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4,224 results on '"Clinical Epidemiology Unit"'

1. Cryotherapy for Human Papillomavirus Clearance in Biopsy-confirmed Cervical Low-grade Squamous Intraepithelial Lesions (Cryotherapy)

Author: Clinical Epidemiology Unit (CEU)
Published: 2010

2. Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights

Author: Josep Ramon Marsal, Iratxe Urreta-Barallobre, Marimar Ubeda-Carrillo, Dimelza Osorio, Blanca Lumbreras, David Lora, Borja M. Fernández-Felix, Gerard Oristrell, Eduard Ródenas-Alesina, Lorena Herrador, Mónica Ballesteros, Javier Zamora, Jose I. Pijoan, Aida Ribera, Ignacio Ferreira-González, Institut Català de la Salut, [Marsal JR, Ribera A, Ferreira-González I] Grup de Recerca de Malalties Cardiovasculars, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBER Epidemiology and Public Health, Madrid, Spain. [Urreta-Barallobre I] CIBER Epidemiology and Public Health, Madrid, Spain. Biodonostia Health Research Institute, Clinical Epidemiology, San Sebastián, Spain. Osakidetza Basque Health Service, Donostialdea Integrated Health Organisation, Donostia University Hospital, Clinical Epidemiology Unit, San Sebastián, Spain. [Ubeda-Carrillo M] Osakidetza Basque Health Service, Donostialdea Integrated Health Organisation, Donostia University Hospital, Library Service, San Sebastián, Spain. [Osorio D, Ballesteros M] CIBER Epidemiology and Public Health, Madrid, Spain. Grup de Recerca d’Epidemiologia i Salut Pública, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Lumbreras B] CIBER Epidemiology and Public Health, Madrid, Spain. Public Health Department, Miguel Hernandez University, Alicante, Spain. [Lora D] CIBER Epidemiology and Public Health, Madrid, Spain. Health Research Institute Hospital 12 de Octubre (imas12), Madrid, Spain. Statistical Studies Department, Universidad Complutense de Madrid (UCM), Madrid, Spain. [Oristrell G] Servei de Cardiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. CIBER Cadiovascular Diseases, Madrid, Spain. [Ródenas-Alesina E] Servei de Cardiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Infart de miocardi - Diagnòstic, Sample Size, Myocardial Infarction, técnicas de investigación::métodos epidemiológicos::diseño de la investigación epidemiológica::tamaño de la muestra [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Humans, Medicine (miscellaneous), Pharmacology (medical), Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Sample Size [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Cardiovascular System, enfermedades cardiovasculares::enfermedades cardíacas::isquemia miocárdica::infarto de miocardio [ENFERMEDADES], Cardiovascular Diseases::Heart Diseases::Myocardial Ischemia::Myocardial Infarction [DISEASES]
Abstract: Background The real impact of the degree of association (DoA) between endpoint components of a composite endpoint (CE) on sample size requirement (SSR) has not been explored. We estimate the impact of the DoA between death and acute myocardial infarction (AMI) on SSR of trials using use the CE of major adverse cardiac events (MACE). Methods A systematic review and quantitative synthesis of trials that include MACE as the primary outcome through search strategies in MEDLINE and EMBASE electronic databases. We limited to articles published in journals indexed in the first quartile of the Cardiac & Cardiovascular Systems category (Journal Citation Reports, 2015–2020). The authors were contacted to estimate the DoA between death and AMI using joint probability and correlation. We analyzed the SSR variation using the DoA estimated from RCTs. Results Sixty-three of 134 publications that reported event rates and the therapy effect in all component endpoints were included in the quantitative synthesis. The most frequent combination was death, AMI, and revascularization (n = 20; 31.8%). The correlation between death and AMI, estimated from 5 trials¸ oscillated between − 0.02 and 0.31. SSR varied from 14,602 in the scenario with the strongest correlation to 12,259 in the scenario with the weakest correlation; the relative impact was 16%. Conclusions The DoA between death and AMI is highly variable and may lead to a considerable SSR variation in a trial including MACE.
Published: 2022

3. Germline TP53 pathogenic variants and breast cancer: A narrative review

Author: Eva Blondeaux, Luca Arecco, Kevin Punie, Rossella Graffeo, Angela Toss, Carmine De Angelis, Lucia Trevisan, Giulia Buzzatti, Sabine C. Linn, Peter Dubsky, Mara Cruellas, Ann H. Partridge, Judith Balmaña, Shani Paluch-Shimon, Matteo Lambertini, Institut Català de la Salut, [Blondeaux E] Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. [Arecco L] Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genoa, Italy. Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. [Punie K] Department of General Medical Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. [Graffeo R] Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland. [Toss A] Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy. [De Angelis C] Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy. [Balmaña J] Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Otros calificadores::Otros calificadores::/genética [Otros calificadores], Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES], General Medicine, Cromosomes humans - Anomalies - Diagnòstic, diagnóstico::técnicas y procedimientos diagnósticos::técnicas de laboratorio clínico::pruebas genéticas [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Genetic Testing [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Oncology, Mama - Càncer - Tractament, Other subheadings::Other subheadings::/genetics [Other subheadings], Mama - Càncer - Aspectes genètics, Radiology, Nuclear Medicine and imaging, fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS]
Abstract: Breast cancer; Prognosis; Treatment Cáncer de mama; Pronóstico; Tratamiento Càncer de mama; Pronòstic; Tractament Approximately 10% of breast cancers are associated with the inheritance of a pathogenic variant (PV) in one of the breast cancer susceptibility genes. Multiple breast cancer predisposing genes, including TP53, are responsible for the increased breast cancer risk. Tumor protein-53 (TP53) germline PVs are associated with Li-Fraumeni syndrome, a rare autosomal dominant inherited cancer predisposition syndrome associated with early-onset pediatric and multiple primary cancers such as soft tissue and bone sarcomas, breast cancer, brain tumors, adrenocortical carcinomas and leukemias. Women harboring a TP53 PV carry a lifetime risk of developing breast cancer of 80–90%. The aim of the present narrative review is to provide a comprehensive overview of the criteria for offering TP53 testing, prevalence of TP53 carriers among patients with breast cancer, and what is known about its prognostic and therapeutic implications. A summary of the current indications of secondary cancer surveillance and survivorship issues are also provided. Finally, the spectrum of TP53 alteration and testing is discussed. The optimal strategies for the treatment of breast cancer in patients harboring TP53 PVs poses certain challenges. Current guidelines favor the option of performing mastectomy rather than lumpectomy to avoid adjuvant radiotherapy and subsequent risk of radiation-induced second primary malignancies, with careful consideration of radiation when indicated post-mastectomy. Some studies suggest that patients with breast cancer and germline TP53 PV might have worse survival outcomes compared to patients with breast cancer and wild type germline TP53 status. Annual breast magnetic resonance imaging (MRI) and whole-body MRI are recommended as secondary prevention. The project was partially funded by a Gilead Sciences Medical Grant (Fellowship Program 2022) (no grant number).
Published: 2023

4. Reliability, Validity, and Feasibility of the Frail-VIG Index

Author: Sebastià Santaeugènia, Edurne Zabaleta-del-Olmo, Jordi Amblàs-Novellas, Juan José Zamora-Sánchez, Anna Torné, Emma Puigoriol, [Torné A] Central Catalonia Chronicity Research Group (C3RG), Centre for Health and Social Care Research (CESS), Faculty of Medicine, University of Vic-Central University of Catalonia (UVIC-UCC), Barcelona, Spain. Departament de geriatria i cures pal·liatives, Hospital Universitari de la Santa Creu Barcelona, Spain. Departament de geriatria i cures pal·liatives, Hospital Universitari de Vic, Barcelona, Spain. [Puigoriol E] Clinical Epidemiology Unit, Consorci Hospitalari de Vic, Barcelona, Spain. Tissue Repair and Regeneration Laboratory (TR2Lab), Faculty of Sciences and Technology, Faculty of Medicine, University of Vic-Central University of Catalonia, Barcelona, Spain. [Zabaleta-del-Olmo E] Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. Gerència Territorial de Barcelona, Institut Català de la Salut (ICS), Barcelona, Spain. Nursing Department, Faculty of Nursing, Universitat de Girona, Girona, Spain. [Zamora-Sánchez J-J] Gerència Territorial de Barcelona, Institut Català de la Salut (ICS), Barcelona, Spain. [Santaeugènia-Gonzàlez SJ] Central Catalonia Chronicity Research Group (C3RG), Centre for Health and Social Care Research (CESS), Faculty of Medicine, University of Vic-Central University of Catalonia (UVIC-UCC), Barcelona, Spain. Programa de cures cròniques, Departament de Salut, Generalitat de Catalunya, Barcelona, Spain. [Amblàs-Novellas J] Central Catalonia Chronicity Research Group (C3RG), Centre for Health and Social Care Research (CESS), Faculty of Medicine, University of Vic-Central University of Catalonia (UVIC-UCC), Barcelona, Spain. Geriatric and Palliative Care Department, Hospital Universitari de la Santa Creu Barcelona, Spain. Geriatric and Palliative Care Department, Hospital Universitari de Vic, Barcelona, Spain. Programa de cures cròniques, Departament de Salut, Generalitat de Catalunya, Barcelona, Spain, and IDIAP Jordi Gol
Subjects: Male, psychometrics, validity, Index (economics), Psychometrics, Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires::Health Surveys::Health Status Indicators [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Intraclass correlation, Health, Toxicology and Mutagenesis, técnicas de investigación::métodos epidemiológicos::recopilación de datos::encuestas y cuestionarios::encuestas de salud::indicadores de salud [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Feasibility studies, 0302 clinical medicine, Diagnòstic, Indicadors de salut, Other subheadings::/diagnosis [Other subheadings], 030212 general & internal medicine, Reliability (statistics), Frailty, Medicina basada en l'evidència, afecciones patológicas, signos y síntomas::procesos patológicos::fragilidad [ENFERMEDADES], Convergent validity, Scale (social sciences), Medicine, Female, Psicometria, medicine.medical_specialty, Evidence-based medicine, Frail Elderly, Otros calificadores::/diagnóstico [Otros calificadores], Article, 03 medical and health sciences, Estudis de viabilitat, Pathological Conditions, Signs and Symptoms::Pathologic Processes::Frailty [DISEASES], medicine, Humans, Geriatric Assessment, Aged, reliability, Receiver operating characteristic, frailty index, business.industry, Persones grans dependents, Public Health, Environmental and Occupational Health, Construct validity, Reproducibility of Results, Physical therapy, Feasibility Studies, business, human activities, 030217 neurology & neurosurgery, feasibility
Abstract: Frailty; Psychometrics; Feasibility Fragilitat; Psicometria; Viabilitat Fragilidad; Psicometría; Viabilidad The study aimed to assess the reliability of the scores, evidence of validity, and feasibility of the Frail-VIG index. A validation study mixing hospitalized and community-dwelling older people was designed. Intraclass correlation coefficient (ICC) was used to assess the inter-rater agreement and the reliability. The construct validity of the Frail-VIG index with respect to the Frailty Phenotype (FP) was evaluated by calculating the area under the receiver operating characteristic curve (AUC-ROC). Convergent validity with the Clinical Frailty Scale (CFS) was assessed using Pearson’s correlation coefficients. The feasibility was evaluated by calculating the average time required to administer the Frail-VIG index and the percentage of unanswered responses. A sample of 527 older people (mean age of 81.61, 56.2% female) was included. The inter-rater agreement and test–retest reliability were very strong: 0.941 (95% CI, 0.890 to 0.969) and 0.976 (95% CI, 0.958 to 0.986), respectively. Results indicated adequate convergent validity of the Frail-VIG index with respect to the FP, AUC-ROC 0.704 (95% CI, 0.622 to 0.786), and a moderate to strong positive correlation between the Frail-VIG index and CFS (r = 0.635, 95% CI, 0.54 to 0.71). The Frail-VIG index administration required an average of 5.01 min, with only 0.34% of unanswered responses. The Frail-VIG index is a reliable, feasible, and valid instrument to assess the degree of frailty in hospitalized and community-dwelling older people.
Published: 2021

5. Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants

Author: Alberta Ferrari, Lucia Del Mastro, Fabio Puglisi, Kevin Punie, Luis Augusto Teixeira, Albert Grinshpun, Riccardo Ponzone, François Duhoux, Jose Alejandro Perez-Fidalgo, Matteo Lambertini, Marcello Ceppi, Arlindo R. Ferreira, Maria Del Pilar Estevez-Diz, Estela Carrasco, Philip D. Poorvu, Christine Rousset-Jablonski, Marie Daphne t’Kint de Roodenbeke, Fedro A. Peccatori, Antonio Di Meglio, Judith Balmaña, Marco Bruzzone, Maria Vittoria Dieci, Anne-Sophie Hamy, Laura De Marchis, Cynthia Villarreal-Garza, Katarzyna Pogoda, Claire Saule, Octavi Cordoba, Rossella Graffeo, Luca Livraghi, Ann H. Partridge, Hatem A. Azim, Lieveke Ameye, Shani Paluch-Shimon, Claire Senechal, Florian Clatot, Olivier Caron, Amir Sonnenblick, Angela Toss, Institut Català de la Salut, [Lambertini M] Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genova, Italy. Department of Medical Oncology, U.O.C, Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy. [Ceppi M] Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy. [Hamy AS] Department of Medical Oncology, Institut Curie, Paris, France. [Caron O] Department of Medical Oncology, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France. [Poorvu PD] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. [Carrasco E, Balmaña J] Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Barcelona Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, and UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], personas::mujeres [DENOMINACIONES DE GRUPOS], Disease, Germline, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, medicine, Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, Neoplasm::Genes, Tumor Suppressor [PHENOMENA AND PROCESSES], Pharmacology (medical), Radiology, Nuclear Medicine and imaging, In patient, Dones joves, Stage (cooking), Cancer genetics, RC254-282, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Science & Technology, fenómenos genéticos::estructuras genéticas::genoma::componentes genómicos::genes::genes de neoplasias::genes supresores de tumores [FENÓMENOS Y PROCESOS], business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Retrospective cohort study, Second primary cancer, medicine.disease, 030104 developmental biology, Persons::Women [NAMED GROUPS], Hormone receptor, 030220 oncology & carcinogenesis, Mama - Càncer - Aspectes genètics, business, BRCA, breast cancer, outcomes, Life Sciences & Biomedicine
Abstract: Càncer de mama; Genètica del càncer Cáncer de mama; Genética del cáncer Breast cancer; Cancer genetics Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR−]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I–III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P
Published: 2021

6. Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer

Author: Olivier Caron, A. Di Meglio, Katarzyna Pogoda, Albert Grinshpun, Jose Alejandro Perez-Fidalgo, Margherita Condorelli, M. Venturelli, Matteo Lambertini, Lieveke Ameye, C. Rousset-Jablonski, Arlindo R. Ferreira, Amir Sonnenblick, E. de Azambuja, Estela Carrasco, Cynthia Villarreal-Garza, T. Peretz-Yablonski, Judith Balmaña, Riccardo Ponzone, Isabelle Demeestere, François Duhoux, Fedro A. Peccatori, Marco Bruzzone, L. Teixeira, Alberta Ferrari, Octavi Cordoba, Fabio Puglisi, Claire Senechal, Philip D. Poorvu, Eva Blondeaux, Marcello Ceppi, Hatem A. Azim, Claire Saule, Kevin Punie, Rossella Graffeo, Luca Livraghi, L. De Marchis, Maria Vittoria Dieci, S. Paluch-Shimon, A.H. Partridge, Florian Clatot, Anne-Sophie Hamy, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Institut Català de la Salut, [Condorelli M] Department of Obstetrics and Gynecology, Hôpital Erasme, Université Libre de Bruxelles (U.L.B.), Fertility Clinic, Brussels. Research Laboratory on Human Reproduction, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. [Bruzzone M, Ceppi M] Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genova. [Ferrari A] Department of Surgical Sciences, General Surgery III-Breast Surgery, Fondazione IRCCS Policlinico San Matteo, Pavia. Department of Clinical Surgical Sciences, University of Pavia, Pavia, Italy. [Grinshpun A] Breast Oncology Unit Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. [Hamy AS] Department of Medical Oncology, Institut Curie, Paris, France. [Carrasco E, Balmaña J] Hereditary Cancer Genetics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Adult, Cancer Research, medicine.medical_specialty, ART, BRCA, breast cancer, fertility, pregnancy, survival, Reproductive Techniques, Assisted, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], medicine.medical_treatment, Breast Neoplasms, Otros calificadores::Otros calificadores::/efectos adversos [Otros calificadores], Intracytoplasmic sperm injection, Breast cancer, Pregnancy, Internal medicine, Other subheadings::Other subheadings::/adverse effects [Other subheadings], medicine, Humans, Original Research, Retrospective Studies, Genetic testing, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], medicine.diagnostic_test, BRCA1 Protein, business.industry, Cancer, Retrospective cohort study, medicine.disease, Embryo transfer, Reproducció humana assistida, Investigative Techniques::Reproductive Techniques::Reproductive Techniques, Assisted [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Germ Cells, Oncology, Mama - Càncer - Aspectes genètics, Female, Ovulation induction, Neoplasm Recurrence, Local, business, técnicas de investigación::técnicas reproductivas::técnicas reproductivas asistidas [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS]
Abstract: Background Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants. Patients and methods This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy. Results Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group. Conclusion This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing., Highlights • No data exist on safety of assisted reproductive techniques (ART) in BRCA-mutated breast cancer patients. • This study investigated outcomes of patients with a post-treatment pregnancy achieved through ART use or naturally. • 2 (9.1%) and 40 (27.4%) patients in the ART and non-ART groups experienced a disease-free survival event. • This study provides encouraging safety data on ART use in BRCA-mutated breast cancer survivors. • ART is feasible when natural conception fails or when survivors opt for carrying out preimplantation genetic testing.
Published: 2021

