Showing papers by "McMaster University published in 2017"
Theo Vos1, Amanuel Alemu Abajobir, Kalkidan Hassen Abate2, Cristiana Abbafati3 +775 more•Institutions (305)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.
10,401 citations
TL;DR: The glmmTMB package fits many types of GLMMs and extensions, including models with continuously distributed responses, but here the authors focus on count responses and its ability to estimate the Conway-Maxwell-Poisson distribution parameterized by the mean is unique.
Abstract: Count data can be analyzed using generalized linear mixed models when observations are correlated in ways that require random effects However, count data are often zero-inflated, containing more zeros than would be expected from the typical error distributions We present a new package, glmmTMB, and compare it to other R packages that fit zero-inflated mixed models The glmmTMB package fits many types of GLMMs and extensions, including models with continuously distributed responses, but here we focus on count responses glmmTMB is faster than glmmADMB, MCMCglmm, and brms, and more flexible than INLA and mgcv for zero-inflated modeling One unique feature of glmmTMB (among packages that fit zero-inflated mixed models) is its ability to estimate the Conway-Maxwell-Poisson distribution parameterized by the mean Overall, its most appealing features for new users may be the combination of speed, flexibility, and its interface’s similarity to lme4
4,497 citations
St George's Hospital1, New York University2, McMaster University3, Brown University4, Catholic University of the Sacred Heart5, Hebron University6, University of Manitoba7, Emory University Hospital8, Hebrew University of Jerusalem9, Sunnybrook Health Sciences Centre10, University of Pittsburgh11, Saint Thomas - West Hospital12, University College London13, Vanderbilt University Medical Center14, Keio University15, Memorial Hospital of South Bend16, Cooper University Hospital17, University of Mississippi Medical Center18, Rush University Medical Center19, University of Ulsan20, Federal University of São Paulo21, Regions Hospital22, St. Michael's Hospital23, Washington University in St. Louis24, Ottawa Hospital25, University of Sydney26, Mount Sinai Hospital27, University of New South Wales28, Fujita Health University29, Christiana Care Health System30, Stanford University31, King Abdullah University of Science and Technology32, University of Kansas33, Harvard University34, California Pacific Medical Center35, University of Amsterdam36, Houston Methodist Hospital37
TL;DR: Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.
Abstract: To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012”. A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.
4,303 citations
St George’s University Hospitals NHS Foundation Trust1, New York University2, McMaster University3, Brown University4, Catholic University of the Sacred Heart5, Autonomous University of Barcelona6, University of Manitoba7, Emory University8, Hebrew University of Jerusalem9, University of Toronto10, University of Pittsburgh11, St Thomas' Hospital12, University College London13, Vanderbilt University14, Keio University15, Memorial Hospital of South Bend16, Rowan University17, University of Mississippi18, Rush University Medical Center19, University of Ulsan20, Universidade Federal do Rio Grande do Sul21, Federal University of São Paulo22, Regions Hospital23, Washington University in St. Louis24, University of Ottawa25, University of Sydney26, University of New South Wales27, Fujita Health University28, University of Copenhagen29, Sapienza University of Rome30, Christiana Care Health System31, Stanford University32, King Abdullah University of Science and Technology33, University of Kansas34, Harvard University35, California Pacific Medical Center36, University of Amsterdam37, Université libre de Bruxelles38, Houston Methodist Hospital39
TL;DR: A consensus committee of 55 international experts representing 25 international organizations was assembled at key international meetings (forSurviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012 as discussed by the authors ).
Abstract: Objective:To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.”Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for
2,414 citations
Otto-von-Guericke University Magdeburg1, University of Bordeaux2, Trinity College, Dublin3, Erasmus University Medical Center4, University of Bologna5, University of Nottingham6, Veterans Health Administration7, McMaster University8, University of Padua9, Hochschule Hannover10, University of New South Wales11
TL;DR: This fifth edition of the Maastricht Consensus Report describes how experts from 24 countries examined new data related to H. pylori infection in the various clinical scenarios and provided recommendations on the basis of the best available evidence and relevance.
