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51. Advantages and disadvantages of the use of the CSF Amyloid β (Aβ) 42/40 ratio in the diagnosis of Alzheimer’s Disease

Author

Markus Otto, Henrik Zetterberg, Piotr Lewczuk, Oskar Hansson, Sylvain Lehmann, Clinical Memory Research Unit [Malmö, Suède], Department of Clinical Sciences [Malmö, Suède], Lund University [Malmö, Suède]-Lund University [Malmö, Suède], Memory Clinic [Malmö, Suède], Skåne University Hospital [Malmö, Suède], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Neurology [Ulm, Allemagne], Universität Ulm - Ulm University [Ulm, Allemagne], Clinical Neurochemistry Laboratory [Göteborg, Suède], Department of Psychiatry and Neurochemistry [Goteborg], Institute of Neuroscience and Physiology [Göteborg]-Sahlgrenska Academy at University of Gothenburg [Göteborg]-Institute of Neuroscience and Physiology [Göteborg]-Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Neurodegenerative Disease [Londres, Royaume-Uni], Institute of Neurology [London], University College of London [London] (UCL)-University College of London [London] (UCL), UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), Department of Psychiatry and Psychotherapy [Erlangen, Allemagne], Universitätsklinikum Erlangen [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Department of Neurodegeneration Diagnostics [Bialystok, Pologne], Medical University of Bialystok [Bialystok, Pologne], Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Universitätsklinikum Erlangen [Erlangen, Allemagne], Fujirebio Europe sponsored this paper, however, it had no influence on its factual content. PL was supported by the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. OH has acquired research support (for the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio and Euroimmun. HZ’s research is supported by the Swedish Research Council, the European Research Council, the Knut and Alice Wallenberg Foundation, the Olav Thon Foundation, the UK Dementia Research Institute at UCL and Swedish State Support for Clinical Research (ALFGBG)., Lund University [Lund]-Lund University [Lund], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Medical University of Białystok (MUB), and Bodescot, Myriam

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Neurology, Amyloid β, Cognitive Neuroscience, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Diagnostic accuracy, Disease, Review, Aβ 42/40 ratio, Alzheimer's Disease, lcsh:RC346-429, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Medizinische Fakultät, Alzheimer Disease, Internal medicine, medicine, Dementia, Humans, ddc:610, Alzheimer’s Disease, Cognitive impairment, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biochemical markers, lcsh:Neurology. Diseases of the nervous system, Cerebrospinal Fluid, Amyloid beta-Peptides, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, Peptide Fragments, 030104 developmental biology, Aβ42/40 ratio, Neurology (clinical), business, 030217 neurology & neurosurgery, Amyloidβ Peptides, Biomarkers
Abstract

International audience; The cerebrospinal fluid (CSF) biochemical markers (biomarkers) Amyloidβ 42 (Aβ42), total Tau (T-tau) and Tau phosphorylated at threonine 181 (P-tau181) have proven diagnostic accuracy for mild cognitive impairment and dementia due to Alzheimer's Disease (AD). In an effort to improve the accuracy of an AD diagnosis, it is important to be able to distinguish between AD and other types of dementia (non-AD). The concentration ratio of Aβ42 to Aβ40 (Aβ42/40 Ratio) has been suggested to be superior to the concentration of Aβ42 alone when identifying patients with AD. This article reviews the available evidence on the use of the CSF Aβ42/40 ratio in the diagnosis of AD. Based on the body of evidence presented herein, it is the conclusion of the current working group that the CSF Aβ42/40 ratio, rather than the absolute value of CSF Aβ42, should be used when analysing CSF AD biomarkers to improve the percentage of appropriately diagnosed patients.

Published
2019

52. Structured peer-led diabetes self-management and support in a low-income country: The ST2EP randomised controlled trial in Mali

Author

Assa Traoré Sidibé, Stéphane Besançon, Cyril Ferdynus, Xavier Debussche, Hélène Delisle, Laetitia Huiart, Maryvette Balcou-Debussche, CHU Sud Saint Pierre [Ile de la Réunion], Centre d'Investigation Clinique de La Réunion - INSERM (CIC 1410), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), ONG Santé Diabète, Institut Coopératif Austral de Recherche en Éducation (ICARE), Université de La Réunion (UR), Réseau des universités pour l'éducation à la santé (Réseau UNIRéS), Université Blaise Pascal - Clermont-Ferrand 2 (UBP), CRSN/Faculté de médecine Université de Montréal, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Universitaire, This work was supported by the Bridges programme of the International Diabetes Federation. BRIDGES (Bringing Research in Diabetes to Global Environments and Systems) is a programme initiated by the International Diabetes Federation, and supported by an educational grant from Lilly Diabetes, https://www.idf.org/our-activities/epidemiology-research/bridges.html. The NGO Santé Diabète received the funding (https://santediabete.org/en, Director: SB). The funders were not involved in the study design, in the collection, analysis and interpretation of the data, as well as in the writing of the report and in the decision to submit the paper or preparation of the manuscript for publication. The authors were independent from study funders., and Univ, Réunion

Subjects
Male, Psychological intervention, lcsh:Medicine, Social Sciences, Type 2 diabetes, Human learning, Mali, Biochemistry, Vascular Medicine, law.invention, Geographical Locations, 0302 clinical medicine, Endocrinology, Learning and Memory, Diabetes mellitus, Randomized controlled trial, law, Health care, Outcome Assessment, Health Care, Medicine and Health Sciences, Diabetes diagnosis and management, Psychology, 030212 general & internal medicine, lcsh:Science, 2. Zero hunger, Multidisciplinary, Middle Aged, 3. Good health, Health education and awareness, Blood pressure, Female, Research Article, Adult, medicine.medical_specialty, Waist, HbA1c, Patients, Endocrine Disorders, 030209 endocrinology & metabolism, Peer Group, 03 medical and health sciences, Patient Education as Topic, medicine, Learning, Humans, Hemoglobin, Developing Countries, Glycated Hemoglobin, Biology and life sciences, business.industry, Self-Management, lcsh:R, Cognitive Psychology, Proteins, Peer group, medicine.disease, Diagnostic medicine, Health Care, Self Care, Diabetes Mellitus, Type 2, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Metabolic Disorders, People and Places, Africa, Physical therapy, Cognitive Science, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Patient education, Neuroscience
Abstract

Objectives Our objective was to evaluate the effectiveness of peer-led self-management education in improving glycaemic control in patients with type 2 diabetes in a low-income country (Mali). Methods We conducted an open-label randomised controlled trial. A total of 151 adults (76% women, mean age 52.5) with type 2 diabetes (HbA1c≥8%), treated in the diabetes consultation units of two secondary health centres in Bamako, were allocated to peer-led structured patient education (n = 76) or conventional care alone (n = 75). The intervention group received 1 year of culturally tailored structured patient education (3 courses of 4 sessions) delivered in the community by five trained peer educators. Both groups underwent conventional diabetes monitoring and follow-up. Primary outcome was the mean absolute change in HbA1c from baseline to 12 months. Results 177 education sessions were delivered to the intervention group. Patient attrition was 8%. From baseline to 12 months, the decrease in HbA1c levels was 1.05% (SD = 2.0; CI95%: 1.54;-0.56) in the intervention group compared with 0.15% (SD = 1.7; CI95%: -0.56; 0.26) in the control group, p = 0.006. Mean BMI change was -1.65 kg/m2 (SD = 2.5; CI95%: -2.25; -1.06) in the intervention group and +0.05 kg/m2 (SD = 3.2; CI95%: -0.71; 0.81) in the control group, p = 0.0005. Mean waist circumference decreased by 3.34 cm (SD = 9.3; CI95%: -5.56;-1.13) in the intervention group and increased by 2.65 cm (SD = 10.3; CI95%: 0.20; 5.09) in the control group, p = 0.0003. Conclusions Peer-led structured patient education delivered over 1 year to patients with poorly controlled type 2 diabetes in Mali yielded substantial improvements in glycaemic control and anthropometric parameters. This is of importance for the scaling up of efficient interventions in low-resource settings in the future. Trial registration ClinicalTrials.gov NCT01485913

Published
2018

53. Avoiding a 'big' baby : local perceptions and social responses toward childbirth-related complications in Menabe, Madagascar

Author

Elliot Rakotomanana, Dolorès Pourette, Carole Pierlovisi, Ranjatiana Randriantsara, Chiarella Mattern, Centre population et développement (CEPED - UMR_D 196), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Paris 5 (UPD5), Institut de Recherche pour le Développement (IRD), Institut National de la Santé et de la Recherche Médicale (INSERM), Muséum national d'Histoire naturelle (MNHN), Université d'Antananarivo, Unité d'Epidémiologie [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), The study 'Reproductive health, therapeutic pathways, and healthcare uptake in the Morondava-Menabe region' was founded by Louvain Cooperation and the Pasteur Institute of Madagascar. The 'Study on sociocultural determinants of stunting' was founded by the United States Agency for International Development. We wish to express our gratitude to them., The authors would like to thank Amber Cripps, Astrid Knoblauch, Chris Gordon, Yandé Thiaw and the three reviewers of the paper., and We also thank the NGOs FAFED and FANOITRA. We would like to thank all those who participated in the studies, the fokontany presidents, healthcare professionals, reninjazas and traditional practitioners, and obviously all the women and men who shared their experience with us.

Subjects
Adult, Maternal mortality, medicine.medical_specialty, Health Knowledge, Attitudes, Practice, Health (social science), Pregnant women's care pathways, Local knowledge, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Mothers, Social issues, 03 medical and health sciences, 0302 clinical medicine, History and Philosophy of Science, Health facility, Nursing, Pregnancy, Health care, medicine, Madagascar, Childbirth, Humans, 030212 general & internal medicine, Qualitative Research, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, 030219 obstetrics & reproductive medicine, [SHS.SOCIO]Humanities and Social Sciences/Sociology, business.industry, Public health, Focus Groups, Delivery, Obstetric, Focus group, Pregnancy Complications, Spouse, Anthropological approach, Childbirth-related complications, Female, Perception, Traditional birth attendant, Psychology, business
Abstract

International audience; In Madagascar, a country where over 60% of deliveries are not attended by a healthcare professional, late or inadequate responses to complications during childbirth account for a great number of maternal deaths. In this article, we analyse local perceptions of birth-related risks and strategies used to avoid these risks or manage complications of childbirth. We conduct this analysis in light of the social meanings of childbirth and the social expectations placed upon women in a context of socioeconomic vulnerability and a challenged public health system. We conducted two separate studies in the district of Morondava (Menabe region) in June 2014 and March 2015, comprising semi-directive interviews with 111 people (59 mothers, 18 members of their immediate en-tourage and 34 institutional or healthcare stakeholders), and eight focus groups discussions-two with community leaders, and six with fathers. The results show that the social pressure exerted on women to give birth without complications leads them to practices aimed at avoiding a "big" baby including dietary restrictions, physical activity, and refusal of iron supplementation intake. During pregnancy, women are usually accompanied by a traditional birth attendant or matron (reninjaza). Further, they use the public health system by attending antenatal consultations. However, women are reluctant to deliver in a health facility, where the practices of health professionals are in discordance with the social realities of women and local beliefs around childbirth. If complications arise, they are explained by social causes. The parturient woman is only taken to a healthcare facility after carrying out rituals and if the problems do not resolve themselves. These findings support recommendations to reduce the cultural distance between health workers and childbearing women, strengthen the collaborations with reninjazas, and inform women and their decision makers (mother, reninjaza, spouse) about nutrition during pregnancy and signs of complications.

