171 results match your criteria: "Toronto E.T.; and the University of Alabama at Birmingham[Affiliation]"
Prior work has revealed sex/gender-dependent autistic characteristics across behavioural and neural/biological domains. It remains unclear whether and how neural sex/gender differences are related to behavioural sex/gender differences in autism. Here, we examined whether atypical neural responses during mentalizing and self-representation are sex/gender-dependent in autistic adults and explored whether 'camouflaging' (acting as if behaviourally neurotypical) is associated with sex/gender-dependent neural responses.
View Article and Find Full Text PDFVX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles.
N Engl J Med
October 2018
From Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Background: The next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector VX-659, in triple combination with tezacaftor and ivacaftor (VX-659-tezacaftor-ivacaftor), was developed to restore the function of Phe508del CFTR protein in patients with cystic fibrosis.
Methods: We evaluated the effects of VX-659-tezacaftor-ivacaftor on the processing, trafficking, and function of Phe508del CFTR protein using human bronchial epithelial cells. A range of oral VX-659-tezacaftor-ivacaftor doses in triple combination were then evaluated in randomized, controlled, double-blind, multicenter trials involving patients with cystic fibrosis who were heterozygous for the Phe508del CFTR mutation and a minimal-function CFTR mutation (Phe508del-MF genotypes) or homozygous for the Phe508del CFTR mutation (Phe508del-Phe508del genotype).
VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles.
N Engl J Med
October 2018
From Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Background: VX-445 is a next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector designed to restore Phe508del CFTR protein function in patients with cystic fibrosis when administered with tezacaftor and ivacaftor (VX-445-tezacaftor-ivacaftor).
Methods: We evaluated the effects of VX-445-tezacaftor-ivacaftor on Phe508del CFTR protein processing, trafficking, and chloride transport in human bronchial epithelial cells. On the basis of in vitro activity, a randomized, placebo-controlled, double-blind, dose-ranging, phase 2 trial was conducted to evaluate oral VX-445-tezacaftor-ivacaftor in patients heterozygous for the Phe508del CFTR mutation and a minimal-function mutation (Phe508del-MF) and in patients homozygous for the Phe508del CFTR mutation (Phe508del-Phe508del) after tezacaftor-ivacaftor run-in.
Current Perspectives on High-Throughput Sequencing (HTS) for Adventitious Virus Detection: Upstream Sample Processing and Library Preparation.
Viruses
October 2018
Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
A key step for broad viral detection using high-throughput sequencing (HTS) is optimizing the sample preparation strategy for extracting viral-specific nucleic acids since viral genomes are diverse: They can be single-stranded or double-stranded RNA or DNA, and can vary from a few thousand bases to over millions of bases, which might introduce biases during nucleic acid extraction. In addition, viral particles can be enveloped or non-enveloped with variable resistance to pre-treatment, which may influence their susceptibility to extraction procedures. Since the identity of the potential adventitious agents is unknown prior to their detection, efficient sample preparation should be unbiased toward all different viral types in order to maximize the probability of detecting any potential adventitious viruses using HTS.
View Article and Find Full Text PDFPrimary immunodeficiency.
Allergy Asthma Clin Immunol
September 2018
4University of Manitoba, Winnipeg, MB Canada.
Primary immunodeficiency disorder (PID) refers to a large heterogeneous group of disorders that result from defects in immune system development and/or function. PIDs are broadly classified as disorders of adaptive immunity (i.e.
View Article and Find Full Text PDFPrimary angiitis of the CNS and reversible cerebral vasoconstriction syndrome: A comparative study.
