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1. Adapting French COVID-19 vaccination campaign duration to variant dissemination

Author

Pascal Roy, Catherine Pothier, Anne Eyraud-Loisel, Nicolas Ponthus, Philippe Vanhems, Simon Pageaud, Jean-Pierre Bertoglio, Alexis Bienvenüe, Nicolas Leboisne, Romain Gauchon, François Gueyffier, Jean Iwaz, Christophe Rigotti, Stéphane Loisel, Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), 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), Université de Lyon, Extraction de Caractéristiques et Identification (imagine), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Université Lumière - Lyon 2 (UL2), Data Mining and Machine Learning (DM2L), Artificial Evolution and Computational Biology (BEAGLE), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Mecanique des Fluides et d'Acoustique (LMFA), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Lyon 1, Ecole Centrale de Lyon, INSA Lyon, Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Ecole Nationale d'Ingénieurs de Saint Etienne (ENISE)-Centre National de la Recherche Scientifique (CNRS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-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), and Rigotti, Christophe

Subjects
0303 health sciences, medicine.medical_specialty, education.field_of_study, business.industry, Public health, Population, Outbreak, International health, Disease, 3. Good health, Vaccination, 03 medical and health sciences, 0302 clinical medicine, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Intensive care, Pandemic, medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030212 general & internal medicine, business, education, 030304 developmental biology, Demography
Abstract

BackgroundThe outbreak of SARS-CoV-2 virus has caused a major international health crisis with serious consequences in terms of public health and economy. In France, two lockdown periods were decided in 2020 to avoid the saturation of intensive care units (ICU) and an increase in mortality. The rapid dissemination of variant SARS-CoV-2 VOC 202012/01 has strongly influenced the course of the epidemic. Vaccines have been rapidly developed. Their efficacy against the severe forms of the disease has been established, and their efficacy against disease transmission is under evaluation. The aim of this paper is to compare the efficacy of several vaccination strategies in the presence of variants in controlling the COVID-19 epidemic through population immunity.MethodsAn agent-based model was designed to simulate with different scenarios the evolution of COVID-19 pandemic in France over 2021 and 2022. The simulations were carried out ignoring the occurrence of variants then taking into account their diffusion over time. The expected effects of three Non-Pharmaceutical Interventions (Relaxed-NPI, Intensive-NPI, and Extended-NPI) to limit the epidemic extension were compared. The expected efficacy of vaccines were the values recently estimated in preventing severe forms of the disease (75% and 94%) for the current used vaccines in France (Pfizer-BioNTech and Moderna since January 11, 2021, and AstraZeneca since February 2, 2021). All vaccination campaigns reproduced an advanced age-based priority advised by the Haute Autorité de Santé. Putative reductions of virus transmission were fixed at 0, 50, 75 and 90%. The effects of four vaccination campaign durations (6-month, 12-month, 18-month and 24-month) were compared.ResultsIn the absence of vaccination, the presence of variants led to reject the Relaxed-NPI because of a high expected number of deaths (170 to 210 thousands) and the significant overload of ICUs from which 35 thousand patients would be deprived. In comparison with the situation without vaccination, the number of deaths was divided by 7 without ICU saturation with a 6-month vaccination campaign. A 12-month campaign would divide the number of death by 3 with Intensive-NPI and by 6 with Extended-NPI (the latter being necessary to avoid ICU saturation). With 18-month and 24-month vaccination campaigns without Extended-NPI, the number of deaths and ICU admissions would explode.ConclusionAmong the four compared strategies the 6-month vaccination campaign seems to be the best response to changes in the dynamics of the epidemic due to the variants. The race against the COVID-19 epidemic is a race of vaccination strategy. Any further vaccination delay would increase the need of strengthened measures such as Extended-NPI to limit the number of deaths and avoid ICU saturation.

Published
2021

2. Protocol of controlled odorant stimulation for reducing apnoeic episodes in premature newborns: a randomised open-label Latin-square study with independent evaluation of the main endpoint (PREMODEUR)

Author

Olivier Claris, Marc Thevenet, Delphine Maucort-Boulch, Jean Iwaz, Huu Kim Nguyen, Sonia Galletti, Patricia Duchamp-Viret, Patricia Franco, Franck Plaisant, Aurore Guyon, Elise Cornaton, Hélène Gauthier-Moulinier, Laurent Remontet, Behrouz Kassai, Andrei Cividjian, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Université de Lyon, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Viret, Patricia, Centre de recherche en neurosciences de Lyon (CRNL), and 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)

Subjects
Tachycardia, Olfactory system, medicine.medical_specialty, Pediatrics, Apnea, Infant, Premature, Diseases, Irritability, neonatology, Sleep medicine, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Intensive Care Units, Neonatal, Intensive care, neonatal intensive & critical care, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neonatology, Risk factor, Child, Randomized Controlled Trials as Topic, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, paediatric intensive & critical care, sleep medicine, Infant, Newborn, Infant, Paediatrics, General Medicine, Doxapram, Odorants, Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], neurophysiology, medicine.symptom, business, Infant, Premature, medicine.drug
Abstract

Introduction Apnoea affects 85% of premature infants under 34 weeks of age and would be an important risk factor for subsequent neuropsychological disorders. Currently, premature children with life-threatening apnoeas receive stimulants such as methylxanthines (mainly, caffeine) or doxapram (an analeptic unlicensed in children under 15). However, these products have undesirable effects (hyperarousal, irritability, sleep disorders, tachycardia) and are not always effective because apnoea does persist in some premature newborns. Previous studies have indicated that odorant stimulation, a non-invasive intervention, may stimulate the respiratory rhythm. The objective of the present protocol is to reduce the occurrence of apnoeic episodes in premature newborns by controlled odorant stimulation added to current pharmacological treatments. Methods and analysis The project is a randomised open-label Latin-square trial with independent evaluation of the main endpoint. It will include 60 preterm neonates from two university hospital neonatal intensive care units over 2 years (2021–2023). Each newborn will receive no (S0), sham (S1) or real olfactory stimulation (S2) in random order. During S2, three distinct odorants (mint, grapefruit and vanilla) will be delivered successively, in puffs, over 24 hours. Mint and grapefruit odours stimulate the main and the trigeminal olfactory pathways, whereas vanilla odour stimulates only the main olfactory pathway. A statistical analysis will compare the incidence of apnoeic episodes during S1 versus S2 using a mixed effects Poisson model. Ethics and dissemination Ethical approval was obtained from the Comité de Protection des Personnes Île-de-France XI (# 2017-AO13-50-53). The results will be disseminated through various scientific meetings, specialised peer-reviewed journals and, whenever possible, posted on appropriate public websites. Trial registration number NCT02851979; Pre-results.

Published
2021
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3. Exposure of paediatric healthcare personnel to nitrous oxide in paediatric care units

Author

Benjamin Riche, Charlotte Pete-Bonneton, Robert Cadot, Amélie Massardier-Pilonchery, Jean Iwaz, Marie-Agnès Denis, Barbara Charbotel, Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), and Université de Lyon-Université de Lyon-Université Gustave Eiffel

Subjects
Male, Operating Rooms, medicine.medical_specialty, Emergency unit, Regular checks, NITROUS OXIDE, Health Personnel, Health, Toxicology and Mutagenesis, Air Pollutants, Occupational, ANAESTHETICS, ANAESTHETIC GASES, MEDECINE, chemistry.chemical_compound, PAEDIATRIC NURSING, Health care, EXPOSITION AU RISQUE, Humans, Medicine, RISK ASSESSMENT, Child, ANESTHESIE, Paediatric care, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, business.industry, OCCUPATIONAL EXPOSURE, Public Health, Environmental and Occupational Health, Nitrous oxide, PROTOXYDE D'AZOTE, Cross-Sectional Studies, chemistry, PAEDIATRIC HOSPITALS, GAZ, RISK FACTORS, Emergency medicine, Childbearing age, Open treatment, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Delivery of Health Care, Healthcare providers
Abstract

Nitrous oxide (N2O) was found responsible for genetic and reproductive toxicities, whereas it is widely used in paediatric care units where most healthcare providers are women of childbearing age. This motivated investigating occupational overexposure and overexposure factors in several paediatric hospital units. A cross-sectional study was carried out in seven healthcare units. On each of 34 healthcare providers, air samples were extracted (portable pumps and Tedlar® bags) and N2O quantified (gas chromatography, pulsed discharge ionization detection, and infrared spectrometry). The data allowed calculating mean instantaneous exposures. The mean instantaneous exposure was: i) four times higher in closed vs. open treatment rooms; ii) two times higher in case of use vs. non-use of N2O; iii) significantly higher in junior vs. senior healthcare providers (by 12%); and, iv) higher during presumably short vs. presumably long procedures (by 20%). Overexposures to N2O were mainly seen in the emergency unit and in day hospitals for thoracic/abdominal diseases and nephrology. Overexposures were frequent during short-duration procedures; among 88 N2O measurements, 77 (87.5%) exceeded the 200 ppm threshold over 15 minutes. The overexposures call for dedicated treatment rooms (with adequate equipment and ventilation), more efficient anaesthetic practices, appropriate training, and regular checks.