7. Specialist health care services use in a European cohort of infants born very preterm

Author: Jennifer Zeitlin, Marina Cuttini, Pernille Pedersen, Eva Cloet, Elaine M. Boyle, Janusz Gadzinowski, Anna-Veera Seppänen, Corine Koopman-Esseboom, Henrique Barros, Florence Bodeau-Livinec, Liis Toome, Anna-Karin Edstedt-Bonamy, Rolf F. Maier, Public Health Sciences, Faculty of Medicine and Pharmacy, Pediatrics, Sorbonne Université (SU), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), École des Hautes Études en Santé Publique [EHESP] (EHESP), DHU Risques Et Grossesse, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Department of Health Sciences [Leicester, UK], University of Leicester, Department of Medicine [Stockholm, Sweden] (Clinical Epidemiology Unit ), Karolinska Institutet [Stockholm], Women's and Children's Health [Stockholm, Sweden], Clinical Care and Management Innovation Research Area [Rome, Italy], Children's Hospital Bambino Gesù IRCCS [Rome], Tallinn Children's Hospital [Tallinn, Estonia], University of Tartu, Children's Hospital [Marburg, Germany] (University Hospital), Philipps University Marburg [Germany], Public Health [Brussels, Belgium], Vrije Universiteit [Brussels] (VUB), Paediatric Neurology [Brussels, Belgium], Universitair Ziekenhuis [Brussels, Belgium], Department of Neonatology [Utrecht, the Netherlands] (Wilhelmina Children's Hospital), University Medical Center [Utrecht], Department of Neonatology [Hvidovre, Denmark], Hvidovre Hospital, Department of Neonatology [Poznań, Poland], Poznan University of Medical Sciences [Poznan, Poland], ISPUP-EPIUnit, University of Porto Medical School and Institute of Public Health, ISPUP-EPIUnit [Porto, Portugal], Universidade do Porto [Porto], The research received funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement No 259882 and received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 633724. Additional funding is acknowledged from the following regions: France (French Institute of Public Health Research/Institute of Public Health and its partners the French Health Ministry, the National Institute of Health and Medical Research, the National Institute of Cancer, and the National Solidarity Fund for Autonomy, grant ANR-11-EQPX-0038 from the National Research Agency through the French Equipex Program of Investments in the Future, and the PremUp Foundation), Poland (2012- 2015 allocation of funds for international projects from the Polish Ministry of Science and Higher Education), Sweden (Stockholm County Council [ALF-project and Clinical Research Appointment] and by the Department of Neonatal Medicine, Karolinska University Hospital), UK (funding for The Neonatal Survey from Neonatal Networks for East Midlands and Yorkshire and the Humber regions). Anna-Veera Seppänen has a doctoral contract funded by Sorbonne Université, Collège Doctoral, Paris, France., Effective Perinatal Intensive Care in Europe (EPICE) research group : BELGIUM: Flanders (E Martens, G Martens, P Van Reempts), DENMARK: Eastern Region (K Boerch, A Hasselager, L Huusom, O Pryds, T Weber), ESTONIA (L Toome, H Varendi), FRANCE: Burgundy, Ile-de France and Northern Region (PY Ancel, B Blondel, A Burguet, PH Jarreau, P Truffert), GERMANY: Hesse (RF Maier, B Misselwitz, S Schmidt), Saarland (L Gortner), ITALY: Emilia Romagna (D Baronciani, G Gargano), Lazio (R Agostino, D DiLallo, F Franco), Marche (V Carnielli), M Cuttini, NETHERLANDS: Eastern & Central (C Koopman-Esseboom, A Van Heijst, J Nijman), POLAND: Wielkopolska (J Gadzinowski, J Mazela), PORTUGAL: Lisbon and Tagus Valley (LM Graça, MC Machado), Northern region (C Rodrigues, T Rodrigues), H Barros, SWEDEN: Stockholm (AK Bonamy, M Norman, E Wilson), UK: East Midlands and Yorkshire and Humber (E Boyle, ES Draper, BN Manktelow), Northern Region (AC Fenton, DWA Milligan), INSERM, Paris (J Zeitlin, M Bonet, A Piedvache)., ANR-11-EQPX-0038/11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011), European Project: 259882,EC:FP7:HEALTH,FP7-HEALTH-2010-two-stage,EPICE(2011), European Project: 633724,H2020,H2020-PHC-2014-two-stage,SHIPS(2015), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vrije Universiteit Brussel (VUB), Universidade do Porto, ANR-11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011), Seppanen, Anna-Veera, Equipements d'excellence - Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance - - RE-CO-NAI2011 - ANR-11-EQPX-0038 - EQPX - VALID, Effective Perinatal Intensive Care in Europe: translating knowledge into evidence based practice - EPICE - - EC:FP7:HEALTH2011-01-01 - 2015-12-31 - 259882 - VALID, Screening to improve Health In very Preterm infantS in Europe - SHIPS - - H20202015-09-01 - 2018-08-31 - 633724 - VALID, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Philipps Universität Marburg = Philipps University of Marburg, Universidade do Porto = University of Porto, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-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, 030506 rehabilitation, medicine.medical_specialty, Population, Clinical Neurology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Developmental Neuroscience, Risk Factors, Intensive care, Health care, medicine, Humans, Pediatrics, Perinatology, and Child Health, Geography, Medical, education, education.field_of_study, business.industry, Medical record, Infant, Newborn, Infant, Low Birth Weight, Patient Acceptance of Health Care, medicine.disease, 3. Good health, Europe, Low birth weight, Socioeconomic Factors, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Child, Preschool, Infant, Extremely Premature, Family medicine, Infant, Small for Gestational Age, Pediatrics, Perinatology and Child Health, Cohort, Small for gestational age, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), medicine.symptom, 0305 other medical science, business, 030217 neurology & neurosurgery, Specialization, Cohort study
Abstract: Children born very preterm require additional specialist care because of the health and developmental risks associated with preterm birth, but information on their health service use is sparse. We sought to describe the use of specialist services by children born very preterm in Europe.We analysed data from the multi-regional, population-based Effective Perinatal Intensive Care in Europe (EPICE) cohort of births before 32 weeks' gestation in 11 European countries. Perinatal data were abstracted from medical records and parents completed a questionnaire at 2 years corrected age (4322 children; 2026 females, 2296 males; median gestational age 29wks, interquartile range [IQR] 27-31wks; median birthweight 1230g, IQR 970-1511g). We compared parent-reported use of specialist services by country, perinatal risk (based on gestational age, small for gestational age, and neonatal morbidities), maternal education, and birthplace.Seventy-six per cent of the children had consulted at least one specialist, ranging across countries from 53.7% to 100%. Ophthalmologists (53.4%) and physiotherapists (48.0%) were most frequently consulted, but individual specialists varied greatly by country. Perinatal risk was associated with specialist use, but the gradient differed across countries. Children with more educated mothers had higher proportions of specialist use in three countries.Large variations in the use of specialist services across Europe were not explained by perinatal risk and raise questions about the strengths and limits of existing models of care.Use of specialist services by children born very preterm varied across Europe. This variation was observed for types and number of specialists consulted. Perinatal risk was associated with specialist care, but did not explain country-level differences. In some countries, mothers' educational level affected use of specialist services.UTILIZACIÓN DE SERVICIOS DE SALUD ESPECIALIZADOS EN UN ESTUDIO DE COHORTE EUROPEO DE NIÑOS NACIDOS MUY PREMATUROS: OBJETIVO: Niños nacidos muy prematuramente requieren cuidados especializados adicionales debido a su salud y a los riesgos asociados con la prematuros, sin embargo la información sobre el uso de servicios de salud es escasa. Buscamos describir la utilización de servicios especializados por niños nacidos muy prematuramente, en Europa. MÉTODO: Analizamos datos de una cohorte de nacimientos ocurridos antes de las 32 semanas de gestación tomados del Effective Perinatal Intensive Care in Europe (EPICE), basado en la población y multirregional, en 11 países europeos. Los datos perinatales fueron extraídos de las historias clínicas y los padres completaron un cuestionario a los 2 años de edad corregida (4.322 niños; 2026 sexo femenino, 2.296 masculino; edad gestacional mediana 29 semanas, rango intercuartílico (IQR) 27-31 semanas; mediana de peso de nacimiento 1.230 gr, IQR 970-1.511 gr). Comparamos el uso de servicios especializados (según informe de los padres) por país, riesgo perinatal (basado en edad gestacional, bajo peso para edad gestacional y morbilidades neonatales), educación materna y lugar de nacimiento. RESULTADOS: En total 65% de los niños habían consultado por lo menos a un especialista, con un rango entre países de 53,7% a 100%. Los especialistas más frecuentemente consultados fueron Oftalmólogos (53,4%) y Fisioterapeutas (48%) pero los especialistas consultados por cada individuo variaron mucho según el país. El riesgo perinatal se asoció al uso de especialista, pero el gradiente varió entre los países. Niños de madres con mayor nivel educativo tuvieron mayor proporción de uso de especialistas en tres países. INTERPRETACIÓN: Las grandes variaciones en el uso de servicios especializados en Europa no fueron explicadas por el riesgo perinatal y arrojan cuestionamientos sobre las fortalezas y limitaciones de los modelos de cuidados existentes.USO DE SERVIÇOS DE SAÚDE ESPECIALIZADOS EM UMA COORTE EUROPÉIA DE LACTENTES NASCIDOS MUITO PREMATUROS: OBJETIVO: Crianças nascidas muito prematuras requerem cuidado especializado adicional por causa dos riscos à saúde e ao desenvolvimento associados ao nascimento premature, mas informações sobreo uso de serviços de saúde são escassas. Procuramos descrever o uso de serviços especializados por crianças nascidas muito prematuras na Europa. MÉTODO: Analisamos dados de uma coorte populacional multi-regional, do Cuidado Intensivo Neonatal Efetivo na Europa (EPICE), com lactentes nascidos antes de 32 semanas de gestação em 11 países europeus. Dados perinatais foram extraídos dos registros médicos, e os pais completaram um questionário com 2 anos de idade corrigida (4.322 crianças; 2.026 do sexo feminino, 2.296 do sexo masculino; idade gestacional mediana 29semanas, intervalo interquartile [IIQ] 27-31sem; peso ao nascimento mediano 1,230g, IIQ 970-1511g). Comparamos o uso de serviços especializados reportados pelos pais por país, risco perinatal (com base na idade gestacional, pequeno para a idade gestacional e morbidades neonatais), educação materna e local de nascimento. RESULTADOS: Setenta e seis por cento das crianças consultou pelo menos um especialista, variando entre países de 53,7 a 100%. Oftalmologistas (53,4%) e fisioterapeutas (48,0%) foram os mais frequentemente consultados, mas os especialistas individuais variaram bastante por país. O risco perinatal se associou com uso de serviços especializados, mas o gradient diferiu entre países. Crianças com mães mais educadas tinham maior proporção de uso de especialistas em três países. INTERPRETAÇÃO: Grandes variações no uso de serviços especializados na Europa não foram explicadas pelo risco perinatal, e levantam questões sobre as forças e limitações dos modelos de cuidado existentes.
Published: 2019

8. Apixaban to Prevent Venous Thromboembolism in Patients with Cancer

Author: Vicky Tagalakis, Mateya Trinkaus, Ranjeeta Mallick, Grégoire Le Gal, Alejandro Lazo-Langner, Ariah Schattner, Philip Kuruvilla, Katerine Marquis, Karim Abou-Nassar, David J. Stewart, Marc Carrier, Debra Witham, Silvana Spadafora, Philip S. Wells, Agnes Y.Y. Lee, Glenwood D. Goss, Sudeep Shivakumar, Avert Investigators, Peter L. Gross, Marc A. Rodger, Danny Hill, Robert El-Maraghi, Anna Tomiak, Tim Ramsay, Thrombosis Program, University of Ottawa [Ottawa], Department of Medicine (Dep Med - MONTREAL), Sir Mortimer B Davis Jewish General Hospital (Jew Gen Hospital - MONTREAL), Department of Medicine (Dep Med - HALIFAX), Dalhousie University [Halifax], Columbia University [New York], Department of Medicine (Dep Med - LONDON - CANADA), University of Western Ontario (UWO), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), School of Environmental Sciences [Norwich], University of East Anglia [Norwich] (UEA), Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, and Ottawa Hospital Research Institute [Ottawa] (OHRI)
Subjects: Male, medicine.medical_specialty, Randomization, Pyridones, [SDV]Life Sciences [q-bio], Administration, Oral, Antineoplastic Agents, Hemorrhage, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, law, Risk Factors, Internal medicine, Neoplasms, medicine, Humans, 030212 general & internal medicine, Aged, Intention-to-treat analysis, business.industry, Incidence, Cancer, General Medicine, Venous Thromboembolism, Middle Aged, medicine.disease, 3. Good health, Intention to Treat Analysis, Clinical trial, Ambulatory, Pyrazoles, Apixaban, Female, business, Complication, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug, Factor Xa Inhibitors
Abstract: Patients with active cancer have an increased risk of venous thromboembolism, which results in substantial morbidity, mortality, and health care expenditures. The Khorana score (range, 0 to 6, with higher scores indicating a higher risk of venous thromboembolism) has been validated to identify patients with cancer at elevated risk for this complication and may help select those who could benefit from thromboprophylaxis.We conducted a randomized, placebo-controlled, double-blind clinical trial assessing the efficacy and safety of apixaban (2.5 mg twice daily) for thromboprophylaxis in ambulatory patients with cancer who were at intermediate-to-high risk for venous thromboembolism (Khorana score, ≥2) and were initiating chemotherapy. The primary efficacy outcome was objectively documented venous thromboembolism over a follow-up period of 180 days. The main safety outcome was a major bleeding episode.Of the 574 patients who underwent randomization, 563 were included in the modified intention-to-treat analysis. Venous thromboembolism occurred in 12 of 288 patients (4.2%) in the apixaban group and in 28 of 275 patients (10.2%) in the placebo group (hazard ratio, 0.41; 95% confidence interval [CI], 0.26 to 0.65; P0.001). In the modified intention-to-treat analysis, major bleeding occurred in 10 patients (3.5%) in the apixaban group and in 5 patients (1.8%) in the placebo group (hazard ratio, 2.00; 95% CI, 1.01 to 3.95; P = 0.046). During the treatment period, major bleeding occurred in 6 patients (2.1%) in the apixaban group and in 3 patients (1.1%) in the placebo group (hazard ratio, 1.89; 95% CI, 0.39 to 9.24).Apixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo. (Funded by the Canadian Institutes of Health Research and Bristol-Myers Squibb-Pfizer Alliance; AVERT ClinicalTrials.gov number, NCT02048865.).
Published: 2019

9. A Novel Risk Locus at 6p21.3 for Epstein-Barr Virus-Positive Hodgkin Lymphoma

Author: James McKay, Matthieu Foll, Pilar Galan, Silvia de Sanjosé, Lenka Foretova, Eric J. Duell, Eve Roman, Karin E. Smedby, Alexandra Nieters, Marc Maynadié, Valerie Gaborieau, Henrik Hjalgrim, Lambertus A. Kiemeney, Arjan Diepstra, Mads Melbye, Kevin Y. Urayama, Rianne Veenstra, Pierluigi Cocco, Nikolaus Becker, Tracy Lightfoot, Ingrid Glimelius, Paul Brennan, Anke van den Berg, Yolanda Benavente, Amelie Chabrier, Mark Lathrop, Manon Delahaye-Sourdeix, Lars J. Vatten, Ruth F. Jarrett, Anthony Staines, Stem Cell Aging Leukemia and Lymphoma (SALL), Translational Immunology Groningen (TRIGR), International Agency for Research on Cancer (IARC), Tokyo Medical and Dental University, University of Groningen, CIBER de Epidemiología y Salud Pública (CIBERESP), Catalan Institute of Oncology, University of Freiburg [Freiburg], Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute (RECAMO), Université de Bourgogne (UB), Dublin City University, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Clinical Epidemiology Unit, Department of Medicine, Uppsala University, University of York, University of Cagliari, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Norwegian University of Science and Technology (NTNU), Radboud Institute for Health Sciences, Radboud University Medical Center [Nijmegen], Genome Quebec Innovation Centre, McGill University = Université McGill [Montréal, Canada], Statens Serum Institut [Copenhagen], University of Glasgow, Institut National du Cancer, France, Spanish Ministry of Health grant CIBERESP PI11/0181008-1555 06/02/0073, Agencia de Gestio d'Ajuts Universitaris i de Recerca-Generalitat de Catalunya (Catalonian Government) 2014SGR756, Ministry of Health of the Czech Republic MZ0 MOU2005, German Jose Carreras Leukemia Foundation DJCLS_R04/08, Federal Office for Radiation Protection StSch4261 StSch4420, EC 5th Framework Program Quality of Life QLK4-CT-2000-00422, EC 6th Framework Program FP6-2003-FOOD-2-B, La Fondation de France 1999-008471, Compagnia di San Paolo-Programma Oncologia, Health Research Board, Leukaemia Lymphoma Research 00/73 06001 08031 05045, Kay Kendall Leukaemia Fund, U.S. NIH R01 CA69269, Nordic Cancer Union 16-02-D, Plan Danmark, Danish Cancer Research Foundation 41-08, Lundbeck Foundation R19-A2364, Danish Cancer Society DP 08-155, Swedish Cancer Society 2009/1084, Dutch Cancer Society (KWF grants) RUG 2000-2315 RUG 2010-4860 RUG 2014-6698, Dutch Organization of Scientific Research (NWO-MW grant) 920-03-136, ProdInra, Migration, Masaryk Memorial Cancer Institute (MMCI), Dublin City University [Dublin] (DCU), and Università degli Studi di Cagliari = University of Cagliari (UniCa)
Subjects: Male, Epstein-Barr Virus Infections, Epidemiology, Genome-wide association study, SUSCEPTIBILITY, DISEASE, Major Histocompatibility Complex, 0302 clinical medicine, Nodular sclerosis, hemic and lymphatic diseases, polycyclic compounds, Netherlands, Aged, 80 and over, 0303 health sciences, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, food and beverages, Middle Aged, Hodgkin Disease, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Chromosomes, Human, Pair 6, Female, INFECTIOUS-MONONUCLEOSIS, SUBTYPE, Adult, Adolescent, Population, Locus (genetics), macromolecular substances, Biology, Scandinavian and Nordic Countries, Polymorphism, Single Nucleotide, SEQUENCE, 03 medical and health sciences, Young Adult, EBV, medicine, SNP, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, education, Epstein–Barr virus infection, 030304 developmental biology, Aged, Case-control study, Epstein-Barr Virus Positive, medicine.disease, Case-Control Studies, Immunology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein–Barr virus (EBV) status, particularly within the MHC region. Methods: We have conducted an SNP imputation study of the MHC region, considering tumor EBV status in 1,200 classical Hodgkin lymphoma (cHL) cases and 5,726 control subjects of European origin. Notable findings were genotyped in an independent study population of 468 cHL cases and 551 controls. Results: We identified and subsequently replicated a novel association between a common genetic variant rs6457715 and cHL. Although strongly associated with EBV-positive cHL [OR, 2.33; 95% confidence interval (CI), 1.83–2.97; P = 7 × 10–12], there was little evidence for association between rs6457715 and the EBV-negative subgroup of cHL (OR, 1.06; 95% CI, 0.92–1.21), indicating that this association was specific to the EBV-positive subgroup (Phet < P = 10−8). Furthermore, the association was limited to EBV-positive cHL subgroups within mixed cell (MCHL) and nodular sclerosis subtypes (NSHL), suggesting that the association is independent of histologic subtype of cHL. Conclusions: rs6457715, located near the HLA-DPB1 gene, is associated with EBV-positive cHL and suggests this region as a novel susceptibility locus for cHL. Impact: This expands the number of genetic variants that are associated with cHL and provides additional evidence for a critical and specific role of EBV in the etiology of this disease. Cancer Epidemiol Biomarkers Prev; 24(12); 1838–43. ©2015 AACR.
Published: 2015

10. No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy

Author: Tatiana Tzenou, Richard Rosenquist, Marie-Paule Lefranc, Karla Plevová, Charles C. Chu, Yorick Sandberg, Gunnar Juliusson, Véronique Giudicelli, Livio Trentin, Mark Catherwood, Frederic Davi, Šárka Pospíšilová, Xiao-Jie Yan, Silvio Veronese, Lesley-Ann Sutton, Carsten Utoft Niemann, Nikos Darzentas, Kostas Stamatopoulos, Achilles Anagnostopoulos, Diane F. Jelinek, David Oscier, Mattias Mattsson, Nicholas Chiorazzi, Karin E. Smedby, Panagiotis Panagiotidis, Chrysoula Belessi, Florence Nguyen-Khac, Marco Montillo, Eva Minga, Paolo Ghia, Anton W. Langerak, Lydia Scarfò, Andreas Agathangelidis, Tait D. Shanafelt, Panagiotis Baliakas, Niki Stavroyianni, Larry Mansouri, Anastasia Hadzidimitriou, Zadie Davis, Fie Juhl Vojdeman, Uppsala Universitet [Uppsala], Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden, Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece, Department of Immunology, Genetics and Pathology [Uppsala, Sueden] (IGP), Uppsala University, Department of Hematology [Uppsala], Università Vita-Salute San Raffaele, Milan, Italy., Strategic Research Program in CLL, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy, Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden, Università Vita e Salute, San Raffaele, Milano, Italy, Strategic Research Program in CLL, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK., The Feinstein Institute for Medical Research, CEITEC-Central European Institute of Technology, MasarykBrno, Czech Republic., Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Hematology, Rigshospitalet, Copenhagen, Denmark, First Department of Propaedeutic Medicine, University of Athens, Athens, Greece, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Medicine Solna, Clinical Epidemiology Unit, Karolinska Institutet, and Hematology Center, Karolinska University Hospital, Stockholm, Sweden, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hematology and Transplantation, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden, Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece, Universita degli Studi di Padova, Venetian Institute Molecular Medicine (VIMM), Department of Hemato-Oncology, Belfast City Hospital, Belfast, UK, University Hospital Brno, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Immunology, Mayo Clinic, Rochester, MV, USA, Mayo Clinic [Rochester], Hematology Department, Nikea General Hospital, Piraeus, Greece, Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden., Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece., Institute of Applied Biosciences, Thessaloniki, Greece., Department of Immunology, Baliakas, Panagioti, Mattsson, Mattia, Hadzidimitriou, Anastasia, Minga, Eva, Agathangelidis, Andrea, Sutton, Lesley-Ann, Scarfo, Lydia, Davis, Zadie, Yan, Xiao-Jie, Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie J, Tzenou, Tatiana, Chu, Charles C, Veronese, Silvio, Mansouri, Larry, Smedby, Karin E, Giudicelli, Véronique, Nguyen-Khac, Florence, Panagiotidis, Panagioti, Juliusson, Gunnar, Anagnostopoulos, Achille, Lefranc, Marie-Paule, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Niemann, Carsten U, Langerak, Anton W, Pospisilova, Sarka, Stavroyianni, Niki, Chiorazzi, Nichola, Oscier, David, Jelinek, Diane F, Shanafelt, Tait, Darzentas, Niko, Belessi, Chrysoula, Davi, Frederic, Ghia, Paolo, Rosenquist, Richard, Stamatopoulos, Kostas, and Immunology
Subjects: Adult, Male, chemorefractorine, Oncology, medicine.medical_specialty, Cyclophosphamide, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], Young Adult, 03 medical and health sciences, 0302 clinical medicine, Drug Therapy, Chemoimmunotherapy, Internal medicine, medicine, Humans, Chronic Lymphocytic Leukemia, [INFO]Computer Science [cs], stereotyped subsets, Online Only Articles, Survival rate, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, [SDV.GEN]Life Sciences [q-bio]/Genetics, Hematology, business.industry, Middle Aged, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Fludarabine, Survival Rate, Leukemia, 030220 oncology & carcinogenesis, Female, Rituximab, Immunotherapy, business, 030215 immunology, medicine.drug
Abstract: The overall survival (OS) of patients with chronic lymphocytic leukemia (CLL) has improved over the last decades mainly due to advances in the understanding of the disease biology and the introduction of novel therapeutic approaches(1). In the present retrospective study we investigated trends in OS in subgroups of cases defined by genetic and immunogenetic features aiming at addressing the question whether advances in chemoimmunotherapy had a uniform impact across all CLL patients. We found that such advances have translated into prolonged OS in all prognostic subgroups examined except those carrying TP53 abnormalities, as expected, but also those assigned to stereotyped subsets #1 and #2, that are generally devoid of such gene aberrations. This latter finding, reported here for the first time, indicates the need for alternative treatment options for these patients.
Published: 2018

