Dillies, Caroline Boursaux-Eude, Claudine Médigue, Philippe Lehours, Jean-Charles Delchier, Laurence Ma, Jean-Michel Thiberge, Jean-Yves Coppée, Hilde De Reuse, Anne Courillon-Mallet, Aurélie Lajus, Christophe Burucoa, Josette Raymond, Agnès Labigne, Génotypage des Pathogènes et Santé Publique (Plate-forme) (PF8), Institut Pasteur [Paris], Intégration et Analyse Génomique (Plate-Forme 4) (PF4), Infection à helicobacter, inflammation et cancer, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Puces à ADN (Plate-Forme 2) (PF2), Génomique (Plate-Forme) - Genomics Platform, Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, CIC Saint-Antoine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Villeneuve Saint Georges, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pathogenèse de Helicobacter, The Role of Peptidoglycan in Bacterial Cell Physiology: Morphology, Resistance to B-Lactams and Host-microbe Interactions, Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall (BGPB), Hôpital Hôtel Dieu, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Cochin [AP-HP], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Institut Pasteur [Paris] (IP), BMC, Ed., Intégration et Analyse Génomique (Plate-Forme), Université Bordeaux Segalen - Bordeaux 2 - Institut National de la Santé et de la Recherche Médicale (INSERM), Puces à ADN (Plate-Forme), Génomique (Plate-Forme), Commissariat à l'énergie atomique et aux énergies alternatives (CEA) - Université d'Evry-Val d'Essonne - Centre National de la Recherche Scientifique (CNRS), Bactériologie (LITEC), CHU de Poitiers, Assistance publique - Hôpitaux de Paris (AP-HP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP), Biologie et Génétique de la Paroi bactérienne, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and CHU Cochin [APHP]

Subjects
MESH: Intestinal Diseases, MESH: Genome, Bacterial, Genome, MESH: Nucleic Acid Hybridization, Cluster Analysis, MESH: Genomic Islands, MESH: Lymphoma, B-Cell, Marginal Zone, MESH: Phylogeny, MESH: Bacterial Proteins, Phylogeny, MESH: Evolution, Molecular, Oligonucleotide Array Sequence Analysis, Genetics, 0303 health sciences, biology, DNA–DNA hybridization, Nucleic Acid Hybridization, MALT lymphoma, Gastritis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Gastritis, Research Article, Biotechnology, Genomic Islands, lcsh:QH426-470, lcsh:Biotechnology, Evolution, Molecular, 03 medical and health sciences, MESH: Gene Expression Profiling, Bacterial Proteins, Species Specificity, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:TP248.13-248.65, medicine, Humans, MESH: Species Specificity, 030304 developmental biology, Synteny, Comparative genomics, MESH: Humans, Helicobacter pylori, 030306 microbiology, Gene Expression Profiling, Lymphoma, B-Cell, Marginal Zone, biology.organism_classification, medicine.disease, MESH: Cluster Analysis, Intestinal Diseases, lcsh:Genetics, Genetic marker, Duodenal Ulcer, MESH: Duodenal Ulcer, MESH: Oligonucleotide Array Sequence Analysis, MESH: Helicobacter pylori, Genome, Bacterial, Comparative genomic hybridization
Abstract

Background elicobacter pylori infection is associated with several gastro-duodenal inflammatory diseases of various levels of severity. To determine whether certain combinations of genetic markers can be used to predict the clinical source of the infection, we analyzed well documented and geographically homogenous clinical isolates using a comparative genomics approach. Results A set of 254 H. pylori genes was used to perform array-based comparative genomic hybridization among 120 French H. pylori strains associated with chronic gastritis (n = 33), duodenal ulcers (n = 27), intestinal metaplasia (n = 17) or gastric extra-nodal marginal zone B-cell MALT lymphoma (n = 43). Hierarchical cluster analyses of the DNA hybridization values allowed us to identify a homogeneous subpopulation of strains that clustered exclusively with cag PAI minus MALT lymphoma isolates. The genome sequence of B38, a representative of this MALT lymphoma strain-cluster, was completed, fully annotated, and compared with the six previously released H. pylori genomes (i.e. J99, 26695, HPAG1, P12, G27 and Shi470). B38 has the smallest H. pylori genome described thus far (1,576,758 base pairs containing 1,528 CDSs); it contains the vacA s2m2 allele and lacks the genes encoding the major virulence factors (absence of cag PAI, bab B, bab C, sab B, and hom B). Comparative genomics led to the identification of very few sequences that are unique to the B38 strain (9 intact CDSs and 7 pseudogenes). Pair-wise genomic synteny comparisons between B38 and the 6 H. pylori sequenced genomes revealed an almost complete co-linearity, never seen before between the genomes of strain Shi470 (a Peruvian isolate) and B38. Conclusion These isolates are deprived of the main H. pylori virulence factors characterized previously, but are nonetheless associated with gastric neoplasia.