Published
2021
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4. Changes in registered malaria cases and deaths in Togo from 2008 to 2017

Author

Anne Thomas, Tchassama Tchadjobo, Muriel Rabilloud, Tchaa Abalo Bakai, Jean Iwaz, Nicolas Voirin, Nagham Khanafer, Tinah Atcha-Oubou, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Programme national de lutte contre le paludisme, Adult, Male, 0301 basic medicine, Microbiology (medical), Adolescent, Epidemiology, [SDV]Life Sciences [q-bio], 030106 microbiology, Population, lcsh:Infectious and parasitic diseases, Antimalarials, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, parasitic diseases, Humans, Medicine, lcsh:RC109-216, National level, 030212 general & internal medicine, Mortality, Child, education, ComputingMilieux_MISCELLANEOUS, Government, education.field_of_study, Surveillance, business.industry, Medical record, 1. No poverty, Infant, General Medicine, medicine.disease, Malaria, 3. Good health, Infectious Diseases, Child, Preschool, Togo, Female, business, Demography
Abstract

Objective: The WHO Malaria Report 2019 stated that “globally, the burden of malaria was lower than ten years ago, but, in the last few years, there has been an increase in the number of malaria cases around the world”. This study reported changes in malaria cases and deaths at the Togo national level (2008–2017) and presented anti-malaria fight results and eradication chances by 2030 in Togo. Methods: Cases and deaths were collected from medical records, monthly reports, and notes of 6000 health workers; then summarized by Region, District, year, and specific subpopulations. Estimates of annual trends of numbers of cases and deaths were obtained through generalized linear models. Results: The number of cases increased by four times, whereas the population increased by 1.3 times (2008–2017). Increases affected all regions and subpopulations; the mean annual relative increases in children

Published
2020
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5. A dashboard for monitoring preventive measures in response to COVID-19 outbreak in the Democratic Republic of Congo

Author

Jean Francois Etard, Muriel Rabilloud, Philippe Vanhems, Benjamin Longo-Mbenza, Patient Wimba, Philippe Bianga Katchunga, Jacques Aimé Bazeboso, René Ecochard, Jean Iwaz, Léon Tshilolo, Université officielle de Bukavu, Université de Lyon, University of Kinshasa (UNIKIN), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-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)-École normale supérieure de Lyon (ENS de Lyon)-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), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), and Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Distancing, media_common.quotation_subject, 030231 tropical medicine, Developing country, Urban environment, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Information system, medicine, 030212 general & internal medicine, media_common, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Data collection, Research, Public health, Public Health, Environmental and Occupational Health, COVID-19, Outbreak, medicine.disease, Democracy, Low-income countries, 3. Good health, Infectious Diseases, Data access, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Business, Medical emergency, Dashboard
Abstract

Background In most health areas, an information system is necessary for an effective fight against COVID-19. Current methods for surveillance of diseases with epidemic potential do not include monitoring the adherence to preventive measures. Furthermore, modern data collection methods depend often on technologies (e.g., cameras or drones) that are hardly available in low-income countries. Simpler solutions could be just as effective. Methods A dashboard was used over a whole week to monitor preventive measures in Bukavu (DRC) by mid-May 2020. It was designed to collect from street passers-by information on the adherence to barrier measures, the level of awareness of these measures, the opinion on their usefulness, and the health status of people in the households. Results Creating a dashboard and collecting the necessary data proved feasible. The use of barrier measures was very limited and that of masks practically nil despite repeated recommendations from the health authorities. The end of each day was the worst moment due to clearly insufficient distancing. Barrier measures were significantly more used in areas where they were best known and most acknowledged. At the time of the study, there were few sick people and only rare severe cases were attributed to COVID-19. Conclusions Creating COVID-19 situation dashboards in limited-resource metropoles is feasible. They give real-time access to data that help fight the epidemic. The findings of this pilot study call for a rapid community awareness actions to back national media-based prevention campaigns.

Published
2020
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6. Diagnostic Performance of Creatinine-Based Equations for Estimating Glomerular Filtration Rate in Adults 65 Years and Older

Author

Dener lizot Rech, Jean Iwaz, Vandréa De Souza, Luciano Selistre, Sandrine Lemoine, Laurence Dubourg, Departamento de Ecologia Evolutiva, Instituto de Ecologıa, Universidad Nacional Autónoma de México (UNAM), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), 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), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, medicine.medical_specialty, Cross-sectional study, [SDV]Life Sciences [q-bio], Urology, Renal function, Kidney Function Tests, urologic and male genital diseases, 01 natural sciences, Risk Assessment, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Interquartile range, Internal Medicine, medicine, Humans, 030212 general & internal medicine, 0101 mathematics, Renal Insufficiency, Chronic, Aged, Original Investigation, Aged, 80 and over, Creatinine, Kidney, Inulin Clearance, urogenital system, business.industry, 010102 general mathematics, Kidney donation, female genital diseases and pregnancy complications, medicine.anatomical_structure, Cross-Sectional Studies, chemistry, Kidney Impairment, Female, France, business, Biomarkers, Glomerular Filtration Rate
Abstract

Importance: Estimating glomerular filtration rate (GFR) is useful in many clinical conditions. However, very few studies have evaluated the performance of GFR-estimating equations in older adults at various degrees of kidney impairment. Objective: To determine the performance of plasma-creatinine-based equations Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI), Lund-Malmo Revised, (LMR), full age spectrum (FAS), and Berlin Initiative Study (BIS) 1 in older adults across a broad spectrum of GFRs. Design, Setting, and Participants: Single-center cross-sectional study performed in France including 2247 participants aged 65 to 90 years who underwent inulin GFR measurements from July 1, 2003, to July 30, 2017, for suspected or established renal dysfunction, for renal risk, before kidney donation, or after kidney transplant. Main Outcomes and Measures: The main outcome measure was GRF measured by inulin clearance. Equation performance criteria considered bias (difference between estimated and measured GFR), precision (interquartile range of the median difference), and accuracy P30 (percentage of estimated GFRs lying between [measured GFR - 30% of measured GFR] and [measured GFR + 30% of measured GFR]). Results: The mean (SD) age of the 2247 participants was 71.5 (5) years and 1192 (53.0%) were male. The difference in median (95% CI) bias was significant between CKD-EPI vs LMR (-4.0 [-4.0 to -3.5 mL/min/1.73 m2; P \textless .001]) and CKD-EPI vs FAS (-2.0 [-3.5 to -2.5] mL/min/1.73 m2, P \textless .001) but not significant between CKD-EPI vs BIS 1 (0.0 [-1.5 to 0.5], P = .07, Mood test). In patients aged 65 to 74 years with measured GFR\textless45 mL/min/1.73 m2, the difference in median P30 (95% CI) was not significant between CKD-EPI vs LMR (P = .08) and CKD-EPI vs FAS (P = .48) but significant vs BIS 1 (P = .004, McNemar test). In subjects 75 years and older, with measured GFR less than 45 mL/min/1.73 m2, LMR and BIS 1 were more accurate than CKD-EPI and FAS (P30 = 74.5 [70.0-79.5] and 73.0 [68.0-78.0] vs 69.0 [64.5-74.0] and 69.0 [65.5-72.0]). In all patients, despite small statistical differences, the performance of CKD-EPI equation was not clinically different from that of LMR, FAS, or BIS 1. Conclusions and Relevance: In a referral group of patients 65 years and older who had GFR estimated using CDK-EPI, LMR, BIS 1, and FAS equations, a comparison with renal inulin clearance found that none of the equations had a superior diagnostic performance. Each had limitations regarding accuracy.

Published
2019
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7. A new simplified and accurate sa-SOFA score

Author

Vincent Piriou, Martin Cour, Frédéric Aubrun, Bernard Allaouchiche, Julien Bohé, Jean Iwaz, Arnaud Friggeri, Fabienne Venet, Laurent Argaud, Alain Lepape, Delphine Maucort-Boulch, Charles-Hervé Vacheron, Thomas Rimmelé, Alexandre Pachot, Guillaume Monneret, Service d'anesthésie-réanimation [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot, Service Anesthésie Réanimation, Hopital Civil, Hospices Civils de Lyon (HCL), Laboratoire d'Immunologie, Hôpital Edouard Herriot [CHU - HCL], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Hôpital de la Croix-Rousse [CHU - HCL], Service d'Anesthésie-Réanimation, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France, parent, Service de Réanimation (Nord), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), 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), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, health care facilities, manpower, and services, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Organ Dysfunction Scores, health services administration, Statistics, Medicine, Humans, 030212 general & internal medicine, p-value, Prospective Studies, Mortality, SOFA score, Organ dysfunction scores, Aged, Retrospective Studies, Inflammation, Intensive care units, Receiver operating characteristic, Sequential organ failure assessment, business.industry, Reproducibility of Results, 030208 emergency & critical care medicine, Middle Aged, Prognosis, Systemic Inflammatory Response Syndrome, respiratory tract diseases, ROC Curve, Area Under Curve, Regression Analysis, Female, business
Abstract

Purpose Several remarks have been raised regarding the variables and cut-points used in the Sequential Organ Failure Assessment (SOFA) score. This study revisited the SOFA score and created a new simplified and accurate sa-SOFA score. Methods The study grouped four prospective cohorts (2005–2016) of patients with Systemic Inflammatory Response Syndrome. It collected 28-day mortality, sociodemographic characteristics, and the SOFA score with all variable values at Day 1. A logistic regression analysis was used to select the most relevant variables and a minimum p value approach with a 10-fold cross-validation were used to find the optimal partition of selected variables. The minimum number of cut-points (2, 3, or 4) was also tested by comparing the distributions of areas under receiver operating characteristic (AUROC) curves. Results Among the 1436 participants, 416 died within 28 days (28.9%). The sa-SOFA kept one variable per dimension and two cut-points per variable. The AUROC curves that investigated the abilities of the sa-SOFA and SOFA scores to predict 28-day mortality were 0.739 [0.712–0.768] and 0.687 [0.656–0.717], respectively (p-value of DeLong test Conclusion Keeping the conventional SOFA dimension variables, the new sa-SOFA proved to be simpler and more accurate in predicting 28-day mortality.