11. How immunological profile drives clinical phenotype of primary Sjögren's syndrome at diagnosis: analysis of 10.500 patients (Sjögren big data project)

Author: Retamozo, Soledad, Acar-Denizli, Nihan, Ng, Wan-Fai, Zeher, Margit, Rasmussen, Astrid, Mandl, Thomas, Seror, Raphaele, Li, Xiaomei, Baldini, Chiara, Gottenberg, Jacques-Eric, Danda, Debashish, Quartuccio, Luca, Priori, Roberta, Hernandez-Molina, Gabriela, Armagan, Berkan, Kruize, Aike A., Kwok, Seung-Ki, Kvarnstrom, Marika, Praprotnik, Sonja, Sene, Damien, Bartoloni, Elena, Solans, Roser, Rischmueller, Maureen, Suzuki, Yasunori, Isenberg, David A., Valim, Valeria, Wiland, Piotr, Nordmark, Gunnel, Fraile, Guadalupe, Bootsma, Hendrika, Nakamura, Takashi, Giacomelli, Roberto, Devauchelle-Pensec, Valerie, Knopf, Andreas, Bombardieri, Michele, Trevisani, Virginia Fernandes, Hammenfors, Daniel S., Pasoto, Sandra G., Gheita, Tamer A., Atzeni, Fabiola, Morel, Jacques, Vollenveider, Cristina, Horvath, Ildiko-Fanny, Sivils, Kathy L., Olsson, Peter, Vita, Salvatore, Sanchez-Guerrero, Jorge, Kilic, Levent, Wahren-Herlenius, Marie, Mariette, Xavier, Manuel Ramos-Casals, Brito-Zeron, Pilar, Michel, Geneviève, H. CIMA-Sanitas, Barcelona, Departement of Statistics, Istanbul, Institute of Cellular Medicine [Newcastle], Newcastle University [Newcastle], Department of Immunology [Debrecen, Hungary], University of Debrecen [Hungary], Oklahoma Medical Research Foundation (OMRF), Department of Rheumatology (Dep Rheumato - Malmo - SUEDE), Skåne University Hospital, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, Departement of Rheumatology and Immunology, Hefei (Anhui Provincial Hospital), Rheumatology Unit (Rheum Unit - PISA), University of Pisa - Università di Pisa, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Department of Clinical Immunology and Rheumatology, Vellore (Christian Medical College & Hospital), Rheumatology Clinic, Academic Hospital S.M. Della Misericordia, Udine, Department of Internal Medicine and Medical Specialties, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Immunology [Mexico City], Natl Inst Pediat, Immunodeficiencies Res Unit, Mexico City, DF, Mexico, Department of Internal Medicine, Ankara (Hacettepe University), University Medical Center [Utrecht], Seoul St Mary's Hospital, Seoul, Karolinska Institutet, Department of Rheumatology, Karolinska University Hospital [Stockholm], Department of Rheumatology (Dep Rheumato - Ljubljana - SLOVENIE), University Medical Centre Slovenia, Département de Médecine interne [Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Department of Medicine [Perugia, Italy] (Rheumatology, Unit), Università degli Studi di Perugia (UNIPG), Department of Internal Medicine, Barcelona, The University of Western Australia (UWA), Division of Rheumatology Kanazawa University Graduate School of Medicine, Kanazawa, Centre for Rheumatology - London, Department of Medicine, Universidade Federal do Espirito Santo, Vitoria, Department of Rheumatology and Internal Medicine, Wroclaw, Department of Medical Sciences, Uppsala (Section of Rheumatology), Department of Internal Medicine, Madrid, Department of Rheumatology and Clinical Immunology Groningen (Dep Rheum - GRONINGEN), University Medical Center Groningen [Groningen] (UMCG), Department of Radiology and Cancer Biology, Nagasaki, Clinical Unit of Rheumatology, L'Aquila, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Otorhinolaryngology/Head and Neck Surgery, Munich, Centre for Experimental Medicine and Rheumatology, London, University of São Paulo (USP), Department of Clinical Science and Department of Rheumatology, Bergen, Rheumatology Division, Hospital das Clinicas, Sao Paulo (HCFMUSP), Universidad Nacional de Córdoba [Argentina], Rheumatology Department, Cairo, Istituto Ortopedico Galeazzi-IRCCS, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, German Hospital, Buenos Aires, Department of Rheumatology, Skane University Hospital, Immunology and Rheumatology Department, Mexico City, Department of Internal Medicine, Ankara, Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden, and CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

12. Age of Transfused Blood in Critically Ill Adults

Author: Lacroix, Jacques, Hébert, Paul C., Fergusson, Dean A., Tinmouth, Alan, Cook, Deborah J., Marshall, John C., Clayton, Lucy, McIntyre, Lauralyn, Callum, Jeannie, Turgeon, Alexis F., Blajchman, Morris A., Walsh, Timothy S., Stanworth, Simon J., Campbell, Helen, Capellier, Gilles, Tiberghien, Pierre, Bardiaux, Laurent, van de Watering, Leo, van der Meer, Nardo J., Sabri, Elham, Vo, Dong, Souweine, Canadian Critical care trials group, Centre de recherche interuniversitaire sur la communication, l’information et la société (CRISIS), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Biodiversity institute of Ontario, University of Guelph, Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, National ICT Australia [Sydney] (NICTA), University of New South Wales [Sydney] (UNSW), Réanimation Médicale CHRU Besançon, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Adult, Male, medicine.medical_specialty, Pediatrics, Time Factors, Critical Illness, Blood preservation, Kaplan-Meier Estimate, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, law.invention, Primary outcome, Double-Blind Method, Randomized controlled trial, law, Internal medicine, medicine, Humans, Aged, Intention-to-treat analysis, Critically ill, business.industry, General Medicine, Length of Stay, Middle Aged, Intention to Treat Analysis, 3. Good health, Logistic Models, Treatment Outcome, Multicenter study, Blood Preservation, Oxygen delivery, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Erythrocyte Transfusion, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Blood bank
Abstract: BACKGROUND: Fresh red cells may improve outcomes in critically ill patients by enhancing oxygen delivery while minimizing the risks of toxic effects from cellular changes and the accumulation of bioactive materials in blood components during prolonged storage.METHODS: In this multicenter, randomized, blinded trial, we assigned critically ill adults to receive either red cells that had been stored for less than 8 days or standard-issue red cells (the oldest compatible units available in the blood bank). The primary outcome measure was 90-day mortality.RESULTS: Between March 2009 and May 2014, at 64 centers in Canada and Europe, 1211 patients were assigned to receive fresh red cells (fresh-blood group) and 1219 patients were assigned to receive standard-issue red cells (standard-blood group). Red cells were stored a mean (±SD) of 6.1±4.9 days in the fresh-blood group as compared with 22.0±8.4 days in the standard-blood group (PCONCLUSIONS: Transfusion of fresh red cells, as compared with standard-issue red cells, did not decrease the 90-day mortality among critically ill adults. (Funded by the Canadian Institutes of Health Research and others; Current Controlled Trials number, ISRCTN44878718.)
Published: 2015

13. Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations

Author: Eva Minga, Karin E. Smedby, Lesley-Ann Sutton, Nicholas Chiorazzi, Myriam Boudjogra, Kostas Stamatopoulos, Karla Plevová, Lone Bredo Pedersen, Zadie Davis, Lydia Scarfò, Andreas Agathangelidis, Monica Facco, Achilles Anagnostopoulos, Maria Chatzouli, Chrysoula Belessi, Athina Tsanousa, Panagiotis Baliakas, Kirsten van Lom, Lefteris Angelis, Yorick Sandberg, Gunnar Juliusson, Diane F. Jelinek, Fie Juhl Vojdeman, Anne Gardiner, Panagiotis Panagiotidis, Anton W. Langerak, Florence Nguyen-Khac, Hana Skuhrová Francová, Frederic Davi, Denis Moreno, Silvio Veronese, Richard Rosenquist, Marie-Paule Lefranc, Nikos Darzentas, Šárka Pospíšilová, Véronique Giudicelli, Xiao-Jie Yan, Charles C. Chu, Christian H. Geisler, Larry Mansouri, David Oscier, Mark Catherwood, Marco Montillo, Anastasia Hadzidimitriou, Livio Trentin, Paolo Ghia, Tait D. Shanafelt, Tatiana Tzenou, Baliakas, P, Agathangelidis, A, Hadzidimitriou, A, Sutton, La, Minga, E, Tsanousa, A, Scarfò, L, Davis, Z, Yan, Xj, Shanafelt, T, Plevova, K, Sandberg, Y, Vojdeman, Fj, Boudjogra, M, Tzenou, T, Chatzouli, M, Chu, Cc, Veronese, S, Gardiner, A, Mansouri, L, Smedby, Ke, Pedersen, Lb, Moreno, D, Van Lom, K, Giudicelli, V, Francova, H, Nguyen Khac, F, Panagiotidis, P, Juliusson, G, Angelis, L, Anagnostopoulos, A, Lefranc, Mp, Facco, M, Trentin, L, Catherwood, M, Montillo, M, Geisler, Ch, Langerak, Aw, Pospisilova, S, Chiorazzi, N, Oscier, D, Jelinek, Df, Darzentas, N, Belessi, C, Davi, F, Ghia, PAOLO PROSPERO, Rosenquist, R, Stamatopoulos K. Ghia P., is Co senior author, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden, Università Vita-Salute San Raffaele, Milan, Italy, Division of Molecular Oncology and Department of Onco-Hematology, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Scientific Institute, Milan, Italy, Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece, Department of Informatics, Aristotle University of Thessaloniki, Thessaloniki, Greece, Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom, The Feinstein Institute for Medical Research, Mayo Clinic [Rochester], Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Hematology, Rigshospitalet, Copenhagen, Denmark, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), First Department of Propaedeutic Medicine, University of Athens, Athens, Greece, Hematology Department, Nikea General Hospital, Piraeus, Greece, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden, Hematology Department and Hematopoietic Cell Transplantation Unit, Georgios Papanicolaou Hospital, Thessaloniki, Greece, Universita degli Studi di Padova, Department of Hemato-Oncology, Belfast City Hospital, Belfast, United Kingdom, Immunology, and Hematology
Subjects: Male, Oncology, medicine.medical_specialty, Chronic lymphocytic leukemia, Immunology, B-cell receptor, Gene Rearrangement, B-Lymphocyte, Heavy Chain, Antineoplastic Agents, Biology, Biochemistry, Time-to-Treatment, Genetic Heterogeneity, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 10. No inequality, ComputingMilieux_MISCELLANEOUS, Survival analysis, Aged, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, B-Lymphocytes, 0303 health sciences, Lymphoid Neoplasia, Hematology, Gene Expression Regulation, Leukemic, Genetic heterogeneity, Cell Biology, Middle Aged, Prognosis, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Survival Analysis, Treatment Outcome, 030220 oncology & carcinogenesis, biology.protein, Immunoglobulin heavy chain, Female, Somatic Hypermutation, Immunoglobulin, Antibody, Immunoglobulin Heavy Chains, IGHV@
Abstract: An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset # 2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset # 2. Within subset # 2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset # 2/IGHV3-21 was enriched for IGHV-unmutated cases (P =.002). Subset # 2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset # 2/IGHV3-21 (22 vs 60 months, P =.001). No such difference was observed between non-subset # 2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset # 2 emerges as uniformly aggressive, contrasting non-subset # 2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.
Published: 2015

14. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study

Author: Menno V. Huisman, Marc Philip Righini, Jeannot Schmidt, Susan R. Kahn, Michael J. Kovacs, Antoine Elias, Thomas L. Ortel, Grégoire Le Gal, Guy Meyer, Patrick Mismetti, Clive Kearon, Gilles Pernod, Marc A. Rodger, Tim Ramsay, David Anderson, Ottawa Hospital Research Institute [Ottawa] (OHRI), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, University of Portsmouth, Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Techniques pour l'Evaluation et la Modélisation des Actions de la Santé (TIMC-IMAG-ThEMAS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'angiologie et d'hémostase (MR), Hôpital Universitaire de Genève, Groupe de recherche sur la thrombose (GRT (EA 3065)), Université Jean Monnet [Saint-Étienne] (UJM), Department of Medicine (DM - McMaster), McMaster University [Hamilton, Ontario], Université Paris Descartes - Paris 5 (UPD5), 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), Université Sorbonne Paris Cité (USPC), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), 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), Institut de Physique du Globe de Paris (IPGP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Duke University Health System (DUHS - DURHAM), Duke University [Durham], Department of Thrombosis and Hemostasis (LEIDEN - DTH), Leiden University Medical Center (LUMC), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), 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 de Brest (UBO)-Université de Brest (UBO), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and 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)
Subjects: Pediatrics, medicine.medical_specialty, medicine.drug_class, Deep vein, [SDV]Life Sciences [q-bio], Clinical Decision-Making, 030204 cardiovascular system & hematology, Decision Support Techniques, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, Humans, Medicine, 030212 general & internal medicine, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Venous Thrombosis, 2. Zero hunger, business.industry, Anticoagulant, Anticoagulants, General Medicine, Middle Aged, medicine.disease, Thrombosis, 3. Good health, Pulmonary embolism, Clinical trial, Venous thrombosis, Treatment Outcome, medicine.anatomical_structure, Cohort, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: Objective To prospectively validate the HERDOO2 rule (Hyperpigmentation, Edema, or Redness in either leg; D-dimer level ≥250 μg/L; Obesity with body mass index ≥30; or Older age, ≥65 years), which states that women with none or one of the criteria can safely discontinue anticoagulants after short term treatment. Design Prospective cohort management study. Setting 44 secondary or tertiary care centres in seven countries. Participants Of 3155 consecutive eligible participants with a first unprovoked venous thromboembolism (VTE, proximal leg deep vein thrombosis or pulmonary embolism) who completed 5-12 months of short term anticoagulant treatment, 370 declined to participate, leaving 2785 enrolled participants. 2.3% were lost to follow-up. Interventions Women with none or one of the HERDOO2 criteria were classified as at low risk of recurrent VTE and discontinued anticoagulants (intervention arm), whereas anticoagulant management for high risk women (≥2 HERDOO2 criteria) and men was left to the discretion of the clinicians and patients (observation arm). Main outcome measure Recurrent symptomatic VTE (independently and blindly adjudicated) over one year of follow-up. Results Of 1213 women, 631 (51.3%) were classified as low risk and 591 discontinued oral anticoagulant treatment. In the primary analysis, 17 low risk women who discontinued anticoagulants developed recurrent VTE during 564 patient years of follow-up (3.0% per patient year, 95% confidence interval 1.8% to 4.8%). In 323 high risk women and men who discontinued anticoagulants, 25 had VTE during 309 patient years of follow-up (8.1%, 5.2% to 11.9%), whereas in 1802 high risk women and men who continued anticoagulants 28 had recurrent VTE during 1758 patient years of follow-up (1.6%, 1.1% to 2.3%). Conclusions Women with a first unprovoked VTE event and none or one of the HERDOO2 criteria have a low risk of recurrent VTE and can safely discontinue anticoagulants after completing short term treatment. Trial registration clinicaltrials.gov NCT00967304.
Published: 2017

15. The risk of venous thromboembolism in renal cell carcinoma patients with residual tumor thrombus

Author: D. W. Yokom, Aurélien Delluc, C. M. Canil, Marc Carrier, N. Reaume, P. Moretto, Ryma Ihaddadene, G. Le Gal, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Interface Physique et Chimie pour le Vivant (IPCV), Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), Université Sciences et Technologies - Bordeaux 1-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Thrombosis Program, University of Ottawa [Ottawa], Clinical Epidemiology Unit, and Ottawa-The Ottawa Hospital
Subjects: Adult, Male, medicine.medical_specialty, Neoplasm, Residual, Time Factors, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Vena Cava, Inferior, Kaplan-Meier Estimate, Hepatic Veins, Nephrectomy, Risk Assessment, Renal Veins, Young Adult, Risk Factors, Renal cell carcinoma, Clinical endpoint, Humans, Medicine, Neoplasm, cardiovascular diseases, Risk factor, Carcinoma, Renal Cell, Aged, Neoplasm Staging, Retrospective Studies, Thrombectomy, Aged, 80 and over, Venous Thrombosis, Portal Vein, business.industry, Hazard ratio, Venous Thromboembolism, Hematology, Middle Aged, medicine.disease, Kidney Neoplasms, 3. Good health, Venous thrombosis, Treatment Outcome, cardiovascular system, Female, Radiology, business, circulatory and respiratory physiology, Cohort study
Abstract: Summary Background The clinical importance of tumor thrombus in patients with renal cell carcinoma is unknown. We sought to determine the long-term risk of venous thromboembolism (VTE) in patients with residual tumor thrombus postextraction, and to evaluate the impact of residual tumor thrombus on overall survival. Patients/methods A cohort study of patients with stage III–IV renal cell carcinoma undergoing nephrectomy was undertaken. The primary endpoint was the risk of VTE during a 2-year follow-up period. The secondary endpoint was 2-year overall survival. Results A total of 170 surgical renal cell carcinoma patients were included, 97 (57.1%) of whom had tumor thrombus. Patients with residual tumor thrombus following surgery had a higher risk of developing VTE than those with complete tumor thrombus resection (hazard ratio [HR] 8.7, 95% confidence interval [CI] 1.7–43.4) and no tumor thrombus (HR 6.5, 95% CI 1.7–24.7). Patient with residual tumor thrombus did not have worse overall survival than those with tumor thrombus completely resected or those without tumor thrombus. Conclusions The presence of residual tumor thrombus is an important risk factor for VTE among renal cell carcinoma patients.
Published: 2014

16. Increased prevalence and severity of radiographic hand osteoarthritis in patients with HIV-1 infection associated with metabolic syndrome: data from the cross-sectional METAFIB-OA study

Author: Pierre Marie Girard, Ida K. Haugen, David T. Felson, Jacqueline Capeau, Soraya Fellahi, Emmanuel Maheu, Francis Berenbaum, Anne-Laurence Tomi, Caroline Rey-Jouvin, Anne Miquel, Karine Lacombe, Jean-Luc Meynard, Manuela Sebire, Jérémie Sellam, Jean-Philippe Bastard, HAL-UPMC, Gestionnaire, Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Radiologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Dpt of Rheumatology [Oslo], Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway, Clinical Epidemiology Unit [Boston], Boston University School of Medicine (BUSM), Boston University [Boston] (BU)-Boston University [Boston] (BU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], CHU Tenon [AP-HP], Department of Rheumatology [Oslo], Diakonhjemmet Hospital, Tufts University School of Medicine [Boston], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, metabolic osteoarthritis, medicine.medical_specialty, Hand Joints, Cross-sectional study, Immunology, Population, General Population Cohort, HIV Infections, Osteoarthritis, metabolic syndrome, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Framingham Heart Study, Rheumatology, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Prevalence, medicine, Humans, Immunology and Allergy, 030212 general & internal medicine, education, 030203 arthritis & rheumatology, education.field_of_study, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Framingham Risk Score, business.industry, aging, Middle Aged, medicine.disease, 3. Good health, Radiography, osteoarthritis, Cross-Sectional Studies, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HIV-1, Physical therapy, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, hand, Metabolic syndrome, business
Abstract: International audience; Objective To determine radiographic hand osteoarthritis (HOA) prevalence in patients with HIV-1 infection in comparison with the general population and to address whether metabolic syndrome (MetS) may increase the risk of HOA during HIV-1 infection.Patients Patients with HIV-1 infection and MetS (International Diabetes Federation, IDF criteria) aged 45–65 years were matched by age and gender to HIV-1-infected subjects without MetS and underwent hand radiographs. Framingham OA cohort was used as general population cohort.Methods Radiographic HOA was defined as Kellgren–Lawrence (KL) score ≥2 on more than one joint. Radiographic severity was assessed by global KL score and number of OA joints. HOA prevalence was compared with that found in the Framingham study, stratified by age and sex. Logistic and linear regression models were used to determine the risk factors of HOA in patients with HIV-1 infection.Results 301 patients (88% male, mean age 53.4±5.0 years) were included, 152 with MetS and 149 without it. Overall, HOA prevalence was 55.6% and was higher for those with MetS than those without it (64.7% vs 46.3%, p=0.002). When considering men within each age group, HOA frequency was greater in patients with HIV-1 infection than the general population (all ages: 55.8% vs 38.7%; p
Published: 2016