Neurology
October 2018
From the Department of Internal Medicine (H.d.B., A.A.), Caen University Hospital; University of Caen-Normandie (H.d.B., E.T., A.A); Biostatistics and Clinical Research Unit (J.-J.P.), Caen University Hospital; Emergency Headache Centre (J.M., C.B.), Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris; Department of Neurology (C.A., A.D.), Montpellier University Hospital; Department of Neuroradiology (G.B., O.N.), Sainte-Anne Hospital, Paris-Descartes University; INSERM UMR 894 (O.N.); Department of Vascular Neurology (M.Z.), Saint Joseph Hospital; Université Paris-Descartes (M.Z.), INSERM UMR S 919, Paris; Department of Neurology (E.T.), Caen University Hospital; University of Caen-Normandie (E.T.), INSERM U919; Department of Neurology (M.-G.B.), Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris, France; and Division of Rheumatology (C.P.), Vasculitis Clinic, Mount Sinai Hospital, Toronto, Ontario, Canada.
Objectives: To further improve the distinction between primary angiitis of the CNS (PACNS) and reversible cerebral vasoconstriction syndrome (RCVS).
Methods: We compared 2 large French cohorts of patients with PACNS (n = 110, retrospectively and prospectively enrolled) and RCVS (n = 173, prospectively enrolled).
Results: Patients with RCVS were predominantly female ( < 0.
Health-related quality of life measure distinguishes between low and high clinical T stages in esophageal cancer.
Ann Transl Med
July 2018
Division of Thoracic Surgery, University of Toronto, Toronto, ON, Canada.
Background: Functional Assessment of Cancer Therapy-Esophagus (FACT-E) is a health-related quality of life (HRQOL) instrument validated in patients with esophageal cancer. It is made up of both a general component and an esophageal cancer subscale (ECS). Our objective was to explore the relationship between baseline FACT-E, ECS and clinically determined T-stage in patients with stage II-IV cancer of the gastroesophageal junction or thoracic esophagus.
View Article and Find Full Text PDFTreatment and Long-Term Outcomes of Primary Central Nervous System Vasculitis.
Stroke
August 2018
Vasculitis Clinic, Division of Rheumatology, Mount Sinai Hospital, Toronto (C.P.).
Background and Purpose- We aimed to analyze the long-term outcomes of patients with primary central nervous system vasculitis according to the different therapeutic strategies used to induce remission. Methods- We assessed the rate of prolonged remission (defined by the absence of relapse at ≥12 months after diagnosis) and the functional status at last follow-up in patients with primary central nervous system vasculitis included in the French cohort, who achieved a first remission according to the 3 main groups of treatments administered: glucocorticoids only (group 1); induction treatment with glucocorticoids and an immunosuppressant, but no maintenance (group 2); and combined treatment with glucocorticoids and an immunosuppressant for induction followed by maintenance therapy (group 3). Good functional status was defined as a modified Rankin Scale score ≤2 at the last follow-up.
View Article and Find Full Text PDFRivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source.
N Engl J Med
June 2018
From the Departments of Medicine-Neurology (R.G.H., M.S., A.S.), Health Research Methods, Evidence, and Impact (S.I.B.), Pathology and Molecular Medicine (G. Pare), and Medicine-Cardiology (S.J.C.), Population Health Research Institute (B.S., P.S., E.T.), and the Thrombosis and Atherosclerosis Research Institute and McMaster University (J.I.W.), Hamilton, ON, the Vancouver Stroke Program, University of British Columbia, Vancouver (O.R.B.), and Sunnybrook Health Sciences Centre, University of Toronto, Toronto (C.J.) - all in Canada; Bayer, Wuppertal (H.M.), Klinik für Neurologie, Charité-Universitätsmedizin Berlin (M.E.), and Bayer (B.K.), Berlin, and Bayer, Leverkusen (C.P.) - all in Germany; the Department of Neurology, University of Pennsylvania, Philadelphia (S.E.K.), and Janssen Research and Development, Spring House (G. Peters) - both in Pennsylvania; Bayer U.S., Pharmaceuticals Clinical Development