Published
2019
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8. Glucose trajectories in cystic fibrosis and their association with pulmonary function

Author

Sylvain Roche, Muriel Rabilloud, C. Llerena, Jean Iwaz, Philippe Reix, Raphaele Nove-Josserand, Isabelle Durieu, Emilie Blond, S. Poupon-Bourdy, Martine Laville, Quitterie Reynaud, Sébastien Quétant, Sandrine Touzet, Hospices Civils de Lyon (HCL), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service de Biostatistiques [Lyon], Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Pôle Information Médicale Evaluation Recherche (IMER), 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), Centre Hospitalier Universitaire [Grenoble] (CHU), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Blood Glucose, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pediatrics, Cystic Fibrosis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Cystic fibrosis-related diabetes, 030209 endocrinology & metabolism, Cystic fibrosis, Body Mass Index, Pulmonary function testing, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Glucose Intolerance, Diabetes Mellitus, medicine, Humans, Respiratory system, Child, Correlation of Data, ComputingMilieux_MISCELLANEOUS, business.industry, Insulin, Glucose Tolerance Test, medicine.disease, Respiratory Function Tests, 3. Good health, Endocrinology, 030228 respiratory system, Pediatrics, Perinatology and Child Health, Disease Progression, Female, France, Abnormality, business, Body mass index
Abstract

Background The prevalence of cystic fibrosis-related diabetes is increasing. This condition is potentially responsible for respiratory decline. Methods At inclusion, then yearly (over three years), 111 children and 117 adults with cystic fibrosis had oral glucose tolerance and insulin tests at one (G1) and 2h (G2). KmL analysis identified homogeneous G1 and G2 glucose trajectories. A linear mixed model quantified the relationships between trajectories and FEV1 changes. Results In children, there were three G1 and four G2 trajectories and FEV1 decrease was not significantly different between G1 or G2 trajectories. In adults, two G1 and four G2 trajectories were identified and FEV1 change was estimated at −0.85/year (95% CI: [−1.54; −0.17], p=0.01) whatever the G1 trajectory and found significantly faster in the high and increasing G2 trajectory (−2.1/year, [−3.9; −0.2], p=0.03). Conclusions In case of persistent G2 abnormality, physicians should be alert for clinical deterioration and intensify patient surveillance.

Published
2018
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9. Evolution of the incidence of hepatitis B virus infection and immunization rates in a large French cohort born between 1960 and 1994

Author

Caroline Scholtes, P. André, Jean Iwaz, C. Ramière, René Ecochard, Laurent Roche, J. Saison, Biologie cellulaire des infections virales – Cell biology of viral infection, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-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)-École normale supérieure de Lyon (ENS de Lyon)-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), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Microbiology (medical), Anonymous testing, Male, Adult, medicine.medical_specialty, medicine.disease_cause, Mass Vaccination, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Epidemiology, Prevalence, Medicine, Humans, 030212 general & internal medicine, Young adult, Retrospective Studies, Hepatitis B virus, business.industry, Incidence (epidemiology), Incidence, Retrospective cohort study, General Medicine, Hepatitis B, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Health policy, 3. Good health, Vaccination, Incidence studies, Infectious Diseases, Cohort, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, Female, France, business, Vaccine, Demography
Abstract

International audience; In France, several successive changes in anti-hepatitis B virus (HBV) vaccination policies occurred since 1982. We estimated the incidence and prevalence of HBV infection according to years of birth 1960 to 1994 in a large sentinel cohort to evaluate the epidemiology of HBV during vaccination policy changes. A retrospective cohort study included data from all HIV, HBV and hepatitis C virus (HCV) screening facilities in Grand Lyon. From 2005 to 2010, all 57113 individuals with complete HBV serologic status were enrolled. Survival analyses modeled separately various ages in each birth cohort. The proportion of immunized individuals increased in birth cohorts 1978 to 1984 (up to 58.3% (95% confidence interval (CI), 43.3-68.2 at age 15). In post-1985 birth cohorts, this proportion decreased to 19.5% (95% CI, 15.5-24) in birth cohort 1987 at age 15. Probability of past or current HBV infection increased constantly in birth cohorts 1960 to 1967, up to 12% (95% CI, 10.4-14) at age 30, then decreased gradually in birth cohorts 1968 to 1991, down to 0.9% (95% CI, 0.7-1.2) at age 17.5. In post-1991 cohorts, the probability of HBV infection increased again, up to 2.5% (95% CI, 1.7-3.6) at age 17.5. HBV incidence fluctuated between 5 and 8 per 1000 person-years in pre-1986 birth cohorts, decreased to 2.1 (95% CI, 1.5-2.7) in birth cohorts 1986 to 1991 but rebounded to 5 (95% CI, 3.5-7.1) in post-1991 birth cohorts. HBV incidence was remarkably high in young adults with noticeable variations concomitantly to vaccination policy changes. A dramatic decline in immunization rate was temporally associated with a sharp rebound of infection after withdrawal of systematic adolescent vaccination in 1998.

Published
2016
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10. Parenchymal lung involvement in adult-onset Still disease: A STROBE-compliant case series and literature review

Author

Isabelle Durieu, Pascal Sève, Jean Iwaz, Mathieu Gerfaud-Valentin, Agathe Gaillard-Coadon, Christiane Broussolle, Yvan Jamilloux, Vincent Cottin, Arnaud Hot, Centre de Référence des Maladies Pulmonaires Rares [Hôpital Louis Pradel - HCL], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Department of Pneumology [Lyon], Hospices Civils de Lyon (HCL), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Lung Diseases, ARDS, medicine.medical_specialty, Patients, Observational Study, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Pulmonary function testing, adult-onset Still disease, 03 medical and health sciences, 0302 clinical medicine, Adrenal Cortex Hormones, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Respiratory system, Lung, interstitial lung disease, 030203 arthritis & rheumatology, business.industry, Retrospective cohort study, General Medicine, Syndrome, acute respiratory distress syndrome, medicine.disease, 3. Good health, hemophagocytic lymphohistiocytosis, classification, Bronchiolitis, Cohort, France, Complication, business, Still's Disease, Adult-Onset, Research Article
Abstract

International audience; Parenchymal lung involvement (PLI) in adult-onset Still's disease (AOSD) has seldom, if ever, been studied. We examine here retrospective cohort AOSD cases and present a review of the literature (1971-2014) on AOSD-related PLI cases.Patients with PLI were identified in 57 AOSD cases. For inclusion, the patients had to fulfill Yamaguchi or Fautrel classification criteria, show respiratory symptoms, and have imaging evidence of pulmonary involvement, and data allowing exclusion of infectious, cardiogenic, toxic, or iatrogenic cause of PLI should be available. This AOSD + PLI group was compared with a control group (non-PLI-complicated AOSD cases from the same cohort).AOSD + PLI was found in 3 out of the 57 patients with AOSD (5.3%) and the literature mentioned 27 patients. Among these 30 AOSD + PLI cases, 12 presented an acute respiratory distress syndrome (ARDS) and the remaining 18 another PLI. In the latter, a nonspecific interstitial pneumonia computed tomography pattern prevailed in the lower lobes, pulmonary function tests showed a restrictive lung function, the alveolar differential cell count was neutrophilic in half of the cases, and the histological findings were consistent with bronchiolitis and nonspecific interstitial pneumonia. Corticosteroids were fully efficient in all but 3 patients. Ten out of 12 ARDS cases occurred during the first year of the disease course. All ARDS-complicated AOSD cases received corticosteroids with favorable outcomes in 10 (2 deceased). Most PLIs occurred during the systemic onset of AOSD.PLI may occur in 5% of AOSDs, of which ARDS is the most severe. Very often, corticosteroids are efficient in controlling this complication

Published
2016
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11. Validation of the French Version of Conners Parent Rating Scale Revised, Short Version: Factorial Structure and Reliability

Author

Olivier Revol, Catherine Mercier, René Ecochard, Michel Bader, Philippe Stéphan, Sylvain Roche, Pierre Fumeaux, Jean Iwaz, Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE)

Subjects
Adult, Male, Psychometrics, Adolescent, [SDV]Life Sciences [q-bio], Poison control, Developmental psychology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, 030225 pediatrics, Humans, Child, Categorical variable, Reliability (statistics), ComputingMilieux_MISCELLANEOUS, Original Research, Psychiatric Status Rating Scales, Construct validity, Reproducibility of Results, Guttman scale, Confirmatory factor analysis, Psychiatry and Mental health, Attention Deficit Disorder with Hyperactivity, Scale (social sciences), Female, France, Psychology, 030217 neurology & neurosurgery
Abstract

Objective: Attention-deficit hyperactivity disorder is one of the most frequent neurodevelopmental disorders. Its diagnosis requires reference questionnaires such as the Conners’ Parent Rating Scale (CPRS). Presently, in French-speaking countries, a few translations of the revised short CPRS have been put to use without previous formal validation. We sought here for the validation of a French version (Lausanne, Switzerland) of the revised short CPRS regarding construct validity, internal consistency, and item reliability in a sample of French schoolchildren. Method: The study involved 795 children and adolescents aged 9 to 19 years from a single school. The factorial structure and item reliability were assessed with a confirmatory factor analysis for ordered categorical variables. The dimension internal consistency was assessed with Guttman’s lambda 6 coefficient. Results: The results confirmed the original and strong 3-dimensional factorial structure (Oppositional, Cognitive Problems/Inattention, and Hyperactivity), showed satisfactory item reliability, and indicated a good dimension internal consistency (Guttman’s lambda 6 coefficient: 0.87, 0.90, and 0.82, respectively, to the 3 dimensions). Conclusions: Thus, the Lausanne French version of the revised short CPRS may be considered validated regarding construct validity and item and dimension reliability; it can be now more confidently used in clinical practice.

Published
2016
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12. Modeling and predicting the long-term effects of various strategies and objectives of varicella-zoster vaccination campaigns

Author

Benjamin Riche, Marie-Laure Kürzinger, Sylvain Roche, Jean Iwaz, René Ecochard, Jean-François Etard, Hélène Bricout, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE)

Subjects
0301 basic medicine, Adult, Male, Herpes Zoster Vaccine, Adolescent, [SDV]Life Sciences [q-bio], 030106 microbiology, Immunology, Herpes Zoster, Herd immunity, Time, Chickenpox Vaccine, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Chickenpox, Environmental health, Drug Discovery, medicine, Humans, 030212 general & internal medicine, Child, ComputingMilieux_MISCELLANEOUS, Pharmacology, Models, Statistical, business.industry, Immunization Programs, Incidence (epidemiology), Infant, Middle Aged, medicine.disease, 3. Good health, Term (time), Vaccination, Vaccination Campaigns, Child, Preschool, Molecular Medicine, Female, business
Abstract

BACKGROUND: Susceptible, exposed, infected, and recovered (SEIR) models are increasingly developed and used, but their simplicity contrasts with the wide variety of scenarios before launching vaccination campaigns. METHODS: We investigated the effects of some model-building choices (targets, pace, coverage rate) on the results of SEIR models in the case of vaccination against varicella and herpes zoster. RESULTS: The analysis demonstrated the need for a progressive unvaccinated to vaccinated transition and a dynamic system-equilibrium before vaccination onset. When several doses are considered, new compartments are needed to account for vaccination histories. For varicella, the delay to reach the expected coverage rate and the pace until reaching this rate have significant impacts, especially on the short-term incidence. The impact of vaccination through herd immunity should be systematically investigated. CONCLUSIONS: Graphs help understanding the progress of instantaneous incidence; however, tables of cumulative average incidence over decades should be preferred because of higher stability.