Published
2010
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7. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer

Author

Renseigné, Non, Habib, Gilbert, Hoen, Bruno, Tornos, Pilar, Thuny, Franck, Prendergast, Bernard, Vilacosta, Isidre, Moreillon, Philippe, De Jesus Antunes, Manuel, Thilen, Ulf, Lekakis, John, Lengyel, Maria, Müller, Ludwig, Naber, Christoph K, Nihoyannopoulos, Petros, Moritz, Anton, Zamorano, Jose Luis, Vahanian, Alec, Auricchio, Angelo, Bax, Jeroen, Ceconi, Claudio, Dean, Veronica, Filippatos, Gerasimos, Funck-Brentano, Christian, Hobbs, Richard, Kearney, Peter, Mcdonagh, Theresa, Mcgregor, Keith, Popescu, Bogdan A, Reiner, Zeljko, Sechtem, Udo, Sirnes, Per Anton, Tendera, Michal, Vardas, Panos, Widimsky, Petr, Aguilar, Rio, Bongiorni, Maria Grazia, Borger, Michael, Butchart, Eric, Danchin, Nicolas, Delahaye, François, Erbel, Raimund, Franzen, Damian, Gould, Kate, Hall, Roger, Hassager, Christian, Kjeldsen, Keld, Mcmanus, Richard, Miró, José M, Mokracek, Ales, Rosenhek, Raphael, San Román Calvar, José A, Seferovic, Petar, Selton-Suty, Christine, Uva, Miguel Sousa, Trinchero, Rita, Van Camp, Guy, Service des maladies infectieuses et tropicales, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ), Service de cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], CIC Saint-Antoine, Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Saint-Antoine [APHP], Department of Earth Science, University of Durham, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, 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), 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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Durham University, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques, Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [APHP]

Subjects
media_common.quotation_subject, MEDLINE, Cardiology, 030204 cardiovascular system & hematology, Health outcomes, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Humans, Quality (business), 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Societies, Medical, media_common, Medical education, Endocarditis, business.industry, Conflict of interest, Evidence-based medicine, medicine.disease, 3. Good health, Europe, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Order (business), Infective endocarditis, Table (database), Cardiology and Cardiovascular Medicine, business
Abstract

Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition, taking into account the impact on outcome, as well as the risk/benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks. The legal implications of medical guidelines have been discussed previously. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC website (http://www.escardio.org/knowledge/guidelines/rules). In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed including assessment of the risk/ benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in Tables 1 and 2 . View this table: Table 1 Classes of recommendations View this table: Table 2 Levels of evidence The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period must be notified to …

Published
2009
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8. Relationship between HIV protease inhibitors and QTc interval duration in HIV-infected patients: a cross-sectional study

Author

Afef Koubaa, Beny Charbit, Pierre-Yves Boëlle, Diane Bollens, Arnaud Rosier, Franck Boccara, Christian Funck-Brentano, Pierre-Marie Girard, Service de Pharmacologie médicale = service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIC Saint-Antoine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Service de Cardiologie [CHU Saint-Antoine], Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Saint-Antoine (UMRS893), Arnaud, Rosier, Service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, HIV Infections, 030204 cardiovascular system & hematology, 0302 clinical medicine, Heart Rate, HIV Protease Inhibitor, Pharmacology (medical), 030212 general & internal medicine, Prospective Studies, MESH: Heart Rate, Prospective cohort study, MESH: Middle Aged, virus diseases, MESH: HIV Infections, Middle Aged, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH: Arrhythmias, Cardiac, Anesthesia, cardiovascular system, Female, circulatory and respiratory physiology, Adult, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Long QT syndrome, electrocardiography, Torsades de pointes, QT interval, 03 medical and health sciences, MESH: Cross-Sectional Studies, Acquired immunodeficiency syndrome (AIDS), Drug Safety, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, long QT syndrome, Humans, Protease inhibitor (pharmacology), cardiovascular diseases, Adverse effect, MESH: HIV Protease Inhibitors, Pharmacology, MESH: Humans, business.industry, HIV protease inhibitors, Arrhythmias, Cardiac, MESH: Adult, medicine.disease, HIV infection, MESH: Prospective Studies, MESH: Male, MESH: Electrocardiography, Cross-Sectional Studies, MESH: Potassium, Potassium, business, MESH: Female
Abstract