Published
2018

54. Single low-dose primaquine for blocking transmission of plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa

Author

Muhindo Mavoko, Htee Khu Naw, Estrella Lasry, Nicholas J. White, Sodiomon B. Sirima, Melissa C. Kapulu, Mores Loolpapit, Marie Claire Henry, Thomas N. Williams, Alfred Ngwa Amambua, Claude Rwagacondo, Rick M. Fairhurst, Nicholas P. J. Day, Joseph Okebe, Umberto D'Alessandro, Mahamadou Diakite, Rindra Randremanana, Mavuto Mukaka, James A. Berkley, Jean-Pierre Van Geertruyden, Charles O Obonyo, Malcolm E. Molyneux, Muna Affara, Philipe Brasseur, Peter G. Kremsner, Pascal Lutumba, Endalamaw Gadisa, Abraham Aseffa, Grace Malenga, Caterina I. Fanello, Grant Dorsey, Karen I. Barnes, Zolia Yah, Jane Achan, Patrice Piola, Kathryn Maitland, Chandy C. John, Davis Nwakanma, Joel J. Jones, W. Robert Taylor, Birgit Schramm, Marie A. Onyamboko, Junior Matangila, Philip Bejon, Geneva University Hospital (HUG), Mahidol Oxford Tropical Medicine Research Unit (MORU), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], KEMRI-Wellcome Trust Research Programme (KWTRP), Imperial College London, University of Oxford [Oxford], Medical Research Council Unit The Gambia (MRC), University of Antwerp (UA), University of Kinshasa (UNIKIN), Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Epicentre [Paris] [Médecins Sans Frontières], Kinshasa Mahidol Oxford Research Unit (KIMORU), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]-Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], Ecole de Santé Publique de Kinshasa (KSPH ou ESP), National Malaria Control Programme, Ministry of Health and Social Welfare, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Malaria Research and Training Center [Bamako, Mali], Université de Bamako, Queen Elizabeth Hospital, University of Liverpool, Kenya Medical Research Institute (KEMRI), Armauer Hansen Research Institute (AHRI), Amref Health Africa [Kenya], African Medical and Research Foundation (AMREF), Centre de Recherche Entomologique de Cotonou (CREC), Ministère de la Santé, University of California [San Francisco] (UCSF), University of California, Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), Groupe de recherche action en santé (GRAS), University of Cape Town, University of Tübingen, TNW is supported by a Fellowship from the Wellcome Trust (202800). The KEMRI–Wellcome Trust Research Programme in Kenya is funded through a Strategic Award from the KEMRI–Wellcome Trust Research Programme (203077). RMF was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, US National Institutes of Health. NJW is a Wellcome Trust Principal Fellow., We acknowledge with gratitude the Demographic Health Survey of USAID for permission to download data from their website. This paper is published with permission from the Director of KEMRI., University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, University of Oxford, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, University of California [San Francisco] (UC San Francisco), University of California (UC), RANDRIAMANANTSOA, Volatiana Manohisoa, and Wellcome Trust

Subjects
Male, Primaquine, Antimalarials / therapeutic use, lcsh:Medicine, MESH: Dose-Response Relationship, Drug, MESH: Clinical Protocols, MESH: Aged, 80 and over, 0302 clinical medicine, Clinical Protocols, MESH: Child, Epidemiology, 030212 general & internal medicine, Malaria, Falciparum, Child, MESH: Plasmodium falciparum, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, biology, MESH: Malaria, Falciparum, Age Factors, 11 Medical And Health Sciences, General Medicine, Middle Aged, MESH: Primaquine, MESH: Infant, 3. Good health, MESH: Glucosephosphate Dehydrogenase Deficiency, Tolerability, MESH: Young Adult, Child, Preschool, Primaquine / administration & dosage, Female, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Research Article, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Plasmodium falciparum, 030231 tropical medicine, Antimalarials / adverse effects, Antimalarials, Malaria, Falciparum / prevention & control, Young Adult, 03 medical and health sciences, Pharmacokinetics, Age-based dosing, General & Internal Medicine, Internal medicine, parasitic diseases, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, MESH: Africa South of the Sahara, Dosing, Africa South of the Sahara, ddc:613, Aged, MESH: Adolescent, MESH: Age Factors, MESH: Humans, Dose-Response Relationship, Drug, business.industry, lcsh:R, Malaria, Falciparum / transmission, MESH: Child, Preschool, Infant, MESH: Adult, medicine.disease, biology.organism_classification, MESH: Antimalarials, MESH: Male, Malaria, Regimen, Glucosephosphate Dehydrogenase Deficiency, Primaquine / adverse effects, Primaquine / therapeutic use, Antimalarials / administration & dosage, Malaria, Falciparum / drug therapy, Transmission blocking, Human medicine, business, MESH: Female
Abstract

Background In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. Methods Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15–0.4 mg PQ base/kg for children aged 1–5 years and 0.15–0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6–11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box–Cox transformation power exponential and tested PQ doses of 1–15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. Results From the Box–Cox transformation power exponential model, five age categories were selected: (i) 6–11 months (n = 39,886, 6.03%), (ii) 1–5 years (n = 261,036, 45.46%), (iii) 6–9 years (n = 20,770, 3.14%), (iv) 10–14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12–0.25), (ii) 0.21 (0.13–0.37), (iii) 0.25 (0.16–0.38), (iv) 0.26 (0.15–0.38) and (v) 0.27 (0.17–0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. Conclusions We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 − 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination. Electronic supplementary material The online version of this article (doi:10.1186/s12916-017-0990-6) contains supplementary material, which is available to authorized users.

Published
2018

55. Use of explicit ICD9-CM codes to identify adult severe sepsis: impacts on epidemiological estimates

Author

J. M. Amate-Blanco, Teresa López-Cuadrado, Carmen Bouza, Plan Nacional de I+D+i (España), Ministerio de Sanidad Política Social e Igualdad (España), Funding was provided by the Spanish National I + D Programme (grant number STPY 1346/09). The funding body had no further role in study design, data collection, analysis, interpretation, writing of the report or the decision to submit the paper for publication., Ministerio de Economía y Competitividad (España), and Ministerio de Sanidad, Servicios Sociales e Igualdad (España)

Subjects
Male, medicine.medical_specialty, Epidemiology, Administrative data, Critical Care and Intensive Care Medicine, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, International Classification of Diseases, Sepsis, Internal medicine, Humans, Medicine, Health services research, 030212 general & internal medicine, Severe sepsis, Aged, Outcome, Surveillance, business.industry, Mortality rate, Incidence (epidemiology), Incidence, Organ dysfunction, Hospital discharge database, 030208 emergency & critical care medicine, Middle Aged, Epidemiologic Studies, Editorial, Spain, Relative risk, Cohort, Emergency medicine, Female, medicine.symptom, Trends, business
Abstract

Background: Severe sepsis is a challenge for healthcare systems, and epidemiological studies are essential to assess its burden and trends. However, there is no consensus on which coding strategy should be used to reliably identify severe sepsis. This study assesses the use of explicit codes to define severe sepsis and the impacts of this on the incidence and in-hospital mortality rates. Methods: We examined episodes of severe sepsis in adults aged ≥18 years registered in the 2006–2011 national hospital discharge database, identified in an exclusive manner by two ICD-9-CM coding strategies: (1) those assigned explicit ICD-9-CM codes (995.92, 785.52); and (2) those assigned combined ICD-9-CM infection and organ dysfunction codes according to modified Martin criteria. The coding strategies were compared in terms of the populations they defined and their relative implementation. Trends were assessed using Joinpoint regression models and expressed as annual percentage change (APC). Results: Of 222 846 episodes of severe sepsis identified, 138 517 (62.2 %) were assigned explicit codes and 84 329 (37.8 %) combination codes; incidence rates were 60.6 and 36.9 cases per 100 000 inhabitants, respectively. Despite similar demographic characteristics, cases identified by explicit codes involved fewer comorbidities, fewer registered pathogens, greater extent of organ dysfunction (two or more organs affected in 60 % versus 26 % of cases) and higher in-hospital mortality (54.5 % versus 29 %; risk ratio 1.86, 95 % CI 1.83, 1.88). Between 2006 and 2011, explicit codes were increasingly implemented. Standardised incidence rates in this cohort increased over time with an APC of 12.3 % (95 % CI 4.4, 20.8); in the combination code cohort, rates increased by 3.8 % (95 % CI 1.3, 6.3). A decreasing trend in mortality was observed in both cohorts though the APC was −8.1 % (95 % CI −10.4, −5.7) in the combination code cohort and −3.5 % (95 % CI −3.9, −3.2) in the explicit code cohort. Conclusions: Our findings suggest greater and increasing use of explicit codes for adult severe sepsis in Spain. This trend will have substantial impacts on epidemiological estimates, because these codes capture cases featuring greater organ dysfunction and in-hospital mortality. We especially thank the Subdirección General de Información Sanitaria (Ministry of Health, Social Services and Equality) for providing the data used in this study. Funding was provided by the Spanish National I + D Programme (grant number STPY 1346/09). The funding body had no further role in study design, data collection, analysis, interpretation, writing of the report or the decision to submit the paper for publication. Sí

Published
2016

56. Underestimation of Leptospirosis Incidence in the French West Indies

Author

Sylvie Cassadou, Martine Ledrans, Pascale Bourhy, Philippe Quénel, Martina Escher, Claude Flamand, Jacques Rosine, Mathieu Picardeau, Institut de Veille Sanitaire (INVS), Cellule de l'Institut de Veille Sanitaire en régions Antilles Guyane, Cellule Interrégionale d'Epidémiologie Antilles-Guyane, Cellule interrégionale d'épidémiologie Antilles-Guyane [CIRE], Unité d'Epidémiologie, Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de Référence de la Leptospirose-Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose-Biologie des Spirochètes, Institut Pasteur [Paris], Institut de recherche, santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CIRE Antilles-Guyane - Gourbeyre, Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, CIRE Antilles-Guyane - Fort de France, The authors received specific funding only from the Institut de Veille Sanitaire, their institution. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conceived and designed the experiments: SC JR CF ME ML PB MP PQ. Performed the experi- ments: SC JR ME PB. Analyzed the data: SC JR CF. Contributed reagents/materials/analysis tools: PB MP. Wrote the paper: SC JR CF ME ML PB MP PQ. Organized and strenghtened the partners network: PQ ML., Jean-Baptiste Adrien, Hélène Bazus, Sylvie Boa, Fabrice Boulard, André Cabié, Arnaud Duthilly, Emilie Gaubert-Maréchal, Stéphanie Guyomard, Cécile Herrmann, Patrick Hoche- dez, Isabelle Lamaury, Claude Olive, Marion Petit-Sinturel, Raphaelle Théodose, the public health nurses of the CVAGS, all the General Practitionners of the two sentinel networks in Guadeloupe and Martinique, the ambulatory labs, the hospital labs, the hospital medical staffs, the Pasteur Institute of Guadeloupe, the Pasteur Institute of Paris and Jude Sweeney for the revision of the English text., Institut Pasteur [Paris] (IP), and École des Hautes Études en Santé Publique [EHESP] (EHESP)

