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201. Patients’ high acceptability of a future therapeutic HIV vaccine in France: a French paradox?

Author: Christophe Lalanne, Thierry Prazuck, Olivier Chassany, Pierre Verger, S. Dimi, Isabelle Aubin-Auger, Martin Duracinsky, C. Majerholc, David Zucman, Emmanuel Mortier, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), COMBE, Isabelle, Hôpital Foch [Suresnes], Recherche Clinique ville-hôpital, Méthodologies et Société (REMES), Université Paris Diderot - Paris 7 (UPD7), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des maladies infectieuses [CHR Orléans], Centre Hospitalier Régional d'Orléans (CHRO), Service de Médecine Interne (LOUIS MOURIER - Med Int), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Médecine interne-Immunologie clinique [Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)
Subjects: Male, 0301 basic medicine, HIV Infections, Confidence, Disease, 0302 clinical medicine, Medical microbiology, Acceptability, Quality of life, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Surveys and Questionnaires, 030212 general & internal medicine, HIV vaccine, AIDS Vaccines, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, Middle Aged, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Research Article, Adult, medicine.medical_specialty, Adolescent, Visual analogue scale, 030106 microbiology, Population, lcsh:Infectious and parasitic diseases, Young Adult, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Humans, lcsh:RC109-216, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, education, Aged, business.industry, HIV, Patient Acceptance of Health Care, Therapeutic vaccine, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Confidence interval, Acceptance, Cross-Sectional Studies, Family medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Forecasting
Abstract: International audience; Background: France is the European country with the lowest level of confidence in vaccines. Measurement of patients' acceptability towards a future therapeutic HIV vaccine is critically important. Thus, the aim of this study was to evaluate patients' acceptability of a future therapeutic HIV vaccine in a representative cohort of French patients living with HIV-AIDS (PLWHs). Methods: This multicentre study used quantitative and qualitative methods to assess PLWHs' opinions and their potential acceptance of a future therapeutic HIV vaccine. Cross-sectional study on 220 HIV-1 infected outpatients, aged 18-75 years. Results: The participants' characteristics were similar to those of the overall French PLWH population. Responses from the questionnaires showed high indices of acceptance: the mean score for acceptability on the Visual Analog Scale VAS was 8.4 of 10, and 92% of patients agreed to be vaccinated if a therapeutic vaccine became available. Acceptability depended on the expected characteristics of the vaccine, notably the duration of its effectiveness: 44% of participants expected it to be effective for life. This acceptance was not associated with socio-demographic, clinical (mode of contamination, duration of disease), quality of life, or illness-perception parameters. Acceptability was also strongly correlated with confidence in the treating physician. Conclusion: The PLWHs within our cohort had high indices of acceptance to a future therapeutic HIV vaccine. Trial registration: This study was retroactively registered on ClinicalTrials.gov with ID: NCT02077101 in February 21, 2014.
Published: 2019

202. Impact of radiotherapy administered simultaneously with systemic treatment in patients with melanoma brain metastases within MelBase, a French multicentric prospective cohort

Author: Stéphane Dalle, Raphaël Porcher, Thierry Lesimple, Marie-Thérèse Leccia, Jean-Philippe Lacour, Sophie Dalac, D. Legoupil, Pauline Tétu, Sameh Mohamed, A. Ballon, Florence Brunet-Possenti, Céleste Lebbé, Clara Allayous, Laurent Mortier, François Aubin, Julie De Quatrebarbes, Pierre-Emmanuel Stoebner, Caroline Dutriaux, Bastien Oriano, Brigitte Dréno, Bernard Guillot, Philippe Saiag, Marie Beylot-Barry, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Cytogénétique Constitutionnelle [Hospices civils de Lyon], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Bordeaux [Bordeaux], Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Hôpital Ambroise Paré [AP-HP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Eugène Marquis (CRLCC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), and CCSD, Accord Elsevier
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, genetic structures, Propensity score, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Systemic therapy, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Prospective Studies, cardiovascular diseases, Stage (cooking), Prospective cohort study, Melanoma, Aged, Proportional Hazards Models, Radiotherapy, Brain Neoplasms, business.industry, MESH: Brain Neoplasms/radiotherapy, Melanoma/drug therapy, Melanoma/radiotherapy, Middle Aged, Brain metastases, medicine.disease, equipment and supplies, Advanced melanoma, Combined Modality Therapy, Confidence interval, 3. Good health, Radiation therapy, 030104 developmental biology, 030220 oncology & carcinogenesis, Propensity score matching, cardiovascular system, Female, Immunotherapy, business, circulatory and respiratory physiology
Abstract: International audience; Background: Melanoma brain metastases (MBMs) are historically associated with poor prognosis. Radiation therapy is conventionally associated with a high local control rate. Development of targeted therapy and immunotherapy has improved overall survival (OS) and intracranial response rate, but about 50% of patients failed to respond to these novel therapies. The objective of this study was to assess the impact of combined radiotherapy (cRT) on overall survival in a large multicenter real-life prospective cohort of patients with MBM treated with immunotherapy or targeted therapy.Patients and methods: Clinical data from 262 patients with MBM were collected via MelBase, a French multicentric biobank prospectively enrolling unresectable stage III or IV melanoma. Two groups were defined: patients receiving cRT (cRT group) or not receiving cRT (no-cRT group). Primary end-point was OS. Propensity score weighting was used to correct for indication bias.Results: Among the 262 patients, 93 (35%) received cRT (cRT group). The patients were treated with immunotherapy in 69% and 60% and with targeted therapy in 31% and 40% of the cRT and no-cRT groups, respectively. With a median follow-up of 6.9 months, median OS was 16.8 months and 6.9 months in the cRT and no-cRT groups, respectively. After propensity score weighting, cRT was associated with longer OS (hazard ratio = 0.6, 95% confidence interval: 0.4-0.8; p=0.007). Median OS after ponderation was 15.3 months and 6.2 months in the cRT and no-cRT groups, respectively.Conclusion: This study shows that cRT may be associated with a significant decrease of 40% in the risk of death in patients with MBM treated with systemic therapy.
Published: 2019

203. Histoire naturelle d’une forme bronchectasiante de la maladie à dépôts de chaînes légères

Author: Anne Guillaumot, Emmanuel Gomez, Magali Colombat, F. Millet, Sandrine Hirschi, A. Chaouat, M.-P. Chenard, B. Mouget, I. Petit, François Chabot, Service de Pneumologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département de radiologie, Institut Gustave Roussy (IGR), Service d'Anatomo-Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: Pulmonary and Respiratory Medicine, Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, 030228 respiratory system, business.industry, [SDV]Life Sciences [q-bio], Medicine, 030212 general & internal medicine, business
Abstract: Resume Introduction L’histoire naturelle des maladies pulmonaires orphelines est rarement connue. Nous presentons l’evolution a long terme d’une forme bronchectasiante de la maladie a depots de chaines legeres (MDCL) d’immunoglobulines non amyloides. Observation Il s’agit d’une femme fumeuse chez qui le diagnostic de dilatation des bronches d’etiologie indeterminee est porte a l’âge de 50 ans. Dix ans apres, l’hypothese d’une MDCL pulmonaire est evoquee devant l’aspect caracteristique des bronchectasies, l’apparition de kyste pulmonaires, l’augmentation du taux serique des chaines legeres Kappa. La confirmation diagnostique est obtenue par biopsie pulmonaire chirurgicale. Aucune hemopathie maligne n’est retrouvee. Durant les 12 ans de suivi, l’aggravation de la dyspnee d’effort est lente et concomitante a l’extension des bronchectasies et des kystes realisant un aspect de pneumopathie multikystique. Les EFR montrent une preservation des volumes pulmonaires et une diminution moderee de la capacite de diffusion du monoxyde de carbone (DLCO). Conclusion Nous decrivons l’evolution d’une presentation rare de la MDCL pulmonaire isolee sous la forme de bronchectasies kystiques diffuses, a parois fines, non secretantes, s’associant a une destruction kystique du parenchyme pulmonaire. L’hypothese d’une MDCL pulmonaire doit etre evoquee devant des bronchectasies atypiques d’etiologie indeterminee.
Published: 2019

204. Facteurs environnementaux et génétiques déterminant la fonction thymique chez l'adulte sain

Author: Leston Araujo, Itaua, Service d'Immunologie et d'Histocompatibilité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Université Sorbonne Paris Cité, and Antoine Toubert
Subjects: TREC, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The thymus is a vital organ for homeostatic maintenance of the peripheral immune system. Age-associated thymic involution is associated with a reduction in tissue mass and thymic cellularity, loss of tissue structure and abnormal architecture leading to a decline in naïve T cell output. However, with the exception of age, the underlying parameters that govern thymic function in healthy humans remain to be defined. We characterized the variability of thymic function among 1000 age- and sex-stratified healthy adults of the Milieu Intérieur cohort, using quantification of TRECs in peripheral blood T cells as a surrogate marker of thymopoiesis. Age and sex were the only nonheritable factors identified that affect thymic function. TREC amounts decreased with age and were higher in women compared to men of all ages. In addition, a genome-wide association study revealed a common variant (rs2204985) within the T cell receptor TCRA-TCRD locus, between the DD2 and DD3 gene segments, which associated with TREC amounts. This association was validated in a replication cohort (MARTHA cohort). Strikingly, transplantation of human hematopoietic stem cells with the rs2204985 GG genotype into immunodeficient mice led to thymopoiesis with higher TRECs, increased thymocyte counts, and a higher TCR repertoire diversity. Our population immunology approach revealed a genetic locus that influences thymopoiesis in healthy children and adults, with potentially broad implications in precision medicine, especially in aging and vaccines, hematopoietic stem cell transplantation and autoimmunity. This study leads also to further study the precise mechanisms of TCRA-TCRD rearrangements at early steps of thymopoiesis.; Le thymus est un organe clé de l’immunité, permettant tout au long de la vie la production de cellules T naïves. L'involution thymique associée à l'âge est liée à une réduction de la masse tissulaire et de la cellularité thymique, ainsi que la perte de la structure tissulaire et de l’architecture normale conduisant à une baisse de la production de cellules T naïfs. Cependant, à l'exception de l'âge, les facteurs environnementaux ou génétiques susceptibles de régir la fonction thymique chez l'Homme restent mal connus. Nous avons caractérisé la variabilité de la fonction thymique chez 1000 adultes sains stratifiés par l’âge et par sexe sur la cohorte Milieu Intérieur, en utilisant la quantification des cercles d’excision (TRECs) dans le sang périphérique comme marqueur de la thymopoïèse. L'âge et le sexe sont les seuls facteurs non héritables identifiés qui affectent la fonction thymique. Les quantités de TREC diminuent avec l'âge étant plus élevée chez les femmes de tout âge. Surtout, une étude d'association pangénomique a révélé l’existence d’un variant génétique (rs2204985) dans le locus TCRA-TCRD, situé entre les segments géniques DD2 et DD3, l’allèle G étant associé à un niveau de TRECs supérieur à l’allèle A. Cette association a été validée dans une cohorte de réplication (cohorte MARTHA). La transplantation de cellules souches hématopoïétiques humaines de foie fetal avec le génotype GG dans des souris immunodéficientes est associée à une thymopoïèse accrue avec des TRECs plus élevés, une augmentation du nombre de thymocytes et aussi une plus grande diversité du répertoire TCRA-TCRD. Notre approche d’immunologie des populations a mis en évidence un variant génétique influençant la thymopoïèse l’adulte sain. Ceci pourrait avoir un impact direct en médecine dite de précision dans les domaines du vieillissement et de la vaccination, en transplantation de cellules souches hématopoïétiques, ainsi qu’en autoimmunité. Ces travaux conduisent également à étudier plus en détail les mécanismes de la thymopoïèse précoce et des réarrangements du locus TCRATCRD.
Published: 2019

205. Use of botulinum toxin A in pelvic floor dysfunctions in the elderly: A review

Author: X, Biardeau, R, Haddad, C, Chesnel, A, Charlanes, C, Hentzen, N, Turmel, S, Campagne, G, Capon, B, Fatton, X, Gamé, C, Jeandel, J, Kerdraon, P, Mares, M, Mezzadri, A-C, Petit, B, Peyronnet, J-M, Soler, C, Thuillier, X, Deffieux, G, Robain, G, Amarenco, P, Manceau, Service d'Urologie, andrologie et transplantation rénale [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital de Rangueil, CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Mutualiste de Rééducation et de Réadaptation Fonctionnelles de KERPAPE [Ploemeur] (CMRRF), Centre Mutualiste de Rééducation et de Réadaptation Fonctionnelles de Kerpape, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Service de gynécologie et obstétrique [Hopital Lariboisière - Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Centre de santé, Centre Hospitalier Universitaire [Rennes], Centre Hospitalier Universitaire [Grenoble] (CHU), CHU CLAMART, Service d'urologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Avicennes University Hospital
Subjects: Benign prostatic hyperplasia, Urinary Bladder, Overactive, Overactive bladder, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Age Factors, MESH: Botulinum Toxins, Type A / administration & dosage, Neuromuscular Agents / administration & dosage, Pelvic Floor Disorders / drug therapy, Neurogenic detrusor overactivity, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Pelvic Floor Disorders, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Injections, Urinary Bladder Neck Obstruction, Neuromuscular Agents, Dyschezia, Fecal incontinence, Humans, Botulinum Toxins, Type A, Urinary Bladder, Neurogenic, Aged
Abstract: International audience; The present article is the final report of a multi-disciplinary meeting supported by the GRAPPPA (group for research applied to pelvic floor dysfunctions in the elderly). The objective was to conduct a comprehensive review on the role of botulinum toxin A (BonTA) in the treatment of pelvic floor dysfunctions in the elderly.Methods: The present article, written as a comprehensive review of the literature, combines data issued from the scientific literature with expert's opinions. Review of the literature was performed using the online bibliographic database MedLine (National Library of Medicine). Regarding intra-detrusor BonTA injections, only articles focusing on elderly patients (>65 yo) were included. Regarding other localizations, given the limited number of data, all articles reporting outcomes of BonTA were included, regardless of studies population age. In case of missing or insufficient data, expert's opinions were formulated.Results: Although, available data are lacking in this specific population, it appears that BonTA could be used in the non-fraily elderly patients to treat overactive bladder or even neurogenic detrusor overactivity, with a success rate comparable to younger population at 3 months (88.9% vs. 91.2%), 6 months (49.4% vs. 52.1%) and 12 months (23.1% vs. 22.3%), as well as a significant decrease in number of voids per day (11.4 vs. 5.29 P
Published: 2019

206. Atypical nasal mass

Author: Xavier Dubernard, M Makeieff, E Drapier, Service d'oto-rhino-laryngologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: Male, medicine.medical_specialty, medicine.diagnostic_test, business.industry, [SDV]Life Sciences [q-bio], Nose Neoplasms, MEDLINE, Magnetic resonance imaging, Endoscopy, Nasal Mass, Middle Aged, Magnetic Resonance Imaging, 03 medical and health sciences, 0302 clinical medicine, Angiomyoma, Otorhinolaryngology, 030220 oncology & carcinogenesis, medicine, Humans, Surgery, Radiology, 030223 otorhinolaryngology, business
Published: 2019

207. A systematic review of surgical site infections following day surgery: a frequentist and a Bayesian meta-analysis of prevalence

Author: D. Pivot, C. Vons, A. Lefebvre, H.-J. Philippe, J.C. Lucet, G. Hoch, B. Grandbastien, M. Beaussier, L.S. Aho Glele, J.-P. Triboulet, K. Astruc, D. Lepelletier, Service d'épidémiologie et d'hygiène hospitalières (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpitaux Privés de Metz (HPMetz), Infection Control Unit [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: Microbiology (medical), medicine.medical_specialty, [SDV]Life Sciences [q-bio], Specialty, 030501 epidemiology, 03 medical and health sciences, Patient satisfaction, Frequentist inference, Prevalence, medicine, Humans, Surgical Wound Infection, 0303 health sciences, 030306 microbiology, business.industry, Bayes Theorem, General Medicine, Random effects model, Confidence interval, 3. Good health, Surgery, Infectious Diseases, Ambulatory Surgical Procedures, Meta-analysis, Population study, Observational study, 0305 other medical science, business
Abstract: Summary Background Since 1990, several studies have focused on safety and patient satisfaction in connection with day surgery. However, to date, no meta-analysis has investigated the overall prevalence of surgical site infections (SSI). Aim To estimate the overall prevalence of SSI following day surgery, regardless of the type of surgery. Method A systematic review and a meta-analysis of the prevalence of SSI following day surgery, regardless of the type of surgery, was conducted, seeking all studies before June 2016. A pooled random effects model using the DerSimonian and Laird approach was used to estimate overall prevalence. A double arcsine transformation was used to stabilize the variance of proportions. After performing a sensitivity analysis to validate the robustness of the method, univariate and multi-variate meta-regressions were used to test the effect of date of publication, country of study, study population, type of specialty, contamination class, time of postoperative patient visit after day surgery, and duration of hospital care. Findings Ninety articles, both observational and randomized, were analysed. The estimated overall prevalence of SSI among patients who underwent day surgery was 1.36% (95% confidence interval 1.1–1.6), with a Bayesian probability between 1 and 2% of 96.5%. The date of publication was associated with the prevalence of SSI (coefficient −0.001, P = 0.04), and the specialty (digestive vs non-digestive surgery) tended to be associated with the prevalence of SSI (coefficient 0.03, P = 0.064). Conclusion The meta-analysis showed a low prevalence of SSI following day surgery, regardless of the surgical procedure.
Published: 2019