Published
2016
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13. Hemophagocytic Lymphohistiocytosis in Intensive Care Unit A 71-Case Strobe-Compliant Retrospective Study

Author

Jean-Christophe Richard, Laurent Argaud, Jacques Ninet, Jean-Christophe Lega, Claude Guérin, Julien Bohé, Yvan Jamilloux, Arnaud Hot, Christiane Broussolle, Thomas Barba, Pascal Sève, Jean Iwaz, Delphine Maucort-Boulch, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Evaluation et modélisation des effets thérapeutiques, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), 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), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, endocrine system, medicine.medical_specialty, Organ Dysfunction Scores, [SDV]Life Sciences [q-bio], Observational Study, Early death, adult patients, Disease, Lymphohistiocytosis, Hemophagocytic, law.invention, Body Temperature, spectrum, law, Risk Factors, hemic and lymphatic diseases, General & Internal Medicine, Medicine, Humans, Hospital Mortality, Intensive care medicine, Critical condition, Aged, Retrospective Studies, Aged, 80 and over, Hemophagocytic lymphohistiocytosis, disease, dysfunction, Adult patients, business.industry, fungi, Age Factors, Retrospective cohort study, General Medicine, Middle Aged, musculoskeletal system, medicine.disease, Intensive care unit, infection, 3. Good health, Intensive Care Units, Cohort, Female, business, hormones, hormone substitutes, and hormone antagonists, Research Article
Abstract

International audience; Hemophagocytic lymphohistiocytosis (HLH) is a critical condition that may lead to organ failure and early death. The aim of this retrospective observational study was to describe a cohort of HLH patients admitted to intensive care unit (ICU) and investigate the risk factors of early death. A positive HLH diagnosis was defined by an HScore \textgreater= 169. Univariate and multivariate analyses were carried out to investigate hospital and 28-day mortality risk factors. Between January 2002 and July 2014, 71 HLH cases were seen at our institution. The overall 28-day mortality (start at ICU admission) and hospital mortality were 38% and 68%, respectively. The factors associated with increased 28-day mortality were the sequential organ failure assessment score at ICU admission (P \textless .001) and advance in age (P = 0.03). The factors associated with increased hospital mortality were a high sequential organ failure assessment score at ICU admission (P \textless 0.01), advance in age (P = 0.04), and the presence of lymphoma-related HLH or HLH of unknown origin (P \textless 0.01). Organ failure overtops the classical early-death risk factors in adult ICU-admitted HLH patients. This failure and the subsequent early death may be prevented by timely specific cytotoxic therapies and the control of the underlying disease.

Published
2015
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14. Clinical features and diagnostic evaluation of 83 biopsy-proven sarcoid uveitis cases

Author

Christiane Broussolle, Camille Febvay, Carole Burillon, Pascal Sève, Jean Iwaz, Laurent Perard, Laurent Kodjikian, Delphine Maucort-Boulch, Yvan Jamilloux, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Service de Biostatistiques [Lyon], and Hospices Civils de Lyon (HCL)

Subjects
Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Biopsy, Fine-Needle, Diagnostic evaluation, Age and sex, Salivary Glands, Minor, Diagnosis, Differential, Uveitis, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, 0302 clinical medicine, Sarcoidosis, Pulmonary, Internal medicine, Biopsy, medicine, Humans, Vision, Ocular, Aged, Retrospective Studies, 030203 arthritis & rheumatology, Aged, 80 and over, medicine.diagnostic_test, business.industry, Retrospective cohort study, Enzyme test, Middle Aged, medicine.disease, Sensory Systems, 3. Good health, Surgery, Ophthalmology, 030221 ophthalmology & optometry, Female, Radiography, Thoracic, Sarcoidosis, business, Tomography, X-Ray Computed, Sarcoid uveitis
Abstract

Aims To determine the clinical features of patients with uveitis with biopsy-proven sarcoidosis, document differences in these features according to ethnicity, age and sex, and assess the diagnostic value of biochemical and imaging examinations. Methods Retrospective study of 83 biopsy-proven sarcoid uveitis cases seen at two Departments of Internal Medicine and two Departments of Ophthalmology between April 2004 and March 2014. Results Caucasian patients presented with uveitis at a later age than non-Caucasian (58 years vs 41 years; p=0.001) and had more often a chronic form (78.3% vs 43.8%; p=0.01). Women had higher rates of chronic macular oedema than men (48.3% vs 14.3%; p=0.01). There were no statistically significant differences between patients aged ≤50 years and patients aged >50 years. ACE levels were high (>62 U/L) in 61.7% and lysozyme levels high (>16.7 mg/L) in 83.9% of tested patients. Chest X-rays and CTs were suggestive of sarcoidosis in 62.8% and 91.2% of cases, respectively. Among 21 patients with positive tomography and negative X-rays, 13 were Caucasian women >50 years. Endoscopic ultrasound-guided fine-needle aspiration of intrathoracic nodes contributed to the diagnosis in 7 patients with normal labial salivary gland and transbronchial biopsies. Any of the enzyme tests together with any of the imaging tests identified 100% of the patients. Conclusions In this largest European series of biopsy-proven sarcoidosis to date, the outstanding diagnostic ability of enzyme test plus imaging test couple suggests that the recourse to invasive procedures should be limited to patients with ocular involvement that would justify systemic treatments.

Published
2015

15. Systemic lupus erythematosus-associated acute transverse myelitis: manifestations, treatments, outcomes, and prognostic factors in 20 patients

Author

Françoise Sarrot-Reynauld, O. Aumaître, Christiane Broussolle, J Saison, Delphine Maucort-Boulch, J Tebib, Romain Marignier, Pascal Sève, Jean Iwaz, Patrice Cacoub, D Vital-Durand, Nicolas Schleinitz, Arnaud Hot, Nathalie Costedoat-Chalumeau, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), 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), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
Adult, Male, medicine.medical_specialty, Cyclophosphamide, [SDV]Life Sciences [q-bio], Anti-Inflammatory Agents, Myelitis, Myelitis, Transverse, Severity of Illness Index, Transverse myelitis, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Adrenal Cortex Hormones, Antiphospholipid syndrome, Internal medicine, medicine, Humans, Lupus Erythematosus, Systemic, Mobility Limitation, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, 030203 arthritis & rheumatology, Systemic lupus erythematosus, Neuromyelitis optica, business.industry, Hydroxychloroquine, Middle Aged, Prognosis, medicine.disease, 3. Good health, Acute Transverse Myelitis, Antirheumatic Agents, Acute Disease, Physical therapy, Female, business, Immunosuppressive Agents, 030217 neurology & neurosurgery, Follow-Up Studies, medicine.drug
Abstract

Background Transverse myelitis is a rare complication of systemic lupus erythematosus (SLE). This retrospective multicentre study identifies the prognostic factors in a relatively large patient series. Patients and methods Twenty patients fulfilled the SLE criteria of the ACR classification and the Transverse Myelitis Consortium Working Group. A severe neurological flare was defined as muscle strength grade Results Myelitis was the first SLE symptom in 12 patients; in the eight others, it occurred 8.6 years (median delay) after SLE onset. Eleven patients presented severe neurological impairments. The treatment included corticosteroids in all patients associated with intravenous cyclophosphamide in 11 and/or hydroxychloroquine in 14. Unfavourable outcomes were observed in 53% of the patients at six months and in 28% at end of follow-up (median: 5.9 years). An initial severe neurological impairment and no cyclophosphamide use were associated with unfavourable neurological outcomes at six months and at end of follow-up, respectively. Conclusion Transverse myelitis may reveal SLE or occur more than 10 years after SLE diagnosis. The initial severity of the neurological flare (with paraplegia) is the main prognostic marker. The study provides arguments for cyclophosphamide use.

Published
2015
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16. Modeling the seasonality of Anopheles gambiae s.s. biting rates in a South Benin sanitary zone

Author

Noël Fonton, André Garcia, Armel Djènontin, Jean Iwaz, Fabien Subtil, Nicolas Moiroux, Olayidé Boussari, René Ecochard, Jean-François Etard, Vincent Corbel, Université d’Abomey-Calavi (UAC), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), and Université d’Abomey-Calavi = University of Abomey Calavi (UAC)

Subjects
Veterinary medicine, Mosquito Control, [SDV]Life Sciences [q-bio], South Benin, Normalized Difference Vegetation Index, Altitude, Anopheles gambiae S, Anopheles, parasitic diseases, medicine, Animals, Benin, Humans, Malaria vector, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, Models, Statistical, biology, Public Health, Environmental and Occupational Health, Insect Bites and Stings, Latent trajectory, modeling, General Medicine, Seasonality, biology.organism_classification, medicine.disease, Classification, Malaria, 3. Good health, Biting rate, Infectious Diseases, Biting, Anopheles gambiae s.s, Malaria vectors, Vector (epidemiology), Parasitology, Seasons
Abstract

BACKGROUND Efficient malaria vector control requires knowledge of spatio-temporal vector dynamics. We have classified village groups according to the biting rate profiles of both Anopheles coluzzii and An. gambiae, the major malaria vectors in these villages. METHODS Mosquitoes were captured by human bait in 28 South Benin villages during 2009. Both An. coluzzii and An. gambiae counts in each village were standardized to focus on changes in the vector biting rate over time. Latent class trajectory modeling, allowing for random intercept at the 'village' level, was adjusted to standardized values. RESULTS The villages could be classified into two groups with distinct vector biting rate profiles (continuous/transient). This classification helped creating a map of vector biting rates in the area. The biting rate profiles were found to be significantly correlated with mean rainfall, altitude, average number of larval sites, and average normalized difference vegetation index. CONCLUSIONS In highly malaria-prone regions, knowledge of vector biting rate profiles is important to improve vector control interventions. A similar methodology may be applied to study the biting rate profiles of other vector-borne infections.