Thrombosis, Whippany, NJ (S.D.B.); Clínica Alemana de Santiago, Santiago, Chile (P.L.); the Department of Neurology and Stroke Center, Beijing Tiantan Hospital, Beijing (Yongjun Wang, Yilong Wang); Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona (A.D.); Pirogov Russian National Research Medical University, Moscow (N.S.); International Clinical Research Center and Neurology Department, St. Anne's University Hospital, Brno, Czech Republic (R.M.); Centro Hospitalar e Universitário de Coimbra, Hospitais da Universidade de Coimbra, Coimbra, Portugal (L.C.); the Department of Clinical Sciences (Neurology), Lund University, and the Department of Neurology and Rehabilitation Medicine, Skåne University Hospital, Lund (A.L.), and the Department of Clinical Neuroscience-Neurology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg (T.T.) - all in Sweden; Instituto Nacional de Neurología y Neurocirugía, Mexico City (A.A.); Hospital St. John of God, Sigmund Freud Private University, Medical Faculty, Vienna (W.L.); the 2nd Department of Neurology, Institute of Psychiatry and Neurology, and the Department of Pharmacology, Medical University of Warsaw, Warsaw, Poland (A.C.); the Department of Internal Medicine, University Hospital Basel, Basel, Switzerland (J.E.); Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo (R.J.G.); Assistance Publique-Hôpitaux de Paris, Bichat Hospital, Paris-Diderot, Sorbonne Paris Cité University, Paris (P.A.); Institute for Neurological Research-Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia, Buenos Aires (S.F.A.); the Department of Neurology, Helsinki University Central Hospital, Helsinki (T.T.); Imperial College London, London (R.V.); Medical School, University of Western Australia, and Sir Charles Gairdner Hospital, Perth, Australia (G.J.H.); the Department of Human Neurosciences, Sapienza University of Rome, Rome (D.T.); the Department of Neurology, Semmelweis University, Budapest, Hungary (D.B.); International University of Health and Welfare, Sanno Hospital and Sanno Medical Center, Tokyo (S.U.); the Department of Medicine, University of Thessaly, Larissa, Greece (G.N.); Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea (B.-W.Y.); the Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels (R.B.); the Department of Neurology, ZorgSaam Hospital, Terneuzen, the Netherlands (R.B.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, United Kingdom (K.W.M.); Shaare Zedek Medical Center, Jerusalem (N.B.); the Department of Neurology, Selcuk University, Konya, Turkey (S.O.); Health Research Board Clinical Research Facility, National University of Ireland, Galway (M.J.O.); Tiervlei Trial Centre and Head of Internal Medicine Karl Bremer Hospital, Bellville, South Africa (M.M.D.V.B.); and Baylor College of Medicine, Houston (W.F.P.).
Background: Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin.
Methods: We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source.
Use of Myocardial T1 Mapping at 3.0 T to Differentiate Anderson-Fabry Disease from Hypertrophic Cardiomyopathy.
Radiology
August 2018
From the Toronto Joint Department of Medical Imaging, Toronto General Hospital, University of Toronto, 585 University Ave, 1 PMB-298, Toronto, ON, Canada M5G 2N2 (G.R.K., S.R., P.T., E.T.N., S.M., K.H.); Division of Cardiology, Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto, ON, Canada (R.M.I., A.M.C., P.T.); and Fred A. Litwin Centre in Genetic Medicine, University Health Network & Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada (C.F.M., S.W.).
Purpose To compare left ventricular (LV) and right ventricular (RV) 3.0-T cardiac magnetic resonance (MR) imaging T1 values in Anderson-Fabry disease (AFD) and hypertrophic cardiomyopathy (HCM) and evaluate the diagnostic value of native T1 values beyond age, sex, and conventional imaging features. Materials and Methods For this prospective study, 30 patients with gene-positive AFD (37% male; mean age ± standard deviation, 45.
View Article and Find Full Text PDFDigital Imaging and Communications in Medicine Whole Slide Imaging Connectathon at Digital Pathology Association Pathology Visions 2017.