208. How to improve vaccine acceptability (evaluation, pharmacovigilance, communication, public health, mandatory vaccination, fears and beliefs)

Author: Geneviève Chêne, Franck Gérald, Thomas Borel, Géraldine Ménin, Farid Kheloufi, Jacques Morel, Marie-Christine Truchet, Claire Roger, Franck Rouby, Véronique Lamarque-Garnier, Jehan-Michel Behier, Odile Launay, Clémentine Schilte, Mathieu Molimard, Alain Dutilleul, Véronique Dufour, Laurent Simon, Arnaud Gagneur, Stéphane Schück, Annick Opinel, Jean-Louis Koeck, François Faurisson, Benoît Soubeyrand, Brigitte Autran, Soizic Courcier, Telma Lery, Odile Gelpi, Xavier Bresse, Sanofi Pasteur [Lyon, France], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pasteur [Paris] (IP), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Takeda France, Les entreprises du Médicament (LEEM), Sanofi Pasteur MSD, Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, Laboratoire GlaxoSmithKline [ Marly-le-Roi], Infovac-France, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Sherbrooke (UdeS), ACS-France - Action Contre les Spondylarthropathies (Action Contre les Spondylarthropathies ), Assistance Publique - Hôpitaux de Marseille (APHM), Direction centrale du service de santé des armées (DCSSA), EVAL Santé, Janssen Cilag, CHU Bordeaux [Bordeaux], Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Kappa, Blossom Vaccinology, Pfizer, Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Le pharmacien de France, and CCSD, Accord Elsevier
Subjects: Vaccination Coverage, 030309 nutrition & dietetics, MESH: Pharmacovigilance, Motivational interviewing, Mandatory Programs, Pharmacovigilance, 0302 clinical medicine, Information system, Information systems, MESH: Health Education / trends, Pharmacology (medical), Health Education, Vaccines, 0303 health sciences, Schools, Communication, Vaccination, Hesitancy, MESH: Vaccination Coverage, MESH: Patient Acceptance of Health Care, Mandatory vaccination, 030205 complementary & alternative medicine, 3. Good health, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Communication, France, Public Health, MESH: Public Health, MESH: Mandatory Programs, medicine.medical_specialty, MESH: Schools, MESH: Vaccination / trends, MESH: Motivation, Education, 03 medical and health sciences, medicine, Humans, Motivation, Medical education, Immunization Programs, Public health, Patient Acceptance of Health Care, MESH: Immunization Programs / trends, MESH: France, MESH: Vaccines, Intervention (law), Immunization, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Business, Vaccine
Abstract: International audience; A flagship recommendation of the citizen's steering committee on immunization, the mandatory immunization for infants extended to 11 vaccines, introduced in January 2018, is part of a set of recommendations that must be considered as a whole, each component being indispensable to the achievement of objectives: restore confidence in vaccination and increase immunization coverage. Roundtable # 6 participants identified a decade of concrete initiatives that could address, at least in part, the committee's recommendations, including: developing information systems and data generation; simplify the vaccination journey and increase vaccination opportunities; developing training of health professionals; learning vaccines at school; using motivational interviewing in educational intervention; undertaking local initiatives; improving supply and communicate on the value of vaccines. To carry out these actions, it has been proposed that a joint ministerial task-force bringing together the different stakeholders at the national level should be set up to promote their implementation and follow-up, and at regional level, the establishment of an Agences régionales de santé awareness plan making vaccination a priority.
Published: 2019

209. Rédiger pour publier, un obstacle à la recherche médicale française ?

Author: Olivier Chassany, F Péretz, Martin Duracinsky, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: 030222 orthopedics, business.industry, Gastroenterology, Library science, Medical research, Medical writing, 03 medical and health sciences, 0302 clinical medicine, Publishing, Political science, Internal Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030212 general & internal medicine, business, Publication, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

210. Nadir CD4 Is Negatively Associated With Antinuclear Antibody Detection in HCV/HIV-Coinfected Patients

Author: Eric Rosenthal, Dominique Salmon, Laure Esterle, Didier Neau, Anne Simon, Linda Wittkop, Isabelle Poizot-Martin, Carla E. Cano, Laurent Alric, Caroline Lascoux-Combe, Camille Gilbert, Anne Gervais, Philippe Sogni, HAL AMU, Administrateur, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital l'Archet, Université de Nice Sophia-Antipolis (UNSA), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Services de Maladies Infectieuses et Tropicales [CHU Bichat], 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 de Bordeaux Pellegrin [Bordeaux], Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Bordeaux [Bordeaux], The authors thank all members of the ANRS CO13-HEPAVIH Study Group and all patients who took part in this study., Scientific Committee of the ANRS CO13 HEPAVIH Study Group: D. Salmon (co-Principal investigator), L. Wittkop (co-Principal Investigator), P. Sogni (co-Principal Investigator), L. Esterle (project manager), P. Trimoulet, J. Izopet, L. Serfaty, V. Paradis, B. Spire, P. Carrieri, M.A. Valantin, G. Pialoux, J. Chas, I. Poizot-Martin, K. Barangue, A. Naqvi, E. Rosenthal, A. Bicart-See, O. Bouchaud, A. Gervais, C. Lascoux-Combe, C. Goujard, K. Lacombe, C. Duvivier, D. Vittecoq, D. Neau, P. Morlat, F. Bani-Sadr, L. Meyer, F. Boufassa, S. Dominguez, B. Autran, A.M. Roque, C. Solas, H. Fontaine, D. Costagliola, L. Piroth, A. Simon, D. Zucman, F. Boué, P. Miailhes, E. Billaud, H. Aumaître, D. Rey, G. Peytavin, V. Petrov-Sanchez, and A. Pailhe., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Service de Médecine Interne [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Pôle Digestif [purpan], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service des maladies infectieuses et tropicales, hôpital Pellegrin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service d'Information médicale [Bordeaux], Pôle de Santé publique [Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)
Subjects: Male, medicine.medical_specialty, Anti-nuclear antibody, Cross-sectional study, Hepatitis C virus, T-Lymphocytes, HIV Infections, Hepacivirus, 030312 virology, Logistic regression, medicine.disease_cause, Autoimmune Diseases, 03 medical and health sciences, Immunophenotyping, Internal medicine, medicine, Humans, Pharmacology (medical), anti–liver kidney microsome antibodies, non–organ-specific autoantibodies, 0303 health sciences, biology, business.industry, Coinfection, anti–smooth muscle actin antibodies, Middle Aged, Hepatitis C, Actins, 3. Good health, CD4 Lymphocyte Count, Infectious Diseases, Cross-Sectional Studies, autoimmune antinuclear, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Antibodies, Antinuclear, Cohort, biology.protein, HIV-1, Microsomes, Liver, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, HCV–HIV coinfection, Antibody, nadir CD4, business, Nadir (topography)
Abstract: Background: Hepatitis C virus (HCV) and HIV infections are associated with higher risk of autoimmune diseases and T-cell dysfunction. Setting: We evaluate prevalence and factors associated with the presence of autoimmune antinuclear (ANA), anti–smooth muscle actin (aSMA), and anti–liver kidney microsome (aLKM1) antibodies (Ab) in HCV/HIV-coinfected patients during the post–combined antiretroviral therapy era. Methods: A cross-sectional observational study nested in the ANRS CO13 HEPAVIH cohort (NCT number: NCT03324633). We selected patients with both ANA testing and T-cell immunophenotyping determination during the cohort follow-up and collected aLKM1 and aSMA data when available. Logistic regression models were built to determine factors associated with the presence of auto-Ab. Results: Two hundred twenty-three HCV/HIV-coinfected patients fulfilled selection criteria. Prevalence of ANA and aSMA was 43.5% and 23.2%, respectively, and both were detected in 13.3% of patients. Isolated aSMA were detected in 9.9% and aLKM1 in 2 patients. In multivariable analysis, only a low nadir CD4 T-cell count was significantly associated with ANA detection. Conclusions: ANA and aSMA detection remain frequent in HCV/HIV-coinfected patients during the post–combined antiretroviral therapy era, despite fair immune restoration. These results advocate for a close monitoring of ANA before immune checkpoint inhibitor therapy in these patients with greater caution for those with a low nadir CD4 T-cell count.
Published: 2019

211. Awareness among French healthcare workers of the transmission of multidrug resistant organisms: a large cross-sectional survey

Author: L, Vaillant, G, Birgand, M, Esposito-Farese, P, Astagneau, C, Pulcini, J, Robert, J R, Zahar, E, Sales-Wuillemin, F, Tubach, J C, Lucet, Lestra, Bénédicte, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imperial College London, Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Hôpital Avicenne [AP-HP], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Laboratoire de Socio-Psychologie et Management du Sport (SPMS), Université de Bourgogne (UB), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, Département d’Epidémiologie et Recherche Clinique [AP-HP Hôpital Bichat - Claude Bernard] (CIC‑EC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Hôpital avicenne, Hôpital Avicenne-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Sorbonne Paris Nord, Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), and Salès-Wuillemin, Edith
Subjects: 0301 basic medicine, Male, Cross-sectional study, Psychological intervention, [SHS.PSY]Humanities and Social Sciences/Psychology, Hand disinfection, Logistic regression, Cross-infection/ *prevention & control, 0302 clinical medicine, Hygiene, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Health care, Pharmacology (medical), 030212 general & internal medicine, media_common, education.field_of_study, Cross Infection, Drug resistance, bacterial, attitudes, Cognition, Drug Resistance, Microbial, Middle Aged, Drug Resistance, Multiple, practice, 3. Good health, Infectious Diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cross-sectional studies, Female, France, Microbiology (medical), Adult, medicine.medical_specialty, Cross-infection/*prevention & control, Attitude of Health Personnel, media_common.quotation_subject, Health Personnel, 030106 microbiology, Population, education, lcsh:Infectious and parasitic diseases, [SHS.PSY] Humanities and Social Sciences/Psychology, 03 medical and health sciences, medicine, Health knowledge, Humans, Healthcare workers, lcsh:RC109-216, bacterial, Infection Control, business.industry, Research, Health knowledge, attitudes, practice, Public Health, Environmental and Occupational Health, Odds ratio, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Family medicine, Drug resistance, Perception, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Health Facilities, business, Factor Analysis, Statistical, Surveys and questionnaires, Health personnel/classification/education
Abstract: Background Much effort has been made over the last two decades to educate and train healthcare professionals working on antimicrobial resistance in French hospitals. However, little has been done in France to assess perceptions, attitudes and knowledge regarding multidrug resistant organisms (MDROs) and, more globally, these have never been evaluated in a large-scale population of medical and non-medical healthcare workers (HCWs). Our aim was to explore awareness among HCWs by evaluating their knowledge of MDROs and the associated control measures, by comparing perceptions between professional categories and by studying the impact of training and health beliefs. Methods A multicentre cross-sectional study was conducted in 58 randomly selected French healthcare facilities with questionnaires including professional and demographic characteristics, and knowledge and perception of MDRO transmission and control. A knowledge score was calculated and used in a logistic regression analysis to identify factors associated with higher knowledge of MDROs, and the association between knowledge and perception. Results Between June 2014 and March 2016, 8716/11,753 (participation rate, 74%) questionnaires were completed. The mean knowledge score was 4.7/8 (SD: 1.3) and 3.6/8 (SD: 1.4) in medical and non-medical HCWs, respectively. Five variables were positively associated with higher knowledge: working in a university hospital (adjusted odds ratio, 1.41, 95% CI 1.16–1.70); age classes 26–35 years (1.43, 1.23–1.6) and 36–45 years (1.19, 1.01–1.40); medical professional status (3.7, 3.09–4.44), working in an intensive care unit (1.28, 1.06–1.55), and having been trained on control of antimicrobial resistance (1.31, 1.16–1.48). After adjustment for these variables, greater knowledge was significantly associated with four cognitive factors: perceived susceptibility, attitude toward hand hygiene, self-efficacy, and motivation. Conclusions We found a low level of MDRO awareness and knowledge of associated control measures among French HCWs. Training on hand hygiene and measures to control MDRO spread may be helpful in shaping beliefs and perceptions on MDRO control among other possible associated factors. Messages should be tailored to professional status and their perception. Other approaches should be designed, with more effective methods of training and cognitive interventions. Trial registration Clinical Trials.gov NCT02265471. Registered 16 October 2014 - Retrospectively registered.
Published: 2019

212. Development and Evaluation of a New Serious Game for Continuing Medical Education of General Practitioners (Hygie): Double-Blinded Randomized Controlled Trial

Author: Philippe Zerr, Léandre Renouard, Hervé Picard, Martin Duracinsky, Louis-Baptiste Jaunay, Lino Peguin, James W. Griffith, Olivier Chassany, Anne-Sophie Ivanoff, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: Male, 020205 medical informatics, media_common.quotation_subject, education, continuing medical education, Health Informatics, Qualitative property, 02 engineering and technology, law.invention, Double-Blind Method, Continuing medical education, Randomized controlled trial, General Practitioners, law, Reading (process), Intervention (counseling), 0202 electrical engineering, electronic engineering, information engineering, Humans, Video game, media_common, general practice, Original Paper, Medical education, Evidence-Based Medicine, pedagogy, Teaching, 4. Education, 05 social sciences, 050301 education, video games, Evidence-based medicine, 3. Good health, Clinical trial, randomized controlled trial, Education, Medical, Continuing, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Psychology, 0503 education
Abstract: Background Continuing medical education is important but time-consuming for general practitioners (GPs). Current learning approaches are limited and lack the ability to engage some practitioners. Serious games are new learning approaches that use video games as engaging teaching material. They have significant advantages in terms of efficiency and dissemination. Objective The aim of this study was to create a serious game and to evaluate it in terms of effectiveness and satisfaction, comparing it with a traditional method of continuing education—article reading. Methods We produced a prototype video game called Hygie on the 5 most common reasons of consultation in general practice using 9 articles from independent evidence-based medicine journals (reviews from Prescrire and Minerva). We created 51 clinical cases. We then conducted a double-blinded randomized trial comparing the learning provided by a week of access to the game versus source articles. Participants were GPs involved as resident supervisors in 14 French university departments of family practice, recruited by email. Primary outcomes were (1) mean final knowledge score completed 3 to 5 weeks after the end of the intervention and (2) mean difference between knowledge pretest (before intervention) and posttest (3 to 5 weeks after intervention) scores, both scaled on 10 points. Secondary outcomes were transfer of knowledge learned to practice, satisfaction, and time spent playing. Results A total of 269 GPs agreed to participate in the study. Characteristics of participants were similar between learning groups. There was no difference between groups on the mean score of the final knowledge test, with scores of 4.9 (95% CI 4.6-5.2) in the Hygie group and 4.6 (95% CI 4.2-4.9) in the reading group (P=.21). There was a mean difference score between knowledge pre- and posttests, with significantly superior performance for Hygie (mean gain of 1.6 in the Hygie group and 0.9 in the reading group; P=.02), demonstrating a more efficient and persistent learning with Hygie. The rate of participants that reported to have used the knowledge they learned through the teaching material was significantly superior in the Hygie group: 77% (47/61) in the Hygie group and 53% (25/47) in the reading group; odds ratio 2.9, 95% CI 1.2-7.4. Moreover, 87% of the opinions were favorable, indicating that Hygie is of interest for updating medical knowledge. Qualitative data showed that learners enjoyed Hygie especially for its playful, interactive, and stimulating aspects. Conclusions We conclude that Hygie can diversify the offering for continuing education for GPs in an effective, pleasant, and evidence-based way. Trial Registration ClinicalTrials.gov NCT03486275; https://clinicaltrials.gov/ct2/show/NCT03486275
Published: 2019