Published
2014
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17. English cross-cultural translation and validation of the neuromuscular score: a system for motor function classification in patients with neuromuscular diseases

Author

C. Berard, Carole Vuillerot, Sandra Donkervoort, Dalil Hamroun, Carsten G. Bönnemann, Anne Rutkowski, I. Poirot, Tianxia Wu, Jahannaz Datsgir, P. Rippert, M. Waite, Melody M. Linton, Jean Iwaz, Christine Payan, M. Leach, Minal S. Jain, Katherine G. Meilleur, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, medicine.medical_specialty, Neuromuscular disease, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Concurrent validity, Score, Physical Therapy, Sports Therapy and Rehabilitation, Severity of Illness Index, Muscular Dystrophies, Article, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Physical medicine and rehabilitation, Surveys and Questionnaires, Activities of Daily Living, medicine, Content validity, Humans, Translations, 030212 general & internal medicine, Cultural Competency, Child, Observer Variation, Rehabilitation, business.industry, Reproducibility of Results, Gross Motor Function Classification System, medicine.disease, Confidence interval, 3. Good health, England, Motor Skills, Child, Preschool, Physical therapy, Female, business, 030217 neurology & neurosurgery, Kappa
Abstract

International audience; Objective: To develop and validate an English version of the Neuromuscular (NM)-Score, a classification for patients with NM diseases in each of the 3 motor function domains: D1, standing and transfers; D2, axial and proximal motor function; and D3, distal motor function.Design: Validation survey.Setting: Patients seen at a medical research center between June and September 2013.Participants: Consecutive patients (N=42) aged 5 to 19 years with a confirmed or suspected diagnosis of congenital muscular dystrophy.Interventions: Not applicable.Main Outcome Measures: An English version of the NM-Score was developed by a 9-person expert panel that assessed its content validity and semantic equivalence. Its concurrent validity was tested against criterion standards (Brooke Scale, Motor Function Measure [MFM], activity limitations for patients with upper and/or lower limb impairments [ACTIVLIM], Jebsen Test, and myometry measurements). Informant agreement between patient/caregiver (P/C)-reported and medical doctor (MD)-reported NM scores was measured by weighted kappa.Results: Significant correlation coefficients were found between NM scores and criterion standards. The highest correlations were found between NM-score D1 and MFM score D1 (rho =-.944, P

Published
2014
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18. Rasch analysis of the motor function measure in patients with congenital muscle dystrophy and congenital myopathy

Author

P. Rippert, Jean Iwaz, Carole Vuillerot, V. Kinet, Carsten G. Bönnemann, René Ecochard, Susana Quijano-Roy, Minal S. Jain, C. Berard, Anne Renders, Allan M. Glanzman, M. Waite, Françoise Girardot, Dalil Hamroun, I. Poirot, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Psychometrics, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Posture, Physical Therapy, Sports Therapy and Rehabilitation, Motor Activity, Motor function, Muscular Dystrophies, Article, Young Adult, Physical medicine and rehabilitation, medicine, Humans, In patient, Child, Motor skill, Aged, Rasch model, Rehabilitation, Reproducibility of Results, Middle Aged, medicine.disease, Congenital myopathy, 3. Good health, Treatment Outcome, Motor Skills, Child, Preschool, Congenital muscular dystrophy, Female, Psychology
Abstract

International audience; Objectives: To monitor treatment effects in patients with congenital myopathies and congenital muscular dystrophies, valid outcome measures are necessary. The Motor Function Measure (MFM) was examined for robustness, and changes are proposed for better adequacy.Design: Observational study based on data previously collected from several cohorts.Setting: Nineteen departments of physical medicine or neuromuscular consultation in France, Belgium, and the United States.Participants: Patients (N=289) aged 5 to 77 years.Interventions: None.Main Outcome Measures: A Rasch analysis examined the robustness of the MFM across the disease spectrum. The 3 domains of the scale (standing position and transfers, axial and proximal motor function, and distal motor function) were independently examined with a partial credit model.Results: The original 32-item MFM did not sufficiently fit the Rasch model expectations in either of its domains. Switching from a 4- to a 3-category response scale in 18 items restored response order in 16. Various additional checks suggested the removal of 7 items. The resulting Rasch-scaled Motor Function Measure with 25 items for congenital disorders of the muscle (Rs-MFM25(CDM)) demonstrated a good fit to the Rasch model. Domain 1 was well targeted to the whole severity spectrum close mean locations for items and persons (0 vs 0.316) whereas domains 2 and 3 were better targeted to severe cases. The reliability coefficients of the Rs-MFM25(CDM) suggested sufficient ability for each summed score to distinguish between patient groups (0.9, 0.8, and 0.7 for domains 1, 2, and 3, respectively). A sufficient agreement was found between results of the Rasch analysis and physical therapists' opinions.Conclusions: The Rs-MFM25(CDM) can be considered a clinically relevant linear scale in each of its 3 domains and may be soon reliably used for assessment in congenital disorders of the muscle. (C) 2014 by the American Congress of Rehabilitation Medicine

Published
2014
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19. Improvement of sample size calculations for binary diagnostic test assessment

Author

Nadine Bossard, Jean Iwaz, C. Dupont, Sébastien Bailly, Muriel Rabilloud, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Diagnostic Tests, Routine, [SDV]Life Sciences [q-bio], Statistics as Topic, Binary number, General Medicine, Sawtooth wave, Function (mathematics), 01 natural sciences, Power law, General Biochemistry, Genetics and Molecular Biology, Binomial distribution, 010104 statistics & probability, 03 medical and health sciences, 0302 clinical medicine, Sample size determination, Case-Control Studies, Sample Size, Statistics, Humans, 030212 general & internal medicine, Sensitivity (control systems), 0101 mathematics, Power function, Mathematics
Abstract

Objective This study aimed to formulate a new R function to improve sample size calculation for more accurate estimations of sensitivity (Se) and specificity (Sp). Methods The developed function is based on the binDesign function of the binGroup R package. This allowed the use of an “exact” method based on the binomial distribution. In addition, the function takes into account a joint testing of Se and Sp and a nonmonotonous behavior of the power function. Results Four tables were generated to display the number of cases (or controls) in joint or separate assessments for an expected combination of Se (or Sp) and a determined difference between the expected Se (or Sp) and the minimum acceptable Se (or Sp). Using the formula for a joint testing of Se and Sp, it resulted in a higher increase of the sample sizes than simply allowing for the sawtooth shape of the power curve. Conclusion Whenever equal Se and Sp values are important, a joint testing should be favored and used for sample size determination.

Published
2014
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20. Adult-onset still disease: manifestations, treatment, outcome, and prognostic factors in 57 patients

Author

Isabelle Durieu, Christiane Broussolle, Pascal Sève, Jean Iwaz, Arnaud Hot, Mathieu Gerfaud-Valentin, Delphine Maucort-Boulch, Jacques Ninet, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Service de Biostatistiques [Lyon], and Hospices Civils de Lyon (HCL)

Subjects
medicine.medical_specialty, Anakinra, business.industry, [SDV]Life Sciences [q-bio], Arthritis, Still Disease, Retrospective cohort study, General Medicine, medicine.disease, Rheumatology, Surgery, Internal medicine, Cohort, medicine, Hypermetabolism, Young adult, business, medicine.drug
Abstract

International audience; We conducted a retrospective observational study to describe a cohort and identify the prognostic factors in adult-onset Still disease (AOSD). Patients enrolled in this retrospective chart review fulfilled either Yamaguchi or Fautrel criteria. Candidate variables were analyzed with logistic unadjusted and adjusted regression models.Fifty-seven patients were seen in the internal medicine (75%) and rheumatology (25%) departments over a mean period of 8.4 years. The median time to diagnosis was 4 months. The course of AOSD was monocyclic in 17 patients, polycyclic in 25, and chronic in 15. The assessment of glycosylated ferritin (GF) in 37 patients was correlated with early diagnosis. Nine F-18-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) scans identified the lymph nodes and glands as the main sites of hypermetabolism. Complications were frequent (n = 19), including reactive hemophagocytic syndrome (n = 8). None of the 3 deaths could be attributed to AOSD. Corticosteroid dependence, as predicted by a low GF level, occurred in 23 patients (45%). A quarter of the patients received tumor necrosis factor-alpha blockers or anakinra with good tolerance. Fever >39.5 degrees C was predictive of monocyclic AOSD, while arthritis and thrombocytopenia were associated with chronic and complicated AOSD, respectively. The youngest patients had the highest risks of resistance to first-line treatments.AOSD remains difficult to diagnose. Mortality is low despite frequent complications. GF and (18)FDG-PET scans were of value in the diagnostic approach. The condition in highly symptomatic patients evolved to systemic AOSD, whereas more progressive patterns with arthritis predicted chronic AOSD.