17. Human leukocyte antigen B27 selects for rare escape mutations that significantly impair hepatitis C virus replication and require compensatory mutations

Author: Susan Ingber, Cesar Oniangue-Ndza, Matthew R. Henn, K. Nitschke, Arthur Y. Kim, Célia Caillet-Saguy, Thomas Kuntzen, Nadine Kersting, Alessandro Sette, Christoph Neumann-Haefelin, Volker Lohmann, Marco Binder, Laura L. Reyor, Michael Kemper, John Sidney, Todd M. Allen, Georg M. Lauer, Julia Schmidt, Kelsey Hills-Evans, Karen A. Power, Stéphane Bressanelli, Robert Thimme, Department of Medicine II, University of Freiburg [Freiburg], Royal rehabilitation centre, Sydney, Laboratory of Epidemiology, Clinical Epidemiology Unit, Istituto Superiore di Sanita [Rome], Laboratoire de virologie moléculaire et structurale (LVMS), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), and Heidelberg University
Subjects: musculoskeletal diseases, MESH: Mutation, [SDV]Life Sciences [q-bio], Hepacivirus, Hepatitis C virus, Epitopes, T-Lymphocyte, MESH: Immunodominant Epitopes, Human leukocyte antigen, CD8-Positive T-Lymphocytes, Virus Replication, medicine.disease_cause, Sensitivity and Specificity, Sampling Studies, Article, Epitope, MESH: Epitopes, T-Lymphocyte, 03 medical and health sciences, 0302 clinical medicine, MESH: Sampling Studies, Genotype, medicine, Humans, MESH: Hepacivirus, HLA-B27 Antigen, 030304 developmental biology, Subgenomic mRNA, MESH: Hepatitis C, Genetics, 0303 health sciences, Mutation, Binding Sites, MESH: Humans, Hepatology, biology, Immunodominant Epitopes, MESH: Virus Replication, biology.organism_classification, Hepatitis C, MESH: CD8-Positive T-Lymphocytes, Virology, MESH: Sensitivity and Specificity, 3. Good health, MESH: Binding Sites, Viral replication, 030211 gastroenterology & hepatology, MESH: HLA-B27 Antigen
Abstract: Human leukocyte antigen B27 is associated with spontaneous viral clearance in hepatitis C virus (HCV) infection. Viral escape within the immunodominant, HLA-B27-restricted, HCV-specific, cluster of differentiation (CD)8+ T-cell epitope, nonstructural protein (NS)5B2841-2849 (ARMILMTHF), has been shown to be limited by viral fitness costs as well as broad T-cell cross-recognition, suggesting a potential mechanism of protection by HLA-B27. Here, we studied the subdominant HLA-B27-restricted epitope, NS5B2936-2944 (GRAAICGKY), to further define the mechanisms of protection by HLA-B27. We identified a unique pattern of escape mutations within this epitope in a large cohort of HCV genotype 1a–infected patients. The predominant escape mutations represented conservative substitutions at the main HLA-B27 anchor residue or a T-cell receptor contact site, neither of which impaired viral replication capacity, as assessed in a subgenomic HCV replicon system. In contrast, however, in a subset of HLA-B27+ subjects, rare escape mutations arose at the HLA-B27 anchor residue, R2937, which nearly abolished viral replication. Notably, these rare mutations only occurred in conjunction with the selection of two equally rare, and structurally proximal, upstream mutations. Coexpression of these upstream mutations with the rare escape mutations dramatically restored viral replication capacity from
Published: 2011

18. Unprovoked Venous Thromboembolism: Short term or Indefinite Anticoagulation? Balancing Long-Term Risk and Benefit

Author: Esteban Gandara, Marc Carrier, G. Le Gal, Marc A. Rodger, Thrombosis Program, University of Ottawa [Ottawa], Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Ottawa Hospital Research Institute [Ottawa] (OHRI), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)
Subjects: medicine.medical_specialty, medicine.drug_class, MEDLINE, MESH: Anticoagulants, 030204 cardiovascular system & hematology, MESH: Venous Thromboembolism, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Health care, medicine, Humans, MESH: Heparin, Low-Molecular-Weight, cardiovascular diseases, 030212 general & internal medicine, Intensive care medicine, MESH: Treatment Outcome, MESH: Humans, business.industry, Vascular disease, Anticoagulant, Anticoagulants, Venous Thromboembolism, Hematology, Heparin, Low-Molecular-Weight, equipment and supplies, medicine.disease, 3. Good health, Venous thrombosis, Treatment Outcome, Oncology, business, Complication, Venous thromboembolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Major bleeding
Abstract: International audience; Whether to continue oral anticoagulant therapy indefinitely after completing 3 to 6 months of oral anticoagulant therapy for "unprovoked" venous thromboembolism (VTE), is one of the most important unanswered questions in VTE management. This long-term decision should be based on balancing the long-term mortality risk from recurrent VTE, largely preventable with oral anticoagulant therapy, against the long-term mortality risk of major bleeding, the principle complication of oral anticoagulant therapy. There exist important knowledge gaps in estimating the long-term mortality risk of recurrent VTE in patients with unprovoked VTE who discontinue therapy and the long-term mortality risk from major bleeding in those who continue oral anticoagulant therapy. These knowledge gaps, reviewed herein, are the source of uncertainty for patients and health care providers wrestling with this important question. One promising solution is recurrent VTE risk stratification where unprovoked VTE patients are categorised as low or high risk for recurrent VTE and clinical decision making is less ambiguous and ultimately will likely lead to better outcomes.
Published: 2010

19. Risk of recurrent venous thromboembolism after a first oestrogen-associated episode

Author: Richard H. White, Karine Lacut, Marc Carrier, Kimberley Do, Philip S. Wells, Michael J. Kovacs, Grégoire Le Gal, David A. Anderson, Susan R. Kahn, Mark Crowther, Marc Philip Righini, Linda M. Vickars, Marc A. Rodger, Isabelle Chagnon, Susan Solymoss, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Division of Hematology (MJK), University of Western Ontario (UWO), Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Department of Medecine [Montréal], McGill University = Université McGill [Montréal, Canada], Ottawa Hospital, Thrombosis Program, University of Ottawa [Ottawa], Department of Medicine, Dalhousie University [Halifax], University of Montreal, McMaster University [Hamilton, Ontario], Service d'angiologie et d'hémostase (MR), and Hôpital Universitaire de Genève
Subjects: Male, Time Factors, medicine.medical_treatment, 030204 cardiovascular system & hematology, MESH: Risk Assessment, MESH: Venous Thromboembolism, MESH: Proportional Hazards Models, 0302 clinical medicine, Recurrence, Risk Factors, MESH: Risk Factors, Prospective Studies, 030212 general & internal medicine, Young adult, Prospective cohort study, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Estrogen Replacement Therapy, Hormone replacement therapy (menopause), Venous Thromboembolism, Hematology, Middle Aged, Europe, Venous thrombosis, Treatment Outcome, MESH: Young Adult, Female, MESH: Contraceptives, Oral, Hormonal, Risk assessment, Cohort study, Adult, Canada, medicine.medical_specialty, Adolescent, MESH: Anticoagulants, Lower risk, Risk Assessment, Contraceptives, Oral, Hormonal, Young Adult, 03 medical and health sciences, MESH: Canada, Internal medicine, MESH: United States, medicine, Humans, cardiovascular diseases, Risk factor, Aged, Proportional Hazards Models, MESH: Adolescent, Gynecology, MESH: Humans, business.industry, MESH: Time Factors, Anticoagulants, MESH: Adult, equipment and supplies, medicine.disease, MESH: Estrogen Replacement Therapy, United States, MESH: Male, MESH: Prospective Studies, MESH: Recurrence, MESH: Europe, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: SummaryThe use of exogenous oestrogen in women with otherwise unprovoked venous thromboembolism (VTE) could be considered sufficient explanation to classify VTE as provoked if the risk of recurrent VTE after 3–6 months of anticoagulant treatment is similar to the risk of recurrent VTE observed after a surgery or prolonged immobilisation. Our objective was to assess the risk of recurrent VTE in women after a first unprovoked episode on oestrogen. The REVERSE study is a cohort study of patients with a first unprovoked VTE treated with anticoagulant treatment for 5–7 months. The risk of recurrent VTE during follow-up was compared between women users and non users of oestrogen at the time of index VTE. Among the 646 patients included, 314 were women, of them 67 were current users of oestrogen at the time of their VTE: 49 were on oral contraceptives and 18 on post-menopausal hormone replacement therapy (HRT). No significant association was found between oestrogen exposure, either oral contraceptives or HRT, and a lower risk of recurrent VTE after adjustment for age, or analysis restricted to women in the same age range as oestrogen contraceptives and HRT users, respectively. The risk of recurrent VTE is low in women after a first otherwise unprovoked oestrogen-associated VTE. However, this risk is not significantly lower than in women whose VTE was not related to oestrogen use.
Published: 2010

20. Prediction of the warfarin maintenance dose after completion of the 10 mg initiation nomogram: do we really need genotyping?

Author: Marc Carrier, S. Tierney, P. S. Wells, G. Le Gal, H. Majeed, Marc A. Rodger, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Thrombosis Program, and University of Ottawa [Ottawa]
Subjects: Male, Time Factors, Vitamin K, Administration, Oral, Clinical prediction rule, 030204 cardiovascular system & hematology, MESH: Risk Assessment, MESH: Venous Thromboembolism, MESH: Genotype, 0302 clinical medicine, Risk Factors, MESH: Drug Monitoring, MESH: Risk Factors, Ambulatory Care, Drug Dosage Calculations, heterocyclic compounds, 030212 general & internal medicine, MESH: Warfarin, Prospective cohort study, MESH: Aged, MESH: Middle Aged, Cumulative dose, Maintenance dose, Age Factors, Venous Thromboembolism, Hematology, Middle Aged, MESH: Predictive Value of Tests, MESH: International Normalized Ratio, 3. Good health, MESH: Reproducibility of Results, Phenotype, MESH: Blood Coagulation, MESH: Administration, Oral, Female, Drug Monitoring, MESH: Hemorrhage, medicine.drug, Adult, medicine.medical_specialty, Genotype, MESH: Ambulatory Care, Hemorrhage, MESH: Nomograms, MESH: Anticoagulants, MESH: Drug Administration Schedule, MESH: Phenotype, Risk Assessment, Drug Administration Schedule, 03 medical and health sciences, Therapeutic index, Predictive Value of Tests, Internal medicine, medicine, Humans, International Normalized Ratio, cardiovascular diseases, MESH: Drug Dosage Calculations, Blood Coagulation, Aged, Retrospective Studies, MESH: Age Factors, MESH: Humans, business.industry, Body Weight, MESH: Time Factors, Warfarin, Anticoagulants, Reproducibility of Results, MESH: Vitamin K, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, Nomogram, MESH: Male, MESH: Body Weight, Surgery, Nomograms, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; INTRODUCTION: Initiation of warfarin therapy is complicated by its narrow therapeutic index and inter-patient dose-effect variability. A '10-mg nomogram' warfarin initiation protocol permits safe therapeutic anticoagulation in outpatients started on warfarin. We aimed to develop a safe and effective warfarin maintenance dose prediction tool in these patients. METHODS: Baseline potential predictor variables were collected on a retrospective cohort of outpatients initiated on warfarin for venous thromboembolism treatment. The primary outcome was the warfarin maintenance dose, defined as mean warfarin dose over the last 10 days of the first month of warfarin treatment. Univariate and multivariate analyses were performed to determine which baseline variables were warfarin maintenance dose predictors. An independent cohort of patients validated the derived warfarin maintenance dose prediction rule. RESULTS: Patient's age and weight, cumulative dose of warfarin over the first week of induction and international normalized ratio (INR) on days 3, 5 and 8 were statistically significant predictors of the warfarin maintenance dose. Our final prediction rule reads: maintenance dose (in mg) = 2.5 + 10% of the first week cumulative dose - INR value at day 8 + 1.5 if INR was below 2.0 at day 5. In the validation cohort, the predicted dose was strongly correlated with the actual maintenance dose (r = 0.88, P < 0.0001). The mean difference between observed and predicted dose was not clinically significant: -0.1 +/- 1.1 mg. CONCLUSION: In outpatients initiated on warfarin using a '10-mg nomogram', a simple prediction rule can accurately predict warfarin maintenance dose. Prospective studies employing the rule are indicated.
Published: 2010

21. Practical application of the 10-mg warfarin initiation nomogram

Author: Philip S. Wells, Sarah Tierney, Marc Carrier, Grégoire Le Gal, Clinical Epidemiology Unit, Ottawa Hospital, Thrombosis Program, University of Ottawa [Ottawa], Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), and Ottawa-The Ottawa Hospital
Subjects: Male, Vitamin K, 030204 cardiovascular system & hematology, MESH: Venous Thromboembolism, MESH: Dose-Response Relationship, Drug, law.invention, Cohort Studies, 0302 clinical medicine, Randomized controlled trial, law, Atrial Fibrillation, Outpatients, Medicine, MESH: Heparin, Low-Molecular-Weight, 030212 general & internal medicine, MESH: Warfarin, MESH: Cohort Studies, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Anticoagulant, Venous Thromboembolism, Hematology, General Medicine, Middle Aged, MESH: International Normalized Ratio, 3. Good health, MESH: Atrial Fibrillation, Venous thrombosis, Treatment Outcome, Drug Therapy, Combination, Female, Disease Susceptibility, MESH: Hemorrhage, Cohort study, medicine.drug, Adult, medicine.medical_specialty, medicine.drug_class, MESH: Disease Susceptibility, Hemorrhage, MESH: Nomograms, MESH: Anticoagulants, MESH: Drug Administration Schedule, Drug Administration Schedule, 03 medical and health sciences, Humans, International Normalized Ratio, Aged, Retrospective Studies, MESH: Humans, Dose-Response Relationship, Drug, business.industry, Warfarin, Anticoagulants, MESH: Vitamin K, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, Heparin, Low-Molecular-Weight, Nomogram, medicine.disease, MESH: Male, MESH: Outpatients, Surgery, Clinical trial, Nomograms, MESH: Drug Therapy, Combination, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Initiation of warfarin therapy is a clinical challenge. A 10-mg warfarin initiation nomogram was recently validated in a randomized controlled trial. We sought to determine the efficacy and safety of this 10-mg warfarin initiation nomogram in 'real-life' daily practice. A retrospective cohort including all outpatients beginning concurrent treatment with warfarin and low-molecular-weight heparin over a 24-month period in our Thrombosis Unit was reviewed. Eight hundred and forty-one patients were included; of them, 640 (76.1%) were started on the nomogram. The nomogram was entirely followed in 324 patients (38.5%). The efficacy and safety profile was similar to that observed in the original clinical trial; 86% of patients managed according to the nomogram reached the international normalized ratio target of 2.0-3.0 within 5 days. Mean duration of low-molecular-weight heparin treatment was 6.0 +/- 1.9 days, and 3.7% of patients had an international normalized ratio of at least 5.0 in the first 4 weeks of treatment. The 10-mg nomogram effectively results in an early therapeutic international normalized ratio with a good safety profile in 'real-life' daily practice.
Published: 2009

22. D‐dimer testing is useful to exclude deep vein thrombosis in elderly outpatients

Author: G. Le Gal, Shannon M. Bates, Marc Carrier, P. S. Wells, David R. Anderson, Thrombosis Program, University of Ottawa [Ottawa], Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Department of Medicine, McMaster University [Hamilton, Ontario], Department of Medicine - Halifax (DRA), Dalhousie University [Halifax], Clinical Epidemiology Program (PSW), and The Ottawa Health Research Institute
Subjects: medicine.medical_specialty, MESH: Diagnostic Techniques, Cardiovascular, MESH: Probability, Deep vein, Diagnostic Techniques, Cardiovascular, MESH: Algorithms, Clinical prediction rule, 030204 cardiovascular system & hematology, MESH: Venous Thromboembolism, Diagnosis, Differential, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, MESH: Aged, 80 and over, 0302 clinical medicine, Predictive Value of Tests, MESH: Diagnosis, Differential, Internal medicine, D-dimer, MESH: Fibrin Fibrinogen Degradation Products, medicine, Humans, In patient, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Aged, Probability, Aged, 80 and over, MESH: Aged, MESH: Humans, business.industry, Venous Thromboembolism, Hematology, medicine.disease, Thrombosis, MESH: Predictive Value of Tests, MESH: Prospective Studies, Surgery, Pre- and post-test probability, medicine.anatomical_structure, Predictive value of tests, business, Algorithms, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; BACKGROUND: Deep vein thrombosis (DVT) can be safely and reliably excluded in patients with a low clinical probability and a negative D-dimer result but the accuracy and utility of such a strategy is unclear in elderly patients. OBJECTIVES: We sought to compare the performance of the Wells pretest probability (PTP) model and D-dimer testing between patients of different age groups and to examine the utility of the two PTP model classification schemes (low/moderate/high vs. unlikely/likely) in excluding DVT in elderly outpatients. PATIENTS/METHODS: Pooled analysis of databases from three prospective diagnostic studies evaluating consecutive outpatients with suspected DVT. RESULTS: A total of 2696 patients were evaluated. DVT was diagnosed in 400 (15%) patients overall and in 50 out of 325 (15.5%) patients > or = 60 years old. The PTP distribution and the prevalence of DVT in each PTP category were similar among the different age groups. The negative predictive values of a low or unlikely PTP score in combination with a negative D-dimer result were 99% for all groups. A negative D-dimer in combination with a low or unlikely PTP excluded 21.7% and 31% of patients > or = 80 years old, respectively. CONCLUSIONS: The combination of a low or unlikely PTP with a negative D-dimer result can effectively and safely exclude DVT in a significant proportion of elderly outpatients. However, this clinical prediction rule needs to be prospectively validated with different D-dimer assays in this specific population.
Published: 2008

23. corregir afiliación

Author: Jose Luis Lopez-Guerra, Pedro Bilbao, P. Willisch, C. Carvajal, Alfonso Gomez-Iturriaga, V. Morillo, E. Hortelano, Ana Irasarri, Arturo Navarro, Francisco Casquero, Jose Ignacio Pijoan, Ana Illescas, Jon Cacicedo, Olga del Hoyo, Raquel Ciervide, [Gomez-Iturriaga,A, Cacicedo,J, Carvajal,C, Hortelano,E, Casquero,F, Del Hoyo,O, Bilbao,P] Department of Radiation Oncology, Hospital Universitario Cruces/ Biocruces Health Research Institute, Barakaldo, Spain. [Navarro,A] Department of Radiation Oncology, Instituto Catalan de Oncología, L'Hospitalet de Llobregat, Barcelona, Spain. [Morillo,V] Department of Radiation Oncology, Hospital de Castellón, Castelló de la Plana, Castelló, Spain. [Willisch,P] Department of Radiation Oncology, Hospital Meixoeiro, Vigo, Pontevedra, Spain. [Lopez-Guerra,JL] Department of Radiation Oncology, Hospital Virgen Del Rocío, Sevilla, Spain. [Illescas,A] Department of Radiation Oncology, Hospital Virgen Macarena, Sevilla, Spain. [Ciervide,R] Department of Radiation Oncology, Hospital San Chinarro, Madrid, Spain. [Irasarri,A, and Pijoan,JI] Clinical Epidemiology Unit, Hospital Universitario Cruces/ Biocruces Heatlh Research Institute, Barakaldo, Spain.
Subjects: Male, medicine.medical_specialty, Palliative care, Anatomy::Urogenital System::Genitalia::Genitalia, Male::Prostate [Medical Subject Headings], Pain medicine, medicine.medical_treatment, Analgesic, Pain, Check Tags::Male [Medical Subject Headings], Bone Neoplasms, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Radioterapia, Information Science::Information Science::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Internal medicine, Palliative radiotherapy, Medicine, Humans, Prospective Studies, Brief Pain Inventory, Neoplasm Metastasis, Prospective cohort study, Bone pain, Aged, Medicine(all), Aged, 80 and over, Radiotherapy, business.industry, Incidence (epidemiology), Bone metastases, Palliative Care, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Follow-Up Studies [Medical Subject Headings], General Medicine, Middle Aged, Diseases::Nervous System Diseases::Neurologic Manifestations::Pain [Medical Subject Headings], Surgery, Radiation therapy, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Peripheral Nervous System Agents::Sensory System Agents::Analgesics [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Dolor irruptivo, Female, medicine.symptom, Neoplasias óseas, Diseases::Neoplasms::Neoplasms by Site::Bone Neoplasms [Medical Subject Headings], business, Pain flare, Research Article
Abstract: Journal Article; Research Support, Non-U.S. Gov't; BACKGROUND Palliative radiotherapy (RT) is an effective treatment for symptomatic bone metastases. Pain flare, a transient worsening of the bone pain after RT, has been described in previous reports with different incidence rates. The aim of the study was to prospectively evaluate the incidence of pain flare following RT for painful bone metastases and evaluate its effects on pain control and functionality of the patients. METHODS Between June 2010 and June 2014, 204 patients were enrolled in this study and 135 patients with complete data were evaluable. Pain flare was defined as a 2- point increase in worst pain score as compared with baseline with no decrease in analgesic intake or a 25% increase in analgesic intake as compared with baseline with no decrease in worst pain score. All pain medications and worst pain scores were collected before, daily during, and for 10 days after RT. The Brief Pain Inventory (BPI) was filled out on the pretreatment and at the 4 weeks follow-up visit. RESULTS There were 90 men (66.7%) and 45 women (33.3%). Mean age was 66 years (SD 9.8). The most common primary cancer site was lung in 42 patients (31.1%), followed by prostate in 27 patients (20.0%). Forty-two patients (31.1%) patients received a single fraction of 8 Gy and 83 (61.5%) received 20 Gy in five fractions. The overall pain flare incidence across all centers was 51/135 (37.7%). The majority of pain flares occurred on days 1-5 (88.2%). The mean duration of the pain flare was 3 days (SD: 3). There were no significant relationships between the occurrence of pain flare and collected variables. All BPI items measured four weeks after end of RT showed significant improvement as compared with pretreatment scores (p
Published: 2015