213. Innate gene signature distinguishes humoral versus cytotoxic responses to influenza vaccination

Author: Nicolas Tchitchek, Angèle Soria, Olivia Bonduelle, Marine Cachanado, Henri Bonnabau, Tabassome Simon, Sylvie Behillil, Béhazine Combadière, Rodolphe Thiébaut, Sylvie van der Werf, Pierre Loulergue, Annika Vogt, Odile Launay, Elena Gonçalves, Alexandra Rousseau, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de Ressources Biologiques APHP-SU (PASS-CRB-APHP-SU), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Admin, Oskar
Subjects: Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], CD8-Positive T-Lymphocytes, Clinical practice, Antibodies, Viral, Granzymes, Influenza A Virus, H1N1 Subtype, 0302 clinical medicine, ComputingMilieux_MISCELLANEOUS, Innate immunity, Immunity, Cellular, Vaccines, Immunogenicity, Vaccination, Antibody titer, General Medicine, Middle Aged, Acquired immune system, 3. Good health, Influenza Vaccines, 030220 oncology & carcinogenesis, Female, Antibody, Adult, Trivalent influenza vaccine, Adolescent, Immunology, Biology, Young Adult, 03 medical and health sciences, Immune system, Influenza, Human, Humans, Innate immune system, Gene Expression Profiling, Influenza A Virus, H3N2 Subtype, Influenza, Immunity, Humoral, Chemokine CXCL10, 030104 developmental biology, Immunization, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Antibody Formation, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Clinical Medicine, Transcriptome, T-Lymphocytes, Cytotoxic
Abstract: BACKGROUND. Systems vaccinology allows cutting-edge analysis of innate biomarkers of vaccine efficacy. We explored a strategy to shape the adaptive immune response by targeting innate immune cells through novel immunization routes. METHODS. This randomized phase I/II clinical study (n = 60 healthy subjects aged 18–45 years old) used transcriptomic analysis to discover early biomarkers of immune response quality after transcutaneous (t.c.), intradermal (i.d.), and intramuscular (i.m.) administration of a trivalent influenza vaccine (TIV, season 2012–2013, 1:1:1 ratio). Safety and immunogenicity (hemagglutinin inhibition [HI], microneutralization [MN] antibodies, and CD4+ and CD8+ effector T cells) were measured at baseline day 0 (d0) and at d21. Blood transcriptome was analyzed at d0 and d1. RESULTS. TIV-specific CD8+ granzyme B+ (GRZ) T cells appeared in more individuals immunized by the t.c. and i.d. routes, whereas immunization by the i.d. and i.m. routes prompted high levels of HI antibody titers and MN against A/H1N1 and A/H3N2 influenza viral strains. The early innate gene signature anticipated immunological outcome by discriminating 2 clusters of individuals with either distinct humoral or CD8 cytotoxic responses. Several pathways explained this dichotomy and confirmed that 9 genes and the serum level of CXCL10 were correlated with either TIV-specific cytotoxic CD8+GRZ+ T cell or antibody responses. A logistic regression analysis demonstrated that these 9 genes and the serum levels of CXCL10 at d1/d0 best predicted TIV-specific CD8+GRZ+ T cell and antibody responses at d21. CONCLUSION. This study provides new insight into the impact of immunization routes and innate signature in the quality of adaptive immune responses. TRIAL REGISTRATION. This study has been registered at ClinicalTrials.gov (NCT01707602). FUNDING. This work was supported by grants from the French Ministry of Health PHRCN 2012 – RCT 12061, INSERM-DGOS, the Fondation pour la Recherche Médicale, and the Société Française de Dermatologie (to AS). These funding sources had no direct role in any aspect of the research or article.
Published: 2019

214. Analysis of the Recomposition of Norms and Representations in the Field of Psychiatry and Mental Health in the Age of Electronic Mental Health: Qualitative Study

Author: Bianca De Rosario, Xavier Briffault, Soraya Kabbaj, Jean-Luc Roelandt, Déborah Sebbane, Vincent Demassiet, Margot Morgiève, CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société (CERMES3 - UMR 8211 / U988 / UM 7), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-École des hautes études en sciences sociales (EHESS), Etablissement Public de Santé mentale de l'Agglomération Lilloise, Centre Collaborateur de l'Organisation Mondiale de la Santé pour la recherche et la formation en santé mentale (CC-OMS), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), École des hautes études en sciences sociales (EHESS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), École des hautes études en sciences sociales (EHESS)-Université Paris Descartes - Paris 5 (UPD5)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), and École des hautes études en sciences sociales (EHESS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: caregivers, ehealth, media_common.quotation_subject, users, Grounded theory, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, eHealth, qualitative analysis, 030212 general & internal medicine, Empowerment, media_common, Medical education, Original Paper, Social work, Mental health, Focus group, psychiatry, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, digital tools, social representations, focus group, Psychology, Autonomy, mental health, Qualitative research
Abstract: Background For the World Health Organization, electronic health (eHealth) is seen as an effective way to improve therapeutic practices and disease prevention in health. Digital tools lead to major changes in the field of mental medicine, but specific analyses are required to understand and accompany these changes. Objective Our objective was to highlight the positions of the different stakeholders of the mental health care system on eHealth services and tools, as well as to establish professional and user group profiles of these positions and the uses of these services. Methods In order to acquire the opinions and expectations of different categories of people, we carried out a qualitative study based on 10 focus groups (n=70, from 3-12 people per group) composed of: general practitioners, psychiatrists, psychologists, social workers, occupational therapists, nurses, caregivers, mental health services users, user representatives, and the general public. The analyses of focus group discussions were performed independently by four investigators through a common analysis grid. The constant comparative method was adopted within this framework. Results The interviewees expressed different problems that new technologies engender in the field of mental health. What was previously strictly under the jurisdiction of physicians now tends to be fragmented and distributed over different groups and locations. New technologies reposition care in the field of domestic, rather than therapeutic, activities, and thus the conception of care as an autonomous activity in the subject’s life is questioned. The ideal of social autonomy through technology is part of the new logic of health democracy and empowerment, which is linked to a strong, contemporary aspiration to perform. Participants emphasized that there was the potential risk of a decrease in autonomy for the digitally engaged patient, while personal empowerment could become a set of obligations. Conclusions This qualitative research highlights the heterogeneity of opinions among the groups and within each group. It suggests that opinions on electronic mental health devices are still far from being stabilized, and that a change management process should be set up to both regulate the development and facilitate the use of these tools.
Published: 2019

215. Liver stiffness and fibrosis-4 alone better predict liver events compared with aspartate aminotransferase to platelet ratio index in a cohort of human immunodeficiency virus and hepatitis C virus co-infected patients from ANRS CO13 HEPAVIH cohort

Author: Laurent Alric, Christine Katlama, Lionel Piroth, Julie Chas, Karine Lacombe, Linda Wittkop, Alissa Naqvi, Eric Rosenthal, Philippe Sogni, Laure Esterle, Didier Neau, Daniel Vittecoq, Dominique Salmon, Isabelle Poizot-Martin, Philippe Morlat, Daniel Garipuy, Karl Barange, Caroline Lascoux-Combe, Anne Gervais, Patrick Miailhes, Mathieu Chalouni, Hugues Aumaitre, Olivier Bouchaud, Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Services des Maladies Infectieuses et Tropicales [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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [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), Service de Maladies Infectieuses et Tropicales [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service des maladies infectieuses et tropicales, hôpital Pellegrin, CHU Bordeaux [Bordeaux], Service des maladies infectieuses [CH Perpignan], Centre Hospitalier Saint Jean de Perpignan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service de Maladies Infectieuses et Tropicales [CHU Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de maladies infectieuses et tropicales [CHU Avicenne], Hôpital Avicenne [AP-HP], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Hôpital Saint-André, Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital l'Archet, Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Hôpital Joseph Ducuing, Service de Gastro-entérologie - Hépatologie [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Maladies infectieuses et tropicales [CHU Tenon], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Hôpital Joseph Ducuing - Varsovie [Toulouse] (HJD), Pôle Maladies de l'appareil digestif [CHU Toulouse], HAL AMU, Administrateur, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Liver Cirrhosis, Male, Cirrhosis, HIV Infections, medicine.disease_cause, Gastroenterology, 0302 clinical medicine, Stage (cooking), 10. No inequality, noninvasive markers, Coinfection, Liver Neoplasms, Age Factors, Alanine Transaminase, Hepatitis C, Middle Aged, 3. Good health, Liver, 030220 oncology & carcinogenesis, Cohort, liver-related events, Elasticity Imaging Techniques, Female, 030211 gastroenterology & hepatology, Gastrointestinal Hemorrhage, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Hepatorenal Syndrome, Hepatitis C virus, Esophageal and Gastric Varices, Risk Assessment, 03 medical and health sciences, Insulin resistance, Internal medicine, medicine, Humans, Aspartate Aminotransferases, Hepatology, Receiver operating characteristic, Platelet Count, business.industry, prediction, Hepatitis C, Chronic, medicine.disease, human immunodeficiency virus/hepatitis C virus co-infection, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Hepatic Encephalopathy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: International audience; Objectives HIV/hepatitis C virus (HCV) co-infection leads to major complications, and noninvasive markers developed to stage liver fibrosis could be used as prognostic markers. We aimed to compare the performances of liver stiffness (LS), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI) to predict liver-related events in HIV/HCV co-infected patients.Patients and methods HIV/HCV co-infected patients from the ANRS CO13 HEPAVIH cohort were included if they had LS, FIB-4, and APRI measurements done in a window of 3 months. Primary outcome was the time between inclusion and occurrence of a liver-related event. Univariable and multivariable Fine and Gray models were performed. Predictive performances were compared by the area under the receiver operating characteristic (AUROC) differences after correction of optimistic by bootstrap samples. Best cutoffs to predict liver-related events were estimated by sensitivity and specificity maximization.Results A total of 998 patients were included. Overall, 70.7% were men. Their median age was 46.8 years. According to LS value, 204 (20.4%) patients had cirrhosis. Overall, 39 patients experienced at least one liver-related event. In univariable analysis, LS AUROC curve was significantly superior to FIB-4 and APRI AUROC curves, being 87.9, 78.2, and 75.0%, respectively. After adjustment on age, CD4 levels, and insulin resistance, no differences were observed. The best cutoffs to identify patients at low or high risk of liver-related events were below 8.5, 1.00, and 0.35 and above 16.5, 4.00, and 1.75 for LS, FIB-4, and APRI, respectively.Conclusion To predict HCV-related events, APRI had lower performance than LS and FIB-4. FIB-4 is as good as LS to predict HCV-related events, suggesting that it can be used for the management of HIV/HCV co-infected patients and replace LS.
Published: 2019

216. The Artificial Kidney Initiation in Kidney Injury 2 (AKIKI2): study protocol for a randomized controlled trial

Author: Béatrice La Combe, Guillaume Thiery, Guillaume Lacave, Julio Badie, Julien Mayaux, Guillaume Louis, Dimitri Titeca-Beauport, Nicolas Chudeau, Didier Thevenin, Nadia Aissaoui, Jean Reignier, Jean Marie Forel, Eric Boulet, Marc Leone, Laurent Argaud, Karim Asehnoune, Adrien Robine, Elisabeth Coupez, Bertrand Pons, Laurent Martin-Lefevre, Sébastien Besset, Guillaume Geri, Jean Pierre Quenot, Marion Beuzelin, Nicolas de Prost, Steven Grangé, Florent Poirson, Saber Barbar, Karim Lakhal, David Hajage, Stéphane Gaudry, Julien Bohé, Christophe Vinsonneau, Alain Combes, Didier Dreyfuss, Jean-Damien Ricard, Saad Nseir, Guillaume Chevrel, Kada Klouche, Sébastien Moschietto, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPC), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Service de Néphrologie-Dialyse-Transplantation [CHU Amiens-Picardie], CHU Amiens-Picardie, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Service de réanimation médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Réanimation Médico-Chirurgicale [Hôpital Louis Mourier], Hôpital Louis Mourier - AP-HP [Colombes], Centre hospitalier de Dieppe, Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), Hôpital les oudaries, Service de Réanimation Médicale Sud, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre hospitalier Marc Jacquet (Melun), Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Service de soins intensifs [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Urgence respiratoire et réanimation médicale, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Service d'anesthésie et réanimation chirurgicale [Nantes], Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunologie - Immunopathologie - Immunothérapeutique (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital avicenne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Service de Biostatistique Santé Publique et Information Médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-CHU Saint Louis [APHP], Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical ICU, Avenue Albert Raymond, Saint-Priest en Jarez 42270, France, Saint-Etienne University Hospital, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de Tribologie et Dynamique des Systèmes (LTDS), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Ecole Nationale d'Ingénieurs de Saint Etienne-Centre National de la Recherche Scientifique (CNRS), Institut de géologie, Université Scientifique et Médicale de Grenoble, CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-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), Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Ecologie et Evolution des Microorganismes (EEM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Time Factors, Hyperkalemia, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), 030204 cardiovascular system & hematology, Kidney, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, law.invention, Time-to-Treatment, 03 medical and health sciences, Study Protocol, 0302 clinical medicine, Randomized controlled trial, law, Oliguria, medicine, Humans, Multicenter Studies as Topic, Pharmacology (medical), 030212 general & internal medicine, Renal replacement therapy, Prospective Studies, Treatment outcome, Randomized Controlled Trials as Topic, Mechanical ventilation, lcsh:R5-920, business.industry, Acute kidney injury, Recovery of Function, Interim analysis, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, Critical care, Anesthesia, Anuria, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, medicine.symptom, business, lcsh:Medicine (General), Kidneys, Artificial
Abstract: Background The Artificial Kidney Initiation in Kidney Injury (AKIKI) trial showed that a delayed renal replacement therapy (RRT) strategy for severe acute kidney injury (AKI) in critically ill patients was safe and associated with major reduction in RRT initiation compared with an early strategy. The five criteria which mandated RRT initiation in the delayed arm were: severe hyperkalemia, severe acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia, serum urea concentration > 40 mmol/l and oliguria/anuria > 72 h. However, duration of anuria/oliguria and level of blood urea are still criteria open to debate. The objective of the study is to compare the delayed strategy used in AKIKI (now termed “standard”) with another in which RRT is further delayed for a longer period (termed “delayed strategy”). Methods/design This is a prospective, multicenter, open-label, two-arm randomized trial. The study is composed of two stages (observational and randomization stages). At any time, the occurrence of a potentially severe condition (severe hyperkalemia, severe metabolic or mixed acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia) suggests immediate RRT initiation. Patients receiving (or who have received) intravenously administered catecholamines and/or invasive mechanical ventilation and presenting with AKI stage 3 of the KDIGO classification and with no potentially severe condition are included in the observational stage. Patients presenting a serum urea concentration > 40 mmol/l and/or an oliguria/anuria for more than 72 h are randomly allocated to a standard (RRT is initiated within 12 h) or a delayed RRT strategy (RRT is initiated only if an above-mentioned potentially severe condition occurs or if the serum urea concentration reaches 50 mmol/l). The primary outcome will be the number of RRT-free days at day 28. One interim analysis is planned. It is expected to include 810 patients in the observational stage and to randomize 270 subjects. Discussion The AKIKI2 study should improve the knowledge of RRT initiation criteria in critically ill patients. The potential reduction in RRT use allowed by a delayed RRT strategy might be associated with less invasive care and decreased costs. Enrollment is ongoing. Inclusions are expected to be completed by November 2019. Trial registration ClinicalTrials.gov, ID: NCT03396757. Registered on 11 January 2018.
Published: 2019

217. Prediction of an acute hypotensive episode during an ICU hospitalization with a super learner machine learning algorithm

Author: Etienne Gayat, Romain Pirracchio, Matthieu Resche-Rigon, Ményssa Cherifa, Antoine Chambaz, Alice Blet, Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-CHU Saint Louis [APHP], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Anesthésie-Réanimation, Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Department of Anesthesia, Burn and Critical Care, University Hospitals Saint-Louis - Lariboisière, AP-HP, Paris, France., Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Department of Anesthesia, Burn and Critical Care, University Hospitals Saint-Louis - Lariboisière, AP-HP, Paris, France, Department of Anesthesia and Peri-operative Care, University of California, San Francisco, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint Louis [APHP]-Institut national du cancer [Boulogne] (INCA), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Université Paris Descartes - Paris 5 (UPD5), Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)
Subjects: Male, Sedation, medicine.medical_treatment, law.invention, Cohort Studies, Machine Learning, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, law, Predictive Value of Tests, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Intensive care, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Mechanical ventilation, Receiver operating characteristic, medicine.diagnostic_test, business.industry, Middle Aged, Intensive care unit, Confidence interval, Hospitalization, Pulse oximetry, Intensive Care Units, Anesthesiology and Pain Medicine, Brier score, Acute Disease, Female, medicine.symptom, Hypotension, business, Algorithm, 030217 neurology & neurosurgery, Algorithms
Abstract: International audience; Background: Acute hypotensive episodes (AHE), defined as a drop in the mean arterial pressure (MAP)
Published: 2019