Published
2014
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21. Cancer net survival on registry data: use of the new unbiased Pohar-Perme estimator and magnitude of the bias with the classical methods

Author

Pascale Grosclaude, Nadine Bossard, Anne-Marie Bouvier, Laurent Roche, Laurent Remontet, Michel Velten, Jean Iwaz, Coraline Danieli, Aurélien Belot, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Cancer Research, Lung Neoplasms, Adolescent, [SDV]Life Sciences [q-bio], Breast Neoplasms, Risk Assessment, 03 medical and health sciences, Age Distribution, 0302 clinical medicine, Breast cancer, Bias, Bias of an estimator, Risk Factors, Cause of Death, Neoplasms, Statistics, medicine, Humans, Registries, Thyroid Neoplasms, 030212 general & internal medicine, Survival analysis, Aged, Mathematics, Estimation, Models, Statistical, Relative survival, Incidence, Age Factors, Prostatic Neoplasms, Cancer, Estimator, Regression analysis, Middle Aged, Prognosis, medicine.disease, Hodgkin Disease, Survival Analysis, 3. Good health, Oncology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Female, France, Colorectal Neoplasms
Abstract

Net survival, the survival which might occur if cancer was the only cause of death, is a major epidemiological indicator required for international or temporal comparisons. Recent findings have shown that all classical methods used for routine estimation of net survival from cancer-registry data, sometimes called "relative-survival methods," provide biased estimates. Meanwhile, an unbiased estimator, the Pohar-Perme estimator (PPE), was recently proposed. Using real data, we investigated the magnitude of the errors made by four "relative-survival" methods (Ederer I, Hakulinen, Ederer II and a univariable regression model) vs. PPE as reference and examined the influence of time of follow-up, cancer prognosis, and age on the errors made. The data concerned seven cancer sites (2,51,316 cases) collected by FRANCIM cancer registries. Net survivals were estimated at 5, 10 and 15 years postdiagnosis. At 5 years, the errors were generally small. At 10 years, in good-prognosis cancers, the errors made in nonstandardized estimates with all classical methods were generally great (+2.7 to +9% points in prostate cancer) and increased in age-class estimations (vs. 5-year ones). At 15 years, in bad- or average-prognosis cancers, the errors were often substantial whatever the nature of the estimation. In good-prognosis cancers, the errors in nonstandardized estimates of all classical methods were great and sometimes very important. With all classical methods, great errors occurred in age-class estimates resulting in errors in age-standardized estimates (+0.4 to +3.2% points in breast cancer). In estimating net survival, cancer registries should abandon all classical methods and adopt the new Pohar-Perme estimator.

Published
2013
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22. Joint use of epidemiological and hospital medico-administrative data to estimate prevalence. Application to French data on breast cancer

Author

Béatrice Trombert, Anne-Marie Schott, Stéphanie Polazzi, Laurent Remontet, Nadine Bossard, N. Mitton, Marc Colonna, F. Olive, Jean Iwaz, F. Gomez, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Cancer Research, medicine.medical_specialty, Pediatrics, Adolescent, Epidemiology, [SDV]Life Sciences [q-bio], Population, MEDLINE, Breast Neoplasms, Disease, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Breast cancer, Age Distribution, Pregnancy, medicine, Prevalence, Humans, 030212 general & internal medicine, Registries, Young adult, education, Aged, education.field_of_study, Models, Statistical, business.industry, Incidence, Middle Aged, medicine.disease, Hospitals, 3. Good health, Cancer registry, Oncology, 030220 oncology & carcinogenesis, Female, France, business, Demography
Abstract

Background Estimate complete, limited-duration, and hospital prevalence of breast cancer in a French Departement covered by a population-based cancer registry and in whole France using complementary information sources. Methods : Incidence data from a cancer registry, national incidence estimations for France, mortality data, and hospital medico-administrative data were used to estimate the three prevalence indices. The methods included a modelling of epidemiological data and a specific process of data extraction from medico-administrative databases. Results : Limited-duration prevalence at 33 years was a proxy for complete prevalence only in patients aged less than 70 years. In 2007 and in women older than 15 years, the limited-duration prevalence at 33 years rate per 100,000 women was estimated at 2372 for Departement Isere and 2354 for whole France. The latter rate corresponded to 613,000 women. The highest rate corresponded to women aged 65–74 years (6161 per 100,000 in whole France). About one third of the 33-year limited-duration prevalence cases were diagnosed five years before and about one fourth were hospitalized for breast-cancer-related care (i.e., hospital prevalence). In 2007, the rate of hospitalized women was 557 per 100,000 in whole France. Among the 120,310 women hospitalized for breast-cancer-related care in 2007, about 13% were diagnosed before 2004. Conclusion : Limited-duration prevalence (long- and short-term), and hospital prevalence are complementary indices of cancer prevalence. Their efficient direct or indirect estimations are essential to reflect the burden of the disease and forecast median- and long-term medical, economic, and social patient needs, especially after the initial treatment.

Published
2012
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23. Changes in the dynamics of the excess mortality rate in chronic phase-chronic myeloid leukemia over 1990-2007: a population study

Author

Jean Iwaz, Catherine Roche-Lestienne, Claude Preudhomme, Nadine Bossard, Thierry Facon, Laurent Remontet, Selim Corm, Franck-Emmanuel Nicolini, Laurent Roche, Jean-Baptiste Micol, Valérie Coiteux, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Immunology, Antineoplastic Agents, Severity of Illness Index, Biochemistry, Piperazines, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, Humans, 030212 general & internal medicine, Survival analysis, Aged, Aged, 80 and over, Relative survival, business.industry, Mortality rate, Myeloid leukemia, Imatinib, Cell Biology, Hematology, Middle Aged, medicine.disease, Survival Analysis, 3. Good health, Surgery, Pyrimidines, Imatinib mesylate, 030220 oncology & carcinogenesis, Benzamides, Leukemia, Myeloid, Chronic-Phase, Multivariate Analysis, Imatinib Mesylate, Female, business, Sokal Score, Chronic myelogenous leukemia, medicine.drug
Abstract

Imatinib has transformed the prognosis and the management of chronic myeloid leukemia (CML) and has probably changed the patterns of mortality rates. We explored this change at each disease severity level (Sokal score) through a flexible statistical modeling of the effect of the year of diagnosis on the excess mortality rate. The study included 691 chronic-phase patients from Nord-Pas-de-Calais French CML registry diagnosed from 1990 to 2007. Imatinib was given to 93% of the patients diagnosed after 2000. Comparing the 1990-1994, 1995-1999, and 2000-2007 periods of diagnosis, the 5-year relative survival improved from 64% to 66% and 88%. The year of diagnosis was associated with a significant reduction of the excess mortality, but only in patients with intermediate to high Sokal scores. In high-risk patients diagnosed in the early 1990s, a peak of excess mortality was observed during the second year of follow-up. That peak decreased progressively over the years of diagnosis until disappearing in patients diagnosed after 2000. This study showed different effects according to Sokal scores of the use of imatinib on mortality in patients with chronic-phase CML and showed that since 2000 the pattern of mortality of high-risk patients became similar to that of intermediate-risk ones.

Published
2011
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24. Diversité des modèles d'évolution des incidences : implication en cancérogenèse ?

Author

Aurélien Belot, G. Buiret, Jean Iwaz, Laurent Remontet, Guy Launoy, Nadine Bossard, René Ecochard, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pulmonary and Respiratory Medicine, 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, [SDV]Life Sciences [q-bio], 3. Good health, 030304 developmental biology
Abstract

Resume Objectif Les cancers ORL, bronchiques et œsophagiens sont principalement lies a la consommation d’alcool et/ou de tabac. L’incidence des cancers ayant les memes facteurs de risque devrait varier de facon similaire dans le temps et l’espace. Le but de cette etude etait d’identifier des groupes de cancers ayant la meme evolution spatiotemporelle. Methodes Cinquante mille neuf cent quatre-vingt cas de dix types de cancers differents ont ete recueillis entre 1982 et 2002 dans six departements francais. Les niveaux d’incidence et leur tendance evolutive ont ete analyses en utilisant un modele âge–cohorte avec un effet aleatoire qui prenait en compte l’heterogeneite entre departements. Resultats Trois groupes de cancers ayant une evolution similaire de l’incidence spatiotemporelle ont ete identifies : (1) cavite orale, oropharynx, hypopharynx, larynx, œsophage et carcinomes epidermoides bronchiques dont les incidences diminuaient uniformement ; (2) adenocarcinomes bronchiques et autres histologies bronchiques dont les incidences augmentaient uniformement ; (3) carcinomes bronchiques a grandes et a petites cellules dont l’evolution des incidences spatiotemporelles etait tres heterogene. Conclusion Par l’utilisation de methodes d’epidemiologie descriptive, differents groupes de cancers ont ete individualises. Cette diversite pourrait suggerer des latences et des sensibilites differentes vis-a-vis des carcinogenes.

Published
2011
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25. Reliability of recording uterine cancer in death certification in France and age-specific proportions of deaths from cervix and corpus uteri

Author

Marjorie Boussac, Jacques Estève, Laurent Remontet, Agnès Rogel, A. Buemi, Arlette Danzon, Michel Velten, Olivier Ganry, Aurélien Belot, Marc Colonna, Anne-Valérie Guizard, Eric Jougla, Jean Iwaz, Patrick Arveux, Florence Suzan, Pascale Grosclaude, L. Chérié-Challine, Nadine Bossard, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Cancer Research, medicine.medical_specialty, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Survival, Epidemiology, Uterus, Uterine Cervical Neoplasms, 030501 epidemiology, Death Certificates, 03 medical and health sciences, 0302 clinical medicine, Uterine cancer, Cause of Death, medicine, Humans, Registries, Cervix, Aged, Cause of death, Aged, 80 and over, Gynecology, Relative survival, business.industry, Not Otherwise Specified, Age Factors, Reproducibility of Results, Cancer, Middle Aged, medicine.disease, medicine.anatomical_structure, Oncology, Data Interpretation, Statistical, 030220 oncology & carcinogenesis, Uterine Neoplasms, Female, France, 0305 other medical science, business, Corpus Uteri
Abstract

French uterine cancer recordings in death certificates include 60% of "uterine cancer, Not Otherwise Specified (NOS)"; this hampers the estimation of mortalities from cervix and corpus uteri cancers. The aims of this work were to study the reliability of uterine cancer recordings in death certificates using a case matching with cancer registries and estimate age-specific proportions of deaths from cervix and corpus uteri cancers among all uterine cancer deaths by a statistical approach that uses incidence and survival data. Deaths from uterine cancer between 1989 and 2001 were extracted from the French National database of causes of death and case-to-case matched to women diagnosed with uterine cancer between 1989 and 1997 in 8 cancer registries. Registry data were considered as "gold-standard". Among the 1825 matched deaths, cancer registries recorded 830 cervix and 995 corpus uteri cancers. In death certificates, 5% and 40% of "true" cervix cancers were respectively coded "corpus" and "uterus, NOS" and 5% and 59% of "true" corpus cancers respectively coded "cervix" and "uterus, NOS". Miscoding cervix cancers was more frequent at advanced ages at death and in deaths at home or in small urban areas. Miscoding corpus cancers was more frequent in deaths at home or in small urban areas. From the statistical method, the estimated proportion of deaths from cervix cancer among all uterine cancer deaths was higher than 95% in women aged 30-40 years old but declined to 35% in women older than 70 years. The study clarifies the reason for poor encoding of uterus cancer mortality and refines the estimation of mortalities from cervix and corpus uteri cancers allowing future studies on the efficacy of cervical cancer screening.