J Pathol Inform
March 2018
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
As digital pathology systems for clinical diagnostic work applications become mainstream, interoperability between these systems from different vendors becomes critical. For the first time, multiple digital pathology vendors have publicly revealed the use of the digital imaging and communications in medicine (DICOM) standard file format and network protocol to communicate between separate whole slide acquisition, storage, and viewing components. Note the use of DICOM for clinical diagnostic applications is still to be validated in the United States.
View Article and Find Full Text PDFAntifungal Combinations for Treatment of Cryptococcal Meningitis in Africa.
N Engl J Med
March 2018
From the Centre for Global Health, Institute for Infection and Immunity, St. George's University of London (S.F.M., A.L., N.S., N. Karunaharan, J.A., T.B., T.S.H.), University College London (R.S.H.), and the MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine (J.B.), London, and Liverpool School of Tropical Medicine, Liverpool (T.C., D.G.L., D.W., S.J.) - all in the United Kingdom; the University of North Carolina Project-Malawi, Kamuzu Central Hospital, Lilongwe (C. Kanyama, C.C., C.H., M.C.H.), Malawi-Liverpool-Wellcome Trust Clinical Research Programme (R.S.H., N. Kalata, K.G., M.P., J.E.) and the College of Medicine, University of Malawi (R.S.H., N. Kalata, K.G., M.P., J.E., J.J.O.), Blantyre, and Dignitas International, Zomba Central Hospital, Zomba (A.K.C., P.B., D.L., J.J.O.) - all in Malawi; University of Dschang, Dschang (C. Kouanfack), Hôpital Central Yaoundé/Site Agence Nationale de Recherche sur le Sida (ANRS) Cameroun, Yaoundé (C. Kouanfack, S. Lontsi, J.-G.N., V.S.), and Douala General Hospital (E.T., Y.N.M.) and University of Douala (Y.N.M.), Douala - all in Cameroon; the Institute for Medical Research and Training (D.C., N.S., N. Karunaharan, P.B.), University Teaching Hospital (D.C., S. Lakhi, N.S., N. Karunaharan, P.B.), and the Department of Internal Medicine and Directorate of Research and Postgraduate Studies, Lusaka Apex Medical University (P.M.), Lusaka, Zambia; the National Institute for Medical Research, Muhimbili Medical Research Centre, Dar Es Salaam, Tanzania (S.M., S. Lesikari); Institut Pasteur, Molecular Mycology Unit (E.T., O.L.), and Paris Descartes University, Necker Pasteur Center for Infectious Diseases and Tropical Medicine, IHU Imagine, Assistance Publique-Hôpitaux de Paris (O.L.), Paris; the Division of Infectious Diseases, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto (A.K.C.); and the University of North Carolina, Chapel Hill (C.H., M.C.H.).
Background: Cryptococcal meningitis accounts for more than 100,000 human immunodeficiency virus (HIV)-related deaths per year. We tested two treatment strategies that could be more sustainable in Africa than the standard of 2 weeks of amphotericin B plus flucytosine and more effective than the widely used fluconazole monotherapy.
Methods: We randomly assigned HIV-infected adults with cryptococcal meningitis to receive an oral regimen (fluconazole [1200 mg per day] plus flucytosine [100 mg per kilogram of body weight per day] for 2 weeks), 1 week of amphotericin B (1 mg per kilogram per day), or 2 weeks of amphotericin B (1 mg per kilogram per day).
Outcomes of Patients With Hypoplastic Left Heart Syndrome Reaching Adulthood After Fontan Palliation: Multicenter Study.
Circulation
February 2018
Toronto Congenital Cardiac Centre for Adults, Peter Munk Cardiac Centre, University Health Network, University of Toronto, Ontario, Canada (W.M.W., E.J.H., S.L.R., C.K.S., R.M.W.).
2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials.
Circulation
February 2018
Center for Drug Evaluation and Research (CDER), United States Food and Drug Administration (FDA), Silver Spring, Maryland (R.J.T.).
This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the US Food and Drug Administration (FDA). The FDA established the Standardized Data Collection for Cardiovascular Trials Initiative in 2009 to simplify the design and conduct of clinical trials intended to support marketing applications. The writing committee recognizes that these definitions may be used in other types of clinical trials and clinical care processes where appropriate.