International audience; AIMS: QTc interval prolongation and torsades de pointes have been reported in HIV-infected patients. Protease inhibitors (PIs) are suspected to contribute to this adverse reaction. However, many factors can prolong QTc interval. We examined factors influencing QTc duration in HIV-infected patients. METHODS: Unselected HIV-infected patients (n = 978) were enrolled in this prospective, single-centre cross-sectional study. Variables related to infection and treatments were collected. A digital electrocardiographic record was recorded in each patient and QT interval duration was measured and corrected using both Bazett's (QTcB) and Fridericia's (QTcF) formula. Results were analysed with a multivariable linear model. RESULTS: After excluding arrhythmias and complete bundle branch blocks, QT interval was measured in 956 patients. The mean (SD) QTcB was 418 ms (23) and QTcF was 405 ms (20). QTc was found prolonged (>450 ms in women and >440 ms in men) in 129 [13.5%; 95% confidence interval (CI) 11.5, 15.8] and 38 (4%; 95% CI 2.9, 5.4) patients using Bazett and Fridericia corrections, respectively. On multivariable analysis, incomplete bundle branch block, ventricular hypertrophy, signs of ischaemic cardiopathy, female gender, White ethnic origin and age were significantly associated with QTc prolongation. The only HIV variable independently associated with QTc prolongation was the duration of infection (P = 0.023). After adjustment, anti-HIV treatment, in particular PI (P = 0.99), was not associated with QTc prolongation. CONCLUSIONS: Although PIs block in vitro hERG current, they are not independently associated with QTc interval prolongation. Prolonged QTc interval in HIV-infected patients is primarily associated with factors commonly known to prolong QT and with the duration of HIV infection.

Published
2009
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9. Modeling the Worldwide Spread of Pandemic Influenza: Baseline Case and Containment Interventions

Author

Vittoria Colizza, Alessandro Vespignani, Alain Barrat, Marc Barthelemy, Alain-Jacques Valleron, School of Informatics, Indiana University, Indiana University [Bloomington], Indiana University System-Indiana University System, Complex Networks Lagrange Laboratory, Institute for Scientific Interchange Foundation, Laboratoire de Physique Théorique d'Orsay [Orsay] (LPT), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), DAM Île-de-France (DAM/DIF), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Saint-Antoine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), and Starita, Sabine

Subjects
Veterinary medicine, Non-Clinical Medicine, Epidemiology, International Cooperation, medicine.disease_cause, Poultry, Disease Outbreaks, 0302 clinical medicine, Japan, [MATH.MATH-MP]Mathematics [math]/Mathematical Physics [math-ph], Pandemic, Influenza A virus, 030212 general & internal medicine, Travel, 0303 health sciences, education.field_of_study, Health Policy, General Medicine, Other Quantitative Biology (q-bio.OT), Quantitative Biology - Other Quantitative Biology, 3. Good health, Europe, Infectious Diseases, Scale (social sciences), Drugs and adverse drug reactions, Human mortality from H5N1, Medicine, Public Health, Seasons, Research Article, Physics - Physics and Society, Canada, Asia, Population, Public Health and Epidemiology, FOS: Physical sciences, Physics and Society (physics.soc-ph), Biology, Antiviral Agents, 03 medical and health sciences, Environmental health, Influenza, Human, medicine, Animals, Humans, Computer Simulation, [MATH.MATH-MP] Mathematics [math]/Mathematical Physics [math-ph], Baseline (configuration management), education, Condensed Matter - Statistical Mechanics, Poultry Diseases, 030304 developmental biology, Stochastic Processes, Statistical Mechanics (cond-mat.stat-mech), Influenza A Virus, H5N1 Subtype, Outbreak, Models, Theoretical, United States, Influenza A virus subtype H5N1, FOS: Biological sciences, Influenza in Birds
Abstract