Subjects
0301 basic medicine, Male, [SDV]Life Sciences [q-bio], Antibodies, Protozoan, Disease, Polymerase Chain Reaction, Dengue fever, 0302 clinical medicine, Environmental protection, Epidemiology, Enzyme-linked immunoassays, Child, Guadeloupe, Aged, 80 and over, Disease surveillance, Incidence (epidemiology), Incidence, lcsh:Public aspects of medicine, Middle Aged, Leptospirosis, Hospitals, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Child, Preschool, Female, France, Martinique, Adult, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, Adolescent, lcsh:RC955-962, 030231 tropical medicine, 030106 microbiology, Enzyme-Linked Immunosorbent Assay, Sensitivity and Specificity, 03 medical and health sciences, Young Adult, Environmental health, Agglutination Tests, medicine, Humans, Aged, Demography, business.industry, Public Health, Environmental and Occupational Health, Infant, Newborn, Outbreak, Infant, Correction, lcsh:RA1-1270, DNA, Protozoan, medicine.disease, Public and occupational health, Immunoglobulin M, business
Abstract

BACKGROUND:Leptospirosis is a neglected zoonosis affecting mainly tropical and subtropical regions worldwide, particularly South America and the Caribbean. As in many other countries, under-reporting of cases was suspected in the French West Indies because of inadequate access to diagnostic tests for the general population. METHODOLOGY/PRINCIPAL FINDINGS:In order to estimate the real incidence of leptospirosis in Guadeloupe and Martinique, a study was performed in 2011 using the three prevailing available biological tests for diagnosis: Microscopic Agglutination Test (MAT), IgM ELISA and PCR. The study investigated inpatients and outpatients and used active case ascertainment from data provided by a general practitioners' sentinel network. The epidemiology of the disease was also described in terms of severity and demographic characteristics. Leptospirosis incidence was estimated at 69.4 (95%CI 47.6-91.1) and 60.6 (95%CI 36.3-85.0) annual cases per 100,000 inhabitants in Guadeloupe and Martinique, respectively, which was 3 and 4 times higher than previous estimations. CONCLUSION/SIGNIFICANCE:Inclusion of PCR and IgM ELISA tests for diagnosis of leptospirosis resulted in improved sensitivity in comparison with MAT alone. Our results highlighted the substantial health burden of the disease in these two territories and the importance of access to appropriate laboratory tests. Based on our results, PCR and IgM ELISA tests have now been included in the list of tests reimbursed by the national system of social security insurance in France. Our results also underline the relevance of implementing an integrated strategy for the surveillance, prevention and control of leptospirosis in the French West Indies.

Published
2016

57. Impact of early complications on outcomes in patients with implantable cardioverter-defibrillator for primary prevention

Author

Maria Soledad Ascoeta, Marie-Cécile Perier, Olivier Piot, Daniel Gras, Laurent Fauchier, Nicolas Sadoul, Pascal Defaye, Didier Klug, Frankie Beganton, Eloi Marijon, Serge Boveda, Vincent Algalarrondo, Dominique Babuty, Christophe Leclercq, Jean-Claude Deharo, Pierre Bordachar, Centre cardiologique du Nord (CCN), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Nouvelles Cliniques Nantaises, Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de cardiologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Clinique Pasteur et Groupe Rythmologie Stimulation Cardiaque/SFC, Clinique Pasteur [Toulouse], Editorial support on the final version of the paper was provided by MedLink Healthcare Communications Ltd and was funded by the authors. ADREC (Association Dyonisienne de Recherche et Enseignement de Cardiologie) provided secretarial assistance., Centre cardiologique du Nord, Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre Hospitalier Universitaire [Grenoble] ( CHU ), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Laboratoire Traitement du Signal et de l'Image ( LTSI ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de cardiologie et maladies vasculaires, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU de Tours, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1

Subjects
Male, Pediatrics, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary artery disease, 0302 clinical medicine, Postoperative Complications, Risk Factors, Medicine, 030212 general & internal medicine, Registries, education.field_of_study, Hematoma, Primary prevention, Sudden death, Incidence (epidemiology), Incidence, Middle Aged, Implantable cardioverter-defibrillator, 3. Good health, Defibrillators, Implantable, Female, France, Cardiology and Cardiovascular Medicine, Cardiomyopathy, Dilated, medicine.medical_specialty, Population, Cardiac resynchronization therapy, Electric Countershock, Risk Assessment, 03 medical and health sciences, Physiology (medical), Humans, Mortality, education, Aged, [ SDV ] Life Sciences [q-bio], business.industry, Implantable cardiac-defibrillator, Odds ratio, medicine.disease, Survival Analysis, Equipment Failure Analysis, Death, Sudden, Cardiac, Tachycardia, Ventricular, Morbidity, Complication, business
Abstract

International audience; Background - The lifesaving benefit of implantable cardioverter-defibrillators (ICDs) has been demonstrated. Their use has increased considerably in the past decade, but related complications have become a major concern. Objective - The purpose of this study was to assess the incidence and effect on outcomes of early (≤30 days) complications after ICD implantation for primary prevention in a large French population. Methods - We analyzed data from 5539 patients from the multicenter French DAI-PP (Défibrillateur Automatique Implantable-Prévention Primaire) registry (2002-2012) who had coronary artery disease or dilated cardiomyopathy and were implanted with an ICD for primary prevention. Results - Overall, early complications occurred in 707 patients (13.5%), mainly related to lead dislodgment or hematoma (57%). Independent factors associated with occurrence of early complications were severe renal impairment (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.17-2.37, P = .02), age ≥75 years (OR 1.01, 95% CI 1.00-1.02, P = .03), cardiac resynchronization therapy (OR 1.58, 95% CI 1.16-2.17, P = .01), and anticoagulant therapy (OR 1.28, 95% CI 1.02-1.61, P = .03). During a mean ± SD follow-up of 3.1 ± 2.3 years, 824 (15.8%) patients experienced ≥1 late complication (>30 days), and 782 (14.9%) patients died. After adjustment, early complications remained associated with occurrence of late complications (OR 2.15, 95% CI 1.73-2.66, P < .0001) and mortality (OR 1.70, 95% CI 1.34-2.17, P = .003). Conclusion - Early complications are common after ICD implantation for primary prevention, occurring in 1 in 7 patients, and are associated with an increased risk of late complications and overall mortality. Further studies are needed to investigate the underlying mechanisms of such associations.

Published
2016

58. Interventions and decision-making at the end of life: the effect of establishing the terminal illness situation

Author

Rafael Montoya-Juárez, María Paz García-Caro, E. Hernández-López, César Hueso-Montoro, F. Ojeda-Virto, C. Campos-Calderón, [Campos-Calderón,C] Foundation of Progress and Health, Andalusian Health Service, Granada, Spain. [Montoya-Juárez,R, Hueso-Montoro,C, García-Caro,MP] Nursing Department, University of Granada, Granada, Spain. [Hernández-López,E] General Hospital of the Virgen de las Nieves of Granada, Andalusian Health Service, Granada, Spain. [Ojeda-Virto,F] Hospital Santa Ana, Andalusian Health Service, Motril, Spain., and This work is part of an investigative project financed by the Department of Health of the Board of Andalucía in its 2010 call for papers, titled ‘Variability of Clinical Practice and Conditional Factors in the Implementation of the Processes of Attention at End of Life’.Ref: PI-0670-2010.

Subjects
Palliative care, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], medicine.medical_treatment, España, Psychological intervention, Chemicals and Drugs::Inorganic Chemicals::Elements::Chalcogens::Oxygen [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Oxygen therapy, Medicine, Analgésicos opioides, Oxígeno, 030212 general & internal medicine, Patient Comfort, Practice Patterns, Physicians', Resuscitation Orders, Health Care::Health Care Facilities, Manpower, and Services::Health Facilities::Hospitals [Medical Subject Headings], Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Medicine(all), Terminal Care, Palliative Care, Do not resuscitate, Symptom management, General Medicine, Prognosis, Hospitals, Humanos, End-of-life care, Teaching/learning strategies, 030220 oncology & carcinogenesis, Peripheral venous catheter, Hospitales, Research Article, medicine.medical_specialty, Clinical Decision-Making, education, M-learning, Prescripciones, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Peripheral Nervous System Agents::Sensory System Agents::Analgesics::Analgesics, Opioid [Medical Subject Headings], Advance Care Planning, Estudios retrospectivos, 03 medical and health sciences, Humans, Terminally Ill, Medical prescription, Órdenes de resucitación, Intensive care medicine, Retrospective Studies, Delivery of care, Hospital care, business.industry, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Emergency Treatment::Resuscitation::Resuscitation Orders [Medical Subject Headings], Andalucía, Retrospective cohort study, Spain, business, Decision making, Physical therapy, Health Care::Health Care Facilities, Manpower, and Services::Health Services::Pharmaceutical Services::Prescriptions [Medical Subject Headings]
Abstract

Background: Mobile learning (m-learning) has becoming very popular in education due to the rapidly advancing technology in our society. The potentials of the mobile applications should be used to enhance the education process. Few mobile applications have been designed to complement the study of physical therapy skills for physiotherapy students. The aim of this study was to investigate whether a mobile application, as a supplement to traditional learning, is useful for physiotherapy students in the acquisition of palpation and ultrasound skills in the shoulder area. Methods: Forty-nine students participated in this single-blinded, randomized controlled study. They were randomly distributed into two groups: experimental, with free access to the mobile application; and control, with access to traditional learning materials on the topic. Objective structured clinical evaluation (OSCE) and multiple-choice questionnaire (MCQ) were used to assess the educational intervention. Then, we also assessed the time taken to get a reliable ultrasound image and to localize a specific shoulder structure by palpation. Results: There was no significant intergroup difference in the acquisition of theoretical knowledge (p = .089). Scores were significantly higher in the experimental group than in the control group for the majority items in the ultrasound assessment; positioning of patient (p < .001), positioning of ultrasound probe (p = 0.007), handling of ultrasound probe (p = .013) and global OSCE (p < .001) and skills in palpation of the shoulder; position of patient (p = .009), direction of palpation contact (p = .021) and global OSCE (p = .034). There were no significant differences in the time required to perform the examination between groups in ultrasound (p = .944) and palpation (p = .393). The results from the post-program survey assessing the global satisfaction with the mobile application were high (8.200 ± .767), on an 11 numeric point rating scale. Conclusion: These results suggest the effectiveness of an m-learning program as a complement to traditional education for developing skills in ultrasound and palpation of the shoulder region in undergraduate physiotherapy students., The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by a grant from the Educational Innovation Unit of the University of Granada, Spain (PID 13–86).