View Article and Find Full Text PDFDouble-target DBS for essential tremor: 8-contact lead for cZI and Vim aligned in the same trajectory.
Neurology
March 2018
From Instituto Sírio-Libanes de Ensino e Pesquisa (M.G.D.S.G., M.I., E.J.L.A., P.R.R., W.O.L.C., E.T.F.), São Paulo, Brazil; and Sunnybrook Research Institute (C.H.), University of Toronto, Canada.
Glecaprevir-Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection.
N Engl J Med
January 2018
From Goethe University Hospital, Frankfurt (S.Z.), and Medizinische Hochschule Hannover, Hannover (H.W.) - both in Germany; Queen Mary University of London, Barts Health, London (G.R.F.); AbbVie, North Chicago (S.W., A.A., J.K., B.F., R.L., T.I.N., T.P.-M., C.-W.L., R.T., F.J.M.), and Northwestern Feinberg School of Medicine, Chicago (S.F.) - both in Illinois; Liver Unit, Auckland City Hospital, Auckland (E.G.), and Christchurch Hospital and University of Otago, Christchurch (C.A.S.) - both in New Zealand; Toronto Centre for Liver Disease, University of Toronto, Toronto (J.J.F.), University of Manitoba, Winnipeg (K.K.), and LAIR Centre, Vancouver, BC (E.T.) - all in Canada; Centre de Recherche sur l'Inflammation, INSERM UMR 1149, Université Paris Diderot, Service d'hépatologie, Assistance Publique-Hôpitaux de Paris Hôpital Beaujon, Clichy (T.A.), Hôpital Saint Joseph, Marseille (M.B.), and Groupe Hospitalier Cochin-Saint Vincent de Paul, Paris (S.P.) - all in France; Ruane Medical and Liver Health Institute, Los Angeles (P.J.R.), Stanford University Division of Gastroenterology and Hepatology, Palo Alto (P.K.), and private practice, Bakersfield (F. Felizarta) - all in California; Klinika Chorób Zakaźnych i Hepatologii UM w Białymstoku, Bialystok, Poland (R.F.); the Texas Liver Institute-University of Texas Health, San Antonio (F.P.), and Baylor College of Medicine, Houston (J.V.); Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (W.-L.C.); Kirby Institute, University of New South Wales Sydney and St. Vincent's Hospital, Sydney (G.J.D.), and Alfred Hospital, Melbourne, VIC (S.K.R.) - both in Australia; Instituto de Investigación Científica del Sur, Ponce (G.S.-A.), and University of Puerto Rico, San Juan (R.S.-M.) - both in Puerto Rico; Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Milan (M.P.); Mayo Clinic, Phoenix, AZ (H.E.V.); Tel Aviv Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.B.); Centro de Investigaciones Clinicas Viña del Mar, Viña del Mar, Chile (F. Fuster); and Samsung Medical Center, Seoul, South Korea (S.-W.P.).
Background: Glecaprevir and pibrentasvir are direct-acting antiviral agents with pangenotypic activity and a high barrier to resistance. We evaluated the efficacy and safety of 8-week and 12-week courses of treatment with 300 mg of glecaprevir plus 120 mg of pibrentasvir in patients without cirrhosis who had hepatitis C virus (HCV) genotype 1 or 3 infection.
Methods: We conducted two phase 3, randomized, open-label, multicenter trials.
Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery.