218. Reducing mortality in newly diagnosed standard-risk acute promyelocytic leukemia in elderly patients treated with arsenic trioxide requires major reduction of chemotherapy: a report by the French Belgian Swiss APL group (APL 2006 trial)

Author: Sylvie Chevret, Olivier Spertini, Xavier Thomas, Gandhi Damaj, Dominique Bordessoule, Lionel Adès, Ramy Rahmé, Arnaud Pigneux, Julie Lejeune, Sebastian Wittnebel, Jean Pierre Marolleau, Sylvie Castaigne, Emmanuel Raffoux, Norbert Vey, Pierre Fenaux, Agnès Guerci-Bresler, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Bordeaux [Bordeaux], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier de Versailles André Mignot (CHV), University of Lausanne (UNIL), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Amiens-Picardie, Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Service de biostatistiques et information médicale [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), DESSAIVRE, Louise, Université de Lausanne = University of Lausanne (UNIL), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité)
Subjects: Acute promyelocytic leukemia, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Newly diagnosed, Disease-Free Survival, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Arsenic Trioxide, Leukemia, Promyelocytic, Acute, Standard Risk, Internal medicine, medicine, Humans, Arsenic trioxide, Online Only Articles, Survival rate, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Chemotherapy, business.industry, Hematology, medicine.disease, [SDV] Life Sciences [q-bio], Clinical trial, Survival Rate, Leukemia, chemistry, 030220 oncology & carcinogenesis, Female, business, 030215 immunology
Abstract: International audience; No abstract available
Published: 2018

219. Pharmacodynamics of eftrenonacog-alfa (rFIX-Fc) in severe hemophilia B patients: A real-life study

Author: Emmanuel Curis, Valérie Roussel-Robert, Michaela Fontenay, Jérôme Duchemin, Amélie Launois, Fiona Furlan, Syrine Ellouze, Natalie Stieltjes, Georges Jourdi, Senade Atsou, Elise Sourdeau, Sophie Combe, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Laboratoire de biomathématiques, EA 7537 [Paris] (BioSTM), Université Paris Cité - UFR Pharmacie [Santé] (UPCité UFR Pharmacie), Université Paris Cité (UPCité)-Université Paris Cité (UPCité), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CCSD, Accord Elsevier, Université de Paris (UP), Université de Paris - UFR Pharmacie [Santé] (UP UFR Pharmacie), Université de Paris (UP)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Recombinant Fusion Proteins, Urology, Hemophilia B, Severity of Illness Index, Thrombin generation, Factor IX, Young Adult, 03 medical and health sciences, Tissue factor, 0302 clinical medicine, Predictive Value of Tests, Extended half-life factor IX, Eftrenonacog alfa, Humans, Medicine, Aged, Pharmacology, Hemostasis, Coagulants, business.industry, Reproducibility of Results, One-stage clotting assay, Middle Aged, Immunoglobulin Fc Fragments, [SDV] Life Sciences [q-bio], Treatment Outcome, 030104 developmental biology, Pharmacodynamics, Mixed effects, Time to peak, Thrombin generation assay, Blood Coagulation Tests, Drug Monitoring, business, Life study, Chromogenic assay, 030217 neurology & neurosurgery
Abstract: International audience; Eftrenonacog-alfa is a recombinant factor IX-Fc fusion protein increasingly prescribed in hemophilia B patients. We aimed to assess its pharmacodynamics (PD) in real-life setting via FIX activity measurement and thrombin generation assay (TGA). Sixty samples from 15 severe hemophilia B treated patients were collected at different time points. FIX activity was measured using product-specific one-stage clotting assay (reference method) and two chromogenic assays (CSA) (Biophen FIX and Rox FIX). TGA was triggered with 1 pM tissue factor. Five parameters were analyzed: lag time (LT), time to peak (TTP), peak height (PH), endogenous thrombin potential (ETP), and velocity. PD models were built to characterize their relationships with FIX activity, using mixed effects models. Mean trough FIX level was estimated at 4.64 (±1.50) IU/dl with a recovery at 0.78 (±0.16) IU/dl per 1 IU/kg injected dose. FIX activity ranged between 1 and 86 IU/dl with 21.5 IU/dl median value. Biophen FIX and Rox FIX allowed reliable measurements except in samples with FIX 30%). PD models revealed that velocity was the most sensitive TGA parameter to FIX activity followed by PH, ETP, TTP and finally LT. Following FIX activity peak after eftrenonacog-alfa injection, velocity decreased first, followed by PH then ETP. Both CSA failed to accurately measure FIX in severe hemophilia B patients receiving eftrenonacog-alfa throughout the measuring range. TGA could be an additional valuable tool to evaluate hemostasis balance in treated patients.
Published: 2021

220. Assessment of Machine Learning to Estimate the Individual Treatment Effect of Corticosteroids in Septic Shock

Author: Charles L. Sprung, Alan Hubbard, Romain Pirracchio, Sylvie Chevret, Djillali Annane, HAL UVSQ, Équipe, San Francisco General Hospital Medical Center [San Francisco, CA, USA], Fielding School of Public Health, University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Hadassah Hebrew University Medical Center [Jerusalem], Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-18-RHUS60004, University of California-University of California, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: Male, Critical Care, Hydrocortisone, Organ Dysfunction Scores, Clinical Decision-Making, 030204 cardiovascular system & hematology, Machine learning, computer.software_genre, law.invention, Machine Learning, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Interquartile range, Intensive care, medicine, Humans, 030212 general & internal medicine, Glucocorticoids, Aged, Randomized Controlled Trials as Topic, Septic shock, business.industry, Absolute risk reduction, General Medicine, Prognosis, medicine.disease, Shock, Septic, 3. Good health, Intensive Care Units, SAPS II, Fludrocortisone, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Risk Adjustment, Artificial intelligence, business, computer, Cohort study
Abstract: International audience; Importance: The survival benefit of corticosteroids in septic shock remains uncertain. Objective: To estimate the individual treatment effect (ITE) of corticosteroids in adults with septic shock in intensive care units using machine learning and to evaluate the net benefit of corticosteroids when the decision to treat is based on the individual estimated absolute treatment effect. Design, Setting, and Participants: This cohort study used individual patient data from 4 trials on steroid supplementation in adults with septic shock as a training cohort to model the ITE using an ensemble machine learning approach. Data from a double-blinded, placebo-controlled randomized clinical trial comparing hydrocortisone with placebo were used for external validation. Data analysis was conducted from September 2019 to February 2020. Exposures: Intravenous hydrocortisone 50 mg dose every 6 hours for 5 to 7 days with or without enteral 50 μg of fludrocortisone daily for 7 days. The control was either the placebo or usual care. Main Outcomes and Measures: All-cause 90-day mortality. Results: A total of 2548 participants were included in the development cohort, with median (interquartile range [IQR]) age of 66 (55-76) years and 1656 (65.0%) men. The median (IQR) Simplified Acute Physiology Score (SAPS II) was 55 [42-69], and median (IQR) Sepsis-related Organ Failure Assessment score on day 1 was 11 (9-13). The crude pooled relative risk (RR) of death at 90 days was 0.89 (95% CI, 0.83 to 0.96) in favor of corticosteroids. According to the optimal individual model, the estimated median absolute risk reduction was of 2.90% (95% CI, 2.79% to 3.01%). In the external validation cohort of 75 patients, the area under the curve of the optimal individual model was 0.77 (95% CI, 0.59 to 0.92). For any number willing to treat (NWT; defined as the acceptable number of people to treat to avoid 1 additional outcome considering the risk of harm associated with the treatment) less than 25, the net benefit of treating all patients vs treating nobody was negative. When the NWT was 25, the net benefit was 0.01 for the treat all with hydrocortisone strategy, -0.01 for treat all with hydrocortisone and fludrocortisone strategy, 0.06 for the treat by SAPS II strategy, and 0.31 for the treat by optimal individual model strategy. The net benefit of the SAPS II and the optimal individual model treatment strategies converged to zero for a smaller number willing to treat, but the individual model was consistently superior than model based on the SAPS II score. Conclusions and Relevance: These findings suggest that an individualized treatment strategy to decide which patient with septic shock to treat with corticosteroids yielded positive net benefit regardless of potential corticosteroid-associated side effect
Published: 2020

221. Low prevalence of Cutibacterium acnes in prostatic tissue biopsies in a French hospital

Author: A.-L. Bidaud, C. Kandel-Aznar, L. Ruffier d'Epenoux, Stéphane Corvec, Pascale Bémer, Anne-Gaëlle Leroy, Aurélie Guillouzouic, G. Karam, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), CCSD, Accord Elsevier, Service d'Anatomo-Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: Male, Pathology, medicine.medical_specialty, Biopsy, [SDV]Life Sciences [q-bio], Microbiology, Phylotypes, 03 medical and health sciences, Molecular level, Prostate, Prevalence, medicine, Humans, Prospective Studies, Gram-Positive Bacterial Infections, Aged, 030304 developmental biology, Prostatic tissue, Inflammation, Mobiluncus, 0303 health sciences, Cutibacterium acnes, 030306 microbiology, business.industry, Propionibacteriaceae, Hospitals, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, medicine.anatomical_structure, Chronicity, Bifidobacterium, France, business
Abstract: International audience; We evaluated the Cutibacterium acnes prevalence in prostatic biopsies and characterized the strains at a molecular level. 18 out of 36 biopsies (50%) were sterile after seven days in culture. C. acnes was observed in only two biopsies. Its prevalence was low (5.6%). Finally, the molecular characterization revealed diverse clusters including phylotypes IA1, IB and II.
Published: 2020

222. Be aware of Shiga-toxin 2f-producing Escherichia coli: case report and false-negative results with certain rapid molecular panels

Author: Alice Dufougeray, Patricia Mariani-Kurkdjian, Aurélie Cointe, André Birgy, Ferielle Louillet, Alice Pascault, Stéphane Bonacorsi, Université de Paris (UP), Service de Néphrologie pédiatrique [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service de Microbiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: Male, 0301 basic medicine, Microbiology (medical), [SDV]Life Sciences [q-bio], 030106 microbiology, medicine.disease_cause, Shiga Toxin, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, 030212 general & internal medicine, False Negative Reactions, Escherichia coli, Escherichia coli Infections, Shiga-Toxigenic Escherichia coli, biology, business.industry, Escherichia coli Proteins, Shiga toxin, General Medicine, 3. Good health, Infectious Diseases, Child, Preschool, Hemolytic-Uremic Syndrome, biology.protein, business, Multilocus Sequence Typing
Abstract: We report a hemolytic uremic syndrome (HUS) case due to Stx2f-producing E. coli illustrating the diagnostic difficulty of this Shiga-toxin subtype. Clinicians should be aware of limits of certain rapid molecular panels that are increasingly being used and may play a role in underestimating the global burden of such infections.
Published: 2020

223. Effect of long-acting β-agonist on bronchodilator response in children with asthma

Author: Corinne Alberti, Jessica Taytard, Nicole Beydon, Jessica Assouline Kabla, Camille Aupiais, Noémie Haziot, Marilyn Fuger, Sophie Jovien, Service de Pneumologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Centre d'Investigation Clinique 1426 (CIC 1426), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Pulmonary and Respiratory Medicine, Spirometry, medicine.medical_specialty, medicine.drug_class, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Pulmonary function testing, 03 medical and health sciences, 0302 clinical medicine, Nothing, Bronchodilator, Administration, Inhalation, medicine, Humans, Albuterol, 030212 general & internal medicine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Child, Intensive care medicine, Asthma, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, medicine.diagnostic_test, business.industry, Conflict of interest, Adrenergic beta-Agonists, medicine.disease, Bronchodilator Agents, 3. Good health, 030228 respiratory system, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Formoterol, Salmeterol, business, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract: Spirometry is the most common pulmonary function test (PFT) used to follow asthmatic patients. It is recommended to withhold Short-Acting Beta 2-Agonists (SABA) a few hours before PFTing, and to withhold Long-Acting Beta 2-Agonists (LABA) for diagnosis purpose but not for the assessment of response to a current treatment [1>]. In asthmatic children, the addition of LABA to inhaled corticosteroids (ICS) has no clear clinical benefit but it has proved to improve baseline Forced Expiratory Volume in 1 s (FEV1) [2]. The maximal increase in FEV1 after a single dose of formoterol was measured 3 h after administration but the remaining effect after 12 h would depend on the inhaled dose [3]. Finally, 25 µg or 50 µg of Salmeterol inhaled at 10 p.m. resulted in higher baseline pulmonary function and decrease in exercise induced bronchoconstriction 10 and 12 h later [4]. In routine practice, children are tested with various delays since last LABA inhalation, but LABA is usually inhaled on the morning of the test ( 12 h) or on the morning the previous day or before (>24 h). It is thought that children with the most recent inhalation should have the best pulmonary function and the lowest reversibility, but the latter has not been studied. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Taytard has nothing to disclose. Conflict of interest: Dr. Aupiais has nothing to disclose. Conflict of interest: Dr. Jovien has nothing to disclose. Conflict of interest: Dr. Assouline Kabla has nothing to disclose. Conflict of interest: Dr. Haziot has nothing to disclose. Conflict of interest: Dr. Fuger has nothing to disclose. Conflict of interest: Dr. Alberti has nothing to disclose. Conflict of interest: Dr. Beydon has nothing to disclose.
Published: 2020

224. Body weight and return to work among survivors of early-stage breast cancer

Author: Lee W. Jones, Ann H. Partridge, Johanna Wassermann, Arnauld S. Gbenou, Stefan Michiels, Agnès Dumas, Fabrice Andre, Mahmoud Ibrahim, Ines Maria Vaz Duarte Luis, Lucia Del Mastro, Thomas Bovagnet, Jérôme Lemonnier, Anne Laure Martin, Laurence Vanlemmens, Antonio Di Meglio, Olivier Arsene, Elise Martin, Sandrine Pinto, Gwenn Menvielle, Jennifer A. Ligibel, Arlindo R. Ferreira, HAL-SU, Gestionnaire, Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Champalimaud Centre for the Unknown [Lisbon], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Hospitalier de Blois (CHB), Centre Hospitalier Régional d'Orléans (CHRO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UNICANCER, Ospedale Policlinico San Martino [Genoa], Memorial Sloane Kettering Cancer Center [New York], Dana-Farber Cancer Institute [Boston], Université Paris-Saclay, Institut Gustave Roussy (IGR), Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Université Lille Nord de France (COMUE)-UNICANCER, Centre Hospitalier de Blois (CH Blois), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Oncostat team [Villejuif]
Subjects: Cancer Research, medicine.medical_specialty, Breast Neoplasms, body mass index, [SDV.CAN]Life Sciences [q-bio]/Cancer, Overweight, lcsh:RC254-282, 03 medical and health sciences, Return to Work, breast cancer, 0302 clinical medicine, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Weight loss, Weight management, Humans, Medicine, Prospective Studies, Survivors, 030212 general & internal medicine, Original Research, 2. Zero hunger, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Obstetrics, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, Oncology, 030220 oncology & carcinogenesis, employment, Cohort, Female, weight loss, medicine.symptom, Underweight, business, survivorship, Weight gain, Body mass index, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; BackgroundMany breast cancer (BC) survivors are employed at diagnosis and are expected to return to work after treatment. Among them, around 50% are overweight or obese. There are limited data about the impact of body weight on their ability to return to work.MethodsWe used data from CANcer TOxicity (NCT01993498), a prospective, multicentre cohort of women with stage I–III BC. Professionally active women who were ≥5 years younger than retirement age were identified. Multivariable logistic regression models examined associations of body mass index (BMI) at diagnosis and subsequent weight changes with non-return to work 2 years after diagnosis, adjusting for psychosocial, treatment and behavioural characteristics.ResultsAmong 1869 women, 689 were overweight or obese. Overall, 398 patients (21.3%) had not returned to work 2 years after diagnosis. Non-return to work was more likely for overweight or obese than underweight or normal weight patients (adjusted OR (aOR) 1.32; 95% CI, 1.01 to 1.75; p=0.045). Weight loss (≥5%) was observed in 15.7% overweight or obese and 8.7% underweight or normal weight patients and was associated with significant increases in physical activity only among overweight or obese patients (mean change, +4.7 metabolic-equivalent-of-task-hour/week; 95% CI +1.9 to +7.5). Overweight or obese patients who lost weight were more likely to return to work compared with those who did not lose weight (aOR of non-return-to-work, 0.48; 95% CI 0.24 to 0.97, p=0.0418), whereas weight loss was associated with increased odds of non-return to work among underweight or normal weight women (aOR 2.07; 95% CI 1.20 to 3.56, p=0.0086) (pinteractionBMI×weight changes=0.0002). The continuous trend of weight gain on non-return to work was significant for overweight or obese patients (aOR for one-percent-unit difference, 1.03; 95% CI 1.01 to 1.06, p=0.030).ConclusionsExcess weight may be a barrier to return to work. Among overweight or obese BC survivors, weight loss was associated with higher rates of return to work, whereas further weight gain was associated with lower likelihood of return to work. Employment outcomes should be evaluated in randomised studies of weight management.
Published: 2020