Published
2016

59. Worksite physical activity interventions and obesity: a review of European studies (the HOPE Project)

Author

Johannes Brug, Cyrus Rostami, Eveline Van Cauwenberghe, Ilse De Bourdeaudhuij, Lea Maes, Frank J. van Lenthe, Jean-Michel Oppert, Anne Vuillemin, Public Health, Centre de Recherche en Nutrition Humaine, Institut National de la Recherche Agronomique (INRA), Department of Public Health, Université libre de Bruxelles (ULB), Department of Movement and Sport Sciences, Universiteit Gent = Ghent University [Belgium] (UGENT), Department of public health, Erasmus University Rotterdam, University Medical Centre, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), The project this paper is part of has been being carried out with financial support from the Commission of the European Communities, SP5A-CT-2006-044128 'Health-Promotion through Obesity Prevention across Europe (HOPE): an Integrated Analysis to Support European Health Policy'. The study does not necessarily reflect the Commission's views and in no way anticipates the Commission's future policy in this area., Epidemiology and Data Science, and EMGO - Lifestyle, overweight and diabetes

Subjects
Gerontology, medicine.medical_specialty, validity, Health (social science), [SDV]Life Sciences [q-bio], Physical fitness, Psychological intervention, Physical activity, Obesity, Intervention studies, Worksite, External, endocrinology and metabolism, nutrition and dietetics, Transportation, Health Promotion, biofilm, law.invention, External validity, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Randomized controlled trial, SDG 3 - Good Health and Well-being, law, Physiology (medical), Intervention (counseling), Medicine, Humans, Generalizability theory, 030212 general & internal medicine, Workplace, Exercise, ComputingMilieux_MISCELLANEOUS, communauté microbienne, 030505 public health, business.industry, Evidence-based medicine, culture, Europe, Physical Fitness, Physical therapy, Original Article, environnement abiotique, 0305 other medical science, business
Abstract

Summary Objective: Our aim was to review the effectiveness of physical activity promotion interventions in the worksite setting in Europe in order to identify those studies that had measured obesity-related outcomes and to evaluate how external validity of the findings had been assessed. Methods: We conducted a review of studies conducted in Europe, published up to December 2009. We assessed levels of evidence regarding effectiveness and analysed external validity using the RE-AIM framework. Results: Studies included (n = 33) were divided in 6 intervention categories. Moderate evidence of effectiveness was found for physical fitness outcomes with exercise training interventions and for physical activity outcomes with active commuting interventions. There was no or inconclusive evidence for obesity-related outcomes for all intervention categories. For external validity, elements receiving the least attention (

Published
2011

60. Patient specific simulation of tumor growth, response to the treatment and relapse of a lung metastasis: a clinical case

Author

Julien Jouganous, Jean Palussière, Thierry Colin, François Cornelis, Olivier Saut, Modélisation Mathématique pour l'Oncologie (MONC), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut Bergonié [Bordeaux], UNICANCER, This study has been carried out within the frame of the LABEX TRAIL, ANR-10-LABX-0057 with financial support from the French State, managed by the French National Research Agency (ANR) in the frame of the 'Investments for the future' Programme IdEx (ANR-10-IDEX-03-02).Experiments presented in this paper were carried out using the PLAFRIM experimental testbed, being developed under the Inria PlaFRIM development action with support from LABRI and IMB and other entities: Conseil R ́egional d’Aquitaine, FeDER, Universit ́e de Bordeaux and CNRS (see https://plafrim.bordeaux.inria.fr/)., Inria Bordeaux, ANR-10-IDEX-0003,IDEX BORDEAUX,Initiative d'excellence de l'Université de Bordeaux(2010), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Oncology, medicine.medical_specialty, Pathology, Radiofrequency ablation, Angiogenesis, medicine.medical_treatment, Lung metastasis, [SDV.CAN]Life Sciences [q-bio]/Cancer, 010103 numerical & computational mathematics, 01 natural sciences, law.invention, Lesion, 03 medical and health sciences, Tumor growth modeling, 0302 clinical medicine, law, Internal medicine, medicine, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], Tumor growth, 0101 mathematics, Clinical data assimilation, Chemotherapy, business.industry, Partial Differential Equations, Patient specific, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, 030220 oncology & carcinogenesis, Clinical case, Medical imaging, medicine.symptom, business
Abstract

In this paper, a parametrization strategy based on reduced order methods is presented for tumor growth PDE models. This is applied to a new simple spatial model for lung metastasis including angiogenesis. The goal is to help clinicians monitoring tumors and eventually predicting their evolution or response to a particular kind of treatment. To illustrate the whole approach, a clinical case including the natural history of the lesion, the response to a chemotherapy, and the relapse before a radiofrequency ablation is presented.

Published
2015

61. Concerns about the widespread use of rodent models for human risk assessments of endocrine disruptors

Author

Gabriel Livera, René Frydman, Delphine Moison, Vincent Muczynski, Alexandra Benachi, René Habert, R. Lambrot, Abdelali Lehraiki, Virginie Rouiller-Fabre, Geraldine Delbes, Tiphany Grisin, Christine Levacher, Marie-Justine Guerquin, Sébastien Messiaen, Thierry N’Tumba-Byn, Stabilité génétique, Cellules Souches et Radiations (SCSR (U_967)), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de gynécologie-obstétrique, médecine de la reproduction [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), The work of our group presented in this paper was supported byUniversité Paris Diderot-Paris 7, CEA, INSERM, the FrenchAgence pour la Santé et la Sécurité dans l’Environnement et le Travail (AFSSET), the French Agence Nationale de SécuritéSanitaire de l’Alimentation, de l’Environnement et du Travail(ANSES Contrat EST62010/2/046), the Agence Nationale de laRecherche (ANR, contrat Phtalatestis and contrat MECABPA)and the Ministère de l’Ecologie, du Développement Durable,des Transports et du Logement (Programme ANTIOPES –Storm). None of the authors received any personal financialremuneration or funding for research studies from anychemical industrial company., ANR-07-SEST-0019,PHTALATESTIS,Effets et mécanismes d'action des phtalates sur le développement et les fonctions du testicule chez la souris et l'homme(2007), ANR-11-CESA-0001,MECABPA,Effets et mécanismes d'action du bisphénol A (BPA) sur le développement et les fonctions des gonades foetales chez la souris, la brebis et l'homme(2011), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Courcelles, Michel, Santé-environnement et Santé-travail - Effets et mécanismes d'action des phtalates sur le développement et les fonctions du testicule chez la souris et l'homme - - PHTALATESTIS2007 - ANR-07-SEST-0019 - SEST - VALID, Contaminants et Environnements : Métrologie, santé, Adaptabilité, Comportements et Usages - Effets et mécanismes d'action du bisphénol A (BPA) sur le développement et les fonctions des gonades foetales chez la souris, la brebis et l'homme - - MECABPA2011 - ANR-11-CESA-0001 - CESA - VALID, Cellules Souches et Radiations (SCSR - U 967), Université Paris-Sud - Paris 11 (UP11) - Commissariat à l'énergie atomique et aux énergies alternatives (CEA) - Université Paris Diderot - Paris 7 (UPD7) - Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Antoine Béclère, and Institut National de la Recherche Scientifique [Québec] (INRS) - Réseau International des Instituts Pasteur (RIIP) - Institut Armand Frappier

Subjects
Animal Experimentation, Male, Embryology, medicine.medical_specialty, Cell type, Rodent, [SDV]Life Sciences [q-bio], Retinoic acid, Rodentia, Review, Endocrine Disruptors, Risk Assessment, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Internal medicine, biology.animal, Testis, Toxicity Tests, medicine, Animals, Humans, Endocrine system, Animal testing, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, Gametogenesis, 030304 developmental biology, 0303 health sciences, Fetus, 030219 obstetrics & reproductive medicine, biology, Phthalate, Obstetrics and Gynecology, Cell Biology, Rats, 3. Good health, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV] Life Sciences [q-bio], Reproductive Medicine, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Models, Animal, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

International audience; Fetal testis is a major target of endocrine disruptors (EDs). During the last 20 years, we have developed an organotypic culture system that maintains the function of the different fetal testis cell types and have used this approach as a toxicological test to evaluate the effects of various compounds on gametogenesis and steroidogenesis in rat, mouse and human testes. We named this test rat, mouse and human fetal testis assay. With this approach, we compared the effects of six potential EDs ((mono-(2-ethylhexyl) phthalate (MEHP), cadmium, depleted uranium, diethylstilboestrol (DES), bisphenol A (BPA) and metformin) and one signalling molecule (retinoic acid (RA)) on the function of rat, mouse and human fetal testis at a comparable developmental stage. We found that the response is similar in humans and rodents for only one third of our analyses. For instance, RA and MEHP have similar negative effects on gametogenesis in the three species. For another third of our analyses, the threshold efficient concentrations that disturb gametogenesis and/or steroidogenesis differ as a function of the species. For instance, BPA and metformin have similar negative effects on steroidogenesis in human and rodents, but at different threshold doses. For the last third of our analyses, the qualitative response is species specific. For instance, MEHP and DES affect steroidogenesis in rodents, but not in human fetal testis. These species differences raise concerns about the extrapolation of data obtained in rodents to human health risk assessment and highlight the need of rigorous comparisons of the effects in human and rodent models, when assessing ED risk.

Published
2014

62. Low health-related quality of life in school-aged children in Tonga, a lower-middle income country in the South Pacific

Author

Boyd Swinburn, Helen Mavoa, Marjory Moodie, Gavin Faeamani, Caroline Tupoulahi-Fusimalohi, Solveig Petersen, Kalesita Fotu, and the Wellcome Trust (UK), the National Health and Medical Research Council (Australia), the Health Research Council (New Zealand), the current paper also by the Swedish Council for Working Life and Social Research and the Olle Engkvist Foundation (Sweden)

Subjects
Male, Economic growth, Epidemiology, Health Status, Distribution (economics), Quality of life, Surveys and Questionnaires, Child, community health, Psychiatry, education.field_of_study, Health Policy, lcsh:Public aspects of medicine, Tonga, 1. No poverty, Public Health, Global Health, Preventive Medicine, Community Health, Population Health, Gender Studies, Public Health, Global Health, Social Medicine and Epidemiology, adolescent health, humanities, 3. Good health, Mental Health, Community health, Income, child health, Original Article, Female, low-income population, mental health, quality of life, Adolescent health, medicine.medical_specialty, Adolescent, Population, Developing country, Psykiatri, RA1-1270, RA407-409.5, RA421-790.95, RA790-790.95, RC49-52, RJ101-103, medicine, Humans, education, Developing Countries, business.industry, Public health, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Mental health, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Cross-Sectional Studies, business, Demography, New Zealand
Abstract

Background : Ensuring a good life for all parts of the population, including children, is high on the public health agenda in most countries around the world. Information about children’s perception of their health-related quality of life (HRQoL) and its socio-demographic distribution is, however, limited and almost exclusively reliant on data from Western higher income countries. Objectives : To investigate HRQoL in schoolchildren in Tonga, a lower income South Pacific Island country, and to compare this to HRQoL of children in other countries, including Tongan children living in New Zealand, a high-income country in the same region. Design : A cross-sectional study from Tonga addressing all secondary schoolchildren (11–18 years old) on the outer island of Vava’u and in three districts of the main island of Tongatapu (2,164 participants). A comparison group drawn from the literature comprised children in 18 higher income and one lower income country (Fiji). A specific New Zealand comparison group involved all children of Tongan descendent at six South Auckland secondary schools (830 participants). HRQoL was assessed by the self-report Pediatric Quality of Life Inventory 4.0. Results : HRQoL in Tonga was overall similar in girls and boys, but somewhat lower in children below 15 years of age. The children in Tonga experienced lower HRQoL than the children in all of the 19 comparison countries, with a large difference between children in Tonga and the higher income countries (Cohen’s d 1.0) and a small difference between Tonga and the lower income country Fiji (Cohen’s d 0.3). The children in Tonga also experienced lower HRQoL than Tongan children living in New Zealand (Cohen’s d 0.6). Conclusion : The results reveal worrisome low HRQoL in children in Tonga and point towards a potential general pattern of low HRQoL in children living in lower income countries, or, alternatively, in the South Pacific Island countries. Keywords : adolescent health; child health; community health; Epidemiology; low-income population; mental health; quality of life (Published: 20 August 2014) Citation : Glob Health Action 2014, 7 : 24896 - http://dx.doi.org/10.3402/gha.v7.24896

Published
2014

63. Impact of therapy escalation on ambulatory care costs among patients with type 2 diabetes in France

Author

Florent Guelfucci, Mondher Toumi, Samuel Aballéa, Nicholas Moore, Emilie Clay, Régis Lassalle, Systèmes Intégrés, Environnement et Biodiversité (SIEB), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-HESAM Université (HESAM), Evaluation des systèmes de soins et santé perçue, Université de la Méditerranée - Aix-Marseille 2, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Pharmaco-Epidémiologie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), This study was supported by an unconditional grant from Boehringer Ingelheim. The sponsor had no influence on study design, conduct, analysis or interpretation, or in the writing of this paper., École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), and BMC, Ed.