24. Screening for Occult Cancer in Unprovoked Venous Thromboembolism

Author: Marc, Carrier, Alejandro, Lazo-Langner, Sudeep, Shivakumar, Vicky, Tagalakis, Ryan, Zarychanski, Susan, Solymoss, Nathalie, Routhier, James, Douketis, Kim, Danovitch, Agnes Y, Lee, Gregoire, Le Gal, Philip S, Wells, Daniel J, Corsi, Timothy, Ramsay, Doug, Coyle, Isabelle, Chagnon, Zahra, Kassam, Hardy, Tao, Marc A, Rodger, A Y, Lee, Thrombosis Program, University of Ottawa [Ottawa], Department of Medecine (OTTAWA - Dpt Med), Department of Medecine [Montréal], McGill University = Université McGill [Montréal, Canada], Department of Medicine (DM - McMaster), McMaster University [Hamilton, Ontario], Arizona Geological Survey, Service d'angiologie et d'hémostase (MR), Hôpital Universitaire de Genève, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, University College Dublin [Dublin] (UCD), Department of Medicine, University of Montreal, Key Laboratory of Silicate Materials Science and Engineering, WUHAN UNIVERSITY OF TECHNOLOGY, Haematology, Clinical Epidemiology Program (PSW), and The Ottawa Health Research Institute
Subjects: Male, Radiography, Abdominal, medicine.medical_specialty, Randomization, Radiography, [SDV]Life Sciences [q-bio], Occult Cancer, Uterine Cervical Neoplasms, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Pelvis, law.invention, 03 medical and health sciences, Prostate cancer, Unprovoked Venous Thromboembolism, 0302 clinical medicine, Randomized controlled trial, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, law, medicine, Humans, 030212 general & internal medicine, Diagnostic Errors, Early Detection of Cancer, Aged, business.industry, Incidence, Prostatic Neoplasms, Cancer, Venous Thromboembolism, General Medicine, Middle Aged, medicine.disease, 3. Good health, medicine.anatomical_structure, Neoplasms, Unknown Primary, Abdomen, Female, Radiology, Tomography, X-Ray Computed, business, Venous thromboembolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: International audience; Venous thromboembolism may be the earliest sign of cancer. Currently, there is a great diversity in practices regarding screening for occult cancer in a person who has an unprovoked venous thromboembolism. We sought to assess the efficacy of a screening strategy for occult cancer that included comprehensive computed tomography (CT) of the abdomen and pelvis in patients who had a first unprovoked venous thromboembolism. We conducted a multicenter, open-label, randomized, controlled trial in Canada. Patients were randomly assigned to undergo limited occult-cancer screening (basic blood testing, chest radiography, and screening for breast, cervical, and prostate cancer) or limited occult-cancer screening in combination with CT. The primary outcome measure was confirmed cancer that was missed by the screening strategy and detected by the end of the 1-year follow-up period. Of the 854 patients who underwent randomization, 33 (3.9%) had a new diagnosis of occult cancer between randomization and the 1-year follow-up: 14 of the 431 patients (3.2%) in the limited-screening group and 19 of the 423 patients (4.5%) in the limited-screening-plus-CT group (P=0.28). In the primary outcome analysis, 4 occult cancers (29%) were missed by the limited screening strategy, whereas 5 (26%) were missed by the strategy of limited screening plus CT (P=1.0). There was no significant difference between the two study groups in the mean time to a cancer diagnosis (4.2 months in the limited-screening group and 4.0 months in the limited-screening-plus-CT group, P=0.88) or in cancer-related mortality (1.4% and 0.9%, P=0.75). The prevalence of occult cancer was low among patients with a first unprovoked venous thromboembolism. Routine screening with CT of the abdomen and pelvis did not provide a clinically significant benefit. (Funded by the Heart and Stroke Foundation of Canada; SOME ClinicalTrials.gov number, NCT00773448.).
Published: 2015

25. Difference in interpretation of computed tomography pulmonary angiography diagnosis of subsegmental thrombosis in patients with suspected pulmonary embolism

Author: Miriam Kimpton, G. Le Gal, Carole Dennie, Marc Carrier, Elena Pena, Rebecca A. Peterson, Department of Radiology (CD - OTTAWA), University of Ottawa [Ottawa], Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Thrombosis Program, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)
Subjects: medicine.medical_specialty, Hemorrhage, Suspected pulmonary embolism, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, medicine, Pulmonary angiography, Humans, In patient, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Hemostasis, business.industry, Anticoagulants, Hematology, medicine.disease, Thrombosis, Pulmonary embolism, Platelet aggregation inhibitor, Radiology, Tomography, Pulmonary Embolism, Tomography, X-Ray Computed, business, Platelet Aggregation Inhibitors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Fibrinolytic agent
Abstract: International audience
Published: 2012

26. Clinical and safety outcomes associated with treatment of acute venous thromboembolism: a systematic review and meta-analysis

Author: Lana A Castellucci, George A. Wells, Philip S. Wells, Doug Coyle, Marc A. Rodger, Marc Carrier, Tammy Clifford, Esteban Gandara, Grégoire Le Gal, Chris Cameron, Thrombosis Program, University of Ottawa [Ottawa], Department of Biochemistry and Molecular Biology, Pennsylvania State University (Penn State), Penn State System-Penn State System, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Haematology, Clinical Epidemiology Program (PSW), The Ottawa Health Research Institute, University College Dublin [Dublin] (UCD), Canadian Agency for Drugs and Technologies in Health (OTTAWA - CADTH), Ottawa, Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, and Department of Medecine (OTTAWA - Dpt Med)
Subjects: Risk, endocrine system, medicine.medical_specialty, medicine.drug_class, Venous Thromboembolism/*drug therapy, [SDV]Life Sciences [q-bio], Low molecular weight heparin, Hemorrhage, Fondaparinux, Lower risk, Gastroenterology, Anticoagulants/adverse effects/*therapeutic use, chemistry.chemical_compound, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Edoxaban, Internal medicine, Hemorrhage/chemically induced, medicine, Humans, Rivaroxaban, business.industry, Hazard ratio, Antagonist, Anticoagulants, Venous Thromboembolism, General Medicine, 3. Good health, chemistry, Anesthesia, Acute Disease, Apixaban, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; Many anticoagulant strategies are available for the treatment of acute venous thromboembolism, yet little guidance exists regarding which drug is most effective and safe. To summarize and compare the efficacy and safety outcomes associated with 8 anticoagulation options (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], or fondaparinux in combination with vitamin K antagonists); LMWH with dabigatran or edoxaban; rivaroxaban; apixaban; and LMWH alone) for treatment of venous thromboembolism. A systematic literature search was conducted using MEDLINE, EMBASE, and the evidence-based medicine reviews from inception through February 28, 2014. Eligible studies were randomized trials reporting rates of recurrent venous thromboembolism and major bleeding in patients with acute venous thromboembolism. Of the 1197 studies identified, 45 trials including 44,989 patients were included in the analyses. Two reviewers independently extracted trial-level data including number of patients, duration of follow-up, and outcomes. The data were pooled using network meta-analysis. The primary clinical and safety outcomes were recurrent venous thromboembolism and major bleeding, respectively. Compared with the LMWH-vitamin K antagonist combination, a treatment strategy using the UFH-vitamin K antagonist combination was associated with an increased risk of recurrent venous thromboembolism (hazard ratio [HR], 1.42; 95% credible interval [CrI], 1.15-1.79). The proportion of patients experiencing recurrent venous thromboembolism during 3 months of treatment were 1.84% (95% CrI, 1.33%-2.51%) for the UFH-vitamin K antagonist combination and 1.30% (95% CrI, 1.02%-1.62%) for the LMWH-vitamin K antagonist combination. Rivaroxaban (HR, 0.55; 95% CrI, 0.35-0.89) and apixaban (HR, 0.31; 95% CrI, 0.15-0.62) were associated with a lower risk of bleeding than was the LMWH-vitamin K antagonist combination, with a lower proportion of patients experiencing a major bleeding event during 3 months of anticoagulation: 0.49% (95% CrI, 0.29%-0.85%) for rivaroxaban, 0.28% (95% CrI, 0.14%-0.50%) for apixaban, and 0.89% (95% CrI, 0.66%-1.16%) for the LMWH-vitamin K antagonist combination. Using meta-analytic pooling, there were no statistically significant differences for efficacy and safety associated with most treatment strategies used to treat acute venous thromboembolism compared with the LMWH-vitamin K antagonist combination. However, findings suggest that the UFH-vitamin K antagonist combination is associated with the least effective strategy and that rivaroxaban and apixaban may be associated with the lowest risk for bleeding.
Published: 2014

27. A simple method to identify patients on long-term warfarin who may derive the most benefit from new oral anticoagulants

Author: Miriam Kimpton, Marc Carrier, Grégoire Le Gal, Nicole Langlois, Shemina Kherani, Philip S. Wells, Thrombosis Program, University of Ottawa [Ottawa], Clinical Epidemiology Program (PSW), The Ottawa Health Research Institute, Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)
Subjects: Male, medicine.medical_specialty, endocrine system, Vitamin K, [SDV]Life Sciences [q-bio], Administration, Oral, Time in therapeutic range, Primary care, Vitamin k, Interquartile range, Internal medicine, Atrial Fibrillation, Outpatients, medicine, Humans, International Normalized Ratio, Blood Coagulation, Aged, business.industry, External validation, Curve analysis, Warfarin, Anticoagulants, nutritional and metabolic diseases, Venous Thromboembolism, Hematology, General Medicine, Middle Aged, 3. Good health, Cross-Sectional Studies, ROC Curve, Female, Blood Coagulation Tests, business, Anticoagulation clinic, medicine.drug
Abstract: International audience; : In many countries, new oral anticoagulants are only covered for patients with suboptimal anticoagulation control on vitamin K antagonists (VKAs). The quality of VKA management is often reported using the time in therapeutic range (TTR). We sought to predict a TTR 65% or less using a surrogate measure [number of changes in VKA dose and number of international normalized ratio (INR) tests] that could be easily determined by primary care physicians. This cross-sectional study included consecutive patients whose VKA therapy was managed in a specialized anticoagulation clinic. Patients were dichotomized according to their TTR in the past 6 months (TTR > or ≤65%). The ability of the number of INR tests and VKA dose changes to predict TTR group was assessed using receiver-operating characteristics (ROC) curve analysis. The analyses included 1381 patients with a median age of 63 years. The mean TTR was 81% (interquartile range 70-90) and 17.4% of patients had a TTR 65% or more. Based on the ROC curve, patients were stratified according to whether they had either 3 or more dose changes or 9 or more INR tests within the last 6 months. The sensitivity to identify patients with TTR 65% or less was 87% and the specificity was 63%. The number of dose changes and the number of INR tests might be used as indicators of TTR; they could offer a simple way for clinicians to identify patients who are good candidates for the new oral anticoagulants. However, external validation studies in different clinical settings are needed to confirm these findings.
Published: 2014

28. Increased risk of preoperative venous thromboembolism in patients with renal cell carcinoma and tumor thrombus: reply

Author: Yokom, D. W., Le Gal, Grégoire, Carrier, Marc, Clinical Epidemiology Program (PSW), The Ottawa Health Research Institute, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Thrombosis Program, University of Ottawa [Ottawa], Clinical Epidemiology Unit, and Ottawa-The Ottawa Hospital
Subjects: Male, [SDV]Life Sciences [q-bio], Thrombosis, Hematology, Venous Thromboembolism, 030204 cardiovascular system & hematology, Kidney Neoplasms, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Humans, Female, Carcinoma, Renal Cell, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract: International audience
Published: 2014

29. Prognostic significance of residual venous obstruction in patients with treated unprovoked deep vein thrombosis A patient-level meta-analysis

Author: Benilde Cosmi, Monica Caprioli, Laura Young, Daniela Poli, Alfonso Iorio, Grégoire Le Gal, Walter Ageno, Paolo Prandoni, Giorgia Saccullo, Emilia Antonucci, Matteo Bonzini, Marc A. Rodger, Sergio Siragusa, Francesco Dentali, Marco P. Donadini, Paul Ockelford, Michael J. Kovacs, James D. Douketis, Donadini, M.P., Ageno, W., Antonucci, E., Cosmi, B., Kovacs, M.J., Le Gal, G., Ockelford, P., Poli, D., Prandoni, P., Rodger, M., Saccullo, G., Siragusa, S., Young, L., Bonzini, M., Caprioli, M., Dentali, F., Iorio, A., Douketis, J.D., Department of Clinical and Experimental Medicine (VARESE - Thrombosis Center), Universitá degli Studi dell’Insubria, Department of Medical-Surgical Critical Area (FLORENCE - Thrombosis Center), Azienda Ospedaliero-Universitaria, Department of Angiology and Blood Coagulation (DABC), University Hospital S Orsola-Malpighi, Division of Hematology (MJK), University of Western Ontario (UWO), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Haematology (AUCKLAND - Haematology), Auckland City Hospital, Department of Cardiothoracic and Vascular Sciences (PADUA - Thromboembolism Unit), Universita degli Studi di Padova, Thrombosis Program, University of Ottawa [Ottawa], Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Department of Internal Medicine (PALERME - Med Int), Università degli studi di Palermo - University of Palermo, Department of Internal Medicine (PARLERME - Med Int), Department of Molecular Medicine (AUCKLAND - Molecular Medicine), University of Auckland [Auckland], Department of Clinical and Experimental Medicine (VARESE - DCEM), Department of Clinical Epidemiology and Biostatistics (HAMILTON - DCEB), McMaster University [Hamilton, Ontario], and Department of Medicine (DM - McMaster)
Subjects: Male, medicine.medical_specialty, Deep vein, [SDV]Life Sciences [q-bio], Unprovoked deep vein thrombosis, Patient-level meta-analysis, 030204 cardiovascular system & hematology, Sensitivity and Specificity, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, Residual venous obstruction, medicine, Humans, 030212 general & internal medicine, cardiovascular diseases, Prospective cohort study, Aged, Proportional Hazards Models, Randomized Controlled Trials as Topic, Thrombectomy, Ultrasonography, Venous Thrombosis, Proportional hazards model, business.industry, Hazard ratio, Anticoagulants, Reproducibility of Results, Thrombosis, Hematology, Venous Thromboembolism, Middle Aged, medicine.disease, Venous Obstruction, Confidence interval, Surgery, medicine.anatomical_structure, Meta-analysis, Multivariate Analysis, Female, Recurrent venous thromboembolism, deep vein thrombosis, residual thrombosis, ultrasonography, vitamin K antagonsists, business
Abstract: SummaryResidual venous obstruction (RVO) could improve the stratification of the risk of recurrence after unprovoked deep vein thrombosis (DVT), but results from clinical studies and study-level meta-analyses are conflicting. It was the objective of this analysis to determine if RVO is a valid predictor of recurrent venous thromboembolism (VTE) in patients with a first unprovoked DVT who had received at least three months of anticoagulant therapy. Individual patient data were obtained from the datasets of original studies, after a systematic search of electronic databases (Medline, Embase, Cochrane Library), supplemented by manual reviewing of the reference lists and contacting content experts. A multivariate, shared-frailty Cox model was used to calculate hazard ratios (HRs) for recurrent VTE, including, as covariates: RVO; age; sex; anticoagulation duration before RVO assessment; and anticoagulation continuation after RVO assessment. A total of 2,527 patients from 10 prospective studies were included. RVO was found in 1,380 patients (55.1%) after a median of six months from a first unprovoked DVT. Recurrent VTE occurred in 399 patients (15.8%) during a median follow-up of 23.3 months. After multivariate Cox analysis, RVO was independently associated with recurrent VTE (HR = 1.32, 95% confidence interval [CI]: 1.06–1.65). The association was stronger if RVO was detected early, i.e. at three months after DVT (HR = 2.17; 95% CI: 1.11–4.25), but non-significant if detected later, i.e. >6 months (HR = 1.19; 95% CI: 0.87–1.61). In conclusion, after a first unprovoked DVT, RVO is a weak overall predictor of recurrent VTE. The association is stronger if RVO is detected at an earlier time (3 months) after thrombosis.
Published: 2014

30. Defining time in therapeutic range for busy clinicians: frequency of dose changes is a good surrogate marker to identify patients with suboptimal anticoagulation with warfarin

Author: Grégoire Le Gal, Abirami Vijenthira, Marc Carrier, Lana A Castellucci, Thrombosis Program, University of Ottawa [Ottawa], Département de médecine, Ottawa Hopital Research Institute, Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Institut de Recherche de l'Hopital Montfort [Ottawa] (IRHM), and Bertignac, Catherine
Subjects: Adult, Male, medicine.medical_specialty, endocrine system, Time Factors, Adolescent, [SDV]Life Sciences [q-bio], Time in therapeutic range, Diagnostic tools, Young Adult, Predictive Value of Tests, Internal medicine, Venous thrombosis, medicine, Humans, Drug Dosage Calculations, International Normalized Ratio, Adverse effect, Blood Coagulation, Aged, Retrospective Studies, Aged, 80 and over, Acenocoumarol, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Surrogate endpoint, business.industry, Warfarin, Anticoagulants, nutritional and metabolic diseases, Hematology, Venous Thromboembolism, Middle Aged, medicine.disease, Surgery, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, Treatment Outcome, Female, Drug Monitoring, business, Venous thromboembolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Introduction Patients on warfarin with sub-optimal time-in-therapeutic-range (TTR) are more likely to have adverse events. Target-specific oral anticoagulants (TSOACs) are approved and can be used as an alternative to warfarin for a number of indications. Further, the efficacy and safety profiles of the TSOACs compared to warfarin are more favourable when the TTR is ≤ 65% for certain indications. Objective We aimed to determine simple, sensitive and specific diagnostic tools to identify TTR ≤ 65% during the initial three months of warfarin therapy. Methods A cross-sectional study including patients newly initiated on warfarin without any interruption for three months was conducted. TTR was calculated using the Rosendaal method. Patients were stratified by TTR (≤ 65% or > 65%). Number of INR measurements, dose changes and INR measurements of ≤ 1.7 or ≥ 4.0 were evaluated as potential diagnostic tools to identify TTR ≤ 65%. Results 670 patients were included. The most common indication for anticoagulation was venous thromboembolism. The mean TTR in the first three months was 68 ± 21% (Range: 10 to 100%). Three or more dose changes identified TTR ≤ 65% and demonstrated a sensitivity and specificity of 90% (95%CI 86 to 93%) and 56% (95%CI 51 to 61%), respectively. Three or more INR measurements of ≤ 1.7 during the initial three months of anticoagulation showed a sensitivity and specificity of 37% (95%CI 32 to 43%) and 98% (95%CI 96 to 99%), respectively. Conclusion Three or more dose changes and three or more INR measurements of ≤ 1.7 could identify patients with a TTR ≤ 65% in the first three months of warfarin therapy.
Published: 2014