225. Efficacy and patient satisfaction in the use of subcutaneous immunoglobulin immunotherapy for the treatment of auto-immune neuromuscular diseases

Author: Jean-Charles Crave, Taylor Pindi Sala, Patrick Cherin, Olivier Chassany, Martin Duracinsky, François Lepira Bompeka, Abir Tadmouri, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: medicine.medical_specialty, medicine.medical_treatment, Immunology, Subcutaneous immunoglobulin, Auto immune, Autoimmune Diseases, Mononeuropathy, 03 medical and health sciences, 0302 clinical medicine, Patient satisfaction, Internal medicine, Immunology and Allergy, Medicine, Humans, Methodological quality, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, business.industry, Immunoglobulins, Intravenous, Polyradiculoneuropathy, Immunotherapy, Neuromuscular Diseases, medicine.disease, 3. Good health, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, Patient Satisfaction, Muscle strength, Quality of Life, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030217 neurology & neurosurgery
Abstract: We reviewed the efficacy of SCIg administration in terms of muscle strength maintenance and patient satisfaction comparing with IVIg in the treatment of auto-immune neuromuscular diseases. A systematic review was conducted, and identified studies from databases (PUBMED, EMBASE, EBSCO, Web of Science and Google Scholar) which were analyzed. The methodological quality of the selected publications was evaluated using the Newcastle-Ottawa Scale. Data were extracted from a total of 11 studies Fixed and random-effect model meta-analyses were performed. For the maintenance of muscle strength, Overall Neuropathy Limitations Scale (ONLS) data from 100 patients diagnosed with multifocal mononeuropathy (MMN) or chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) were pooled together. Switching to subcutaneous immunoglobulin administration led to a significant improvement (fixed effects model, p = 0.002). In data collected using the Medical Research Council Scale for Muscle Strength data from 140 patients with a wider range of disorders, a small but significant improvement in overall strength was observed in the SCIg group (p 0.0001). In addition, the results of two studies measuring health-related quality of life and patient satisfaction were pooled. Data from 49 patients suffering from MMN, CIDP, and a variety of different myopathies demonstrated a small but significant increase in the mean 36-Item Short Form Survey (SF-36) scores (p 0.0001). A highly significant difference was revealed when comparing data from 119 patients' responses to the Life Quality Index questionnaire (LQI) assessing patient satisfaction (p 0.0001). This is the first analysis showing that SCIg is more effective than IVIg in improving Patient Reported Outcomes in auto-immune neuromuscular disease. These results should permit a broad range of patients to self-administer immunoglobulin treatments at home, potentially improving patient acceptability while reducing hospital visits and healthcare costs for the treatment of chronic auto-immune neuropathies.
Published: 2018

226. Lymphocytes NK : un rôle majeur dans le contrôle immunologique de la leucémie myéloïde chronique

Author: Agnès Guerci-Bresler, Nicolas Dulphy, Ali G. Turhan, Delphine Rea, Antoine Toubert, Service d'Immunologie et d'Histocompatibilité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d’anesthésie et de réanimation chirurgicale [CHR D'orléans] (Hôpital La Source), and Centre Hospitalier Régional d'Orléans (CHRO)-Hôpital La Source (Orléans)
Subjects: education.field_of_study, business.industry, [SDV]Life Sciences [q-bio], Cell, Population, Myeloid leukemia, General Medicine, medicine.disease, General Biochemistry, Genetics and Molecular Biology, 3. Good health, 03 medical and health sciences, Leukemia, Myelogenous, Haematopoiesis, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Medicine, Stem cell, business, education, Tyrosine kinase, 030215 immunology
Abstract: Convincing clinical and experimental evidence is converging on the essential role of NK (Natural Killer) cells in the recognition and eradication of tumors. Recent studies emphasized the role of NK cells in the immune control of chronic myeloid leukemia (CML), a malignancy arising from hematopoietic stem cells, and the treatment of which has been revolutionized by the use of tyrosine kinase inhibitors (TKI). Three major findings are emerging: 1) the impairment of the numbers and function of NK cells at diagnosis, 2) the restoration of the NK cell function and numbers during remissions induced with TKI therapies and 3) the potential role of the more mature NK CD56dim cell population in maintaining relapse-free survival after stopping TKI therapy. Immunological control of CML by NK cells which has been suspected for several decades is thus a new field of investigation for future therapies.
Published: 2018

227. L’accès aux soins des étrangers en situation irrégulière en France : une prise en charge au titre de la pauvreté et de la compassion

Author: Céline Gabarro, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Unite de recherche migrations et sociétés (URMIS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut de recherche pour le développement [IRD] : UR205-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Côte d'Azur (UCA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut de recherche pour le développement [IRD] : UR205-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Côte d'Azur (UCA)
Subjects: [SHS.SOCIO]Humanities and Social Sciences/Sociology, 05 social sciences, 050602 political science & public administration, 0507 social and economic geography, 050703 geography, 0506 political science, [SHS]Humanities and Social Sciences
Abstract: International audience; Cet article s’intéresse au type de couverture maladie et de droits qui sont fournis en France aux étrangers en situation irrégulière à travers les exemples de l’aide médicale d’Etat (AME) et du fonds des soins urgents et vitaux (FSUV). Pour cela, il revient sur l’évolution des référentiels d’affiliation en matière de protection maladie, de 1945 jusqu’à la mise en place de l’AME au début des années 2000. Il montre que nous sommes passés d’une prise en charge pensée en termes de droit social (au même titre que les autres assurés) à une prise en charge différentialiste basée sur une affiliation au titre de la pauvreté (l’aide médicale d’Etat) ou de la compassion (le fonds des soins urgents et vitaux). Ce nouveau référentiel d’affiliation stigmatise les étrangers en situation irrégulière et rend leur prise en charge moins légitime et plus sujette à débats.
Published: 2018

228. Trends in seasonal influenza vaccine coverage of target groups in France, 2006/07 to 2015/16: Impact of recommendations and 2009 influenza A(H1N1) pandemic

Author: Pierre Loulergue, Aurélie Bocquier, Daniel Lévy-Bruhl, Lisa Fressard, Pierre Verger, Sébastien Cortaredona, Florence Galtier, COMBE, Isabelle, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Santé publique France - French National Public Health Agency [Saint-Maurice, France], F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CIC Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Epidemiology, Target groups, coverage, Chronic liver disease, Disease Outbreaks, Seasonal influenza, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Influenza A Virus, H1N1 Subtype, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pandemic, influenza vaccines, 030212 general & internal medicine, Child, Aged, 80 and over, Vaccination, Middle Aged, 3. Good health, H1n1 pandemic, Child, Preschool, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, Seasons, Research Article, Adult, trends, Adolescent, 030231 tropical medicine, 03 medical and health sciences, Young Adult, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, Virology, Influenza, Human, medicine, Humans, In patient, segmented regression, Pandemics, Aged, business.industry, Immunization Programs, Public Health, Environmental and Occupational Health, Infant, Newborn, Infant, Influenza a, medicine.disease, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Health Care Surveys, recommendations, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, business, Demography
Abstract: Background and aims Seasonal influenza vaccination (SIV) uptake (SIVU) rates in France are below target. We (i) describe trends in French SIVU over 10 consecutive seasons among different target groups and (ii) examine the effects of the 2009 influenza A(H1N1) pandemic and the publication of new SIV recommendations in 2011 and 2013. Methods Our study was based on records of vaccines delivered in community pharmacies for a permanent, representative sample of 805,000 beneficiaries of the French National Health Insurance Fund. For the first objective, we analysed SIVU rate trends among ≥ 65 year olds as well as among Results After the 2009 pandemic, except for the target group with liver diseases, where the difference was not statistically significant, SIVU fell significantly in all groups during the 2010/11 season, remaining relatively stable until 2015/16 in groups not targeted by new recommendations. Crude SIVU rates in 2015/16 were 48% (43,950/91,794) for ≥ 65 year olds and between 16% (407/2,565) and 29% (873/3,056) for Conclusions Our results suggest: (i) a prolonged confidence crisis in SIV, initially impelled by the 2009 pandemic vaccination campaign; (ii) that new recommendations are ineffective without additional measures. Interventional research in this field is a priority.
Published: 2018

229. T-cell and Transcriptomic Responses to Prime-boost Strategies of 3 HIV Vaccines(MVA HIV-B; LIPO-5; GTU-MultiHIV B)-ANRS/INSERM VRI01 Trial

Author: Richert, Laura, Wiedemann, Aurelie, Launay, Odile, Lucht, Frederic, Poizot-Martin, Isabelle, Lacabaratz, Christine, Hocini, Hakim, Lhomme, Edouard, Bauduin, Claire, Surenaud, Mathieu, Guillaumat, Lydia, Lefebvre, Cécile, Hardel, Lucile, Rieux, Véronique, Delahaye, Solenne, Rouch, Elodie, Reijonen, Kalevi, Levy, Yves, Thiébaut, Rodolphe, Lelievre, Jean-Daniel, Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Bordeaux [Bordeaux], FIT Biotech Ltd. [Tampere], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), and Admin, Oskar
Subjects: [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MORPH3Eus, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ComputingMilieux_MISCELLANEOUS, SISTM
Abstract: International audience
Published: 2018

230. Transfusion en obstétrique : le point de vue de l’anesthésiste en salle de naissance

Author: C. Langlois, Service d'Anesthésie-Réanimation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: Gynecology, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Biochemistry (medical), Clinical Biochemistry, Hematology, medicine.disease, 3. Good health, Uterine atony, Red blood cell, medicine.anatomical_structure, Blood loss, medicine, Platelet, business
Abstract: Uterine atony is the primary cause of post-partum haemorrhage. Blood loss in a maternity setting is difficult to recognize. Early and empiric use of fixed transfusion red blood cell:plasma:platelet ratios is controversial and may not be justified for all causes of haemorrhage.
Published: 2019

231. Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study)

Author: Philippe Le Corvoisier, Jules Alexandre Desmeules, Célia Lloret-Linares, Jean-Luc Cracowski, Wissam El-Hage, L. Yon, Kyle Heron, Frank Bellivier, Frédéric Haesebaert, Siamak Davani, Damien Montange, Thomas Desmidt, Olivier Doumy, Antoine Yrondi, Fanny Moliere, Raphaëlle-Marie Richieri, Philippe Vignaud, Sophie Morange, Marie Besson, Sylvie Chevret, Isabelle Nieto, Marion Leboyer, Jérôme Holtzmann, F. Galtier, Fabienne Calvas, Julien Déglon, Pierre-Michel Llorca, Emmanuel Haffen, Philippe Courtet, Youssef Daali, Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 ( UM1 ) -IFR76-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de pharmacologie et innovation dans le diabète ( CPID ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Investigation Clinique ( CIC ), Hospices Civils de Lyon ( HCL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU de Lyon, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne ( NPsy-Sydo ), CHU Clermont-Ferrand-Université Clermont Auvergne ( UCA ), Clinique Psychiatrique Universitaire [Tours], CHRU Tours, Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire ( HP2 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, 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 ), CIC - CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), UR 1341 Alimentation et adaptations digestives, nerveuses et comportementales, Institut National de la Recherche Agronomique ( INRA ) -Alimentation Humaine ( ALIM.H ) -Alimentation et adaptations digestives, nerveuses et comportementales ( ADNC ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Geneva University Hospital (HUG), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance Publique - Hôpitaux de Marseille (APHM), CHU Clermont-Ferrand, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Laval [Québec] (ULaval), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre d'Investigation Clinique [Grenoble] (CIC Grenoble ), CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Fondation FondaMental [Créteil], CHU Toulouse [Toulouse], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Bordeaux [Bordeaux], University of Bristol [Bristol], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Lausanne University Hospital, Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Douhairie, Marie-Laurence, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
Subjects: Male, Oncology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Venlafaxine, Pharmacology, 030226 pharmacology & pharmacy, ATP-Binding Cassette, Sub-Family B, Member 1/metabolism, Adolescent, Adult, Aged, Aged, 80 and over, Antidepressive Agents, Second-Generation/blood, Antidepressive Agents, Second-Generation/pharmacokinetics, Antidepressive Agents, Second-Generation/therapeutic use, Cytochrome P-450 CYP2C19/metabolism, Cytochrome P-450 CYP2D6/metabolism, Cytochrome P-450 CYP3A/metabolism, Depressive Disorder, Major/drug therapy, Depressive Disorder, Major/metabolism, Female, France, Genotype, Humans, Middle Aged, Phenotype, Switzerland, Treatment Outcome, Venlafaxine Hydrochloride/blood, Venlafaxine Hydrochloride/pharmacokinetics, Venlafaxine Hydrochloride/therapeutic use, Young Adult, Study Protocol, [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 0302 clinical medicine, 80 and over, Cytochrome P-450 CYP3A, Medicine, Pharmacology (medical), Major depressive episode, ComputingMilieux_MISCELLANEOUS, ddc:615, ddc:617, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Venlafaxine Hydrochloride, Area under the curve, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Antidepressive Agents, 3. Good health, Cytochrome P-450 CYP2D6, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Antidepressive Agents, Second-Generation, medicine.symptom, medicine.drug, CYP2D6, medicine.medical_specialty, Major/drug therapy/metabolism, CYP2C19, [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, 03 medical and health sciences, Pharmacokinetics, lcsh:RA1190-1270, Internal medicine, Member 1/metabolism, ATP Binding Cassette Transporter, Subfamily B, Member 1, Dosing, lcsh:Toxicology. Poisons, Second-Generation/blood/pharmacokinetics/therapeutic use, Depressive Disorder, Depressive Disorder, Major, Sub-Family B, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, lcsh:RM1-950, [SCCO.NEUR] Cognitive science/Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Cytochrome P-450 CYP2C19, lcsh:Therapeutics. Pharmacology, Venlafaxine Hydrochloride/blood/pharmacokinetics/therapeutic use, ATP-Binding Cassette, Personalized medicine, business, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 030217 neurology & neurosurgery
Abstract: It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the “in vivo” measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis. The goal of this project is to explore the relationship between the activity of drug-metabolizing enzymes (DME), assessed by a phenotypic approach, and the concentrations of Venlafaxine (VLX) + O-demethyl-venlafaxine (ODV), the efficacy and tolerance of VLX. This study is a multicentre prospective non-randomized open trial. Eligible patients present a major depressive episode, MADRS over or equal to 20, treatment with VLX regardless of the dose during at least 4 weeks. The Phenotype Visit includes VLX and ODV concentration measurement. Following the oral absorption of low doses of omeprazole, midazolam, dextromethorphan, and fexofenadine, drug metabolizing enzymes activity is assessed by specific metabolite/probe concentration ratios from a sample taken 2 h after cocktail administration for CYP2C19, CYP3A4, CYP2D6; and by the determination of the limited area under the curve from the capillary blood samples taken 2–3 and 6 h after cocktail administration for CYP2C19 and P-gp. Two follow-up visits will take place between 25 and 40 days and 50–70 days after inclusion. They include assessment of efficacy, tolerance and observance. Eleven french centres are involved in recruitment, expected to be completed within approximately 2 years with 205 patients. Metabolic ratios are determined in Geneva, Switzerland. By showing an association between drug metabolism and VLX concentrations, efficacy and tolerance, there is a hope that testing drug metabolism pathways with a phenotypical approach would help physicians in selecting and dosing antidepressants. The MARVEL study will provide an important contribution to increasing the knowledge of VLX variability and in optimizing the use of methods of personalized therapy in psychiatric settings. ClinicalTrials.gov NCT02590185 (10/27/2015). This study is currently recruiting participants.
Published: 2017