Subjects
medicine.medical_specialty, medicine.medical_treatment, Endocrinology, Diabetes and Metabolism, Pharmacy, Type 2 diabetes, 03 medical and health sciences, Nursing care, 0302 clinical medicine, Ambulatory care, Internal medicine, Diabetes mellitus, Type 2 diabetes mellitus, medicine, Cost analysis, Insulin, 030212 general & internal medicine, Oral antidiabetics, health care economics and organizations, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, business.industry, 030503 health policy & services, Type 2 Diabetes Mellitus, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Endocrinology, Ambulatory, 0305 other medical science, business, Research Article, Renal function
Abstract

International audience; BACKGROUND: This study compares annual ambulatory care expenditures per patient with type 2 diabetes mellitus (T2DM) in France according to treatment phase and renal function status. METHODS: Records from patients with T2DM were extracted from a health insurance database. Patients were classified in subgroups, by treatment phase: oral/GLP1 monotherapy, double therapy, triple therapy or insulin therapy, and according to renal function status (identified using pharmacy, lab and consultation claims). Annual ambulatory expenditures were estimated from the national insurance perspective by year (from 2005 to 2010) and subgroup. RESULTS: The number of patients ranged from 9,682 to 11,772 between 2005 and 2010. The average annual expenditure per individual in 2010 ranged from [euro sign]3,017 (standard deviation: [euro sign]3,829) for monotherapy to [euro sign]3,609 +/- [euro sign]3,801 for triple therapy, and [euro sign]7,398 +/- [euro sign]5,487 with insulin (adjusted ratio insulin therapy/monotherapy: 2.36, p < 0.001). Similar differences between treatement stages were found in previous years. Additional costs for insulin were mainly related to nursing care (multiplied by 18.42, p < 0.001), medical devices and pharmacy costs. DM-attributable drug costs were mainly related to antidiabetic drugs (28% for monotherapy to 71% for triple therapy), but also to cardiovascular system drugs (21% for monotherapy to 51% with insulin) and nervous system drugs (up to 8% with insulin). Declining renal function was associated with an increase in expenses by 12% to 53% according to treatment stage. CONCLUSIONS: Overall, ambulatory care expenditures increase with treatment escalation and declining renal function amongst patients with T2DM. Insulin therapy is associated with substantially increased costs, related to pharmacy, nursing care and medical device costs.

Published
2013

64. The potential for integrated care programmes to improve quality of care as assessed by patients with COPD: early results from a real-world implementation study in The Netherlands

Author

Jane M. Cramm, Anna P. Nieboer, Maureen P.M.H. Rutten-van Mölken, Funding This research was supported by a grant provided by The Netherlands Organisation for Health Research and Development (ZonMw) [project no. 300030201]. The views expressed in the paper are those of the authors., and Health Economics (HE)

Subjects
medicine.medical_specialty, Health (social science), Sociology and Political Science, Copd patients, chronic care, integrated care, disease management, COPD, chronic care model, Pulmonary disease, Medicine, Disease management (health), Quality of care, Chronic care, lcsh:R5-920, Research and Theory, business.industry, Health Policy, medicine.disease, Integrated care, Early results, Physical therapy, business, lcsh:Medicine (General)
Abstract

Objective: We investigated whether patients with chronic obstructive pulmonary disease (COPD) who were enrolled in disease-management programmes (DMPs) felt that they received a better quality of care than non-enrolled COPD patients. Methods: Our cross-sectional study was performed among patients (n = 665) enrolled in four DMPs in The Netherlands. We also evaluated COPD patients (n = 227) not enrolled in such programmes. Patients' assessment of chronic-illness care (PACIC) was measured with a 20-item questionnaire. The instrument had five pre-defined domains: patient activation (three items), delivery-system/practice design (three items), goal setting/tailoring (five items), problem solving/contextual (four items), and follow-up/coordination (five items). Results: The mean overall PACIC score (scale: 1-5) of enrolled DMP patients was 2.94, and that of non-enrolled DMP patients was 2.73 (p ≤ 0.01). Differences in the same direction were found in the subscales of patient activation (p ≤ 0.01), delivery-system/practice design (p ≤ 0.001), and problem solving/contextual (p ≤ 0.001). Conclusions: Our results suggest that even in the early stages of implementation, DMPs for COPD may significantly improve care.

Published
2012

65. High-pressure intrapleural chemotherapy: feasibility in the pig model

Author

Bernard Royer, Alain Bernard, Bruno Chauffert, Pablo Ortega-Deballon, Olivier Facy, Guy Magnin, Pierre-Benoit Pagès, Sylvain Ladoire, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de chirurgie cardio-vasculaire, Service d'anesthésie réanimation, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Laboratoire de Pharmacologie Clinique et Toxicologie [Besancon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), This paper was supported by research grants from the French National League against Cancer, from the Regional Council of Burgundy and from the University Hospital of Dijon (France)., Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Laboratoire de Pharmacologie Clinique et Toxicologie [CHRU Besancon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), BMC, Ed., Service de chirurgie cardio-vasculaire et thoracique (CHU Dijon), and Service d'anesthésie - réanimation chirurgicale [CHU de Dijon]

Subjects
medicine.medical_specialty, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Swine, Pleural Neoplasms, lcsh:Surgery, Intra arterial chemotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, lcsh:RC254-282, Deoxycytidine, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, chemistry.chemical_compound, pressure, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Surgical oncology, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, medicine, Tumor Cells, Cultured, Animals, Humans, Intrapleural chemotherapy, Pleural Neoplasm, [ SDV.MHEP.CHI ] Life Sciences [q-bio]/Human health and pathology/Surgery, pig model, Cisplatin, business.industry, Research, Pig model, lcsh:RD1-811, intrapleural intracavitary chemotherapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Gemcitabine, 3. Good health, Surgery, 030228 respiratory system, chemistry, Oncology, 030220 oncology & carcinogenesis, High pressure, Feasibility Studies, Female, business, medicine.drug
Abstract

Background The usual treatments for pleural malignancies are mostly palliative. In contrast, peritoneal malignancies are often treated with a curative intent by cytoreductive surgery and intraperitoneal chemotherapy. As pressure has been shown to increase antitumor efficacy, we applied the concept of high-pressure intracavitary chemotherapy to the pleural space in a swine model. Methods Cisplatin and gemcitabine were selected because of their antineoplasic efficacy in vitro in a wide spectrum of cancer cell lines. The pleural cavity of 21 pigs was filled with saline solution; haemodynamic and respiratory parameters were monitored. The pressure was increased to 15-25 cm H2O. This treatment was associated with pneumonectomy in 6 pigs. Five pigs were treated with chemotherapy under pressure. Results The combination of gemcitabine (100 mg/l) and cisplatin (30 mg/l) was highly cytotoxic in vitro. The maximum tolerated pressure was 20 cm H20, due to haemodynamic failure. Pneumonectomy was not tolerated, either before or after pleural infusion. Five pigs survived intrapleural chemotherapy associating gemcitabine and cisplatin with 20 cm H2O pressure for 60 min. Conclusions High-pressure intrapleural chemotherapy is feasible in pigs. Further experiments will establish the pharmacokinetics and determine whether the benefit already shown in the peritoneum is also obtained in the pleura.

Published
2012

66. Effectiveness of Core Stability Exercises and Recovery Myofascial Release Massage on Fatigue in Breast Cancer Survivors: A Randomized Controlled Clinical Trial

Author

César Fernández-de-las-Peñas, Manuel Arroyo-Morales, Rosario del Moral-Avila, María Belén Feriche-Fernández-Castanys, Irene Cantarero-Villanueva, Carolina Fernández-Lao, [Cantarero-Villanueva,I, Fernández-Lao,C, Arroyo-Morales,M] Department of Physical Therapy, Health Sciences Faculty, University of Granada, Granada, Spain. [Moral-Avila,R del] Radiotherapy Breast Oncology Unit, University Hospital Virgen de las Nieves, Granada, Spain. [Fernández-de-Las-Peñas,C] Department of Physical Therapy, Occupational Therapy, Rehabilitation, and Physical Medicine, King Juan Carlos university, Alcorcón, Spain. [Feriche-Fernández-Castanys,MB] Physical Education Department, Faculty of Sciences, Physical Activity, and Sports, University of Granada, Granada, Spain., and The paper was funded by a Research Project Grant (FIS ETES-PI0890418 and 10/02749) from the Health Institute Carlos III and PN I+D+I 2008–2011, Madrid, Spanish. Government and a Grant of Andalusian Health Service, Junta de Andalucia (PI-0457-2010).

Subjects
medicine.medical_specialty, Article Subject, Terapia por Ejercicio, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Physical Therapy Modalities::Musculoskeletal Manipulations::Massage [Medical Subject Headings], Named Groups::Persons::Survivors [Medical Subject Headings], Masaje, Sobrevivientes, Breast cancer, Physical medicine and rehabilitation, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Fatigue [Medical Subject Headings], medicine, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Depression (differential diagnoses), Massage, Fatiga, business.industry, Neoplasias de la Mama, Femenino, Core stability, Ensayos Clínicos Controlados Aleatorios como Asunto, lcsh:Other systems of medicine, lcsh:RZ201-999, medicine.disease, Trunk, Myofascial release, Clinical trial, Check Tags::Female [Medical Subject Headings], Complementary and alternative medicine, Physical therapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Physical Therapy Modalities::Exercise Therapy [Medical Subject Headings], business, After treatment, Research Article
Abstract

The purpose of the present paper was to evaluate the effects of an 8-week multimodal program focused on core stability exercises and recovery massage with DVD support for a 6-month period in physical and psychological outcomes in breast cancer survivors. A randomized controlled clinical trial was performed. Seventy-eight (n=78) breast cancer survivors were assigned to experimental (core stability exercises plus massage-myofascial release) and control (usual health care) groups. The intervention period was 8 weeks. Mood state, fatigue, trunk curl endurance, and leg strength were determined at baseline, after the last treatment session, and at 6 months of followup. Immediately after treatment and at 6 months, fatigue, mood state, trunk curl endurance, and leg strength exhibited greater improvement within the experimental group compared to placebo group. This paper showed that a multimodal program focused on core stability exercises and massage reduced fatigue, tension, depression, and improved vigor and muscle strength after intervention and 6 months after discharge.