Abstract: Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.
2,219 citations
Ohio State University1, Vanderbilt University2, Heidelberg University3, Iuliu Hațieganu University of Medicine and Pharmacy4, Duke University5, University of Lausanne6, Lehigh University7, McMaster University8, Fox Chase Cancer Center9, University of Texas at Austin10, Nemocnice Na Bulovce11, Bristol-Myers Squibb12
TL;DR: Nivolumab was not associated with significantly longer progression‐free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD‐L1 expression level of 5% or more.
Abstract: BackgroundNivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non–small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)–positive NSCLC. MethodsWe randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more. ResultsAmong the 423 patients with a PD-L1 expression level of 5% or more, the media...
1,840 citations
TL;DR: The Comprehensive Antibiotic Resistance Database (CARD) is a manually curated resource containing high quality reference data on the molecular basis of antimicrobial resistance (AMR), with an emphasis on the genes, proteins and mutations involved in AMR.
Abstract: The Comprehensive Antibiotic Resistance Database (CARD; http://arpcardmcmasterca) is a manually curated resource containing high quality reference data on the molecular basis of antimicrobial resistance (AMR), with an emphasis on the genes, proteins and mutations involved in AMR CARD is ontologically structured, model centric, and spans the breadth of AMR drug classes and resistance mechanisms, including intrinsic, mutation-driven and acquired resistance It is built upon the Antibiotic Resistance Ontology (ARO), a custom built, interconnected and hierarchical controlled vocabulary allowing advanced data sharing and organization Its design allows the development of novel genome analysis tools, such as the Resistance Gene Identifier (RGI) for resistome prediction from raw genome sequence Recent improvements include extensive curation of additional reference sequences and mutations, development of a unique Model Ontology and accompanying AMR detection models to power sequence analysis, new visualization tools, and expansion of the RGI for detection of emergent AMR threats CARD curation is updated monthly based on an interplay of manual literature curation, computational text mining, and genome analysis
1,726 citations
Queen Mary University of London1, Winthrop-University Hospital2, Karolinska Institutet3, Boston Children's Hospital4, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico5, Harvard University6, University of Colorado Denver7, McMaster University8, University of Auckland9, Katholieke Universiteit Leuven10, University of Tampere11, University of Birmingham12, Pennsylvania State University13, University of Otago14, QIMR Berghofer Medical Research Institute15, Dartmouth College16, Menzies Research Institute17, Medical University of Łódź18, University of Delhi19, Jikei University School of Medicine20
TL;DR: Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall and patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.
Abstract: Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect. Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials. Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015. Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D 3 or vitamin D 2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome. Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit. Systematic review registration PROSPERO CRD42014013953.
1,431 citations
TL;DR: The InTBIR Participants and Investigators have provided informed consent for the study to take place in Poland.