232. A human immune system mouse model with robust lymph node development

Author: Hugo Mouquet, Grégory Jouvion, Helene Strick-Marchand, Ai Ing Lim, Nicolas Serafini, Zacarias Garcia, Philippe Bousso, Yan Li, Daniela Finke, Olivier Schwartz, Timothée Bruel, Ayrin Kök, Franck Bourgade, Guillemette Masse-Ranson, Thierry Hieu, Antoine Toubert, Mathilde Dusséaux, James P. Di Santo, Immunité Innée - Innate Immunity, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Dynamiques des Réponses immunes - Dynamics of Immune Responses, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Réponse humorale aux pathogènes, Neuropathologie expérimentale / Experimental neuropathology, Institut Pasteur [Paris]-Université de Paris (UP), Animalerie centrale (Plate-forme), Institut Pasteur [Paris], Service d'Immunologie et d'Histocompatibilité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Developmental Immunology, University of Basel (Unibas), This work was supported by the Agence Nationale de la Recherche (ANR) programme RPIB (Im_HIS to J.P.D.), the Laboratoire d’Excellence REVIVE (grant ANR-10-LABX-73 to Y.L. and J.P.D.), the Laboratoire d’Excellence Vaccine Research Institute (grant ANR-10-LABX-77 to T.B. and O.S.), the Laboratoire d’Excellence Milieu Intérieur (grant ANR-10-LABX-69 to H.M.), the Laboratoire d’Excellence IBEID (grant ANR-10-LABX-62 to O.S.), the Agence Nationale de Recherche sur le SIDA et les hepatitis (grant 15465 to O.S.), the European Commission Seventh Framework Programme no. 305578 (PathCO, to J.P.D.), the European Research Council (grant ERC-2013-StG 337146 to A.K. and T.H., grant ERC-2017-AvG 771167 to P.B.), Gilead Sciences (grant 00397 to G.M.-R. and J.P.D.), the Institut Pasteur (Core grant to J.P.D., G5 Program to H.M.), and INSERM (Core grant to J.P.D.)., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 305578,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,PATHCO(2012), European Project: 337146,EC:FP7:ERC,ERC-2013-StG,HUMANTIVIRUSES(2014), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), and Institut Pasteur [Paris]-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Male, T-Lymphocytes, MESH: Lymph Nodes, HIV Infections, Biochemistry, MESH: Mice, Knockout, MESH: HIV-1, Mice, MESH: Animals, Lymph node, Mice, Knockout, MESH: Cytokines, B-Lymphocytes, Mice, Inbred BALB C, MESH: Virus Latency, MESH: HIV Infections, 3. Good health, Virus Latency, medicine.anatomical_structure, Lymphatic system, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, MESH: Immunoglobulin Class Switching, Cytokines, Female, Lymph, Biotechnology, Interleukin Receptor Common gamma Subunit, MESH: Mice, Transgenic, Transgene, MESH: Mice, Inbred BALB C, Mice, Transgenic, Biology, MESH: Models, Immunological, 03 medical and health sciences, Immune system, Thymic Stromal Lymphopoietin, Immunity, MESH: Mice, Inbred C57BL, MESH: B-Lymphocytes, medicine, Animals, Humans, Secondary lymphoid tissue, Molecular Biology, MESH: Mice, MESH: Humans, MESH: Interleukin Receptor Common gamma Subunit, Models, Immunological, Cell Biology, Immunoglobulin Class Switching, MESH: Male, Mice, Inbred C57BL, 030104 developmental biology, MESH: T-Lymphocytes, Immunoglobulin class switching, Immunology, HIV-1, Lymph Nodes, MESH: Female
Abstract: International audience; Lymph nodes (LNs) facilitate the cellular interactions that orchestrate immune responses. Human immune system (HIS) mice are powerful tools for interrogation of human immunity but lack secondary lymphoid tissue (SLT) as a result of a deficiency in Il2rg-dependent lymphoid tissue inducer cells. To restore LN development, we induced expression of thymic-stromal-cell-derived lymphopoietin (TSLP) in a Balb/c Rag2-/-Il2rg-/-SirpaNOD (BRGS) HIS mouse model. The resulting BRGST HIS mice developed a full array of LNs with compartmentalized human B and T cells. Compared with BRGS HIS mice, BRGST HIS mice have a larger thymus, more mature B cells, and abundant IL-21-producing follicular helper T (TFH) cells, and show enhanced antigen-specific responses. Using BRGST HIS mice, we demonstrated that LN TFH cells are targets of acute HIV infection and represent a reservoir for latent HIV. In summary, BRGST HIS mice reflect the effects of SLT development on human immune responses and provide a model for visualization and interrogation of regulators of immunity.
Published: 2017

233. La pression cricoïdienne en question

Author: Laurence Oehlkern, Jean-Etienne Bazin, Service d'Anesthésie-Réanimation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Pôle de Médecine Périopératoire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand
Subjects: 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, business.industry, [SDV]Life Sciences [q-bio], Emergency Medicine, Medicine, 030208 emergency & critical care medicine, Emergency Nursing, business
Published: 2016

234. The right to be forgotten: a change in access to insurance and loans after childhood cancer?

Author: Tan Dat Nguyen, Anne Laprie, Brice Fresneau, Pierre-Yves Bondiau, Carole Rubino, Rodrigue S. Allodji, Agnès Dumas, Catherine Guibout, Ibrahima Diallo, Hélène Pacquement, Chiraz El-Fayech, Florent de Vathaire, Nadia Haddy, Odile Oberlin, Dominique Valteau-Couanet, Gilles Vassal, Institut Jean Godinot [Reims], UNICANCER, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre d'épidémiologie et de santé publique des armées [Marseille] (CESPA), Service de Santé des Armées, Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'oncologie pédiatrique [Institut Curie, Paris], Institut Curie [Paris], Institut Claudius Regaud, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Université Paul-Valéry - Montpellier 3 (UPVM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut de Recherche pour le Développement (IRD [France-Sud]), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Université Paul-Valéry - Montpellier 3 (UPVM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut de Recherche pour le Développement (IRD [France-Sud])
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Disease, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Neoplasms, Humans, Medicine, 030212 general & internal medicine, Child, Socioeconomic status, health care economics and organizations, ComputingMilieux_MISCELLANEOUS, Insurance, Health, [SHS.SOCIO]Humanities and Social Sciences/Sociology, Oncology (nursing), business.industry, Public health, Medical record, Cancer, medicine.disease, 3. Good health, Survival Rate, Oncology, Loan, Child, Preschool, 030220 oncology & carcinogenesis, Family medicine, Quality of Life, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Follow-Up Studies, Cohort study
Abstract: Access to insurance for a loan or a mortgage is an important issue for childhood cancer survivors. The aim of this study was to describe difficulties experienced by adult survivors. A total of 1920 survivors treated before the age of 18 in five French cancer centers responded to a questionnaire in 2010. Survivors who had tried to obtain a loan were asked if they had experienced difficulties, which were defined as experiencing rejection, higher premiums, or exclusions. The questionnaire investigated health problems related to the circulatory, respiratory, digestive, urinary, endocrine, hormonal, and nervous systems. Second tumors, diabetes mellitus, cardiac disease, and stroke were ascertained from a physician’s report or medical records. Multivariable analyses were conducted to identify the characteristics of survivors reporting difficulties. Difficulties were experienced by 10.4% of those who had tried to obtain a small loan (n = 787) and by 30.1% of those who had tried to obtain a home loan (n = 909). Disclosure of childhood cancer to the insurer and amputation surgery were negatively associated with insurance accessibility, even when controlling for age, gender, education, health-related unemployment, familial situation, and severe or life-threatening conditions such as cardiovascular diseases, second cancers, or diabetes. This study showed that the financial burden of cancer can extend decades after diagnosis. Thanks to a 2016 law, French cancer survivors no longer have to disclose their cancer to insurers after a fixed number of years. This law will probably lessen the socioeconomic burden of cancer.
Published: 2017

235. What’s new in catheter-related infection: skin cleansing and skin antisepsis

Author: Vineet Chopra, Olivier Mimoz, Jean-François Timsit, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, University of Michigan [Ann Arbor], University of Michigan System, Service d'anesthésie - réanimation chirurgicale [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord
Subjects: medicine.medical_specialty, Skin cleansing, Pain medicine, [SDV]Life Sciences [q-bio], Antisepsis, Administration, Cutaneous, Critical Care and Intensive Care Medicine, 2-Propanol, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology, medicine, Humans, 030212 general & internal medicine, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, Skin, business.industry, Chlorhexidine, 030208 emergency & critical care medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Catheter-Related Infections, 3. Good health, Disinfection, Anti-Infective Agents, Local, business, Vascular Access Devices, Disinfectants
Abstract: International audience
Published: 2016

236. Early treated HIV-infected children remain at risk of growth retardation during the first five years of life: Results from the ANRS-PEDIACAM cohort in Cameroon

Author: Albert Faye, Casimir Ledoux Sofeu, Calixte Ida Penda, Josiane Warszawski, Francis Ateba Ndongo, Roch Giorgi, Suzie Tetang Ndiang, Camelia Protopopescu, Mathurin Cyrille Tejiokem, Georgette Guemkam, HAL AMU, Administrateur, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Laboratoire d'Epidémiologie et de Santé Publique, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Douala, Fondation Chantal Biya (FCB), Centre Hospitalier Essos [Yaoundé, Cameroun], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pédiatrie, Hopital Robert Debré (APHP), Université Paris Diderot - Paris 7 (UPD7), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: Male, 0301 basic medicine, Pediatrics, Epidemiology, Cohort Studies, Families, Child Development, 0302 clinical medicine, Risk Factors, Antiretroviral Therapy, Highly Active, Cameroon, 030212 general & internal medicine, Children, Wasting, Growth Disorders, Human evolution, 2. Zero hunger, Multidisciplinary, Growth retardation, Incidence, Incidence (epidemiology), HIV diagnosis and management, Growth restriction, Anemia, Hematology, 3. Good health, Hominid Evolution, Diarrhea, Cohort, Infectious diseases, Medicine, Female, Hominin Evolution, Underweight, medicine.symptom, 0305 other medical science, Infants, Research Article, HIV infections, medicine.medical_specialty, Child Growth, Referral, Science, 030106 microbiology, Context (language use), Viral diseases, Risk Assessment, Time-to-Treatment, 03 medical and health sciences, medicine, Humans, Nutrition, Medicine and health sciences, Evolutionary Biology, 030505 public health, business.industry, Malnutrition, Infant, Newborn, Public Health, Environmental and Occupational Health, Infant, Biology and Life Sciences, Anthropometry, medicine.disease, Diagnostic medicine, Organismal Evolution, Age Groups, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, People and Places, Population Groupings, Observational study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Introduction Little is known about the long-term outcome of growth in early treated infants in resources limited countries. Here, we compared growth parameters over the first 5 years of life of early treated HIV-infected and uninfected children and identified factors associated with growth retardation, taking into account informative censorship. Methods Data used in this study were obtained from the ANRS-Pediacam cohort based in three referral hospitals in Cameroon (The Maternity of the Central hospital/Mother and Child Center of the Chantal Biya Foundation in Yaounde, the Essos Hospital Center in Yaounde and the Laquintinie Hospital in Douala). Anthropometric indices [weight-for-age (WAZ), weight-for-length (WLZ), and length-for-age (LAZ) Z-scores] were calculated using data from this observational study. Of the four groups included, three were followed from the first week of life: HIV-infected (HI, n = 69), HIV-exposed uninfected (HEU, n = 205) and HIV-unexposed uninfected (HUU, n = 196), and the last group constituted of HIV-infected infants not followed from first week of life but diagnosed before 7 months of age (HIL, n = 141). We performed under the Missing At Random hypothesis a multiple imputation by a conditional approach of missing data on different covariates, except the anthropometric parameters. To take account of informative censorship, recurrent events and interval censoring, we used markov multi-state model for panel data to describe the incidence of growth retardation (defined as WAZ or WLZ or LAZ Results During the first 5 years, 27.5% of children experienced underweight (WAZ P P = 0.01 respectively) and stunting for HIL (aHR = 8.4 (95%CI: 2.4–29.7). HEU and HUU infants were not different according to stunting and wasting. However, the risk of underweight was higher in HEU compared to HUU children (aHR = 5.0 (CI: 1.4–10.0), P = 0.001). Others associated factors were younger age, chronic pathologies, small size at birth, diarrhea, CD4 Conclusions Despite early antiretroviral treatment HIV-infected children are at high risk of wasting and stunting within the first 5 years period of follow up. Nutritional status of HIV infected children should be closely monitored even in the context of early treatment.
Published: 2019

237. Impact of lymphovascular space invasion on a nomogram for predicting lymph node metastasis in endometrial cancer

Author: Emmanuel Barranger, Emile Daraï, Patrick Aristizabal, Roman Rouzier, Dominique Luton, Karine Bassot, Olivier Graesslin, Françoise Clavel-Chapelon, Martin Koskas, Bassam Haddad, Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIC Hôpital Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine-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 Hospitalier Universitaire de Reims (CHU Reims), Service de gynécologie et obstétrique [Hopital Lariboisière - Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier Intercommunal de Créteil (CHIC), Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], CHU Tenon [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), and Institut Curie [Paris]
Subjects: Adult, Risk, Oncology, medicine.medical_specialty, Lymphovascular space invasion, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Hysterectomy, Nomogram, Decision Support Techniques, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Endometrial cancer, Predictive Value of Tests, Internal medicine, medicine, Humans, Neoplasm Invasiveness, Lymph node, Aged, Neoplasm Staging, Aged, 80 and over, Univariate analysis, 030219 obstetrics & reproductive medicine, Receiver operating characteristic, business.industry, Obstetrics and Gynecology, Middle Aged, medicine.disease, Lymphovascular, Endometrial Neoplasms, 3. Good health, Nomograms, Logistic Models, medicine.anatomical_structure, ROC Curve, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Multivariate Analysis, Linear Models, Lymph Node Excision, Female, Lymphadenectomy, Prediction, business
Abstract: International audience; Objective: The aim of this study was to evaluate the impact of lymphovascular space invasion (LVSI) on nomogram-based predictions of lymph node (LN) metastasis in endometrial cancer. Methods: The data from 485 patients with presumed stage I or II endometrial cancer who underwent hysterectomy and lymphadenectomy were analyzed. Calibration curves were designed and compared for three different subgroups: LVSI-positive tumors (n = 113), LVSI-negative tumors (n = 213) and LVSI-undetermined tumors (n = 159). Results: In the entire population, the nomogram showed good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.80 and was well calibrated. In the subgroup analyses, in LVSI-positive, LVSI-negative and LVSI-undetermined patients, the nomogram was not well calibrated (p of the U index of 0.028, 0.087 and 0.011, respectively) with underestimation in LVSI-positive patients and overestimation in LVSI-negative and LVSI-undetermined patients of LN metastasis. In the univariate analysis and after adjusting for the LN metastasis probability provided by the nomogram, LVSI-positive tumors were associated with an increased risk for LN metastasis compared with LVSI-negative tumors (RR = 7.29 [3.87-13.7] and 5.04 [2.30-11.08], respectively). In contrast, the univariate analysis and after adjusting for the LN metastasis probability provided by the nomogram showed that LVSI-undetermined tumors were not associated with an increased risk for LN metastasis compared with LVSI-negative tumors (RR = 0.73 [0.32-1.69] and 1.26 [0.47-3.37], respectively). Conclusions: Our results suggested that LVSI should be considered to be an independent risk factor for LN metastasis. In this multicenter study, the risk for LN metastasis is similar when the LVSI is negative or is not detailed in the pathological report.
Published: 2013

238. Natural killer cell licensing after double cord blood transplantation is driven by the self-HLA class I molecules from the dominant cord blood

Author: Hélène Moins-Teisserenc, Antoine Toubert, Jean-Michel Cayuela, Katia Gagne, Pascale Loiseau, Nicolas Dulphy, Eliane Gluckman, Nicolas Guillaume, Régis Peffault de Latour, Guylaine Henry, Gérard Socié, Christelle Retière, Marie Robin, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Alloimmunité-Autoimmunité-Transplantation (A2T), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Laboratoire d'Histocompatibilité et d'Immunogénétique [EFS Nantes], Etablissement Français du Sang [Nantes], Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Immunologie et d'Histocompatibilité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Eurocord [AP-HP Hôpital Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Dulphy, Nicolas, Université Paris Cité (UPCité), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Adult, Male, chemical and pharmacologic phenomena, Cord Blood Stem Cell Transplantation, Immunogenetics, Human leukocyte antigen, HLA-C Antigens, Biology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Natural killer cell, 03 medical and health sciences, medicine, Humans, Receptor, Online Only Articles, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Cord blood transplantation, ComputingMilieux_MISCELLANEOUS, 4. Education, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Natural killer T cell, Allografts, Hematologic Diseases, Killer Cells, Natural, 030104 developmental biology, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Cord blood, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Immunology, Female, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy
Abstract: Natural killer (NK) cells gain functionality through an educational process (“licensing”) that depends on killer immunoglobulin-like receptor (KIR) recognition of self-HLA class I molecules. In allogenic double umbilical cord blood stem cell transplantation (2CBT), the respective roles of the
Published: 2016