Published
2012
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67. Risk of brain tumours in relation to estimated RF dose from mobile phones: results from five Interphone countries

Author

Lynne D. Richardson, Elisabeth Cardis, Martine Vrijheid, Alistair Woodward, Graham G. Giles, Rodrigo Villegas, Jordi Figuerola, Marie-Élise Parent, Daniel Krewski, Bruce K. Armstrong, Martine Hours, Julianne Brown, Avital Jarus-Hakak, L. Montestruq, Louise Nadon, Angela Chetrit, Chen Hoffmann, Siegal Sadetzki, Mary L. McBride, Joseph D. Bowman, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Sydney School of Public Health, The University of Sydney, Engineering and Physical Hazards Branch, National Institute for Occupational Safety and Health, Cancer Epidemiology Centre, Cancer Council Victoria, Centre for MEGA Epidemiology, University of Melbourne-School of Population Health, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), McLaughlin Centre for Population Health Risk Assessment, University of Ottawa [Ottawa], BC Cancer Research Centre, BC Cancer Agency (BCCRC), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Cancer and Radiation Epidemiology Unit, Chaim Sheba Medical Center-Gertner Institute, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], School of Population Health, University of Auckland [Auckland], Department of Diagnostic Imaging, Chaim Sheba Medical Center, Department of Population health, Hospital Research Centre-University of Montreal, Funding for the Interphone Study was provided by the European Fifth Framework Program, 'Quality of Life and Management of Living Resources' (contract QLK4-CT-1999901563), the International Union against Cancer (UICC). The UICC received funds for this purpose from the Mobile Manufacturers' Forum and GSM Association. Provision of funds to the Interphone Study investigators via the UICC was governed by agreements that guaranteed Interphone's complete scientific independence. The terms of these agreements are publicly available at http://www.iarc.fr/en/research-groups/RAD/RCAd.html Specific additional funds were provided for the development and analysis of the radio frequency exposure gradient and by the Fondation Santé et Radiofréquences, France and the Bundesamt fuer Strahlenschutz, Germany. The Australian centre was supported by the National Health and Medical Research Council (EME grant 219129), and BKA was supported by the University of Sydney Medical Foundation Program Grant and Julianne Brown by an Australian Postgraduate Award. The Cancer Council NSW and the Cancer Council Victoria provided most of the infrastructure for the project in Australia. The Canada-Montréal data collection was funded by a grant from the Canadian Institutes of Health Research (project MOP-42525). Additionally, Dr Siemiatycki's research team was partly funded by the Canada Research Chair programme and by the Guzzo-CRS Chair in Environment and Cancer. Dr. Parent had salary support from the Fonds de recherche en santé du Québec. The other Canadian centres were supported by a universityeindustry partnership grant from the Canadian Institutes of Health Research (CIHR), the latter including partial support from the Canadian Wireless Telecommunications Association. The CIHR universityeindustry partnerships program also includes provisions that ensure complete scientific independence of the investigators. DK is the NSERC/SSHRC/McLaughlin Chair in Population Health Risk Assessment at the University of Ottawa. Additional funding for the study in France was provided by l'Association pour la Recherche sur le Cancer (ARC) (contract 5142) and three network operators (Orange, SFR, Bouygues Télécom). The funds provided by the operators represented 5% of the total cost of the French study and were governed by contracts guaranteeing the complete scientific independence of the investigators. In New Zealand, funding was provided by the Health Research Council, Hawkes Bay Medical Research Foundation and the Cancer Society of New Zealand. The findings and conclusions in this paper have not been formally disseminated by the National Institute for Occupational Safety and Health and should not be construed to represent any agency determination or policy.

Subjects
Oncology, Male, epidemiological study, MESH: Neoplasms, Radiation-Induced, Neoplasms, Radiation-Induced, Radio Waves, non-ionising radiation, MESH: Logistic Models, MESH: Meningioma, MESH: Radio Waves, MESH: Electromagnetic Fields, MESH: Glioma, 0302 clinical medicine, MESH: New Zealand, MESH: Risk Factors, Mobile phones, 030212 general & internal medicine, MESH: Middle Aged, ionising radiation, Brain Neoplasms, MESH: Israel, risk assessment, Brain, MESH: Case-Control Studies, RF exposure assessment, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, Original Article, epidemiology, Female, physics, Algorithms, electromagnetic fields, medicine.medical_specialty, MESH: Radiation Dosage, Rf exposure, MESH: Australia, MESH: Algorithms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Radiation Dosage, Meningioma, 03 medical and health sciences, MESH: Canada, Glioma, Internal medicine, medicine, cancer, Humans, MESH: Humans, business.industry, MESH: Time Factors, Public Health, Environmental and Occupational Health, Case-control study, MESH: Adult, Odds ratio, medicine.disease, MESH: Meningeal Neoplasms, hygiene/occupational hygiene, MESH: Male, MESH: Odds Ratio, Surgery, nervous system diseases, MESH: France, Increased risk, Multicenter study, MESH: Cellular Phone, business, MESH: Female, Cell Phone
Abstract

International audience; OBJECTIVES: The objective of this study was to examine the associations of brain tumours with radio frequency (RF) fields from mobile phones. METHODS: Patients with brain tumour from the Australian, Canadian, French, Israeli and New Zealand components of the Interphone Study, whose tumours were localised by neuroradiologists, were analysed. Controls were matched on age, sex and region and allocated the 'tumour location' of their matched case. Analyses included 553 glioma and 676 meningioma cases and 1762 and 1911 controls, respectively. RF dose was estimated as total cumulative specific energy (TCSE; J/kg) absorbed at the tumour's estimated centre taking into account multiple RF exposure determinants. RESULTS: ORs with ever having been a regular mobile phone user were 0.93 (95% CI 0.73 to 1.18) for glioma and 0.80 (95% CI 0.66 to 0.96) for meningioma. ORs for glioma were below 1 in the first four quintiles of TCSE but above 1 in the highest quintile, 1.35 (95% CI 0.96 to 1.90). The OR increased with increasing TCSE 7+ years before diagnosis (p-trend 0.01; OR 1.91, 95% CI 1.05 to 3.47 in the highest quintile). A complementary analysis in which 44 glioma and 135 meningioma cases in the most exposed area of the brain were compared with gliomas and meningiomas located elsewhere in the brain showed increased ORs for tumours in the most exposed part of the brain in those with 10+ years of mobile phone use (OR 2.80, 95% CI 1.13 to 6.94 for glioma). Patterns for meningioma were similar, but ORs were lower, many below 1.0. CONCLUSIONS: There were suggestions of an increased risk of glioma in long-term mobile phone users with high RF exposure and of similar, but apparently much smaller, increases in meningioma risk. The uncertainty of these results requires that they be replicated before a causal interpretation can be made.

Published
2011

68. In Vitro and Ex Vivo Evaluation of Smart Infra-Red Fluorescent Caspase-3 Probes for Molecular Imaging of Cardiovascular Apoptosis

Author

Bruno Delest, Vincent Richard, Marc Massonneau, Manuelle Debunne, Jean-Paul Henry, Christian Thuillez, Anthony Romieu, Christophe Portal, Françoise Lallemand, Heidi Ligeret, Pierre-Yves Renard, Ebba Brakenhielm, Pauline Noack, Pharmacologie des Dysfonctionnements Endotheliaux et Myocardiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), QUantitative Imaging in Drug Development [Saint-Etienne du Rouvray] (QUIDD / Technopôle du Madrillet), Technopôle du Madrillet, Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), This paper was supported by La Région Haute Normandie via the CRUNCh program (CPER 2007–2013) and IUF (Institut Universitaire de France)., Brakenhielm, Ebba, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie Organique Fine (IRCOF), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), and Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pathology, medicine.medical_specialty, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.IMM] Life Sciences [q-bio]/Immunology, Article Subject, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Caspase 3, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Annexin, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Radiology, Nuclear Medicine and imaging, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, Chemistry, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Fluorescence, In vitro, 3. Good health, Cell biology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Apoptosis, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Molecular imaging, Ex vivo, Research Article
Abstract

Purpose. The aim of this paper is to develop new optical bioprobes for the imaging of apoptosis.Procedure. We developed quenched near-infrared probes which become fluorescent upon cleavage by caspase-3, the key regulatory enzyme of apoptosis.Results. Probes were shown to be selectively cleaved by recombinant caspase-3. Apoptosis of cultured endothelial cells was associated with an increased fluorescent signal for the cleaved probes, which colocalized with caspase-3 and was reduced by the addition of a caspase-3 inhibitor. Flow cytometry demonstrated a similar profile between the cleaved probes and annexin V.Ex vivoexperiments showed that sections of hearts obtained from mice treated with the proapoptotic drug doxorubicin displayed an increase in the fluorescent signal for the cleaved probes, which was reduced by a caspase-3 inhibitor.Conclusion. We demonstrated the capacity of these novel probes to detect apoptosis by optical imagingin vitroandex vivo.

Published
2011

69. Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murine model of peritoneal carcinomatosis

Author

Patrick Rat, Hervé Tixier, François Radais, Delphine Delroeux, François Ghiringhelli, Sylvain Ladoire, Olivier Facy, Pablo Ortega-Deballon, Bruno Chauffert, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Chirurgie Digestive [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), This paper was supported by grants from the French National League against Cancer (Committees of Saône et Loire, Nièvre, and Côte d'Or)., BMC, Ed., Service de chirurgie digestive et cancérologie, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service de chirurgie digestive [Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Service d'oncologie médicale, and CHU Amiens-Picardie

Subjects
MESH : Hyperthermia, Induced, MESH : Rats, Inbred Strains, Cancer Research, Pathology, Pharmacology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Peritoneal Neoplasm, 0302 clinical medicine, MESH : Tumor Cells, Cultured, Tumor Cells, Cultured, Medicine, MESH: Peritoneal Neoplasms, MESH : Female, MESH: Animals, Peritoneal Neoplasms, Ovarian Neoplasms, MESH : Cell Survival, 0303 health sciences, MESH : Rats, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, MESH: Rats, Inbred Strains, 3. Good health, MESH : Antineoplastic Agents, MESH: Ovarian Neoplasms, Epinephrine, Oncology, MESH: Cell Survival, 030220 oncology & carcinogenesis, Female, medicine.drug, Hyperthermia, medicine.medical_specialty, MESH: Rats, Cell Survival, MESH: Epinephrine, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, MESH : Cisplatin, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH : Peritoneal Neoplasms, In vivo, Animals, Humans, MESH: Tumor Cells, Cultured, MESH: Hyperthermia, Induced, 030304 developmental biology, Cisplatin, MESH: Humans, MESH : Ovarian Neoplasms, business.industry, Research, MESH : Humans, Rats, Inbred Strains, Hyperthermia, Induced, medicine.disease, MESH : Disease Models, Animal, Rats, Disease Models, Animal, MESH: Cisplatin, Apoptosis, MESH : Epinephrine, Cancer cell, MESH: Antineoplastic Agents, MESH : Animals, MESH: Disease Models, Animal, business, Ovarian cancer, MESH: Female
Abstract

Background The best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis. Methods Four groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured in vivo (tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and in vitro (cytotoxicity on human ovarian cancer cells). Results In vitro, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. In vivo, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia. Conclusion Adrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug.