Background The highly pathogenic H5N1 avian influenza virus, which is now widespread in Southeast Asia and which diffused recently in some areas of the Balkans region and Western Europe, has raised a public alert toward the potential occurrence of a new severe influenza pandemic. Here we study the worldwide spread of a pandemic and its possible containment at a global level taking into account all available information on air travel. Methods and Findings We studied a metapopulation stochastic epidemic model on a global scale that considers airline travel flow data among urban areas. We provided a temporal and spatial evolution of the pandemic with a sensitivity analysis of different levels of infectiousness of the virus and initial outbreak conditions (both geographical and seasonal). For each spreading scenario we provided the timeline and the geographical impact of the pandemic in 3,100 urban areas, located in 220 different countries. We compared the baseline cases with different containment strategies, including travel restrictions and the therapeutic use of antiviral (AV) drugs. We investigated the effect of the use of AV drugs in the event that therapeutic protocols can be carried out with maximal coverage for the populations in all countries. In view of the wide diversity of AV stockpiles in different regions of the world, we also studied scenarios in which only a limited number of countries are prepared (i.e., have considerable AV supplies). In particular, we compared different plans in which, on the one hand, only prepared and wealthy countries benefit from large AV resources, with, on the other hand, cooperative containment scenarios in which countries with large AV stockpiles make a small portion of their supplies available worldwide. Conclusions We show that the inclusion of air transportation is crucial in the assessment of the occurrence probability of global outbreaks. The large-scale therapeutic usage of AV drugs in all hit countries would be able to mitigate a pandemic effect with a reproductive rate as high as 1.9 during the first year; with AV supply use sufficient to treat approximately 2% to 6% of the population, in conjunction with efficient case detection and timely drug distribution. For highly contagious viruses (i.e., a reproductive rate as high as 2.3), even the unrealistic use of supplies corresponding to the treatment of approximately 20% of the population leaves 30%–50% of the population infected. In the case of limited AV supplies and pandemics with a reproductive rate as high as 1.9, we demonstrate that the more cooperative the strategy, the more effective are the containment results in all regions of the world, including those countries that made part of their resources available for global use., A metapopulation stochastic epidemic model for influenza shows the need to include air transportation when assessing the occurrence probability of global outbreaks. The impact of the use of antiviral drugs is also measured., Editors' Summary Background. Seasonal outbreaks (epidemics) of influenza—a viral infection of the nose, throat, and airways—affect millions of people and kill about 500,000 individuals every year. Regular epidemics occur because flu viruses frequently make small changes in the viral proteins (antigens) recognized by the human immune system. Consequently, a person's immune-system response that combats influenza one year provides incomplete protection the next year. Occasionally, a human influenza virus appears that contains large antigenic changes. People have little immunity to such viruses (which often originate in birds or animals), so they can start a global epidemic (pandemic) that kills millions of people. Experts fear that a human influenza pandemic could be triggered by the avian H5N1 influenza virus, which is present in bird flocks around the world. So far, fewer than 300 people have caught this virus but more than 150 people have died. Why Was This Study Done? Avian H5N1 influenza has not yet triggered a human pandemic, because it rarely passes between people. If it does acquire this ability, it would take 6–8 months to develop a vaccine to provide protection against this new, potentially pandemic virus. Public health officials therefore need other strategies to protect people during the first few months of a pandemic. These could include international travel restrictions and the use of antiviral drugs. However, to get the most benefit from these interventions, public-health officials need to understand how influenza pandemics spread, both over time and geographically. In this study, the researchers have used detailed information on air travel to model the global spread of an emerging influenza pandemic and its containment. What Did the Researchers Do and Find? The researchers incorporated data on worldwide air travel and census data from urban centers near airports into a mathematical model of the spread of an influenza pandemic. They then used this model to investigate how the spread and health effects of a pandemic flu virus depend on the season in which it emerges (influenza virus thrives best in winter), where it emerges, and how infectious it is. Their model predicts, for example, that a flu virus originating in Hanoi, Vietnam, with a reproductive number (R0) of 1.1 (a measure of how many people an infectious individual infects on average) poses a very mild global threat. However, epidemics initiated by a virus with an R0 of more than 1.5 would often infect half the population in more than 100 countries. Next, the researchers used their model to show that strict travel restrictions would have little effect on pandemic evolution. More encouragingly, their model predicts that antiviral drugs would mitigate pandemics of a virus with an R0 up to 1.9 if every country had an antiviral drug stockpile sufficient to treat 5% of its population; if the R0 was 2.3 or higher, the pandemic would not be contained even if 20% of the population could be treated. Finally, the researchers considered a realistic scenario in which only a few countries possess antiviral stockpiles. In these circumstances, compared with a “selfish” strategy in which countries only use their antiviral drugs within their borders, limited worldwide sharing of antiviral drugs would slow down the spread of a flu virus with an R0 of 1.9 by more than a year and would benefit both drug donors and recipients. What Do These Findings Mean? Like all mathematical models, this model for the global spread of an emerging pandemic influenza virus contains many assumptions (for example, about viral behavior) that might affect the accuracy of its predictions. The model also does not consider variations in travel frequency between individuals or viral spread in rural areas. Nevertheless, the model provides the most extensive global simulation of pandemic influenza spread to date. Reassuringly, it suggests that an emerging virus with a low R0 would not pose a major public-health threat, since its attack rate would be limited and would not peak for more than a year, by which time a vaccine could be developed. Most importantly, the model suggests that cooperative sharing of antiviral drugs, which could be organized by the World Health Organization, might be the best way to deal with an emerging influenza pandemic. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040013. The US Centers for Disease Control and Prevention has information about influenza for patients and professionals, including key facts about avian influenza and antiviral drugs The US National Institute of Allergy and Infectious Disease features information on seasonal, avian, and pandemic flu The US Department of Health and Human Services provides information on pandemic flu and avian flu, including advice to travelers World Health Organization has fact sheets on influenza and avian influenza, including advice to travelers and current pandemic flu threat The UK Health Protection Agency has information on seasonal, avian, and pandemic influenza The UK Department of Health has a feature article on bird flu and pandemic influenza

Published
2007
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