31. Non-OO blood type influences the risk of recurrent venous thromboembolism. A cohort study

Author: Nancy Carson, Marc A. Rodger, Grégoire Le Gal, Philip S. Wells, Susan Solymoss, Marc Carrier, Tim Ramsay, Isabelle Chagnon, David A. Anderson, Mark Crowther, Susan R. Kahn, Nicole Langlois, Esteban Gandara, Julian Little Ma, Michael J. Kovacs, Judy Kovacs, Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Thrombosis Program, University of Ottawa [Ottawa], Department of Medicine (LONDON ONTARIO - Med), University of Western Ontario (UWO), Department of Medecine [Montréal], McGill University = Université McGill [Montréal, Canada], Centre for Clinical Epidemiology and Community Studies (CCECS), Jewish General Hospital, Department of Medicine, Dalhousie University [Halifax], University of Montreal, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), McMaster University [Hamilton, Ontario], Institut des Matériaux Jean Rouxel (IMN), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN), Department of Epidemiology and Community Medicine (OTTAWA - Epidemio), and Department of Pediatrics (OTTAWA - Pedia)
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Administration, Oral, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Risk Factors, Internal medicine, medicine, Humans, 030212 general & internal medicine, cardiovascular diseases, Risk factor, Aged, Blood type, First episode, business.industry, Hazard ratio, Anticoagulants, Hematology, Venous Thromboembolism, Middle Aged, medicine.disease, Thrombosis, 3. Good health, Surgery, Discontinuation, Blood Grouping and Crossmatching, Withholding Treatment, Cohort, Blood Group Antigens, Female, business, Cohort study, Follow-Up Studies
Abstract: SummaryThe role of ABO blood type as a risk factor for recurrent venous thromboembolism (VTE) in patients with a first unprovoked VTE who complete oral anticoagulation therapy is unknown. The aim of this study was to determine if non-OO blood type is a risk factor for recurrent VTE in patients with a first unprovoked VTE who completed 5–7 months of anticoagulant therapy. In an ongoing cohort study of patients with unprovoked VTE who discontinued oral anticoagulation after 5–7 months of therapy, six single nucleotide polymorphisms sites were tested to determine ABO blood type using banked DNA. The main outcome was objectively proven recurrent VTE. Mean follow-up for the cohort was 4.19 years (SD 2.16). During 1,553 patient-years of follow-up, 101 events occurred in 380 non-OO patients (6.5 events per 100 patient years; 95% CI 5.3–7.7) compared to 14 events during 560 patient years of follow-up in 129 OO patients (2.5 per 100 patient years; 95% CI 1.2–3.7), the adjusted hazard ratio was 1.98 (1.2–3.8). In conclusion, non-OO blood type is associated with a statistically significant and clinically relevant increased risk of recurrent VTE following discontinuation of anticoagulant therapy for a first episode of unprovoked VTE.
Published: 2013

32. Bladder cancer index: cross-cultural adaptation into Spanish and psychometric evaluation

Author: Schmidt, Stefanie, Riel, Ricard, Frances, Albert, Lorente Garín, José Antonio, Bonfill Cosp, Xavier, Martinez Zapata, María José, Morales Suárez-Varela, María, De la Cruz, Javier, Emparanza, José Ignacio, Sánchez-Pérez, María José, Zamora, Javier, Ramos Goñi, Juan Manuel, Alonso, Jordi, Ferrer, Montserrat, Becerra, Virginia, Pardo Cladellas, Yolanda, Garin, Olatz, Orrego Villagran, Carola, Suñol, Rosa, Osorio, Dimelza, Canovas, Esther, Sancho Pardo, Gemma, Bolívar, Ignasi, Bachs, Jordi, Maroto, Pablo, Quintana, María Jesús, Martín Lorente, Cristina, Algaba, Ferran, Palou Redorta, Joan, Esquena Fernández, Salvador, Puigvert, Fundació, Vernooij, Robin W.M., Martínez, Arnaia, Pijoan Zubizarreta, J. I., Martínez, Lorea, Castro Diaz, D. M., Bastida, J. L., Suárez Pacheco, Armando, López, C. G., Cozar Olmo, J. M, Martínez, Carmen, Chan, Daisy Chang, Sanchez Perez, M. J., Díaz Moratinos, A. I., Luis, A. M., Hervás, A., Ocaña, C. V., Varona, C., Burgos, Javier, Polo Rubio, J. A., López-Fando Lavalle, L., Jimenez Cidre, M. A., Garcia, A. M., Farras, N. P., Lopez, R. M., Garcia, S. S., Abraira, Víctor, Dos Santos, V. G., De la Cámara, A. G., Martinez, J. P., Muñoz, H. G., Cabeza Rodríguez, M. A., Díaz, I. R., Sanz Jaka, J. P., Velásquez, M. J., González, A. L., Morales, M., Camps, Carlos, Díaz, C. C., Vidal, E. M., Ballester, F. S., Juan Escudero, J. U., Peidro, J. P., Torrecilla, J. L., Ramos Campos, M. M., Cebollada, M. M., EMPARO-CU Study Group, [Schmidt,S, Alonso,J, Ferrer,M] Health Services Research Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. [Schmidt,S, Alonso,J] Department of Experimental and Health Sciences, Universidad Pompeu Fabra (UPF), Barcelona, Spain. [Schmidt,S, Bonfill,X, Martinez-Zapata,MJ, Morales Suarez-Varela,M, dela Cruz,J, Emparanza,JI, Sánchez,MJ, Zamora,J, Ferrer,M] CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Riel,R] Center of Primary Health Care El Clot, Barcelona, Spain. [Frances,A, Lorente Garin,JA] Department of Urology, Hospital del Mar, Barcelona, Spain. [Bonfill,X, Martinez-Zapata,MJ] Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain. [ Bonfill,X, Ferrer,M] Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. [Morales Suarez-Varela,M] Unit of Public Health and Environmental Care, Department of Preventive Medicine, University of Valencia, Valencia, Spain. [Morales Suarez-Varela,M] Center for Public Health Research (CSISP), Valencia, Spain. [dela Cruz,J] Hospital 12 de Octubre, Madrid, Spain. [Emparanza,JI] Clinical Epidemiology Unit, Hospital Universitario Donostia, BioDonostia, San Sebastian, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria de Granada, Granada, Spain. [Zamora,J] Clinical Biostatistics Unit, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain. [Ramos Goñi,JM HTA Unit of the Canary Islands Health Service (SESCS), Tenerife, Spain. [Ramos Goñi,JM] Health Services Research on Chronic Patients Network (REDISSEC), Bilbao, Spain., This work was supported by grants from Instituto de Salud Carlos III FEDER (PS09/02139, PS09/01204, PS09/01619, PS09/02555, PI12/00772) and from AGAUR (2012FI_B1 00177, and 2009 SGR 1095).
Subjects: Male, Psychometrics, Aparell urinari, Surveys and Questionnaires, Prospective cohort study, Càncer, media_common, Language, Cognition, General Medicine, Patient outcome, Control de qualitat, Neoplasias de la Vejiga Urinaria, Estudios de Validación, Psicometría, Bufeta -- Càncer, Female, Psicometria, Clinical psychology, Cross-Cultural Comparison, Quality of life, medicine.medical_specialty, Urinary bladder neoplasms, Psychiatry and Psychology::Behavioral Disciplines and Activities::Psychological Tests::Psychometrics [Medical Subject Headings], Publication Characteristics::Study Characteristics::Validation Studies [Medical Subject Headings], Cronbach's alpha, Disciplines and Occupations::Social Sciences::Quality of Life [Medical Subject Headings], medicine, Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Urologic Neoplasms::Urinary Bladder Neoplasms [Medical Subject Headings], media_common.cataloged_instance, Humans, European Union, European union, Aged, Neoplasm Staging, Gynecology, Analysis of Variance, Bladder cancer, business.industry, Research, Public Health, Environmental and Occupational Health, Construct validity, Translating, medicine.disease, Cross-cultural studies, United States, Validation studies, Patient outcomes, Calidad de Vida, business
Abstract: Background: The Bladder Cancer Index (BCI) is so far the only instrument applicable across all bladder cancer patients, independent of tumor infiltration or treatment applied. We developed a Spanish version of the BCI, and assessed its acceptability and metric properties. Methods: For the adaptation into Spanish we used the forward and back-translation method, expert panels, and cognitive debriefing patient interviews. For the assessment of metric properties we used data from 197 bladder cancer patients from a multi-center prospective study. The Spanish BCI and the SF-36 Health Survey were self-administered before and 12 months after treatment. Reliability was estimated by Cronbach’s alpha. Construct validity was assessed through the multi-trait multi-method matrix. The magnitude of change was quantified by effect sizes to assess responsiveness./nResults: Reliability coefficients ranged 0.75-0.97. The validity analysis confirmed moderate associations between the BCI function and bother subscales for urinary (r = 0.61) and bowel (r = 0.53) domains; conceptual independence among all BCI domains (r ≤ 0.3); and low correlation coefficients with the SF-36 scores, ranging 0.14-0.48. Among patients reporting global improvement at follow-up, pre-post treatment changes were statistically significant for the urinary domain and urinary bother subscale, with effect sizes of 0.38 and 0.53. Conclusions: The Spanish BCI is well accepted, reliable, valid, responsive, and similar in performance compared to the original instrument. These findings support its use, both in Spanish and international studies, as a valuable and comprehensive tool for assessing quality of life across a wide range of bladder cancer patients. This work was supported by grants from Instituto de Salud Carlos III FEDER(PS09/02139; PS09/01204; PS09/01619; PS09/02555; PI12/00772) and from AGAUR (2012FI_B1 00177; 2009 SGR 1095).
Published: 2013

33. Outpatient treatment of symptomatic pulmonary embolism: a systematic review and meta-analysis

Author: Siavash Piran, Grégoire Le Gal, Marc Philip Righini, Philip S. Wells, Esteban Gandara, Marc A. Rodger, Marc Carrier, Thrombosis Program, University of Ottawa [Ottawa], Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Service d'angiologie et d'hémostase (MR), and Hôpital Universitaire de Genève
Subjects: medicine.medical_specialty, medicine.drug_class, Deep vein, [SDV]Life Sciences [q-bio], Low molecular weight heparin, Hemorrhage, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Recurrence, Internal medicine, Outpatients, medicine, Ambulatory Care, Humans, 030212 general & internal medicine, cardiovascular diseases, Adverse effect, ddc:616, business.industry, Mortality rate, Hematology, Venous Thromboembolism, medicine.disease, Confidence interval, 3. Good health, Pulmonary embolism, Surgery, medicine.anatomical_structure, Treatment Outcome, Meta-analysis, business, Pulmonary Embolism
Abstract: International audience; BACKGROUND: Patients with acute deep vein thrombus (DVT) can safely be treated as outpatients. However the role of outpatient treatment in patients diagnosed with a pulmonary embolism (PE) is controversial. We sought to determine the safety of outpatient management of patients with acute symptomatic PE. MATERIALS AND METHODS: A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews. Pooled proportions for the different outcomes were calculated. RESULTS: A total of 1258 patients were included in the systematic review. The rate of recurrent venous thromboembolism (VTE) in patients with PE managed as outpatients was 1.47% (95% CI: 0.47 to 3.0%; I(2): 65.4%) during the 3 month follow-up period. The rate of fatal PE was 0.47% (95% CI: 0.16 to 1.0%; I(2): 0%). The rates of major bleeding and fatal intracranial hemorrhage were 0.81% (95% CI: 0.37 to 1.42%; I(2): 0%) and 0.29% (95% CI: 0.06 to 0.68%; I(2): 0%), respectively. The overall 3 month mortality rate was 1.58% (95% CI: 0.71 to 2.80%; I(2): 45%). The event rates were similar if employing risk stratification models versus using clinical gestalt to select appropriate patients for outpatient management. CONCLUSIONS: Independent of the risk stratification methods used, the rate of adverse events associated with outpatient PE treatment seems low. Based on our systematic review and pooled meta-analysis, low-risk patients with acute PE can safely be treated as outpatients if home circumstances are adequate.
Published: 2013

34. HLA Shared Epitope and ACPA: Just a Marker or an Active Player?

Author: Paola Migliorini, John Sidney, Laëtitia Michou, Elisabeth Petit Teixeira, Ilaria Puxeddu, Alessandro Sette, François Cornelis, Federico Pratesi, Université de Pise, Laboratoire de recherche européen pour la polyarthrite rhumatoïde (GenHotel), Université d'Évry-Val-d'Essonne (UEVE), Laboratory of Epidemiology, Clinical Epidemiology Unit, Istituto Superiore di Sanita [Rome], La Jolla Institute for Immunology [La Jolla, CA, États-Unis], University of Pisa - Università di Pisa, and Istituto Superiore di Sanità (ISS)
Subjects: musculoskeletal diseases, Immunology, Antigen presentation, Arthritis, Human leukocyte antigen, Biology, Epitope, Antibodies, Arthritis, Rheumatoid, 03 medical and health sciences, Epitopes, 0302 clinical medicine, Immune system, Antigen, immune system diseases, Rheumatoid, medicine, Immunology and Allergy, Humans, Animals, Allele, skin and connective tissue diseases, Autoantibodies, 030203 arthritis & rheumatology, Genetics, Antigen Presentation, Proteins, HLA-DR Antigens, medicine.disease, Antibodies, Anti-Idiotypic, Anti-Idiotypic, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, biology.protein, Citrulline, Antibody, 030217 neurology & neurosurgery, HLA-DRB1 Chains
Abstract: International audience; Autoantibody production is genetically controlled and anti-citrullinated protein/peptide antibodies (ACPA) are not an exception to the rule. ACPA are highly specific markers of rheumatoid arthritis (RA) and are also associated with a more severe disease course. The production of ACPA is almost invariably observed in HLA-shared epitope (SE) positive patients. The DRB1 alleles sharing SE are those conferring susceptibility to RA. SE alleles behave like immune response genes, controlling both the specificity and the amount of ACPA produced. These data suggest a role of SE in the presentation of citrullinated antigens. The ability of SE alleles to bind selectively to citrullinated sequences as compared to the native counterparts has been demonstrated in the case of peptides derived from several joint associated proteins (vimentin, fibrinogen and cartilage intermediate-layer protein). On the contrary, EBV-derived citrullinated peptides do not display a biologically relevant binding to SE alleles even if the immune response to VCPs is under the genetic control of these alleles (namely *0401 and *0404). Thus, the presentation of citrullinated epitopes does not represent the only molecular mechanisms underlying the HLA-DRB1 effect on ACPA production.
Published: 2013

35. Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention of venous thromboembolism: systematic review and network meta-analysis

Author: Marc A. Rodger, George A. Wells, Doug Coyle, Esteban Gandara, Chris Cameron, Marc Carrier, Philip S. Wells, Tammy Clifford, Grégoire Le Gal, Lana A Castellucci, Thrombosis Program, University of Ottawa [Ottawa], Epidemiology and Community Medicine (OTTAWA - ECM), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Canadian Agency for Drugs and Technologies in Health (OTTAWA - CADTH), Ottawa, Department of Medicine, Ottawa Hospital, and Calvez, Ghislaine
Subjects: Vitamin K, [SDV]Life Sciences [q-bio], MESH: Calcium Channel Blockers, 030204 cardiovascular system & hematology, MESH: Venous Thromboembolism, 0302 clinical medicine, Rivaroxaban, Recurrence, Medicine, MESH: Animals, 030212 general & internal medicine, MESH: Organ Specificity, Absolute risk reduction, Venous Thromboembolism, General Medicine, MESH: Muscle, Smooth, Vascular, MESH: Thiophenes, Dabigatran, 3. Good health, [SDV] Life Sciences [q-bio], MESH: beta-Alanine, MESH: Platelet Aggregation Inhibitors, Meta-analysis, Anesthesia, MESH: Chemistry, Apixaban, MESH: Cats, MESH: Hemorrhage, medicine.drug, medicine.medical_specialty, MESH: Terminology as Topic, MESH: Rats, Pyridones, Morpholines, MEDLINE, MESH: Morpholines, Hemorrhage, Thiophenes, MESH: Anticoagulants, Placebo, MESH: Nervous System Diseases, 03 medical and health sciences, Internal medicine, MESH: Pyridones, Humans, MESH: Aspirin, MESH: Humans, Aspirin, business.industry, Anticoagulants, MESH: Cardiovascular Diseases, MESH: Vitamin K, MESH: Chemical Phenomena, Odds ratio, MESH: Recurrence, MESH: Heart, beta-Alanine, Pyrazoles, Benzimidazoles, business, MESH: Benzimidazoles, Platelet Aggregation Inhibitors, MESH: Pyrazoles
Abstract: International audience; OBJECTIVE: To summarise and compare the efficacy and safety of various oral anticoagulants (dabigatran, rivaroxaban, apixaban, and vitamin K antagonists) and antiplatelet agents (acetylsalicylic acid) for the secondary prevention of venous thromboembolism. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Literature search using Medline (1950 to present), Embase (1980 to present), and the Cochrane Register of Controlled Trials using the OVID interface. Publications from potentially relevant journals were also searched by hand. REVIEW METHODS: Randomised controlled trials of patients receiving anticoagulants, antiplatelet drugs, or placebo or observation for secondary prevention of venous thromboembolism. Selected outcomes were rates of recurrent venous thromboembolism and major bleeding. Two reviewers independently extracted data onto standardised forms. RESULTS: 12 articles met our inclusion criteria, with 11,999 patients evaluated for efficacy and 12,167 for safety. All treatments reduced the risk of recurrent venous thromboembolism. Compared with placebo or observation, vitamin K antagonists at a standard adjusted dose (target international normalised ratio 2.0-3.0) showed the highest risk difference (odds ratio 0.07; 95% credible interval 0.03 to 0.15) and acetylsalicylic acid showed the lowest risk difference (0.65; 0.39 to 1.03). Risk of major bleeding was higher with a standard adjusted dose of vitamin K antagonists (5.24; 1.78 to 18.25) than with placebo or observation. Fatal recurrent venous thromboembolism and fatal bleeding were rare. Detailed subgroup and individual patient level data were not available. CONCLUSIONS: All oral anticoagulants and antiplatelet agents investigated in this analysis were associated with a reduced recurrence of venous thromboembolism compared with placebo or observation, although acetylsalicylic acid was associated with the lowest risk reduction. Vitamin K antagonists given at a standard adjusted dose was associated with the greatest risk reduction in recurrent venous thromboembolism, but also the greatest risk of major bleeding.
Published: 2013

36. Family history of venous thromboembolism (VTE) as a predictor for recurrent VTE in unprovoked VTE patients

Author: P. S. Wells, Michael J. Kovacs, Karine Gauthier, Marc A. Rodger, G. Le Gal, Thrombosis Program, University of Ottawa [Ottawa], Division of Hematology (MJK), University of Western Ontario (UWO), Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Time Factors, Deep vein, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, 0302 clinical medicine, Recurrence, Risk Factors, Surveys and Questionnaires, Medicine, 030212 general & internal medicine, Prospective Studies, Family history, Oral anticoagulation, Aged, 80 and over, education.field_of_study, Hematology, Venous Thromboembolism, Middle Aged, Thrombosis, 3. Good health, Pulmonary embolism, Pedigree, medicine.anatomical_structure, Phenotype, Female, Major bleeding, Adult, medicine.medical_specialty, Adolescent, Population, Disease-Free Survival, 03 medical and health sciences, Young Adult, Humans, Genetic Predisposition to Disease, cardiovascular diseases, education, Intensive care medicine, Blood Coagulation, Aged, Proportional Hazards Models, business.industry, Anticoagulants, medicine.disease, equipment and supplies, Multivariate Analysis, business, Venous thromboembolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is a common potentially lethal condition [1-2]. Treatment with oral anticoagulation (OAC) therapy is effective at reducing recurrent VTE, but long-term oral anticoagulation therapy needs to be counterbalanced with the risk of major bleeding. Identification of subgroups of patients with unprovoked VTE that have lower and higher risk of recurrent VTE is important to help tailor length of anticoagulation in this population. © 2012 International Society on Thrombosis and Haemostasis.
Published: 2013

37. Venous thromboembolism in cancer clinical trials: recommendation for standardized reporting and analysis

Author: Carrier, M., Khorana, A. A., Zwicker, J. I., Lyman, G. H., Le Gal, Grégoire, Lee, A. Y. Y., Renseigné, Non, Thrombosis Program, University of Ottawa [Ottawa], Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Calvez, Ghislaine
Subjects: Pathology, medicine.medical_specialty, Clinical Trials as Topic, MESH: Humans, MESH: Clinical Trials as Topic, Cancer clinical trial, business.industry, [SDV]Life Sciences [q-bio], Hematology, Venous Thromboembolism, Malignancy, medicine.disease, MESH: Venous Thromboembolism, [SDV] Life Sciences [q-bio], Internal medicine, Neoplasms, medicine, Humans, MESH: Neoplasms, business, Venous thromboembolism, ComputingMilieux_MISCELLANEOUS
Abstract: Carrier M, Khorana AA, Zwicker JI, Lyman GH, Le Gal G and Lee AYY on behalf of the subcommittee on Haemostasis and Malignancy for the SSC of the ISTH. Venous thromboembolism in cancer clinical trials: recommendation for standardized reporting and analysis. J Thromb Haemost 2012; 10: 2599–601.
Published: 2012

38. Predictors of post-thrombotic syndrome in a population with a first deep vein thrombosis and no primary venous insufficiency