Published
2011

70. Role of mental disorders in nosocomial infections after hip fracture treatment

Author

Nicolás Benítez-Parejo, Encarnacion Cruz, Emilio Perea-Milla, Enrique Guerado, Juan Ramon Cano, CIBER Epidemioloǵıa y Salud Ṕublica (CIBERESP), [Guerado,E, Cano,JR, Cruz,E] Department of Orthopaedic Surgery and Traumatology, Hospital Costa del Sol, University of Malaga. [Benitez-Parejo,N, Perea-Milla,E] Department of Research, Statistics, and Epidemiology, CIBERESP, Hospital Costa del Sol, University of Malaga., and This paper was performed with a grant from the Carlos III Institute (The Spanish Ministry of Science and Innovation) to the authors’ network of research group on Clinical pidemiology (CIBERESP)

Subjects
musculoskeletal diseases, Microbiology (medical), Diseases::Wounds and Injuries::Fractures, Bone::Hip Fractures [Medical Subject Headings], medicine.medical_specialty, Article Subject, Psychiatry and Psychology::Mental Disorders [Medical Subject Headings], Infección Hospitalaria, Diseases::Bacterial Infections and Mycoses::Infection::Cross Infection [Medical Subject Headings], Hip fracture surgery, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Iatrogenic Disease [Medical Subject Headings], Microbiology, lcsh:Infectious and parasitic diseases, Virology, medicine, lcsh:RC109-216, Multiple logistic regression analysis, Fracturas de Cadera, Enfermedad Iatrogénica, Hip surgery, Hip fracture, business.industry, Odds ratio, medicine.disease, Confidence interval, Surgery, Infectious Diseases, Trastornos Mentales, Parasitology, business, Research Article
Abstract

The association between mental disorders (MDs) and iatrogenic complications after hip fracture surgery has been poorly studied. Among iatrogenic complications, nosocomial infections (NIs) are a major factor in hip fracture surgery. The aim of this paper was to determine whether patients with a MD and a hip fracture develop more NIs after hip surgery than patients with no MD. We studied 912 patients who underwent surgery for a hip fracture (223 patients with a MD who underwent surgery for a hip fracture and 689 control patients without a MD who also underwent surgery for a hip fracture) and followed them after surgery. Univariable and multivariable analyses were performed using simple and multiple logistic regression analysis (confidence interval, crude and adjusted odds ratios, andPvalue). We found that MDs, gender, and comorbidities were not associated with a higher risk of developing a NI after surgery for a hip fracture. Only age increases the risk of a NI.

Published
2010

71. PGC-1β: A Regulator of Mitochondrial Function with Subtle Roles in Energy Metabolism

Author

Adrienn Kis, Mark Campbell, Mohammad Bohlooly-Y, Keira Curtis, Barbara Cannon, Matej Orešič, E. Dale Abel, Vlad G. Zaha, Gema Medina-Gomez, Sheldon E. Litwin, Mercedes Jimenez-Linan, Antonio Vidal-Puig, Sihem Boudina, Kimberly T Fountain, Leonard H Storlien, Miguel López, Margaret Blount, Ping Hu, Helena M. Feldmann, Christopher J. Lelliott, Mikael Bjursell, Natasa Petrovic, Dongfang Zhang, Nadeene Parker, Maria Strömstedt, Aline Meirhaeghe, Michael Snaith, Autard, Delphine, Department of Clinical Biochemistry, University of Cambridge [UK] (CAM), AstraZeneca, The Wenner-Gren Institute, Stockholm University, Division of Cardiology, University of Utah, Division of Endocrinology, Metabolism, and Diabetes, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Technical Research Centre of Finland, VTT Technical Research Centre of Finland (VTT), The work presented in this paper was supported by grants from the British Heart Foundation, Wellcome Trust Integrative Physiology, and Diabetes Wellness Research Foundation (to AVP lab), and NIH grants RO1HL73167 and UO1HL70525 from the National Institutes of Health and the Ben and Iris Margolis Foundation (to EDA - Established Investigator of the American Heart Association). Support was from the European Union (DLARFID), the Swedish Research Council, and the Swedish Cancer Society (to BC lab).

Subjects
Male, MESH: Cold Temperature, Adipose tissue, White adipose tissue, Mitochondrion, MESH: Mice, Knockout, Mitochondria, Heart, chemistry.chemical_compound, Mice, Norepinephrine, 0302 clinical medicine, Adipose Tissue, Brown, Heart Rate, Brown adipose tissue, Body Fat Distribution, Diabetes/Endocrinology/Metabolism, MESH: Thermogenesis, MESH: Animals, Biology (General), MESH: Heart Rate, Mice, Knockout, Mammals, 0303 health sciences, MESH: Muscle, Skeletal, General Neuroscience, MESH: Energy Metabolism, Heart, Thermogenesis, Mus (Mouse), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, MESH: Gene Expression Regulation, Mitochondria, Cold Temperature, medicine.anatomical_structure, Liver, MESH: Adipose Tissue, White, Synopsis, Female, MESH: Mitochondria, Heart, General Agricultural and Biological Sciences, Metabolic Networks and Pathways, Research Article, MESH: Electron Transport Chain Complex Proteins, medicine.medical_specialty, QH301-705.5, MESH: Mitochondria, MESH: Trans-Activators, Adipose Tissue, White, Biology, MESH: Diet, Atherogenic, MESH: Adipose Tissue, Brown, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Adrenergic Agents, Internal medicine, MESH: Norepinephrine, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, MESH: Body Fat Distribution, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Muscle, Skeletal, MESH: Mice, 030304 developmental biology, Soleus muscle, General Immunology and Microbiology, Triglyceride, Body Weight, medicine.disease, MESH: Adrenergic Agents, MESH: Male, MESH: Body Weight, MESH: Heart, Endocrinology, chemistry, Electron Transport Chain Complex Proteins, Gene Expression Regulation, MESH: Metabolic Networks and Pathways, Trans-Activators, Diet, Atherogenic, Steatosis, Energy Metabolism, MESH: Female, 030217 neurology & neurosurgery, Transcription Factors, MESH: Liver
Abstract

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1β (PGC-1β) has been implicated in important metabolic processes. A mouse lacking PGC-1β (PGC1βKO) was generated and phenotyped using physiological, molecular, and bioinformatic approaches. PGC1βKO mice are generally viable and metabolically healthy. Using systems biology, we identified a general defect in the expression of genes involved in mitochondrial function and, specifically, the electron transport chain. This defect correlated with reduced mitochondrial volume fraction in soleus muscle and heart, but not brown adipose tissue (BAT). Under ambient temperature conditions, PGC-1β ablation was partially compensated by up-regulation of PGC-1α in BAT and white adipose tissue (WAT) that lead to increased thermogenesis, reduced body weight, and reduced fat mass. Despite their decreased fat mass, PGC1βKO mice had hypertrophic adipocytes in WAT. The thermogenic role of PGC-1β was identified in thermoneutral and cold-adapted conditions by inadequate responses to norepinephrine injection. Furthermore, PGC1βKO hearts showed a blunted chronotropic response to dobutamine stimulation, and isolated soleus muscle fibres from PGC1βKO mice have impaired mitochondrial function. Lack of PGC-1β also impaired hepatic lipid metabolism in response to acute high fat dietary loads, resulting in hepatic steatosis and reduced lipoprotein-associated triglyceride and cholesterol content. Altogether, our data suggest that PGC-1β plays a general role in controlling basal mitochondrial function and also participates in tissue-specific adaptive responses during metabolic stress., The authors conduct an in-depth analysis of a PGC-1β knockout mouse; these animals posses specific defects in basal mitochondrial function and adaptation to metabolic stress.

Published
2006

72. Peroxisome proliferator-activated receptor-α activation as a mechanism of preventive neuroprotection induced by chronic fenofibrate treatment

Author

Olivier Pétrault, Bernard Dupuis, Isabelle Six, Régis Bordet, Patrick Gelé, Christophe Furman, Bart Staels, Dominique Deplanque, Roméo Cecchelli, Patrick Duriez, Muriel Bouly, Didier Leys, Jean-Charles Fruchart, Stéphane Nion, Université Lille 2 - Faculté de Médecine, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Récepteurs nucléaires, lipoprotéines et athérosclérose, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Réseau International des Instituts Pasteur (RIIP), Université d'Artois (UA), Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), P.G. was supported by a grant from 'Conseil Régional Nord Pas de Calais et Centre Hospitalier Régional et Universitaire de Lille. ' This work was supported by grants from ' Génopole Lille Nord-Pas de Calais '(#01360124) and Institut National de la Santé et de la Recherche Médicale (CReS4CR02F)., and We thank Alexandra Tavernier-Sommerville for her assistance with the English version of this paper.

Subjects
Middle Cerebral Artery, Mouse, Nitric Oxide Synthase Type II, Receptors, Cytoplasmic and Nuclear, Peroxisome proliferator-activated receptor, medicine.disease_cause, Rats, Inbred WKY, Mice, 0302 clinical medicine, Fenofibrate, Mice, Knockout, chemistry.chemical_classification, 0303 health sciences, biology, General Neuroscience, Infarction, Middle Cerebral Artery, Cerebral Infarction, Intercellular Adhesion Molecule-1, Neuroprotection, Vasodilation, Nitric oxide synthase, Stroke, Neuroprotective Agents, Cerebrovascular Circulation, Middle cerebral artery, medicine.symptom, medicine.drug, PPAR-α, medicine.medical_specialty, Adhesion proteins, Nitric Oxide Synthase Type III, Development/Plasticity/Repair, Ischemia, Vascular Cell Adhesion Molecule-1, Mice, Transgenic, Inflammation, Time, 03 medical and health sciences, Apolipoproteins E, medicine.artery, Internal medicine, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, business.industry, Prevention, medicine.disease, Rats, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, chemistry, Oxidative stress, biology.protein, Nitric Oxide Synthase, business, 030217 neurology & neurosurgery, Transcription Factors
Abstract

International audience; The treatment of ischemic strokes is limited to the prevention of cerebrovascular risk factors and to the modulation of the coagulation cascade during the acute phase. Anew therapeutic strategy could be to preventively protect the brain against noxious biological reactions induced by cerebral ischemia such as oxidative stress and inflammation to minimize their neurological consequences. Here, we show that a peroxisome proliferator-activated receptor (PPAR-α) activator, fenofibrate, protects against cerebral injury by anti-oxidant and antiinflammatory mechanisms. A 14 d preventive treatment with fenofibrate reduces susceptibility to stroke in apolipoprotein E-deficient mice as well as decreases cerebral infarct volume in C57BL/6 wild-type mice. The neuroprotective effect of fenofibrate is completely absent in PPAR-α-deficient mice, suggesting that PPAR-α activation is involved as a mechanism of the protection against cerebral injury. Furthermore, this neuroprotective effect appears independently of any improvement in plasma lipids or glycemia and is associated with (1) an improvement in middle cerebral artery sensitivity to endothelium-dependent relaxation unrelated to an increase in nitric oxide synthase (NOS) type III expression, (2) a decrease in cerebral oxidative stress depending on the increase in numerous antioxidant enzyme activities, and (3) the prevention of ischemia-induced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in cerebral vessels without any change in NOS II expression. These data demonstrate that PPAR-α could be a new pharmacological target to preventively reduce the deleterious neurological consequences of stroke in mice and suggest that PPAR-α activators could preventively decrease the severity of stroke in humans.