N Engl J Med
November 2017
From the Department of Anesthesia (C.D.M., G.M.T.H.) and the Department of Surgery, Division of Cardiac Surgery (S.V.), Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital (J.H., A.C.), Sunnybrook Health Sciences Center (S.F.), AHRC, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Dalla Lana School of Public Health (K.E.T.), and AHRC, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Department of Medicine and Institute of Health Policy, Management and Evaluation (P.J.), University of Toronto, and the Departments of Medicine, Laboratory Medicine, and Pathobiology, Institute of Health Policy, Management, and Evaluation, University of Toronto, and the Division of Hematology, Mount Sinai Hospital, Canadian Blood Services (N.S.), Toronto, Population Health Research Institute (R.P.W., E.B.-C.), Hamilton Health Sciences Centre (R.P.W., E.B.-C., K.C.), and McMaster University (R.P.W., E.B.-C., S.S.), Hamilton, ON, Ottawa Hospital Research Institute, University of Ottawa, Ottawa (D.A.F.), the Department of Anesthesia, Foothills Medical Centre, University of Calgary, Calgary, AB (A.J.G.), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC (É.M.), the Departments of Anesthesia and Medicine, Division of Critical Care, Centre Hospitalier de l'Université de Montréal, Montreal (F.M.C.), the Departments of Anesthesia and Surgery, University of Manitoba, St. Boniface Hospital, Winnipeg (H.P.G.), the Department of Anesthesiology and Critical Care Medicine, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Laval, QC (F.L.), and the Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton (S.M.B.) - all in Canada; the Department of Cardiothoracic Anesthesia, Rigshospitalet, Copenhagen University Hospital, Copenhagen (B.K.); Medical Research Institute of New Zealand, Wellington (S.M., P.J.Y.), and Waikato Hospital, Hamilton (K.B.) - both in New Zealand; the Department of Surgery, University of Melbourne (A.R., C.R.), and the Department of Anaesthesia and Pain Management, Royal Melbourne Hospital (C.R.), Melbourne, VIC, and the Department of Anaesthesia, Royal Adelaide Hospital, Discipline of Acute Care Medicine, University of Adelaide, Adelaide, SA (T.W.P.) - all in Australia; Fundación Cardioinfantil-Instituto de Cardiología, Bogota, and Universidad Autónoma de Bucaramanga, Bucaramanga - both in Colombia (J.C.V.); the University of Basel, Department of Anesthesia, Surgical Intensive Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, Basel, and Klinik Hirslanden, Zurich - both in Switzerland (M.D.S.); the Department of Cardiothoracic Anesthesia, National Heart Center, and the Department of Anesthesiology, Singapore General Hospital, Singapore (N.C.H.); and Heart Care Associates, Ahmedabad, India (C.M.).
Background: The effect of a restrictive versus liberal red-cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear.
Methods: In this multicenter, open-label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery) to a restrictive red-cell transfusion threshold (transfuse if hemoglobin level was <7.5 g per deciliter, starting from induction of anesthesia) or a liberal red-cell transfusion threshold (transfuse if hemoglobin level was <9.
Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis.
N Engl J Med
November 2017
From the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.M.R.); the Arizona Respiratory Center, University of Arizona, Tucson (C.D.); the Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research, Hannover, Germany (F.C.R.); Hadassah Hebrew University Medical Center, Jerusalem, Israel (E.K.); Alfred Health, Melbourne, VIC, Australia (J.W.); St. Michael's Hospital, Toronto (E.T.); Vertex Pharmaceuticals, Boston (N.N., C.S., L.H., E.P.I., C.M., J.L.-H.); and Imperial College and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.).
Background: Cystic fibrosis is an autosomal recessive disease caused by mutations in the CFTR gene that lead to progressive respiratory decline. Some mutant CFTR proteins show residual function and respond to the CFTR potentiator ivacaftor in vitro, whereas ivacaftor alone does not restore activity to Phe508del mutant CFTR.
Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3, crossover trial to evaluate the efficacy and safety of ivacaftor alone or in combination with tezacaftor, a CFTR corrector, in 248 patients 12 years of age or older who had cystic fibrosis and were heterozygous for the Phe508del mutation and a CFTR mutation associated with residual CFTR function.
A natural history study of X-linked myotubular myopathy.