239. Angle of fetal head progression measured using transperineal ultrasound as a predictive factor of vacuum extraction failure

Author: Bultez, Thierry, Quibel, Thibault, Bouhanna, Philippe, Popowski, Thomas, Resche-Rigon, Matthieu, Rozenberg, Patrick, Service de gynécologie et obstétrique [CHI Poissy-Saint Germain], CHI Poissy-Saint-Germain, Service de biostatistiques et information médicale [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: body regions, surgical procedures, operative, [SDV]Life Sciences [q-bio], vacuum extraction, technology, industry, and agriculture, angle of progression, transperineal ultrasound, ultrasonography, operative delivery
Abstract: International audience; OBJECTIVE: To evaluate the predictive value of angle of progression (AoP) of the fetal head for a failed vacuum delivery.METHODS: This was a prospective observational study that included women with a singleton pregnancy of ≥ 37 weeks' gestation, in cephalic presentation requiring vacuum extraction. Transperineal ultrasound was performed immediately before vacuum extraction, although AoP was measured on stored images after delivery. Vacuum extraction was defined as failed when the duration of extraction exceeded 20 min or the vacuum cup detached more than three times. We compared the demographic and ultrasound data of failed vacuum deliveries with those that were successful. The predictive value of AoP for failure of vacuum delivery was calculated.RESULTS: AoP was measured in 235 women. Vacuum extractions failed in 30 (12.8%) women (29/184 nulliparous and 1/51 parous) and resulted in 28 vaginal deliveries by forceps and two Cesarean deliveries. Median AoP was significantly lower in the vacuum failure group compared with those with successful vacuum delivery (136.6° (interquartile range (IQR), 129.8-144.1°) vs 145.9° (IQR, 135.0-158.4°); P
Published: 2016

240. Attitude, knowledge and factors associated with influenza and pneumococcal vaccine uptake in a large cohort of patients with secondary immune deficiency

Author: Odile Launay, Paul Loubet, Matthieu Groh, Pierre Verger, Pierre Loulergue, Philippe Blanche, Solen Kernéis, CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Malbec, Odile
Subjects: Male, Health Knowledge, Attitudes, Practice, [SDV]Life Sciences [q-bio], Logistic regression, Cohort Studies, Pneumococcal Vaccines, 0302 clinical medicine, Surveys and Questionnaires, 030212 general & internal medicine, Young adult, Aged, 80 and over, Vaccination, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Pneumococcal infections, Infectious Diseases, Knowledge, Influenza Vaccines, Molecular Medicine, Female, Pneumococcal, France, Cohort study, Adult, medicine.medical_specialty, Adolescent, Pneumococcal Infections, 03 medical and health sciences, Immunocompromised Host, Young Adult, Internal medicine, Influenza, Human, medicine, Humans, Immunocompromised, Aged, 030203 arthritis & rheumatology, Autoimmune disease, General Veterinary, General Immunology and Microbiology, business.industry, Public Health, Environmental and Occupational Health, Immunologic Deficiency Syndromes, medicine.disease, Influenza, Transplantation, Pneumococcal vaccine, Attitudes, Immunology, business
Abstract: International audience; Background: Immunocompromised patients are at increased risk for severe influenza and invasive pneumococcal diseases. Population-specific vaccine recommendations are thus warranted. This study aimed to estimate the prevalence and predictors of influenza and pneumococcal vaccine uptake in a large cohort of patients with secondary immune deficiency. Methods: An anonymous online survey was submitted to the members of 11 French associations of immunocompromised patients. The questionnaire included questions concerning underlying disease, care and treatment, flu and pneumococcal vaccine uptake, attitudes and knowledge about vaccination. Factors associated with vaccine uptake were assessed by multivariate logistic regression. Results: Among the 10,897 solicited patients, 3653 agreed to participate (33.5%): 75% were female, 20% aged 65+, 79% were followed for an autoimmune disease, 13% were solid organ recipients or waiting for transplantation and 8% were treated for hematological malignancies. 3109 (85%) participants were treated with immunosuppressive therapy. Self-reported vaccine uptake was 59% (95%CI [57-60]) against seasonal influenza and 49% (95%CI [47-50]) against pneumococcal diseases. Better knowledge of and favorable attitudes toward vaccination were positively associated with vaccine uptake while being treated with a biological therapy was negatively associated. Conclusion: Despite specific recommendations regarding immunocompromised patients, influenza and pneumococcal vaccination rates do not reach recommended levels. Targeted information campaigns on vaccination toward these populations should be implemented to improve vaccine coverage and thus reduce the burden of infections.
Published: 2015

241. Direct comparison of logistic regression and recursive partitioning to predict lymph node metastasis in endometrial cancer

Author: Françoise Clavel-Chapelon, Roman Rouzier, Dominique Luton, Emile Daraï, Bassam Haddad, Emmanuel Barranger, Martin Koskas, Olivier Graesslin, Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Dpt gynécologie [CHU Bichat], 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), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de gynécologie et obstétrique [Hopital Lariboisière - Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier Intercommunal de Créteil (CHIC), Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], CHU Tenon [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 Curie [Paris], Service de Gynécologie - Obstétrique [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPC), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Oncology, medicine.medical_specialty, Adolescent, Calibration (statistics), medicine.medical_treatment, [SDV]Life Sciences [q-bio], Recursive partitioning, Hysterectomy, Logistic regression, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Discriminative model, Endometrial cancer, Internal medicine, medicine, Humans, Aged, Neoplasm Staging, Aged, 80 and over, Lymph node metastasis, 030219 obstetrics & reproductive medicine, Receiver operating characteristic, business.industry, Score, Obstetrics and Gynecology, Middle Aged, Prognosis, medicine.disease, Carcinoma, Papillary, Confidence interval, Cystadenocarcinoma, Serous, Endometrial Neoplasms, Logistic Models, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Lymph Node Excision, Female, Lymphadenectomy, Neoplasm Grading, business, Prediction, Adenocarcinoma, Clear Cell, Follow-Up Studies
Abstract: ObjectiveThe purpose was to compare logistic regression model (LRM) and recursive partitioning (RP) to predict lymph node metastasis in early-stage endometrial cancer.Methods/MaterialsThree models (1 LRM and 2 RP, a simple and a complex) were built in a same training set extracted from the Surveillance, Epidemiology, and End Results database for 18,294 patients who underwent hysterectomy and lymphadenectomy for stage I or II endometrial cancer. The 3 models were validated in a same validation set of 499 patients. Model performance was quantified with respect to discrimination (evaluated by the areas under the receiver operating characteristics curves) and calibration.ResultsIn the training set, the areas under the receiver operating characteristics curves were similar for LRM (0.80 [95% confidence interval [CI], 0.79–0.81]) and the complex RP model (0.79 [95% CI, 0.78–0.80]) and higher when compared with the simple RP model (0.75 [95% CI, 0.74–0.76]). In the validation set, LRM (0.77 [95% CI, 0.75–0.79]) outperformed the simple RP model (0.72 [95% CI, 0.70–0.74]). The complex RP model had good discriminative performances (0.75 [95% CI, 0.73–0.77]). Logistic regression model also outperformed the simple RP model in terms of calibration.ConclusionsIn these real data sets, LRM outperformed the simple RP model to predict lymph node metastasis in early-stage endometrial cancer. It is therefore more suitable for clinical use considering the complexity of an RP complex model with similar performances.
Published: 2015

242. La pratique du soupçon de fraude dans l'instruction des dossiers d'aide médicale d'Etat

Author: Gabarro, Céline, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Unite de recherche migrations et sociétés (URMIS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut de recherche pour le développement [IRD] : UR205-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Côte d'Azur (UCA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut de recherche pour le développement [IRD] : UR205-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Côte d'Azur (UCA)
Subjects: [SHS.SOCIO]Humanities and Social Sciences/Sociology, [SHS.SCIPO]Humanities and Social Sciences/Political science, [SHS]Humanities and Social Sciences
Abstract: International audience; Ce chapitre s’intéresse au rôle de la logique du soupçon dans l’instruction des demandes d’aide médicale d’Etat (AME). En revenant sur la genèse de l’AME, il montre dans un premier temps que sa création répond à un mouvement associatif en faveur de la lutte contre l’exclusion qui a permis la mise en place de règles de simplification administrative. Ces règles sont toutefois en partie réformées suite au développement d’une vision gestionnaire de la Sécurité sociale en France, ce qui entraîne l’émergence d’un mouvement de lutte contre la fraude. Dans un deuxième temps, le chapitre analyse comment le soupçon de fraude s’immisce dans les pratiques des agents à travers les réformes du droit à l’aide médicale d’Etat puis, dans un dernier point, comment ces agents se saisissent de ces questions et interprètent ces réformes en fonction du sens qu’ils donnent à leur travail.
Published: 2015

243. Impact of early enteral versus parenteral nutrition on mortality in patients requiring mechanical ventilation and catecholamines: study protocol for a randomized controlled trial (NUTRIREA-2)

Author: Didier Thevenin, Hoang-Nam Bui, Jérôme Devaquet, Virginie Maxime, Ahmed El Kalioubie, Erika Parmentier, Frédéric Martino, Véronique Leray, Jean-Paul Mira, Jean Etienne Herbrecht, Emmanuelle Mercier, Mercé Jourdain, Carole Schwebel, L. Brisard, Olivier Gontier, Nathalie Rolin, Daniel da Silva, Anne Bretagnol, Vlad Botoc, Vincent Das, Emilie Greau, Jean-Philippe Rigaud, Bertrand Guidet, Michael Darmon, Frédéric Bellec, Jean Reignier, Karim Asehnoune, Christophe Guitton, Saad Nseir, Nadia Anguel, Amélie Le Gouge, Hervé Dupont, Michel Sirodot, Bruno Giraudeau, Frédérique Ganster, Gaël Piton, Ferhat Meziani, René Robert, Jack Richecoeur, Jean-Baptiste Lascarrou, Emmanuel Canet, Michel Djibré, Ali Ait Hssain, Benoit Misset, Stéphanie Martin, Jean-Pierre Quenot, Stéphane Gaudry, Philippe Letocart, Pierre Asfar, Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Centre hospitalier universitaire de Nantes (CHU Nantes), Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Départemental Les Oudairies, CHU La Roche sur Yon, CHU Amiens-Picardie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier de la Région d'Annecy (Pringy), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Bordeaux [Bordeaux], Hôpitaux de Chartres [Chartres], CHU Clermont-Ferrand, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Hôpital de Dieppe, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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), Hôpital Raymond Poincaré [AP-HP], Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Lille, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier de Melun, Hopital Montauban, Centre Hospitalier Intercommunal André Grégoire [Montreuil] (CHI André Gregoire), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Hôtel-Dieu de Nantes, Centre Hospitalier Régional d'Orléans (CHRO), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Cochin [AP-HP], Hopital Saint-Louis [AP-HP] (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier Saint-Joseph [Paris], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Centre Hospitalier Rodez, Hôpital de Saint-Denis, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CH de Saint-Malo [Broussais], CHU Strasbourg, Hôpital Foch [Suresnes], Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CH Beauvais, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Université Francois Rabelais [Tours], PRES Centre-Val de Loire Université, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPC), and Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée)
Subjects: Research design, Parenteral Nutrition, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Enteral administration, law.invention, Study Protocol, Mechanical ventilation, Nosocomial infection, Catecholamines, 0302 clinical medicine, Clinical Protocols, Randomized controlled trial, Risk Factors, law, Vasoconstrictor Agents, Pharmacology (medical), Hospital Mortality, 030212 general & internal medicine, Shock, 3. Good health, Intensive Care Units, Treatment Outcome, Research Design, Shock (circulatory), France, medicine.symptom, medicine.medical_specialty, Critical Care, Critical Illness, Shock, Cardiogenic, Nutritional Status, 03 medical and health sciences, Enteral Nutrition, Intensive care, medicine, Humans, In patient, Mortality, Intensive care medicine, Vasoactive drugs, business.industry, 030208 emergency & critical care medicine, Respiration, Artificial, Parenteral nutrition, Energy Intake, business, Biomarkers
Abstract: International audience; BACKGROUND: Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation (IMV) and the most commonly prescribed treatment in intensive care units (ICUs). International guidelines consistently indicate that enteral nutrition (EN) should be preferred over parenteral nutrition (PN) whenever possible and started as early as possible. However, no adequately designed study has evaluated whether a specific nutritional modality is associated with decreased mortality. The primary goal of this trial is to assess the hypothesis that early first-line EN, as compared to early first-line PN, decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock. METHODS/DESIGN: The NUTRIREA-2 study is a multicenter, open-label, parallel-group, randomized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours, combined with vasoactive drugs, for shock. Patients will be allocated at random to first-line PN for at least 72 hours or to first-line EN. In both groups, nutritional support will be started within 24 hours after IMV initiation. Calorie targets will be 20 to 25 kcal/kg/day during the first week, then 25 to 30 kcal/kg/day thereafter. Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution (no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L). On day 7, all patients receiving PN and having no contraindications to EN will be switched to EN. In both groups, supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake. We plan to recruit 2,854 patients at 44 participating ICUs. DISCUSSION: The NUTRIREA-2 study is the first large randomized controlled trial designed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients. Enrollment started on 22 March 2013 and is expected to end in November 2015. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01802099 (registered 27 February 2013).
Published: 2014

244. Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide

Author: Alexandra Audemard-Verger, Nicolas Martin Silva, Céline Verstuyft, Nathalie Costedoat-Chalumeau, Aurélie Hummel, Véronique Le Guern, Karim Sacré, Olivier Meyer, Eric Daugas, Cécile Goujard, Audrey Sultan, Thierry Lobbedez, Lionel Galicier, Jacques Pourrat, Claire Le Hello, Michel Godin, Rémy Morello, Marc Lambert, Eric Hachulla, Philippe Vanhille, Guillaume Queffeulou, Jacky Potier, Jean-Jacques Dion, Pierre Bataille, Dominique Chauveau, Guillaume Moulis, Dominique Farge-Bancel, Pierre Duhaut, Bernadette Saint-Marcoux, Alban Deroux, Jennifer Manuzak, Camille Francès, Olivier Aumaitre, Holy Bezanahary, Laurent Becquemont, Boris Bienvenu, Université de Lausanne (UNIL), Département de Néphrologie et Transplantation d'organes, Faculté de Médecine [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Service de Néphrologie - Médecine Interne, CHU Amiens-Picardie-hôpital Sud, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Bases Moleculaires de l'Homeostasie Cutanee : Inflammation, Reparation et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de dermatologie et allergologie [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Médecine Interne [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Cochin [AP-HP], Unité de Biostatistique et de Recherche Clinique (UBRC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Barrière et passage des médicaments, Université Paris-Sud - Paris 11 (UP11)-IFR141, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Référence des Maladies auto-immunes systémiques rares d'Ile-de-Frances [Hopital Cochin], CHU Necker - Enfants Malades [AP-HP], Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université de Paris (UP), Laboratoire Génie électrique et électronique de Paris (GeePs), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), UMR 1599, Centre National de la Recherche Scientifique (CNRS), Service de Médecine Interne et Immunologie clinique [AP-HP Hôpital Bicêtre], Hôpital Bicêtre, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de médecine interne [CHU Caen], Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Service de Néphrologie - Immunologie Clinique [Toulouse], CHU Toulouse [Toulouse]-PRES Université de Toulouse, Département de Médécine Vasculaire [CHU Caen], Nouvelles Cibles Pharmacologiques de la Protection Endothéliale et de l'Insuffisance Cardiaque (EnVI), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Syndicat des eaux du Vivier, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Hôpital Claude Huriez [Lille], Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Service de Néphrologie, Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Service de Néphrologie [CHPC - Site Louis Pasteur], Site Louis Pasteur [CHPC], CH Centre Hospitalier Public du Cotentin (CHPC)-CH Centre Hospitalier Public du Cotentin (CHPC), and CH Centre Hospitalier Public du Cotentin (CHPC)
Subjects: Male, Heredity, Physiology, [SDV]Life Sciences [q-bio], Lupus nephritis, lcsh:Medicine, Pharmacology, urologic and male genital diseases, Pathology and Laboratory Medicine, chemistry.chemical_compound, Mathematical and Statistical Techniques, 0302 clinical medicine, Drug Metabolism, Gene Frequency, Medicine and Health Sciences, lcsh:Science, Glutathione Transferase, Multidisciplinary, Proteinuria, Middle Aged, Lupus Nephritis, Genetic Mapping, Creatinine, 030220 oncology & carcinogenesis, Physical Sciences, Female, medicine.symptom, Glutathione S-Transferase pi, Statistics (Mathematics), Immunosuppressive Agents, Research Article, Glomerular Filtration Rate, medicine.drug, Adult, Drug-Related Side Effects and Adverse Reactions, Cyclophosphamide, Immunology, Variant Genotypes, Biology, Research and Analysis Methods, Polymorphism, Single Nucleotide, digestive system, Autoimmune Diseases, Young Adult, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, Genetics, medicine, Humans, Pharmacokinetics, Statistical Methods, Alleles, Genetic Association Studies, Retrospective Studies, 030203 arthritis & rheumatology, Renal Physiology, Evolutionary Biology, Population Biology, lcsh:R, Biology and Life Sciences, Glutathione, medicine.disease, Cytochrome P-450 CYP2C19, Cytochrome P-450 CYP2B6, chemistry, Genetic Loci, Multivariate Analysis, Genetic Polymorphism, lcsh:Q, Clinical Immunology, Clinical Medicine, Population Genetics, Mathematics, Drug metabolism
Abstract: International audience; Objective To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST). Methods We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria 105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile -> 105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02-24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed. Conclusion This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.
Published: 2016