Published
2003

73. CCKA, but not CCKB, agonists suppress the hyperlocomotion induced by endogenous enkephalins, protected from enzymatic degradation by systemic RB 101

Author

Bernard P. Roques, Valérie Daugé, P. J. Corringer, Pharmacochimie moléculaire et structurale, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), We wish to thank Dr. A. Beaumont and Dr.J.Vierek for the stylistic revision of the paper, and C. Dupuis for her assistance in drafting it. We are grateful to S.Turcaud and P. Coric for the synthesis of RB 101., Cova Rodrigues, Ana, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Enkephalin, Narcotic Antagonists, [SDV]Life Sciences [q-bio], Clinical Biochemistry, RB-101, Devazepide, Inhibitor of enkephalin degradation, MESH: Amino Acid Sequence, Toxicology, Biochemistry, MESH: Benzodiazepinones, Behavioral Neuroscience, Mice, 0302 clinical medicine, Interactions between CCK and enkephalins, MESH: Enkephalins, MESH: Animals, Disulfides, Enzyme Inhibitors, MESH: Cholecystokinin, MESH: Peptide Fragments, MESH: Devazepide, 0303 health sciences, Benzodiazepinones, MESH: Receptors, Cholecystokinin, Chemistry, digestive, oral, and skin physiology, Enkephalins, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Naltrexone, CCKA and CCKB agonists, MESH: Motor Activity, [SDV] Life Sciences [q-bio], [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Enzyme Inhibitors, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Naltrexone, MESH: Narcotic Antagonists, Cholecystokinin, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Agonist, Locomotor activity, medicine.medical_specialty, medicine.drug_class, Phenylalanine, Molecular Sequence Data, Motor Activity, 03 medical and health sciences, MESH: Phenylalanine, Naltrindole, Internal medicine, medicine, Animals, MESH: Disulfides, Amino Acid Sequence, Opioid peptide, MESH: Mice, Biological Psychiatry, 030304 developmental biology, Pharmacology, MESH: Molecular Sequence Data, Antagonist, Peptide Fragments, MESH: Male, Endocrinology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Receptors, Cholecystokinin, Physiological agonism and antagonism, 030217 neurology & neurosurgery
Abstract

International audience; Interactions between CCKergic and enkephalinergic systems were studied in mice using behavioral responses measured in Animex. The hyperlocomotion induced by 5 mg/kg of RB 101, a mixed inhibitor of enkephalin-degrading enzymes able to cross the blood-brain barrier, was previously shown to be mediated by delta-opioid receptor stimulation. The IP administration of a CCKA agonist, Boc-Tyr-Lys-(CONH-o-tolyl)-Asp-Phe-NH2 (0.1, 1, 10 micrograms/kg), suppressed the hyperlocomotion produced by IV injection of 5 mg/kg of RB 101. The effect of the CCKA agonist was suppressed by a selective CCKA antagonist, devazepide, injected IP at doses of 20 and 200 micrograms/kg and was potentiated by the selective delta-opioid antagonist naltrindole at the doses of 0.03 mg/kg. IP injection of the selective CCKB agonist BC 264 (0.1-1 mg/kg) did not modify the RB 101-induced hyperlocomotor effect. These results reinforce the observed physiological antagonism between the endogenous CCK and opioid systems but are at variance with the responses measured in stressful conditions. It is concluded that CCKA, but not CCKB, receptor activation counteracts the opioid-related hyperlocomotion.

Published
1995

74. Which placebo to cure depression? A thought-provoking network meta-analysis

Author

Bruno Falissard, Florian Naudet, Jean Michel Reymann, Philippe Charlier, Bruno Millet, Anne Solène Maria, Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Service de Psychiatrie, Centre Hospitalier Guillaume Régnier, Troubles du comportement alimentaire de l'adolescent (UMR_S 669), Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Médecine légale, Anatomo-pathologie et Paléopathologie [CHU Raymond Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Laboratoire Ethique Politique et Santé (EA 4569), Université Paris Descartes - Paris 5 (UPD5), Unité de Méthodologie des Essais Thérapeutiques, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Laboratoire de Pharmacologie Expérimentale et Clinique, Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR)-Université de Rennes (UR)-Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR), Service de Santé Publique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, This paper was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM)., Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Laboratoire de Pharmacologie Expérimentale et Clinique, Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Comportement et noyaux gris centraux [Rennes], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université européenne de Bretagne ( UEB ) -CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Troubles du comportement alimentaire de l'adolescent ( UMR_S 669 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ), Médecine légale, Anatomo-pathologie et Paléopathologie, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP Hôpital Raymond Poincaré [Garches], Laboratoire Ethique Politique et Santé ( EA 4569 ), Université Paris Descartes - Paris 5 ( UPD5 ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Laboratoire de Pharmacologie Expérimentale et Clinique, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse, Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Université de Rennes (UR)-Université de Rennes (UR)-Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), and BMC, Ed.

Subjects
medicine.medical_specialty, Psychotherapist, Alternative medicine, Major depressive disorder, Placebo, Publication bias, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, 030212 general & internal medicine, Psychiatry, Depression (differential diagnoses), Medicine(all), Fluoxetine, business.industry, Rank (computer programming), General Medicine, Antidepressants, medicine.disease, 3. Good health, Meta-analysis, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], business, 030217 neurology & neurosurgery, Research Article, medicine.drug
Abstract

International audience; BACKGROUND: Antidepressants are often considered to be mere placebos despite the fact that meta-analyses are able to rank them. It follows that it should also be possible to rank different placebos, which are all made of sucrose. To explore this issue, which is rather more epistemological than clinical, we designed an unusual meta-analysis to investigate whether the effects of placebo in one situation are different from the effects of placebo in another situation. METHODS: Published and unpublished studies were searched for by three reviewers on Medline, the Cochrane Library, Embase, clinicaltrials.gov, Current Controlled Trial, in bibliographies, and by mailing key organizations. The following studies in first-line treatment for major depressive disorder were considered to construct an "evidence network": 1) randomized controlled trials (RCTs) versus placebo on fluoxetine, venlafaxine and 2) fluoxetine versus venlafaxine head-to-head RCTs.Two network meta-analyses were run to indirectly compare response and remission rates among three different placebos: 1) fluoxetine placebo, 2) venlafaxine placebo, and 3) venlafaxine/fluoxetine placebo (that is, placebo compared to both venlafaxine and fluoxetine). Publication biases were assessed using funnel plots and statistically tested. RESULTS: The three placebos were not significantly different in terms of response or remission. The antidepressant agents were significantly more efficacious than the placebos, and venlafaxine was more efficacious than fluoxetine. The funnel plots, however, showed a major publication bias. CONCLUSION: The presence of significant levels of publication bias indicates that we cannot even be certain of the conclusion that sucrose equals sucrose in trials of major depressive disorder. This result should remind clinicians to step back to take a more objective view when interpreting a scientific result. It is of crucial importance for their practice, far more so than ranking antidepressant efficacy.

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75. Influence of multiple APOE genetic variants on cognitive function in a cohort of older men – results from the Normative Aging Study

Author

David G. Cox, Jia Zhong, Marc G. Weisskopf, Elena Colicino, Marco Sanchez-Guerra, Joel Schwartz, Diddier Prada, Andrea A. Baccarelli, Lifang Hou, Melinda C. Power, Avron Spiro, Luis A. Herrera, Pantel S. Vokonas, Department of Environmental Health, Harvard School of Public Health, Unidad de Investigación Biomédica en Cáncer, Universidad Nacional Autónoma de México (UNAM)-Instituto Nacional de Cancerología – Instituto de Investigaciones Biomédicas, Department of Biomedical Informatics, Universidad Nacional Autónoma de México (UNAM), Department of Epidemiology, Department of Epidemiology [Baltimore], Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Department of Veterans Affairs, VA Boston Healthcare System, DP is financially supported by Consejo Nacional de Ciencia y Tecnología(CONACYT) and the Fundación México en Harvard from the program'Postdoctoral Fellowships in the Sciences at Harvard University: Mexico'.Thepresent work has been supported by a grant from the National Institute ofEnvironmental Health Sciences (NIEHS) (R01ES021733).MP is supported by a grant from the National Institute of Aging (NIA) (T32AG027668). AS was supported by a Senior Research Career Scientist award fromthe Clinical Science Research and Development Service for the US Departmentof Veterans Affairs. The US Department of Veterans Affairs (VA) Normative AgingStudy (NAS) is supported by the Cooperative Studies Program/ERIC, USDepartment of Veterans Affairs, and is a research component of theMassachusetts Veterans Epidemiology Research and Information Center(MAVERIC). Additional support to the VA Normative Aging Study was providedby the US Department of Agriculture, Agricultural Research Service (contract53-K06-510). The views expressed in this paper are those of the authors and donot necessarily represent the views of the US Department of Veterans Affairs., Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM)-Instituto Nacional de Cancerología – Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Taibi, Nadia

Subjects
Oncology, Apolipoprotein E, Gerontology, Adult, Male, medicine.medical_specialty, Aging, Genetic variants, Genotype, Cognitive decline, Neuropsychological Tests, Odds, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Apolipoproteins E, Cognition, Polymorphism (computer science), Internal medicine, medicine, Humans, MESH: APOE, Epsilon, Alleles, Haplotypes, Genotyping, 030304 developmental biology, Aged, Aged, 80 and over, 0303 health sciences, Polymorphism, Genetic, Haplotype, Middle Aged, Psychiatry and Mental health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Psychology, Cognition Disorders, 030217 neurology & neurosurgery, APOE, Research Article
Abstract

Background APOE is the biomarker with the greatest known influence on cognitive function; however, the effect of complex haplotypes involving polymorphisms rs449647, rs405509, rs440446, rs429358 and rs7412 has never been studied in older populations. Methods We evaluated APOE polymorphisms using multiplex PCR for genotyping and Mini-Mental State Examination (MMSE) to evaluate cognitive function in 819 individuals from VA Normative Aging Study. Results Combinatorial analysis of all polymorphisms and individual analysis of polymorphisms rs449647, rs405509, rs440446 and rs7412 did not show any association with cognitive performance. Polymorphism rs429358 was associated with better cognitive performance (odds of MMSE ≤ 25 = 0.63, 95% CI 0.42-0.95; p = 0.03) in the oldest subsample (5th quintile of age) (odds of MMSE ≤ 25 = 0.34; 95% CI 0.13-0.86; p = 0.02). APOE allele ε4 was also associated with better cognitive performance (odds of MMSE ≤ 25 = 0.61, 95% CI 0.40-0.94; p = 0.02), also in the oldest subsample (odds of MMSE ≤ 25 = 0.35, 95% CI 0.14-0.90; p = 0.03). Conclusions These results suggest a beneficial effect of polymorphism rs429358 in the oldest men. Electronic supplementary material The online version of this article (doi:10.1186/s12888-014-0223-x) contains supplementary material, which is available to authorized users.

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