Neurology
September 2017
From the Division of Neurology (K.A., E.T., C.-T.N., J.J.D.) and Program for Genetics and Genome Biology (E.T., J.J.D.), Hospital for Sick Children; Departments of Paediatrics (K.A., J.J.D.), Computer Science (M.G.), and Molecular Genetics (J.J.D.), University of Toronto, Ontario, Canada; Cure CMD (R.A., S.d.C., A.R.), Torrance, CA; Autodesk Research (M.G.), Toronto, Ontario, Canada; Kaiser SCPMG (A.R.), Torrance, CA; Physical Medicine and Rehabilitation (J.H.), University of Michigan, Ann Arbor; and Division of Genetics and Genomics (A.H.B.), The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, MA.
Objective: To define the natural history of X-linked myotubular myopathy (MTM).
Methods: We performed a cross-sectional study that included an online survey (n = 35) and a prospective, 1-year longitudinal investigation using a phone survey (n = 33).
Results: We ascertained data from 50 male patients with MTM and performed longitudinal assessments on 33 affected individuals.
Concordance of Time-of-Flight MRA and Digital Subtraction Angiography in Adult Primary Central Nervous System Vasculitis.
AJNR Am J Neuroradiol
October 2017
Department of Neuroradiology (G.B., O.N.), Centre Hospitalier Sainte-Anne, Université Paris-Descartes, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 894, Paris, France.
Background And Purpose: 3D-TOF-MRA and DSA are 2 available tools to demonstrate neurovascular involvement in primary central nervous system vasculitis. We aimed to compare the diagnostic concordance of vessel imaging using 3D-TOF-MRA and DSA in patients with primary central nervous system vasculitis.
Materials And Methods: We retrospectively identified all patients included in the French primary central nervous system vasculitis cohort of 85 patients who underwent, at baseline, both intracranial 3D-TOF-MRA and DSA in an interval of no more than 2 weeks and before treatment initiation.
Paradoxical Suppression of Atherosclerosis in the Absence of microRNA-146a.
Circ Res
August 2017
From the Toronto General Hospital Research Institute, University Health Network, Ontario, Canada (H.S.C, R.B., A.L., Z.C., E.A.S., N.K., S.A.M., M.H., M.I.C., C.S.R., J.E.F.); Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada (H.S.C, R.B., A.L., Z.C., E.A.S., N.K., S.A.M., M.H., M.I.C., C.S.R., J.E.F.); Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, Toronto, Ontario, Canada (H.S.C, R.B., A.L., Z.C., E.A.S., N.K., M.H., M.I.C., C.S.R., J.E.F.); Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Germany (M.N.-J., A.S.); INSERM, Unit 970, Paris Cardiovascular Research Center-PARCC, France (A.H., C.M.B.); University of Ottawa Heart Institute, Ontario, Canada (M.-A.N., M.G., K.J.R.); and Pharmacology and Nutritional Sciences, University of Kentucky, Lexington (L.C., T.L., R.E.T.).
Rationale: Inflammation is a key contributor to atherosclerosis. MicroRNA-146a (miR-146a) has been identified as a critical brake on proinflammatory nuclear factor κ light chain enhancer of activated B cells signaling in several cell types, including endothelial cells and bone marrow (BM)-derived cells. Importantly, miR-146a expression is elevated in human atherosclerotic plaques, and polymorphisms in the precursor have been associated with risk of coronary artery disease.
View Article and Find Full Text PDFEpidemiologic Evaluation of Human Papillomavirus Type Competition and the Potential for Type Replacement Post-Vaccination.
PLoS One
July 2017
McGill University, Department of Oncology, Montreal, Québec, Canada.
Background: Millions of women have been vaccinated with one of two first-generation human papillomavirus (HPV) vaccines. Both vaccines remain in use and target two oncogenic types (HPVs 16 and 18); however, if these types naturally compete with others that are not targeted, type replacement may occur following reductions in the circulating prevalence of targeted types. To explore the potential for type replacement, we evaluated natural HPV type competition in unvaccinated females.
View Article and Find Full Text PDFOsimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer.