Published
2011

26. Long-term outcomes of chronic minimally conscious and vegetative states

Author

C. Fischer, Jacques Luauté, F. Quelard, Dominique Boisson, L. Tell, Delphine Maucort-Boulch, Jean Iwaz, T. Sarraf, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, 030506 rehabilitation, medicine.medical_specialty, Pediatrics, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Time Factors, Adolescent, Consciousness, Logistic regression, Disability Evaluation, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Outcome Assessment, Health Care, medicine, Humans, Glasgow Coma Scale, Longitudinal Studies, Young adult, Child, Aged, Retrospective Studies, Aged, 80 and over, Coma, Persistent Vegetative State, Glasgow Outcome Scale, Minimally conscious state, Retrospective cohort study, Recovery of Function, Middle Aged, medicine.disease, humanities, Surgery, Logistic Models, Predictive value of tests, Female, Neurology (clinical), medicine.symptom, 0305 other medical science, Psychology, 030217 neurology & neurosurgery
Abstract

Objective: The present retrospective cohort study compares the long-term functional outcome, improvement or deterioration, of patients considered in a vegetative state (VS) or a minimally conscious state (MCS) 1 year after coma onset, then yearly for up to 5 years. Methods: We reviewed the clinical courses of 12 patients in VS and 39 in MCS. The outcomes were assessed at 2, 3, 4, and 5 years after injury using the 5 categories of the Glasgow Outcome Scale plus an additional category for patients in MCS. A logistic regression analysis investigated the relationships between each outcome and 10 predictor variables. Four of these variables were auditory evoked potentials recorded at the early stage of coma. Results: None of the patients in VS improved during the follow-up period: 1 was lost to follow-up, 9 died, and 2 remained in VS. Among patients in MCS, 3 were lost to follow-up, 14 died, 9 remained in MCS, and 13 emerged from MCS with severe disabilities. VS, age >39 years, and bilateral absence of cortical components of middle-latency auditory evoked potentials were significantly associated with deterioration. Conclusions: In contrast to patients in VS, a third of patients in MCS improved more than 1 year after coma onset. This emphasizes the need to define reliable boundaries between VS and MCS using repeated clinical evaluations and all imaging and neurophysiologic tools available today.

Published
2010

27. Patient versus general practitioner perception of problems with treatment adherence in type 2 diabetes: From adherence to concordance

Author

Dominique Ploin, Marie Flori, Sophie Figon, Gilbert Souweine, Sylvie Erpeldinger, Jean-Paul Riou, Patrick Imbert, Jean Iwaz, Vincent Aroles, Alain Moreau, Angélique Denis, Unité de recherche Amélioration, Génétique et Physiologie Forestières (AGPF), Institut National de la Recherche Agronomique (INRA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Service d'urgence et de réanimation pédiatriques [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Moreau, Alain, Unité de recherche Amélioration, Génétique et Physiologie Forestières (UAGPF), Laboratoire Biostatistique-Santé (LBS), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS), Sciences et Société, Historicité, Éducation et Pratiques (EA S2HEP), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
Adult, Male, concordance, Pediatrics, medicine.medical_specialty, Multivariate analysis, Concordance, 030209 endocrinology & metabolism, Type 2 diabetes, Disease, primary healthcare, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Type 2 diabetes mellitus, medicine, Humans, patient non-adherence, 030212 general & internal medicine, Depression (differential diagnoses), ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Physician-Patient Relations, Primary Health Care, business.industry, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, doctor-patient relationship, 3. Good health, Diabetes Mellitus, Type 2, Multivariate Analysis, Patient Compliance, Doctor–patient relationship, Anxiety, Female, medicine.symptom, Family Practice, business, Psychosocial
Abstract

To determine the prevalence of problems with treatment adherence among type-2 diabetic patients with regards to medication, dietary advice, and physical activity; to identify the associated clinical and psychosocial factors; and to investigate the degree of agreement between patient-perceived and GP-perceived adherence.Consecutive patients were solicited during visits to 39 GPs. In total, 521 patients self-reported on treatment adherence, anxiety and depression, and disease perception. The GPs reported clinical and laboratory data and patients' adherence. A multivariate analysis identified the factors associated with adherence problems.Problems of adherence to medication, dietary advice, and physical activity recommendations were reported by 17%, 62%, and 47% of the patients, respectively. Six independent factors were found associated with adherence problems: young age, body-mass index (BMI)30 kg/m(2), glycosylated haemoglobin (HbA(1c))8%, single life, depression, and perception of medication as a constraint. Agreement between patients' and GPs' assessments of treatment problems reached 70%.In type 2 diabetes, problems with dietary advice or physical activity are far more frequent than problems with medication, and not all physicians are fully aware of patients' problems. More active listening and shared decision-making should enhance adherence and improve outcomes.

Published
2009

28. A 7-year longitudinal follow-up of intellectual development in children with congenital hemiplegia

Author

Jean Iwaz, C. Berard, Sibylle Gonzalez-Monge, Muriel Rabilloud, Fatima Abbas-Chorfa, Annie Ritz, Baya Boudia, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Pediatrics, medicine.medical_specialty, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Intellectual development, Adolescent, Developmental Disabilities, Intelligence, Hemiplegia, 050105 experimental psychology, Lateralization of brain function, Functional Laterality, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Child Development, Sex Factors, Developmental Neuroscience, medicine, Humans, 0501 psychology and cognitive sciences, Early childhood, Child, Cerebral Cortex, Neuronal Plasticity, Intelligence quotient, 05 social sciences, Wechsler Scales, Gestational age, medicine.disease, Child development, Confidence interval, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, Neurology (clinical), Psychology, Cognition Disorders, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Aims Our aim was to examine intellectual development in children with congenital hemiplegia from early childhood to adolescence. Method Full-scale IQ (FIQ), Verbal IQ (VIQ), and Performance IQ (PIQ) scores were measured in 32 participants (19 males, 13 females) with congenital hemiplegia at mean ages of 4 years 6 months (SD 7mo; 31 participants), 7 years (SD 6mo; 23 participants), and 14 years (SD 1y 5mo; 26 participants). Results The FIQ and VIQ scores did not change with age, but the PIQ declined significantly (0.7 points per year; p=0.004). The estimated mean (95% confidence intervals) scores in males born at term with right-sided lesions without epilepsy were FIQ 106.5 (95.29–117.74), VIQ 105.9 (95.57–116.24), and PIQ 103.7 (93.19–114.31). Those means were negatively associated with preterm birth. PIQ was negatively associated with epilepsy. VIQ increased more quickly in males and in children with right-sided lesions. Interpretation The results confirm previous findings of FIQ stability, PIQ decline, the impact of epilepsy, and the status of females with left-sided lesions, and also reveal the effect of gestational age at birth. They underline the importance of management focused on nonverbal functions and further the debate about the early lateralization of language, the ‘crowding effect’, and the difference in brain plasticity between males and females.

Published
2009
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29. Structural equations to model relationships between pulmonary function fatty acids and oxidation in cystic fibrosis

Author

Isabelle Durieu, Gabriel Bellon, Jean-Paul Steghens, Maud Tournoud, Jean Iwaz, René Ecochard, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE)

Subjects
Adult, Vitamin, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Adolescent, Cystic Fibrosis, medicine.medical_treatment, Clinical Biochemistry, Models, Biological, Cystic fibrosis, Antioxidants, Lipid peroxidation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Lipid oxidation, medicine, Humans, 030212 general & internal medicine, Child, Carotenoid, chemistry.chemical_classification, Arachidonic Acid, Vitamin E, Fatty Acids, Infant, Vitamins, General Medicine, Glutathione, Middle Aged, medicine.disease, Respiratory Function Tests, 3. Good health, Solubility, 030228 respiratory system, chemistry, Biochemistry, Child, Preschool, Arachidonic acid, Oxidation-Reduction
Abstract

To illustrate the advantages of structural equation models in biomedical research using the complex example of cystic fibrosis.595 blood samples from 312 patients were tested. The model studied the effects of age, BMI and clinical condition on seven major latent variables: pulmonary function, lipid oxidation status, vitamins A and E, glutathione, carotenoids, two essential fatty acids and arachidonic acid.The model confirmed previous associations: positive (fatty acids, arachidonic acid, carotenoids and vitamins with pulmonary function and with lipid oxidation) and negative (glutathione with pulmonary function). It also verified the decrease in fatty acids during bronchial exacerbation and the increase in fatty acids and lipid oxidation after antibiotic treatment. Above all, the model revealed new positive associations between lipid oxidation and carotenoid levels and between lipid oxidation and vitamin A and E levels.Structural equations dealt easily with the great number of outcome variables of the example. They deserve a central place in biomedical issues involving too many correlated factors to help physicians and statisticians conceive biological models that best represent reality.