Author: Arnaud Perrier, Marc A. Rodger, P. S. Wells, Isabelle Chagnon, Susan R. Kahn, M. T. Betancourt, Tim Ramsay, Christina Holcroft, G. Le Gal, David Anderson, Mark Crowther, Michael J. Kovacs, Jean-Philippe Galanaud, Linda M. Vickars, Richard H. White, Susan Solymoss, Centre for Clinical Epidemiology and Community Studies (CCECS), Jewish General Hospital, Thrombosis Program, University of Ottawa [Ottawa] (uOttawa), Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Division of Hematology (MJK), University of Western Ontario (UWO), Department of Medicine - Halifax (DRA), Dalhousie University [Halifax], Department of Medicine (DM - HSC Montréal), University of Montreal, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medecine [Montréal], McGill University, Department of Medicine (DM - McMaster), McMaster University [Hamilton, Ontario], Interfaces, Traitements, Organisation et Dynamique des Systèmes (ITODYS (UMR_7086)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Department of Medicine (UDSM), UC Davis School of Medicine, Department of Medicine (UBC - St Paul Hospital), University of British Colombia, University of Ottawa [Ottawa], Université de Brest (UBO)-Université de Brest (UBO), McGill University = Université McGill [Montréal, Canada], and Université Paris Diderot - Paris 7 (UPD7)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH: Dilatation, Pathologic, Time Factors, Deep vein, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, MESH: Risk Assessment, Postthrombotic Syndrome, 0302 clinical medicine, MESH: Risk Factors, MESH: Drug Monitoring, Risk Factors, Odds Ratio, Prevalence, Medicine, MESH: Obesity, Prospective Studies, MESH: Aged, Venous Thrombosis, education.field_of_study, MESH: Middle Aged, MESH: Postthrombotic Syndrome, MESH: Venous Insufficiency, Hematology, Middle Aged, United States/epidemiology, Venous Thrombosis/diagnosis/drug therapy/epidemiology, Prognosis, Thrombosis, MESH: Predictive Value of Tests, 3. Good health, MESH: International Normalized Ratio, Europe, medicine.anatomical_structure, Anticoagulants/therapeutic use, 030220 oncology & carcinogenesis, Female, Drug Monitoring, Drug Monitoring/methods, Post-thrombotic syndrome, Dilatation, Pathologic, Adult, medicine.medical_specialty, Canada, Population, Canada/epidemiology, macromolecular substances, MESH: Anticoagulants, Risk Assessment, MESH: Multivariate Analysis, MESH: Prognosis, Europe/epidemiology, Veins, 03 medical and health sciences, MESH: Canada, Predictive Value of Tests, MESH: United States, otorhinolaryngologic diseases, Humans, cardiovascular diseases, Postthrombotic Syndrome/diagnosis/drug therapy/epidemiology, International Normalized Ratio, Obesity, education, MESH: Prevalence, Aged, MESH: Humans, MESH: Veins, business.industry, MESH: Time Factors, Venous Insufficiency/epidemiology, Anticoagulants, MESH: Adult, Obesity/epidemiology, Veins/pathology, medicine.disease, MESH: Male, MESH: Odds Ratio, MESH: Prospective Studies, United States, Surgery, carbohydrates (lipids), stomatognathic diseases, Venous Insufficiency, Concomitant, MESH: Venous Thrombosis, ddc:618.97, Multivariate Analysis, MESH: Europe, business, Complication, Venous thromboembolism, MESH: Female
Abstract: International audience; BACKGROUND: Post-thrombotic syndrome (PTS) is the most frequent complication of deep vein thrombosis (DVT). Its diagnosis is based on clinical characteristics. However, symptoms and signs of PTS are non-specific, and could result from concomitant primary venous insufficiency (PVI) rather than DVT. This could bias evaluation of PTS. METHODS: Using data from the REVERSE multicenter study, we assessed risk factors for PTS in patients with a first unprovoked unilateral proximal DVT 5-7 months earlier who were free of clinically significant PVI (defined as absence of moderate or severe venous ectasia in the contralateral leg). RESULTS: Among the 328 patients considered, the prevalence of PTS was 27.1%. Obesity (odds ratio [OR] 2.6 [95% confidence interval (CI) 1.5-4.7]), mild contralateral venous ectasia (OR 2.2 [95% CI 1.1-4.3]), poor International Normalized Ratio (INR) control (OR per additional 1% of time with INR < 2 during anticoagulant treatment of 1.018 [95% CI 1.003-1.034]) and the presence of residual venous obstruction on ultrasound (OR 2.1 [95% CI 1.1-3.7]) significantly increased the risk for PTS in multivariable analyses. When we restricted our analysis to patients without any signs, even mild, of contralateral venous insufficiency (n = 244), the prevalence of PTS decreased slightly to 24.6%. Only obesity remained an independent predictor of PTS (OR 2.6 [95% CI 1.3-5.0]). Poor INR control and residual venous obstruction also increased the risk, but the results were no longer statistically significant (OR 1.017 [95% CI 0.999-1.035] and OR 1.7 [95% CI 0.9-3.3], respectively). CONCLUSIONS: After a first unprovoked proximal DVT, obese patients and patients with even mild PVI constitute a group at increased risk of developing PTS for whom particular attention should be paid with respect to PTS prevention. Careful monitoring of anticoagulant treatment may prevent PTS.
Published: 2012

39. Cigarette smoking and lung cancer-relative risk estimates for the major histological types from a pooled analysis of case-control studies

Author: Kurt Straif, Rodica Stanescu Dumitru, Lorenzo Simonato, Cristina Fortes, Adrian Cassidy, Karl-Heinz Jöckel, Lorenzo Richiardi, Vladimir Janout, Georg Johnen, Lenka Foretova, Irene Brüske, Vladimir Bencko, Jolanta Lissowska, Franco Merletti, Peter Rudnai, Benjamin Kendzia, Beate Pesch, Jack Siemiatycki, Charles M. Rudin, Heinz Erich Wichmann, Dario Consonni, David Zaridze, Marie-Élise Parent, Neonila Szeszenia-Dabrowska, Per Gustavsson, Wolfgang Ahrens, Isabelle M. Gross, Paul Brennan, Hermann Pohlabeln, Eleonora Fabianova, Neil E. Caporaso, Ann Olsson, Isabelle Stücker, Thomas Brüning, Paolo Boffetta, Maria Teresa Landi, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], Institute for Medical Informatics, Biometry, and Epidemiology, University Hospital of Essen, Bremen Institute for Prevention Research and Social Medicine, University of Bremen, International Agency for Cancer Research (IACR), Institute of Epidemiology, Helmholtz-Zentrum München (HZM), Cancer Epidemiology Unit, Université de Turin-CPO-Piemonte, Department of Environmental Medicine and Public Health, Universita degli Studi di Padova, Clinical Epidemiology Unit, IDI-IRCCS, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Unit of Epidemiology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico-Ospedale Maggiore Policlinico, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Institute of Carcinogenesis, Russian Cancer Research Centre, Roy Castle Lung Cancer Research Programme, University of Liverpool-Cancer Research Centre, The Nofer Institute of Occupational Medicine, National Institute of Environment Health, The M Sklodowska-Curie Cancer Center, Institute of Oncology, Epidémiologie environnementale des cancers, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Occupational Health, Regional Authority of Public Health-Specialized State Health Institute, National Institute of Public Health [Romania] (INSP), Institute of Hygiene and Epidemiology, Charles University [Prague] (CU)-1st Faculty of Medicine, Masaryk Memorial Cancer Institute, Masaryk Memorial Cancer Institute (RECAMO), Department of Preventive Medicine, Faculty of Medicine-Palacky University Olomouc, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine [Baltimore], The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai [New York] (MSSM), International Prevention Research Institute (IPRI), Grant sponsor: German Social Accident Insurance, Grant number: FP 271, Grant sponsors: Canadian Institutes of Health Research and Guzzo-SRC Chair in Environment and Cancer, the Fondation de France, the German Federal Ministry of Education, Science, Research, and Technology and the Ministry of Labour and Social Affairs, EC's INCO-COPERNICUS Program, Polish State Committee for Science Research, Roy Castle Foundation, NIH/NCI/DCEG Intramural Research Program, Lombardy Region, INAIL and the European Union Nuclear Fission Safety Program, Italian Association for Cancer Research, Region Piedmont, Compagnia di San Paolo, Europe Against Cancer Program, the Swedish Council for Work Life Research and the Swedish EPA, Pesch, B., Kendzia, B., Gustavsson, P., Jöckel, K.-H., Johnen, G., Pohlabeln, H., Olsson, A., Ahrens, W., Gross, I.M., Brüske, I., Wichmann, H.-E., Merletti, F., Richiardi, L., Simonato, L., Fortes, C., Siemiatycki, J., Parent, M.-E., Consonni, D., Landi, M.T., Caporaso, N., Zaridze, D., Cassidy, A., Szeszenia-Dabrowska, N., Rudnai, P., Lissowska, J., Stücker, I., Fabianova, E., Dumitru, R.S., Bencko, V., Foretova, L., Janout, V., Rudin, C.M., Brennan, P., Boffetta, P., Straif, K., and Brüning, T.
Subjects: Male, Oncology, Cancer Research, Lung Neoplasms, Medizin, cigarette smoking, Tobacco smoke, 0302 clinical medicine, Prevalence, Child, 0303 health sciences, education.field_of_study, relative risk characterization, Smoking, Middle Aged, Prognosis, 3. Good health, Europe, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Adenocarcinoma, Female, tobacco smoke, Adult, Risk, Canada, medicine.medical_specialty, Adolescent, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Young Adult, 03 medical and health sciences, stem cells, Internal medicine, medicine, Humans, education, Lung cancer, Neoplasm Staging, 030304 developmental biology, Gynecology, cigarette smoking, lung cancer, relative risk characterization, tobacco smoke, stem cells, business.industry, Case-control study, Odds ratio, medicine.disease, Small Cell Lung Carcinoma, Confidence interval, respiratory tract diseases, lung cancer, lung cancer, cigarette smoking, Case-Control Studies, Relative risk, business
Abstract: International audience; Lung cancer is mainly caused by smoking, but the quantitative relations between smoking and histologic subtypes of lung cancer remain inconclusive. By using one of the largest lung cancer datasets ever assembled, we explored the impact of smoking on risks of the major cell types of lung cancer. This pooled analysis included 13,169 cases and 16,010 controls from Europe and Canada. Studies with population controls comprised 66.5% of the subjects. Adenocarcinoma (AdCa) was the most prevalent subtype in never smokers and in women. Squamous cell carcinoma (SqCC) predominated in male smokers. Age-adjusted odds ratios (ORs) were estimated with logistic regression. ORs were elevated for all metrics of exposure to cigarette smoke and were higher for SqCC and small cell lung cancer (SCLC) than for AdCa. Current male smokers with an average daily dose of >30 cigarettes had ORs of 103.5 (95% confidence interval (CI): 74.8-143.2) for SqCC, 111.3 (95% CI: 69.8-177.5) for SCLC and 21.9 (95% CI: 16.6-29.0) for AdCa. In women, the corresponding ORs were 62.7 (95% CI: 31.5-124.6), 108.6 (95% CI: 50.7-232.8) and 16.8 (95% CI: 9.2-30.6), respectively. Although ORs started to decline soon after quitting, they did not fully return to the baseline risk of never smokers even 35 years after cessation. The major result that smoking exerted a steeper risk gradient on SqCC and SCLC than on AdCa is in line with previous population data and biological understanding of lung cancer development.
Published: 2012

40. Clinical decision rules in venous thromboembolism

Author: Grégoire Le Gal, Marc A. Rodger, Marc Carrier, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Thrombosis Program, University of Ottawa [Ottawa], Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, and Ottawa Hospital
Subjects: Research design, Male, medicine.medical_specialty, Clinical Biochemistry, MEDLINE, 030204 cardiovascular system & hematology, Decision Support Techniques, Course of action, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Sex factors, Risk Factors, medicine, Humans, 030212 general & internal medicine, Disease management (health), Intensive care medicine, Clinical decision, Probability, business.industry, Age Factors, Anticoagulants, Disease Management, Venous Thromboembolism, Prognosis, 3. Good health, Oncology, Research Design, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Venous thromboembolism, Algorithms
Abstract: International audience; Current prevention, diagnostic management and therapeutic management strategies for venous thromboembolism (VTE) almost all include an assessment of the clinical probability. Clinical decision rules (CDRs) are decision making tools using combinations of simple available clinical predictors to define a probability of an outcome which can be used in a preventative strategy, diagnostic course of action or therapeutic course of action. CDRs provide accurate and reproducible estimates of clinical outcomes. The best performing CDRs are built and validated following strict methodological standards. In this paper we critically review the use of CDRs in prevention, diagnosis and treatment of VTE and highlight those CDRs that are ready for the prime time of daily clinical use.
Published: 2012

41. Symptomatic sub-segmental pulmonary embolism: what is the next step?

Author: G. Le Gal, Marc Carrier, Marc Philip Righini, Thrombosis Program, University of Ottawa [Ottawa], Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Service d'angiologie et d'hémostase (MR), Hôpital Universitaire de Genève, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)
Subjects: medicine.medical_specialty, Pulmonary Artery, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Recurrence, Multidetector Computed Tomography, Case fatality rate, Severity of illness, medicine, Pulmonary angiography, Humans, 030212 general & internal medicine, Observer Variation, business.industry, Patient Selection, Incidence (epidemiology), Mortality rate, Anticoagulants, Reproducibility of Results, Hematology, Prognosis, medicine.disease, 3. Good health, Pulmonary embolism, Pre- and post-test probability, Predictive value of tests, Practice Guidelines as Topic, Radiology, Pulmonary Embolism, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The introduction of computed tomography pulmonary angiography (CTPA) has led to an increase in the incidence of pulmonary embolism (PE) diagnosis. However, the case fatality rate is lower and the mortality rates of PE have remained unchanged suggesting a lower severity of illness. Specifically, the multiple-detector CTPA increased the rate of subsegmental filling defect reported in patients with suspected PE. Whether these filling defects reported on CTPA would correlate to true SSPE on pulmonary angiography or are actually artifacts is unknown. The inter-observer agreement for SSPE diagnosis among radiologists with varied levels of experienced is low (κ of 0.38 (95% CI: 0.0 to 0.89). Furthermore, the clinical importance of a symptomatic SSPE diagnosed by CTPA is unclear. SSPE are frequent on pulmonary angiography in patients with a low probability ventilation-perfusion (V/Q) scan for suspected PE. Several prospective management cohort studies have demonstrated that patients with low or intermediate V/Q scan results can be safely managed without anticoagulation by combining the scan results to the pre-test probability (PTP) of PE and compression ultrasonography. Although clinical equipoise exists, the majority of patients diagnosed with SSPE on CTPA are currently treated with anticoagulant therapy. Only a small number of patients with SSPE diagnosed by CTPA and without DVT who did not receive anticoagulation treatment have been reported in the literature. None of these patients suffered recurrent symptomatic VTE (PE or DVT) during the three-month follow-up period (0%; 95% CI: 0 to 7.4%) suggesting that SSPE might be clinically unimportant. These conclusions are only hypothesis generating and need to be confirmed in prospective clinical management studies before changing clinical practice. © 2012 International Society on Thrombosis and Haemostasis.
Published: 2012

42. Comparison of the Villalta post-thrombotic syndrome score in the ipsilateral vs. contralateral leg after a first unprovoked deep vein thrombosis

Author: P. S. Wells, J-P Galanaud, G. Le Gal, Richard H. White, Tim Ramsay, Christina Holcroft, David Anderson, Susan Solymoss, Michael J. Kovacs, Susan R. Kahn, Arnaud Perrier, Mark Crowther, Linda M. Vickars, Isabelle Chagnon, M. T. Betancourt, Marc A. Rodger, Centre for Clinical Epidemiology and Community Studies (CCECS), Jewish General Hospital, Thrombosis Program, University of Ottawa [Ottawa], Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Division of Hematology (MJK), University of Western Ontario (UWO), Department of Medicine - Halifax (DRA), Dalhousie University [Halifax], Department of Medicine (DM - HSC Montréal), University of Montreal, Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Department of Medecine [Montréal], McGill University = Université McGill [Montréal, Canada], Department of Medicine (DM - McMaster), McMaster University [Hamilton, Ontario], Department of Internal Medicine (AP), Geneva University Hospital (HUG), Department of Medicine (UDSM), UC Davis School of Medicine, Department of Medicine (UBC - St Paul Hospital), and University of British Colombia
Subjects: Male, Time Factors, Deep vein, 030204 cardiovascular system & hematology, France/epidemiology, Postthrombotic Syndrome, Switzerland/epidemiology, 0302 clinical medicine, Risk Factors, Prevalence, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, ddc:616, Venous Thrombosis, Hematology, Middle Aged, United States/epidemiology, Venous Thrombosis/diagnosis/drug therapy/epidemiology, Prognosis, Thrombosis, 3. Good health, medicine.anatomical_structure, Anticoagulants/therapeutic use, Lower Extremity, Predictive value of tests, Female, France, Switzerland, Post-thrombotic syndrome, Adult, medicine.medical_specialty, Canada, Lower Extremity/blood supply, Canada/epidemiology, Signs and symptoms, macromolecular substances, Postthrombotic Syndrome/diagnosis/epidemiology/prevention & control, Risk Assessment, Decision Support Techniques, 03 medical and health sciences, Predictive Value of Tests, otorhinolaryngologic diseases, medicine, Humans, cardiovascular diseases, Aged, business.industry, Anticoagulants, medicine.disease, United States, Surgery, carbohydrates (lipids), stomatognathic diseases, business, Complication, Venous thromboembolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; BACKGROUND: Post-thrombotic syndrome (PTS) is the most frequent complication of a deep vein thrombosis (DVT). International guidelines recommend assessing PTS with the Villalta scale, a clinical measure that incorporates venous symptoms and signs in the leg ipsilateral to a DVT. However, these signs and symptoms are not specific for PTS and their prevalence and relevance in the contralateral leg have not previously been studied. METHODS: Using data from the REVERSE prospective multicentre cohort study, we compared the Villalta total score and prevalence of venous signs and symptoms in the ipsilateral vs. contralateral leg in patients with a first, unilateral DVT 5 to 7 months previously. RESULTS: Among the 367 patients analyzed, the mean Villalta score was higher in the ipsilateral than in the contralateral leg (mean ± standard deviation [SD] 3.7 [3.4] vs. 1.9 [2.5], respectively; P4) was present in 31.6% (n=116) of patients. Among these, 39.7% (n=46) of patients had a Villalta score >4 in the contralateral leg, and the distribution of Villalta symptoms and signs components was similar between the legs. CONCLUSIONS: Villalta scores in the ipsilateral and contralateral legs are strongly correlated. Almost half of cases considered to be PTS might reflect pre-existing symptomatic chronic venous disease. Alternatively, patients with pre-existing chronic venous disease might be more prone to developing PTS after a DVT. Performing a bilateral assessment of Villalta scores at the acute phase of DVT could be of clinical interest from a diagnostic, prognostic and therapeutic point of view.
Published: 2012

43. Does the Pulmonary Embolism Severity Index accurately identify low risk patients eligible for outpatient treatment?

Author: Marc Carrier, Grégoire Le Gal, Petra M. G. Erkens, Martin H. Prins, Gauruv Bose, Marc A. Rodger, Philip S. Wells, Alex Yi-Hao Shen, Esteban Gandara, Department of General Practice (CAPHRI), Maastricht University [Maastricht], Department of Medicine, Ottawa Hospital, Clinical Epidemiology Unit, Thrombosis Program, University of Ottawa [Ottawa], Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Department of Epidemiology (MHP), Ottawa-The Ottawa Hospital, Promovendi PHPC, Epidemiologie, MUMC+: KIO Kemta (9), Family Medicine, Biochemie, and RS: CAPHRI School for Public Health and Primary Care
Subjects: Male, medicine.medical_specialty, medicine.drug_class, Low molecular weight heparin, 030204 cardiovascular system & hematology, Severity of Illness Index, Cohort Studies, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, outpatient treatment, Risk Factors, Internal medicine, Outpatients, Severity of illness, medicine, Humans, Intensive care medicine, Adverse effect, Aged, Retrospective Studies, COPD, pulmonary embolism severity index, medicine.diagnostic_test, business.industry, Ventilation/perfusion scan, Age Factors, Retrospective cohort study, Hematology, Middle Aged, Prognosis, medicine.disease, 3. Good health, Pulmonary embolism, 030228 respiratory system, Female, Pulmonary Embolism, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study
Abstract: International audience; INTRODUCTION: The pulmonary embolism severity index (PESI) and the recently derived simplified PESI prognostic model have been developed to estimate the risk of 30-day mortality in patients with acute PE. We sought to assess if the PESI and simplified PESI prognostic models can accurately identify adverse events and to determine the rates of events in patients treated as outpatients. METHODS: A retrospective cohort study of patients with acute pulmonary embolism (PE) presenting at the Ottawa Hospital (Canada) was conducted between 1 January 2007 and 31 December 2008. RESULTS: Two hundred and forty three patients were included. A total of 118 (48.6%) and 81 (33.3%) were classified as low risk patients using the original and simplified PESI prognostic models respectively. None of the low risk patients died within the 3months of follow-up. One hundred and fifteen (47.3%) patients were safely treated as outpatients with no deaths or bleeding episodes and only 1 recurrent event within the first 14days or after 30days of follow-up. Thirty four (29.6%) of these outpatients were classified as high risk patients according to the original PESI and 54 (47.0%) to the simplified PESI prognostic model. CONCLUSION: Both PESI strategies accurately identify patients with acute PE who are at low risk and high risk for short-term adverse events. However, 30 to 47% of patients with acute PE and a high risk PESI score were safely managed as outpatients. Future research should be directed at developing tools that predict which patients would benefit from inpatient management.
Published: 2012

44. Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded

Author: Douwe H. Biesma, Renée A. Douma, Melanie Tan, Shannon M. Bates, Jeffrey S. Ginsberg, Gerben C. Mol, Arnaud Perrier, Marc Carrier, Gualtiero Palareti, Henri Bounameaux, Pieter Willem Kamphuisen, Marc Philip Righini, Cristina Legnani, Grégoire Le Gal, Roger E. G. Schutgens, Other departments, Department of Vascular Medicine (DVM - AMC), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Section of Vascular Medicine (SVM), Leiden University Medical Center (LUMC), Department of Hematology (UMCU), University Medical Center [Utrecht], Department of Medicine, McMaster University [Hamilton, Ontario], Service de médecine interne générale (SMIG), Hôpital Universitaire de Genève, Department of Angiology and Blood Coagulation (DABC), University Hospital S Orsola-Malpighi, Internal Medicine (StA Hospital), St Antonius Hospital, Service d'angiologie et d'hémostase (MR), Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Department of Internal Medicine (GCM), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Vascular Medicine (DVM - Groningen), University Medical Center Groningen [Groningen] (UMCG), Cardiovascular Centre (CVC), and Vascular Ageing Programme (VAP)
Subjects: Adult, Male, medicine.medical_specialty, pulmonary embolism, diagnosis, Deep vein, venous thromboembolism, 030204 cardiovascular system & hematology, Sensitivity and Specificity, deep vein thrombosis, Cohort Studies, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, SUSPECTED PULMONARY-EMBOLISM, 0302 clinical medicine, Reference Values, D-dimer, EXCLUSION, medicine, Humans, ASSAY, 030212 general & internal medicine, STRATEGY, Online Only Articles, Aged, Retrospective Studies, ddc:616, Aged, 80 and over, Venous Thrombosis, business.industry, Age Factors, Retrospective cohort study, Hematology, Middle Aged, medicine.disease, Prognosis, Thrombosis, Confidence interval, Surgery, Pulmonary embolism, CLINICAL PROBABILITY, Venous thrombosis, medicine.anatomical_structure, hemostasis, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study
Abstract: BackgroundD-dimer testing to rule out deep vein thrombosis is less useful in older patients because of a lower specificity. An age-adjusted D-dimer cut-off value increased the proportion of older patients (>50 years) in whom pulmonary embolism could be excluded. We retrospectively validated the efficacy of this cut-off combined with clinical probability for the exclusion of deep vein thrombosis.Design and MethodsFive management study cohorts of 2818 consecutive outpatients with suspected deep vein thrombosis were used. Patients with non-high or unlikely probability of deep vein thrombosis were included in the analysis; four different D-dimer tests were used. The proportion of patients with a normal D-dimer test and the failure rates were calculated using the conventional (500 mg/L) and the age-adjusted D-dimer cut-off (patient's age x 10 mg/L in patients >50 years).ResultsIn 1672 patients with non-high probability, deep vein thrombosis could be excluded in 850 (51%) patients with the age-adjusted cut-off value versus 707 (42%) patients with the conventional cut-off value. The failure rates were 7 (0.8; 95% confidence interval 0.3-1.7%) for the age-adjusted cut-off value and 5 (0.7%, 0.2-1.6%) for the conventional cut-off value. The absolute increase in patients in whom deep vein thrombosis could be ruled out using the age-adjusted cut-off value was largest in patients >70 years: 19% among patients with non-high probability.ConclusionsThe age-adjusted cut-off of the D-dimer combined with clinical probability greatly increases the proportion of older patients in whom deep vein thrombosis can be safely excluded.
Published: 2012

45. Risk of post-thrombotic syndrome after subtherapeutic warfarin anticoagulation for a first unprovoked deep vein thrombosis: results from the REVERSE study

Author: Richard H. White, Tim Ramsay, Arnaud Perrier, G. Le Gal, Susan Solymoss, David Anderson, Michael J. Kovacs, Susan R. Kahn, Mark Crowther, Linda M. Vickars, Isabelle Chagnon, M. T. Betancourt, Marc A. Rodger, P. S. Wells, R S Chitsike, Centre for Clinical Epidemiology and Community Studies (CCECS), Jewish General Hospital, Thrombosis Program, University of Ottawa [Ottawa], Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Division of Hematology (MJK), University of Western Ontario (UWO), Department of Medicine - Halifax (DRA), Dalhousie University [Halifax], Department of Medicine (DM - HSC Montréal), University of Montreal, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medecine [Montréal], McGill University = Université McGill [Montréal, Canada], Department of Medicine (DM - McMaster), McMaster University [Hamilton, Ontario], Department of Internal Medicine (AP), Geneva University Hospital (HUG), Department of Medicine (UDSM), UC Davis School of Medicine, Department of Medicine (UBC - St Paul Hospital), and University of British Colombia
Subjects: Male, Time Factors, Postthrombotic Syndrome/blood/diagnosis/etiology, Deep vein, 030204 cardiovascular system & hematology, Postthrombotic Syndrome, 0302 clinical medicine, Risk Factors, Odds Ratio, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Venous Thrombosis, ddc:616, Anticoagulants/administration & dosage, Hematology, Middle Aged, Thrombosis, Europe, Venous thrombosis, medicine.anatomical_structure, Treatment Outcome, Female, Post-thrombotic syndrome, medicine.drug, Adult, medicine.medical_specialty, Canada, macromolecular substances, Risk Assessment, 03 medical and health sciences, Warfarin/administration & dosage, Venous Thrombosis/blood/complications/diagnosis/drug therapy, Predictive Value of Tests, Internal medicine, medicine, otorhinolaryngologic diseases, Humans, International Normalized Ratio, Risk factor, Blood Coagulation, Aged, business.industry, Warfarin, Anticoagulants, Odds ratio, medicine.disease, Surgery, carbohydrates (lipids), stomatognathic diseases, Blood Coagulation/drug effects, Multivariate Analysis, bacteria, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Risk factors for the post-thrombotic syndrome (PTS) remain poorly understood. Objectives: In this multinational multicenter study, we evaluated whether subtherapeutic warfarin anticoagulation was associated with development of PTS. Methods: Patients with a first unprovoked deep venous thrombosis (DVT) received standard anticoagulation for 5-7 months and were then assessed for PTS. The time in the therapeutic range was calculated from the international normalized ratio (INR) data. An INR below 2, more than 20% of the time, was considered as subtherapeutic anticoagulation. Results: Of the 349 patients enrolled, 97 (28%) developed PTS. The overall frequency of PTS in patients with subtherapeutic anticoagulation was 33.5%, compared to 21.6% in those with an INR below 2 for ≤20% of the time (p=0.01). During the first 3 months of therapy, the odds ratio (OR) for developing PTS if a patient had subtherapeutic anticoagulation was 1.78 (95% CI 1.10-2.87). After adjusting for confounding variables, the OR was 1.84 (95% CI 1.13-3.01). Corresponding ORs for the full period of anticoagulation were 1.83 (95% CI 1.14-3.00) [crude] and 1.88 (95% CI 1.15-3.07) [adjusted]. Conclusion: Subtherapeutic warfarin anticoagulation after a first unprovoked DVT was significantly associated with the development of PTS. © 2012 International Society on Thrombosis and Haemostasis.
Published: 2012

46. Baseline imaging after therapy for unprovoked venous thromboembolism: a randomized controlled comparison of baseline imaging for diagnosis of suspected recurrence

Author: Carol Gonsalves, P. S. Wells, Michael J. Kovacs, G. Le Gal, A. Hamadah, T. Alwasaidi, Marc A. Rodger, Melissa A. Forgie, Dimitrios Scarvelis, Marc Carrier, Thrombosis Program, University of Ottawa [Ottawa], Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Division of Hematology (MJK), and University of Western Ontario (UWO)
Subjects: Adult, Male, medicine.medical_specialty, Post hoc, 030204 cardiovascular system & hematology, MESH: Anticoagulants, MESH: Venous Thromboembolism, 03 medical and health sciences, 0302 clinical medicine, Recurrence, medicine, Humans, In patient, 030212 general & internal medicine, cardiovascular diseases, Baseline (configuration management), MESH: Humans, MESH: Middle Aged, business.industry, Anticoagulants, MESH: Adult, Hematology, Venous Thromboembolism, Middle Aged, medicine.disease, equipment and supplies, MESH: Male, 3. Good health, Pulmonary embolism, MESH: Recurrence, Anticoagulant therapy, Female, Radiology, business, Venous thromboembolism, MESH: Female, Vascular obstruction, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study
Abstract: International audience; BACKGROUND: After a first unprovoked venous thromboembolism (VTE), many patients have residual pulmonary and/or lower limb vascular obstruction following completion of short-term anticoagulation. Residual vascular obstruction may complicate the diagnosis of recurrent VTE. Whether baseline imaging, conducted after completion of anticoagulation, helps in interpreting diagnostic testing in patients who subsequently have suspected recurrent VTE is unknown. STUDY DESIGN: The REVERSE study is a cohort study whose primary aim was to derive a clinical decision rule to guide the duration of anticoagulation after a first unprovoked VTE. All patients underwent baseline imaging after completing 5-7 months of anticoagulant therapy. We performed a post hoc randomized controlled comparison among 121 patients investigated for a suspected recurrent VTE during follow-up: the decision on recurrent VTE with or without baseline imaging was made available to two independent adjudicators. RESULTS: The proportion of patients not classifiable for recurrent VTE was statistically significantly higher in the group with no baseline imaging than in the group with baseline imaging: one in five as compared with one in 25. The interobserver agreement between the two adjudicators was better in the group with baseline imaging than in the group with no baseline imaging: κ-values were 0.78 and 0.54, respectively. CONCLUSIONS: In patients with a first unprovoked VTE, baseline imaging at completion of anticoagulant therapy helps in interpreting diagnostic tests performed in cases of suspected recurrent VTE.
Published: 2011

47. Polyfunctional type-1, -2, and -17 CD8⁺ T cell responses to apoptotic self-antigens correlate with the chronic evolution of hepatitis C virus infection

Author: Daniele Accapezzato, Marino Paroli, Vincenzo Barnaba, Enza Piccolella, Stefania Morrone, Alfonso Mele, John Sidney, Enea Spada, Paola Del Porto, Emanuele Trella, Silvia Piconese, Debora Franceschini, Alessandro Sette, Department of Internal Medicine and Medical Specialities, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Biology and Biotechnology 'Charles Darwin', Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Dipartimento di Scienze e Biotecnologie Medico-Chirurgiche, Department of Molecular Medicine, National Centre of Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanita [Rome], Laboratory of Epidemiology, Clinical Epidemiology Unit, La Jolla Institute for Immunology [La Jolla, CA, États-Unis], Réseau International des Instituts Pasteur (RIIP), Fondazione Andrea Cesalpino, This work was supported by: European Union grants (IMECS n. 201169, FP7-Health-2007-A and SPHYNX n. 261365, FP7-Health-2010), Ministero della Sanita (Ricerca finalizzata [RFPS-2006-3-337923 and RFPS-2007-1-636647], Istituto Superiore di Sanita [Progetti AIDS-2006 and -2008]), Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) (Programmi di ricerca di interesse nazionale [PRIN]-2008/10 n. 7245/1, Fondo per gli investimenti di ricerca di base [FIRB]- 2011/13 n. RBAP10TPXK), Fondazione Cariplo (progetti n. 13535 and 3603 2010/12), and Associazione Italiana per la Ricerca sul Cancro (AIRC) (progetto 'Investigator Grant' [IG]-2010/13 n. 10756)
Subjects: Male, Epitopes, T-Lymphocyte, Apoptosis, Antigen Processing and Recognition, Autoimmunity, MESH: T-Lymphocyte Subsets, Hepacivirus, CD8-Positive T-Lymphocytes, Adaptive Immunity, medicine.disease_cause, Autoantigens, Hepatitis, 0302 clinical medicine, T-Lymphocyte Subsets, Cytotoxic T cell, MESH: Hepacivirus, Biology (General), Immune Response, 0303 health sciences, MESH: Middle Aged, T Cells, Middle Aged, MESH: CD8-Positive T-Lymphocytes, Hepatitis C, 3. Good health, medicine.anatomical_structure, MESH: Autoantigens, MESH: Young Adult, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Disease Progression, [SDV.IMM]Life Sciences [q-bio]/Immunology, Medicine, Infectious diseases, MESH: Disease Progression, Female, Research Article, Adult, QH301-705.5, T cell, Hepatitis C virus, Immune Cells, Immunology, Antigen-Presenting Cells, Viral diseases, Biology, Microbiology, Virus, MESH: Epitopes, T-Lymphocyte, Immune Activation, 03 medical and health sciences, Young Adult, Antigen, Virology, Genetics, medicine, Humans, Avidity, Molecular Biology, Immunity to Infections, 030304 developmental biology, MESH: Hepatitis C, MESH: Humans, MESH: Apoptosis, T-cell receptor, Immunity, HIV, MESH: Adult, Immune Defense, RC581-607, MESH: Male, Parasitology, Clinical Immunology, Immunologic diseases. Allergy, MESH: Female, CD8, 030215 immunology
Abstract: Caspase-dependent cleavage of antigens associated with apoptotic cells plays a prominent role in the generation of CD8+ T cell responses in various infectious diseases. We found that the emergence of a large population of autoreactive CD8+ T effector cells specific for apoptotic T cell-associated self-epitopes exceeds the antiviral responses in patients with acute hepatitis C virus infection. Importantly, they endow mixed polyfunctional type-1, type-2 and type-17 responses and correlate with the chronic progression of infection. This evolution is related to the selection of autoreactive CD8+ T cells with higher T cell receptor avidity, whereas those with lower avidity undergo prompt contraction in patients who clear infection. These findings demonstrate a previously undescribed strict link between the emergence of high frequencies of mixed autoreactive CD8+ T cells producing a broad array of cytokines (IFN-γ, IL-17, IL-4, IL-2…) and the progression toward chronic disease in a human model of acute infection., Author Summary The emergence of a large population of mixed polyfunctional (type-1, -2, -17) CD8+ T cell effector responses specific for apoptotic T cell-associated self-epitopes rather than the dysfunction or altered quality of virus-specific CD8+ T cells is associated with the progression toward chronic disease in the human model of acute HCV infection. The chronic evolution is associated with the selection of autoreactive CD8+ T cells with higher T cell receptor avidity, whereas those with lower avidity undergo prompt contraction, as seen in patients undergoing infection resolution. We suggest that these autoreactive responses are secondary to the viral persistence and can participate to the HCV-related immunopathology. This data has implications for the prognosis and therapy of infections undergoing chronic evolution.
Published: 2011

48. The management of a sub-segmental pulmonary embolism: a cross-sectional survey of Canadian thrombosis physicians

Author: Miriam Kimpton, P. S. Wells, Susan R. Kahn, Michael J. Kovacs, G. Le Gal, Marc Carrier, Marc A. Rodger, David Anderson, Thrombosis Program, University of Ottawa [Ottawa], Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre for Clinical Epidemiology and Community Studies (CCECS), Jewish General Hospital, Department of Medecine [Montréal], McGill University = Université McGill [Montréal, Canada], Division of Hematology (MJK), University of Western Ontario (UWO), Department of Medicine - Halifax (DRA), and Dalhousie University [Halifax]
Subjects: MESH: Pulmonary Embolism, medicine.medical_specialty, Cross-sectional study, MEDLINE, 030204 cardiovascular system & hematology, MESH: Anticoagulants, MESH: Disease Management, 03 medical and health sciences, 0302 clinical medicine, MESH: Cross-Sectional Studies, MESH: Canada, MESH: Diagnosis, Differential, Medicine, MESH: Physicians, 030212 general & internal medicine, Disease management (health), ComputingMilieux_MISCELLANEOUS, MESH: Humans, business.industry, Hematology, medicine.disease, Thrombosis, Pulmonary embolism, Emergency medicine, Medical emergency, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2011

49. Low prevalence of JAK2 V617F mutation in patients with first unprovoked venous thromboembolism

Author: Rodger, Marc A, Kekre, Natasha, Le Gal, Grégoire, Kahn, Susan R, Wells, Philip S, Anderson, David A, Chagnon, Isabelle, Solymoss, Sussan, Crowther, Mark, Perrier, Arnaud, White, Richard, Vickars, Linda, Ramsay, Timothy, Betancourt, Marisol T, Kovacs, Michael J, Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Thrombosis Program, University of Ottawa [Ottawa], Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medecine [Montréal], McGill University = Université McGill [Montréal, Canada], Ottawa Hospital, Department of Medicine, Dalhousie University [Halifax], University of Montreal, McMaster University [Hamilton, Ontario], Service de médecine interne générale (SMIG), and Hôpital Universitaire de Genève
Subjects: ddc:616, Male, Janus Kinase 2/genetics, MESH: Humans, MESH: Middle Aged, MESH: Mutation, Venous Thromboembolism/enzymology/genetics, MESH: Polymorphism, Single Nucleotide, Venous Thromboembolism, Janus Kinase 2, Middle Aged, Polymorphism, Single Nucleotide, MESH: Janus Kinase 2, MESH: Male, MESH: Venous Thromboembolism, Mutation, Prevalence, Humans, Female, MESH: Female, ComputingMilieux_MISCELLANEOUS, MESH: Prevalence, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2011

50. Controversies in diagnosis of pulmonary embolism

Author: Stein, P. D., Sostman, H. D., Dalen, J. E., Bailey, D. L., Bajc, M., Goldhaber, S. Z., Goodman, L. R., Gottschalk, A., Hull, R. D., Matta, F., Pistolesi, M., Tapson, V. F., Weg, J. G., Wells, P. S., Woodard, P. K., Bailey, Dl, Bajc, M, Coleman, Re, Freeman, Lm, Frey, Ka, Gottschalk, A, Goodman, Lr, Naidich, Dp, Sostman, Hd, Woodard, Pk, Dalen, Je, Douketis, Jd, Elliott, Cg, Geibel, A, Goldhaber, Sz, Le Gal, G, Hales, Ca, Harris, B, Huisman, Mv, Hull, Rd, Kearon, C, Kucher, N, Leeper, Kv, Matta, F, Miniati, M, Pistolesi, M, Prandoni, Paolo, Sasahara, Aa, Stein, Pd, Tapson, Vf, Weg, Jg, Wells, Ps, Wakefield, T., Department of Internal Medicine and Research and Advanced Studies Program (DIMRASP), Michigan State University [East Lansing], Michigan State University System-Michigan State University System, Cardiovascular Division (SZG), Brigham and Women's Hospital [Boston], Thrombosis Research Unit, University of Calgary, Clinical Epidemiology Unit, Ottawa Hospital, Thrombosis Program, University of Ottawa [Ottawa], Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)
Subjects: Male, MESH: Pulmonary Embolism, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Single-photon emission computed tomography, Scintigraphy, MESH: Tomography, Emission-Computed, Single-Photon, 030218 nuclear medicine & medical imaging, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, MESH: Diagnosis, Differential, medicine, Humans, MESH: Data Collection, MESH: Lung, Lung, Tomography, Emission-Computed, Single-Photon, MESH: Angiography, Ct pulmonary angiography, MESH: Humans, medicine.diagnostic_test, business.industry, Data Collection, Angiography, Hematology, General Medicine, Lung scan, medicine.disease, MESH: Male, 3. Good health, Pulmonary embolism, Acute Disease, MESH: Acute Disease, Female, Radiology, Chest radiograph, business, Nuclear medicine, Pulmonary Embolism, Tomography, X-Ray Computed, MESH: Tomography, X-Ray Computed, Lower limbs venous ultrasonography, Perfusion, MESH: Female
Abstract: International audience; The approach to the diagnosis of acute pulmonary embolism (PE) is under constant revision with advances in technology, noninvasive approaches, and increasing awareness of the risks of ionizing radiation. Optimal approaches in some categories of patients are controversial. Data are insufficient for evidence-based recommendations. Therefore, this survey of investigators in the field was undertaken. Even among experts there were marked differences of opinion regarding the approach to the diagnosis of acute PE. Although CT pulmonary angiography was usually the imaging test of choice, the respondents were keenly aware of the dangers of ionizing radiation. In view of advances in scintigraphic diagnosis since the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) trial, ventilation/perfusion (V/Q) lung scans or perfusion scans alone and single photon emission computed tomography (SPECT) V/Q lung scans are often recommended. The choice depends on the patient's age, gender, and complexity of the findings on the plain chest radiograph.
Published: 2011

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