245. Current uses and indications for indocyanine green angiography

Author: Desmettre, T., Cohen, S.Y., M. Devoisselle, J., Gaudric, A., Service d'ophthalmologie [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC)
Subjects: genetic structures, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, FLUORESCENCE PROPERTIES, [CHIM.MATE]Chemical Sciences/Material chemistry, RETINAL-PIGMENT EPITHELIUM, MACULAR DEGENERATION, eye diseases, SCANNING LASER OPHTHALMOSCOPE, PHOTODYNAMIC THERAPY, FUNDUS CAMERA, VIDEOANGIOGRAPHY, ANGIOID STREAKS, sense organs, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, OCCULT CHOROIDAL NEOVASCULARIZATION, CENTRAL SEROUS CHORIORETINOPATHY
Abstract: International audience; A full interpretation of indocyanine green angiography images involves not only optical issues but also pharmacokinetic and biochemical aspects. These issues may involve biochemical changes in the fluorescence yield and the affinity of the molecule for lipoproteins and phospholipids. For age related macular degeneration (AMD), the advent of photodynamic therapy and especially anti-VEGF drugs has increased the use of OCT in assessing treatment response and guiding retreatment. The ease and advantages of OCT have become increasingly associated with a decreasing interest in ICG angiography, which is becoming less well suited for the current management of AMD. An aging population, the efficacy of anti-VEGF drugs and the relative rarity of polypoidal choroidal vasculopathy (PCV) in Europe are factors contributing to our proportional increase in AMD patients. However, aside from AMD, the indications for ICG angiography remain little changed over the last decade: it remains important in diagnosing PCV and choroidal hemangiomas, since their prognosis and treatment are specific. Similarly, for certain inflammatory conditions such as Multiple Evanescent White Dot Syndrome (MEWDS) or Birdshot chorioretinitis, the value of ICG angiography remains significant. In addition, for the treatment of chronic Central Serous Chorioretinopathy, ICG angiography helps to find sites of leakage which otherwise might have been missed. The ICG angiographic appearance in this setting may also have prognostic value. Although the indications for ICG angiography are currently decreasing for AMD, these other conditions represent a large enough number of patients to justify the continued use of this original test, which remains complementary to other chorioretinal imaging techniques.
Published: 2011

246. Multiplex assays for the identification of serological signatures of SARS-CoV-2 infection: an antibody-based diagnostic and machine learning study

Author: Narimane Nekkab, Stéphane Pelleau, Jason Rosado, Stéphane Petres, Annalisa Meola, François Dejardin, Ivo Mueller, Caroline Demeret, Jérôme De Seze, Samira Fafi-Kremer, Benjamin Terrier, Solen Kernéis, Charlotte Cockram, Rhea J. Longley, Marija Backovic, Arnaud Fontanet, Sarah H. Merkling, Timothée Bruel, Michael T. White, Malaria : parasites et hôtes - Malaria : parasites and hosts, Institut Pasteur [Paris], Santé publique : épidémiologie & sciences de l'information biomédicale (ED 393), Sorbonne Université (SU), Régulation spatiale des Génomes - Spatial Regulation of Genomes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Virologie Structurale - Structural Virology, Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe Mobile d'Infectiologie [APHP Centre, Paris], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire de Virologie [Strasbourg], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, Virus et Immunité - Virus and immunity, Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Plateforme technologique Production et purification de protéines recombinantes – Production and Purification of Recombinant Proteins Technological Platform (PPR), University of Melbourne, The Walter and Eliza Hall Institute of Medical Research (WEHI), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), This work was supported by the European Research Council (MultiSeroSurv ERC Starting Grant 852373, MTW), l'Agence Nationale de la Recherche and Fondation pour la Recherche Médicale (CorPopImm, MTW), and the Institut Pasteur International Network (CoronaSeroSurv, MTW). JR was supported by the Pasteur Paris University International PhD Program. CC was supported by the European Research Council 771813. The French COVID cohort is supported by the REACTing consortium and by the French Directorate General for Health., European Project: 852373,ERC-2019-STG,MultiSeroSurv(2020), European Project: 771813,SynarchiC, Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), CHU Cochin [AP-HP], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Pasteur-Cnam risques infectieux et émergents (PACRI), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris], Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), European Project: 771813,ERC-2017-COG,SynarchiC(2018), Gestionnaire, HAL Sorbonne Université 5, Algorithms and multiplex assays for integrated serological surveillance of malaria and neglected tropical diseases - MultiSeroSurv - - ERC-2019-STG2020-02-01 - 2025-01-31 - 852373 - VALID, Investigating the functional architecture of microbial genomes with synthetic approaches - SynarchiC - - ERC-2017-COG2018-04-01 - 2023-09-30 - 771813 - VALID, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Vaccine Research Institute [Créteil, France] (VRI), ANR-20-COVI-0077,Covid-Metrics,Econométrie, Série Temporelles, et Gestion des risques de Covid-19(2020), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and 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)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)
Subjects: Microbiology (medical), Adult, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Machine learning, computer.software_genre, Antibodies, Viral, Microbiology, Sensitivity and Specificity, Serology, Machine Learning, 03 medical and health sciences, 0302 clinical medicine, Antigen, Seroepidemiologic Studies, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Credible interval, Medicine, Seroprevalence, Humans, Multiplex, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, business.industry, SARS-CoV-2, COVID-19, Bayes Theorem, Articles, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Immunoglobulin M, Immunoglobulin G, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Artificial intelligence, Antibody, business, computer, 030217 neurology & neurosurgery
Abstract: International audience; BackgroundInfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces an antibody response targeting multiple antigens that changes over time. This study aims to take advantage of this complexity to develop more accurate serological diagnostics.MethodsA multiplex serological assay was developed to measure IgG and IgM antibody responses to seven SARS-CoV-2 spike or nucleoprotein antigens, two antigens for the nucleoproteins of the 229E and NL63 seasonal coronaviruses, and three non-coronavirus antigens. Antibodies were measured in serum samples collected up to 39 days after symptom onset from 215 adults in four French hospitals (53 patients and 162 health-care workers) with quantitative RT-PCR-confirmed SARS-CoV-2 infection, and negative control serum samples collected from healthy adult blood donors before the start of the SARS-CoV-2 epidemic (335 samples from France, Thailand, and Peru). Machine learning classifiers were trained with the multiplex data to classify individuals with previous SARS-CoV-2 infection, with the best classification performance displayed by a random forests algorithm. A Bayesian mathematical model of antibody kinetics informed by prior information from other coronaviruses was used to estimate time-varying antibody responses and assess the sensitivity and classification performance of serological diagnostics during the first year following symptom onset. A statistical estimator is presented that can provide estimates of seroprevalence in very low-transmission settings.FindingsIgG antibody responses to trimeric spike protein (Stri) identified individuals with previous SARS-CoV-2 infection with 91·6% (95% CI 87·5–94·5) sensitivity and 99·1% (97·4–99·7) specificity. Using a serological signature of IgG and IgM to multiple antigens, it was possible to identify infected individuals with 98·8% (96·5–99·6) sensitivity and 99·3% (97·6–99·8) specificity. Informed by existing data from other coronaviruses, we estimate that 1 year after infection, a monoplex assay with optimal anti-Stri IgG cutoff has 88·7% (95% credible interval 63·4–97·4) sensitivity and that a four-antigen multiplex assay can increase sensitivity to 96·4% (80·9–100·0). When applied to population-level serological surveys, statistical analysis of multiplex data allows estimation of seroprevalence levels less than 2%, below the false-positivity rate of many other assays.InterpretationSerological signatures based on antibody responses to multiple antigens can provide accurate and robust serological classification of individuals with previous SARS-CoV-2 infection. This provides potential solutions to two pressing challenges for SARS-CoV-2 serological surveillance: classifying individuals who were infected more than 6 months ago and measuring seroprevalence in serological surveys in very low-transmission settings.FundingEuropean Research Council. Fondation pour la Recherche Médicale. Institut Pasteur Task Force COVID-19.
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247. Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study

Author: Marianne Autié, Pascale Massin, Philippe Mailly, Maud Righini, C. Vincentelli, Pierre Gascon, Nicolas Venteclef, Anne Dutour, Xavier Guillonneau, Stéphane Germain, Frédéric Matonti, Bénédicte Dupas, Benjamin Alos, Rodrigue Garcia, Florence Sabatier, Marie Houssays, Jean-Pierre Riveline, Lucile Vignaud, Tiphaine Vidal-Trecan, Louisa Goumidi, Samaher Besbes, Matthieu Proust, Jennifer Marie-Louise, Patricia Ancel, Bénédicte Gaborit, Laurent Muller, Fawaz Alzaid, Jean-François Gautier, Jean-Baptiste Julla, Ali Erginay, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Lariboisière, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Carcinose Angiogenèse et Recherche Translationnelle, Angiogenese et recherche translationnelle (CART U965), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Assistance Publique - Hôpitaux de Marseille (APHM), Polytech'Paris - Sorbonne Université, Sorbonne Université (SU), Service d'ophthalmologie [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANR-14-CE15-0004,Angiosafe-T2D,GLP-1 et angiogenèse : safety dans le traitement du diabète de type 2 ?(2014), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité)
Subjects: Blood Glucose, Male, estimated glomerular filtration rate, Angiogenesis, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, dipeptidyl peptidase-IV inhibitors, Type 2 diabetes, Biochemistry, Neovascularization, chemistry.chemical_compound, Mice, angiogenesis, 0302 clinical medicine, Endocrinology, HUVEC, DR, glucagon-like peptide 1 receptor agonist, Morphogenesis, eGFR, three-dimensional, T2D, 0303 health sciences, Neovascularization, Pathologic, micro-RNA, angiosafe Type 2 diabetes study, Diabetic retinopathy, CI, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, GLP-1RA, VEGF, 3. Good health, 7-AAD, diabetic retinopathy, 7-aminoactinomycin D, HPC, Female, type 2 diabetes, hematopoietic progenitor cell, medicine.symptom, medicine.drug, Retinopathy, 3D, medicine.medical_specialty, endocrine system, Ig, Human umbilical vein endothelial cell, 030209 endocrinology & metabolism, Glucagon-Like Peptide-1 Receptor, Retina, 03 medical and health sciences, Internal medicine, retinopathy, medicine, Animals, Humans, Hypoglycemic Agents, fundus photography, glucagon like peptide 1 receptor agonist, Glucagon-like peptide 1 receptor, 030304 developmental biology, Aged, miRNA, Liraglutide, business.industry, Biochemistry (medical), Endothelial Cells, medicine.disease, vascular endothelial growth factor type 2 diabetes, DPP-IV, chemistry, Diabetes Mellitus, Type 2, confidence interval, Exenatide, Glycated hemoglobin, business, immunoglobulin, Biomarkers, Follow-Up Studies
Abstract: AimsRecent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR). The aim of the AngioSafe type 2 diabetes (T2D) study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models.MethodsWe performed two studies in humans. In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR, as diagnosed with retinal imaging (fundus photography). In study 2, a randomized 4-week trial, we assessed the effect of liraglutide on circulating hematopoietic progenitor cells (HPCs), and angio-miRNAs.We then studied the experimental effect of Exendin-4, on key steps of angiogenesis: in vitro on human endothelial cell proliferation, survival and three-dimensional vascular morphogenesis; and in vivo on ischemia-induced neovascularization of the retina in mice.ResultsIn the cohort of 3154 T2D patients, 10% displayed severe DR. In multivariate analysis, sex, disease duration, glycated hemoglobin (HbA1c), micro- and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR, while no association was found with GLP-1RA exposure (o 1.139 [0.800–1.622], P = .47). We further showed no effect of liraglutide on HPCs, and angio-miRNAs. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells, no effect on total length and number of capillaries. Finally, in vivo, we showed that exendin-4 did not exert any negative effect on retinal neovascularization.ConclusionsThe AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR.
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248. Dictionnaire Hachette juniors

Author: Philippe AMIEL, Paul Bonnevie, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: [SHS.LANGUE]Humanities and Social Sciences/Linguistics, ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 1980

249. Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID ‐19 in type 2 diabetes

Author: Charline Potier, Tiphaine Vidal-Trecan, Jean-François Gautier, Bénédicte Gaborit, Ronan Roussel, Fawaz Alzaid, Stéphane Germain, Gilberto Velho, Marc Diedisheim, Jean-Baptiste Julla, Jean-Pierre Riveline, Nicolas Venteclef, Louis Potier, Philippe Manivet, Elise Dalmas, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Service d'endocrinologie, diabétologie et nutrition [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service d'endocrinologie, diabète et maladies métaboliques, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Diabétologie et Endocrinologie, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-19-CE14-0005,MitoFLAME,Bioénergétique mitochondriale de l'inflammation métabolique: Dérépression de la respiration mitochondriale comme nouvelle approche thérapeutique dans le diabète de type 2(2019), Gestionnaire, HAL Sorbonne Université 5, Bioénergétique mitochondriale de l'inflammation métabolique: Dérépression de la respiration mitochondriale comme nouvelle approche thérapeutique dans le diabète de type 2 - - MitoFLAME2019 - ANR-19-CE14-0005 - AAPG2019 - VALID, and École Pratique des Hautes Études (EPHE)
Subjects: 0301 basic medicine, Male, SARS‐CoV-2, Medicine (General), endocrine system diseases, Lipopolysaccharide Receptors, Monocytopenia, Type 2 diabetes, QH426-470, Severity of Illness Index, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Monocytes, SARS‐CoV‐2, 0302 clinical medicine, Immunophenotyping, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Chemokine CCL2, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Articles, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, monocyte, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Molecular Medicine, Female, type 2 diabetes, type 2 diabetes Subject Categories Immunology, Microbiology, Article, 03 medical and health sciences, R5-920, COVID‐19, Intensive care, Lymphopenia, Severity of illness, medicine, Genetics, Humans, Risk factor, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Aged, business.industry, Interleukin-6, SARS-CoV-2, Monocyte, nutritional and metabolic diseases, COVID-19, medicine.disease, Virology & Host Pathogen Interaction, 030104 developmental biology, Metabolism, Diabetes Mellitus, Type 2, inflammation, Immunology, Leukocytes, Mononuclear, Lymphocytopenia, business, 030217 neurology & neurosurgery
Abstract: International audience; Early in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk factor for severe disease and mortality. Inflammation is central to the aetiology of both conditions where variations in immune responses can mitigate or aggravate disease course. Identifying at-risk groups based on immunoinflammatory signatures is valuable in directing personalised care and developing potential targets for precision therapy. This observational study charac-terised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leucocyte populations in peripheral circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lympho-cytopenia and specific loss of cytotoxic CD8 + lymphocytes were associated with severe COVID-19 and requirement for intensive care in both non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia restricted to classical CD14 Hi CD16 À monocytes was specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Increased expression of inflammatory markers reminiscent of the type 1 interferon pathway (IL6, IL8, CCL2, INFB1) underlaid the immunophenotype associated with T2D. These immunophenotypic and hyperinflammatory changes may contribute to increased voracity of COVID-19 in T2D. These findings allow precise identification of T2D patients with severe COVID-19 as well as provide evidence that the type 1 interferon pathway may be an actionable therapeutic target for future studies.
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250. Dictionnaire pratique du français - Hachette

Author: Philippe AMIEL, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: [SHS.LANGUE]Humanities and Social Sciences/Linguistics, ComputingMilieux_MISCELLANEOUS
Abstract: International audience

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