Published
2009

30. Plasma fatty acids and lipid hydroperoxides increase after antibiotic therapy in cystic fibrosis

Author

Jocelyne Drai, Fatima Abbas-Chorfa, Isabelle Durieu, René Ecochard, Jean-Paul Steghens, Jean Iwaz, Puget M, Gabriel Bellon, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, Vitamin, Lipid Peroxides, medicine.medical_specialty, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Adolescent, Cystic Fibrosis, Exacerbation, Phospholipid, 030204 cardiovascular system & hematology, medicine.disease_cause, Cystic fibrosis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Forced Expiratory Volume, Internal medicine, Blood plasma, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Child, 2. Zero hunger, chemistry.chemical_classification, business.industry, Fatty Acids, Infant, Fatty acid, Middle Aged, medicine.disease, Anti-Bacterial Agents, Oxidative Stress, Endocrinology, chemistry, Child, Preschool, Cholesteryl ester, Regression Analysis, Female, lipids (amino acids, peptides, and proteins), business, Oxidative stress
Abstract

The present authors investigated whether cystic fibrosis is linked to a defect in fatty acids and assessed the impact of the main patients' characteristics on the levels of several fatty acids, mostly during respiratory exacerbation and after antibiotic therapy. Fatty acid phospholipid and cholesteryl ester levels were measured in stable-state patients and controls. No differences were found concerning either the fractions of palmitic and oleic acids or the cholesteryl esters of alpha-linolenic and arachidonic acids. However, phospholipids of alpha-linolenic and arachidonic acids, as well as cholesteryl esters and phospholipids of stearic and linoleic acids, were lower in patients than in controls, but fractions of dihomo-gamma-linolenic, docosatetraenoic, docosapentaenoic, palmitoleic and eicosatrienoic acids were higher. Fatty acid levels, oxidative stress markers, nutrients, body mass index and forced expiratory volume in one second (FEV(1)) were measured in patients before and after antibiotic courses for bronchial exacerbation. After adjustments, palmitic, stearic, alpha-linolenic, linoleic, arachidonic, palmitoleic and oleic acids generally decreased during exacerbation but almost all increased after antibiotic courses. Nearly all fractions increased along with FEV(1) and a positive relationship linked fatty acids to lipid hydroperoxides. There was no general drop in fatty acids. Patients' fatty acid profiles depended on the pulmonary function and the inflammation state.

Published
2007

31. Proportion of long-term event-free survivors and lifetime of adult patients not cured after a standard acute lymphoblastic leukemia therapeutic program: adult acute lymphoblastic leukemia-94 trial

Author

Veéronique Lheéritier, Denis Fiere, Jean Iwaz, Reneé Ecochard, Quoc-Hung Le, Xavier Thomas, Mauricette Michallet, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Biostatistiques santé, and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE)

Subjects
Adult, Male, Cancer Research, Pediatrics, medicine.medical_specialty, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Adolescent, Oncogene Proteins, Fusion, [SDV]Life Sciences [q-bio], Genes, abl, Disease-Free Survival, Leukocyte Count, Risk Factors, Multicenter trial, White blood cell, Acute lymphocytic leukemia, Antineoplastic Combined Chemotherapy Protocols, Odds Ratio, medicine, Humans, Treatment Failure, Acute leukemia, L-Lactate Dehydrogenase, Performance status, business.industry, Cancer, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, medicine.disease, Confidence interval, Survival Rate, medicine.anatomical_structure, Oncology, Karyotyping, Adult Acute Lymphoblastic Leukemia, Female, business, Myeloid-Lymphoid Leukemia Protein, Follow-Up Studies
Abstract

BACKGROUND. In adult acute lymphoblastic leukemia, treatment results generally are expressed in terms of overall survival or disease-free survival at 3 years. In this investigation, the authors attempted to express the results in terms of the proportion of long-term disease-free survivors and in terms of lifetime in patients who developed recurrent disease or died. METHODS. Univariate and multivariate analyses were used to assess the influence of different covariates on the 2 result criteria in 922 participants in the Adult Acute Lymphoblastic Leukemia-94 multicenter trial. RESULTS. The proportion of long-term survivors was 21.5% (95% confidence interval [95% CI], 18.1–25.4%) and was higher in women than in men. The proportion decreased with increasing age, white blood cell count, and lactate dehydrogenase level. The lowest proportion was observed in patients ages 44 years to 55 years (11.4%; 95% CI, 7–17.9%) and in patients with the t(9;22) BCR-ABL karyotype (13.4%; 95% CI, 8.8–19.8%), and the highest proportion was observed in patients with the t(4;11) MLL-AF4 karyotype (31.3%; 95% CI, 18.2–48.3%). The mean expected lifetime of patients who were not cured was 11.4 months (95% CI, 9.1–14.1 months). It was longer in men than in women and was shorter with increasing age, performance status, hemoglobin level, and white blood cell count. CONCLUSIONS. The results of this study highlighted and specified the importance of some classic prognostic factors in patients with acute lymphoblastic leukemia. Cancer 2007. © 2007 American Cancer Society.

Published
2007

32. Initial and late prognostic factors to predict survival in adult acute lymphoblastic leukaemia

Author

Quoc-Hung Le, Jean Iwaz, Mauricette Michallet, Véronique Lhéritier, Xavier Thomas, René Ecochard, Denis Fiere, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, medicine.medical_specialty, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Adolescent, [SDV]Life Sciences [q-bio], Lactic dehydrogenase, Gastroenterology, Translocation, Genetic, Immunophenotyping, 03 medical and health sciences, 0302 clinical medicine, Late phase, Internal medicine, medicine, Overall survival, Humans, 030304 developmental biology, Proportional Hazards Models, 0303 health sciences, Adult patients, Proportional hazards model, business.industry, Hazard ratio, Age Factors, Hematology, General Medicine, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, 3. Good health, Surgery, Treatment Outcome, 030220 oncology & carcinogenesis, Initial phase, Karyotyping, Multivariate Analysis, Lymphoblastic leukaemia, Female, business, Follow-Up Studies
Abstract

Factors able to predict overall survival in adult patients with acute lymphoblastic leukaemia were assessed according to the period since initiation of the treatment using a Cox proportional hazards model. This period covers successively an initial period during the induction treatment and a consolidation period during the postinduction treatment. From 1994 to 2002, 922 patients with acute lymphoblastic leukaemia (excluding French-American-British L3 subtype) were enrolled in a multicentre protocol and followed, with a mean follow up of 58 months. A multivariate time-segmented analysis was performed on 658 patients. Analyses of the initial (before 100 d) and the late phases were realised after stratification on the type of induction treatment and on the different treatment strategies respectively. Age was the sole factor that influenced survival during the initial phase (hazard ratio 1.48 per 10-yr increase; P

Published
2006

33. Whipple's disease with muscle impairment

Author

Anne Tristan, Jean Iwaz, Nathalie Streichenberger, Marie Puget, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
DNA, Bacterial, Male, myalgia, Pathology, medicine.medical_specialty, Physiology, [SDV]Life Sciences [q-bio], Diagnosis, Differential, Tropheryma whipplei, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Physiology (medical), Actinomycetales, medicine, Humans, 030212 general & internal medicine, Whipple's disease, Muscle, Skeletal, Myopathy, Myositis, Aged, Muscle biopsy, medicine.diagnostic_test, biology, business.industry, Whipple Disease, Ceftriaxone, medicine.disease, biology.organism_classification, Magnetic Resonance Imaging, Muscular Disorders, Atrophic, Muscle atrophy, Anti-Bacterial Agents, 3. Good health, Treatment Outcome, Neurology (clinical), medicine.symptom, business, Actinomycetales Infections, 030217 neurology & neurosurgery
Abstract

A 67-year-old man presented with myalgia, muscle atrophy, and a history of seronegative polyarthritis. Blood tests showed inflammation but no hematologic or immunologic abnormalities. Muscle biopsy revealed no vasculitis or myositis but Tropheryma whipplei was detected by polymerase chain reaction in muscle, blood, and duodenum specimens; this was confirmed by immunohistochemistry. Ceftriaxone led to clinical improvement. Although rare, Whipple's disease should be considered in the differential diagnosis of diffuse myopathy. Muscle Nerve, 2006

Published
2006

34. Modelling the progression towards duodenal cancer among patients with familial polyposis on the basis of two different score profiles

Author

Jean Iwaz, F. Boutitie, Christelle Gutknecht, René Ecochard, Jean-Christophe Saurin, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Oncology, medicine.medical_specialty, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Epidemiology, Patient subgroups, Bayesian inference, Familial adenomatous polyposis, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Duodenal Neoplasms, Internal medicine, medicine, Humans, Prospective Studies, business.industry, Bayes Theorem, Regression analysis, Middle Aged, Prognosis, medicine.disease, Regression, Surgery, Adenomatous Polyposis Coli, 030220 oncology & carcinogenesis, Disease Progression, Linear Models, symbols, Female, 030211 gastroenterology & hepatology, France, Duodenal cancer, business, Gibbs sampling
Abstract

The objective was to design a method that considers, on clinical arguments, the likely existence of patient subgroups with different evolution profiles. The method is applied in familial adenomatous polyposis to predict the proportion of patients that would develop duodenal cancer. A subject-specific linear mixed-effects model was elaborated to explicitly model heterogeneity in regression parameters. The estimates of the parameters were obtained by Bayesian inference using Gibbs sampling. The application concerned two potential polyposis subgroups: stable-state and progressive. Each patient's score was expressed in function of his putative subgroup, the reference subgroup mean score (intercept), the rate of change (slope), and time. The estimated proportion of stable-state patients was 35%. In progressive-state patients, the estimated annual score increase was 0.38 (95% CI: 0.27-0.48). The regression model predicted that the proportion of patients with a scoreor = 9 is near 43% at age 60 (36-50%) and 50% at 70 (43-57%). The method indicates the evolution profile of each subject, which facilitates therapeutic decisions. The modelling may be extended to other more complex situations with several subgroups, with different change rates, or with various genetic or therapeutic profiles.

Published
2005

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