N Engl J Med
February 2017
From the State Key Laboratory in Oncology in South China, Sir Y.K. Pao Centre for Cancer, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong (T.S.M.), the Division of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong General Hospital, and Guangdong Academy of Medical Sciences, Guangzhou (Y.-L.W.), and the Department of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing (Y.H.) - all in China; the Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, (M.-J.A.), and the Yonsei Cancer Center, Department of Internal Medicine, Division of Medical Oncology, Yonsei University College of Medicine (H.R.K.), Seoul, South Korea; the Thoracic Oncology Unit, Medical Oncology Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan (M.C.G.); the Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.); the Department of Medical Oncology and Haematology, Princess Margaret Cancer Centre, Toronto (F.A.S.); the Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan (H.A.); the Department of Thoracic Oncology, the Netherlands Cancer Institute, Plesmanlaan, Amsterdam (W.S.M.E.T.); the Clinical Research Unit, Division of Cancer Services, St. George Hospital, Kogarah, NSW, Australia (C.K.L.); the Department of Hematology-Oncology, Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany (M.S.); AstraZeneca, Cambridge, United Kingdom (A.T., H.M., M.M., S.G.); and the Department of Thoracic-Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston (V.A.P.).
Background: Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR-TKI sensitizing and T790M resistance mutations in patients with non-small-cell lung cancer. The efficacy of osimertinib as compared with platinum-based therapy plus pemetrexed in such patients is unknown.
Methods: In this randomized, international, open-label, phase 3 trial, we assigned 419 patients with T790M-positive advanced non-small-cell lung cancer, who had disease progression after first-line EGFR-TKI therapy, in a 2:1 ratio to receive either oral osimertinib (at a dose of 80 mg once daily) or intravenous pemetrexed (500 mg per square meter of body-surface area) plus either carboplatin (target area under the curve, 5 [AUC5]) or cisplatin (75 mg per square meter) every 3 weeks for up to six cycles; maintenance pemetrexed was allowed.
Predictors of Variation in CYP2A6 mRNA, Protein, and Enzyme Activity in a Human Liver Bank: Influence of Genetic and Nongenetic Factors.
J Pharmacol Exp Ther
January 2017
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada (J-A.T., R.F.T.); Department of Pharmacology and Toxicology (J-A.T., R.F.T.) and Department of Psychiatry (R.F.T.), University of Toronto, Toronto, Ontario, Canada; Department of Pharmaceutics (B.P., K.G.C, K.E.T.) and Center for Exposures, Diseases, Genomics, and Environment (P.S.), University of Washington, Seattle, Washington; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee (A.C., E.G.S.)
Cytochrome P450 2A6 CYP2A6: metabolizes several clinically relevant substrates, including nicotine, the primary psychoactive component in cigarette smoke. Smokers vary widely in their rate of inactivation and clearance of nicotine, altering numerous smoking phenotypes. We aimed to characterize independent and shared impact of genetic and nongenetic sources of variation in CYP2A6 mRNA, protein, and enzyme activity in a human liver bank (n = 360).
View Article and Find Full Text PDFChecklist for Early Recognition and Treatment of Acute Illness (CERTAIN): evolution of a content management system for point-of-care clinical decision support.
BMC Med Inform Decis Mak
October 2016
Multidisciplinary Epidemiology and Translational Research in Intensive Care (M.E.T.R.I.C.), Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 1ST Street SW, Rochester, MN, USA.
Background: The Checklist for Early Recognition and Treatment of Acute Illness (CERTAIN) is an international collaborative project with the overall objective of standardizing the approach to the evaluation and treatment of critically ill patients world-wide, in accordance with best-practice principles. One of CERTAIN's key features is clinical decision support providing point-of-care information about common acute illness syndromes, procedures, and medications in an index card format.
Methods: This paper describes 1) the process of developing and validating the content for point-of-care decision support, and 2) the content management system that facilitates frequent peer-review and allows rapid updates of content across different platforms (CERTAIN software, mobile apps, pdf-booklet) and different languages.