Abstract: Additional co-authors: Endre Czeiter, Marek Czosnyka, Ramon Diaz-Arrastia, Jens P Dreier, Ann-Christine Duhaime, Ari Ercole, Thomas A van Essen, Valery L Feigin, Guoyi Gao, Joseph Giacino, Laura E Gonzalez-Lara, Russell L Gruen, Deepak Gupta, Jed A Hartings, Sean Hill, Ji-yao Jiang, Naomi Ketharanathan, Erwin J O Kompanje, Linda Lanyon, Steven Laureys, Fiona Lecky, Harvey Levin, Hester F Lingsma, Marc Maegele, Marek Majdan, Geoffrey Manley, Jill Marsteller, Luciana Mascia, Charles McFadyen, Stefania Mondello, Virginia Newcombe, Aarno Palotie, Paul M Parizel, Wilco Peul, James Piercy, Suzanne Polinder, Louis Puybasset, Todd E Rasmussen, Rolf Rossaint, Peter Smielewski, Jeannette Soderberg, Simon J Stanworth, Murray B Stein, Nicole von Steinbuchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Anneliese Synnot, Braden Te Ao, Olli Tenovuo, Alice Theadom, Dick Tibboel, Walter Videtta, Kevin K W Wang, W Huw Williams, Kristine Yaffe for the InTBIR Participants and Investigators
1,354 citations
McMaster University1, University of Montpellier2, Transylvania University3, Ghent University Hospital4, University of Sydney5, Humanitas University6, University of South Florida7, Leiden University Medical Center8, RMIT University9, Federal University of Bahia10, Pierre-and-Marie-Curie University11, Saint Louis University12, University of Porto13, Katholieke Universiteit Leuven14, Medical University of Łódź15, University of Tartu16, Oslo University Hospital17, Royal College of Surgeons in Ireland18, University of California, San Diego19, University of Barcelona20, University of Padua21, Monash University22, Charles University in Prague23, University of Manchester24, Ajou University25, University of Genoa26, Nippon Medical School27, University of Aberdeen28, University of Edinburgh29, Kerman Medical University30, Medical University of Warsaw31, National Institutes of Health32, Vilnius University33, University of Turku34, Nova Southeastern University35, Boston Children's Hospital36, Beijing Tongren Hospital37, Charité38
TL;DR: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR, addressing the relative merits of using oral H1‐antihistamines, intranasal H1-antihistsamines, IntranasAL corticosteroids, and leukotriene receptor antagonists either alone or in combination.
Abstract: Background Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. Objective We sought to provide a targeted update of the ARIA guidelines. Methods The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. Results The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. Conclusions Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.
1,098 citations
TL;DR: Most patients will be better served by first-line treatment with bismuth quadruple therapy or concomitant therapy consisting of a PPI, clarithromycin, amoxicillin, and metronidazole.
TL;DR: In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo and was associated with increased lipid levels.
Abstract: BackgroundTofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy. MethodsWe conducted three phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib therapy in adults with ulcerative colitis. In the OCTAVE Induction 1 and 2 trials, 598 and 541 patients, respectively, who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib (10 mg twice daily) or placebo for 8 weeks. The primary end point was remission at 8 weeks. In the OCTAVE Sustain trial, 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib (either 5 mg or 10 mg twice daily) or placebo for 52 weeks. The primary...
TL;DR: A review of the field of hydrogels and aerogels incorporating nanocelluloses can be found in this paper, where over 200 references are summarized in comprehensive tables and a discussion of the challenges and benefits of using CNCs and CNFs as reinforcing agents in conventional plastics is presented.
Abstract: Naturally derived cellulose nanocrystals (CNCs) and cellulose nanofibrils (CNFs) are emerging nanomaterials that display high strength, high surface area, and tunable surface chemistry, allowing for controlled interactions with polymers, nanoparticles, small molecules, and biological materials. Industrial production of nanocelluloses is increasing rapidly with several companies already producing on the tons-per-day scale, intensifying the quest for viable products across many sectors. While the hydrophilicity of the nanocellulose interface has posed a challenge to the use of CNCs and CNFs as reinforcing agents in conventional plastics, it is a significant benefit for creating reinforced or structured hydrogel composites (or, when dried, aerogels) exhibiting both mechanical reinforcement and a host of other desirable properties. In this context, this Review describes the quickly growing field of hydrogels and aerogels incorporating nanocelluloses; over 200 references are summarized in comprehensive tables ...
McMaster University1, University of Toronto2, St. Michael's Hospital3, St James's University Hospital4, Harvard University5, Tufts Medical Center6, University of Bologna7, Magna Græcia University8, Sapienza University of Rome9, University of Barcelona10, Baylor College of Medicine11, French Institute of Health and Medical Research12, University of British Columbia13, Royal Columbian Hospital14, Hospital de Sant Pau15, Hofstra University16, Lenox Hill Hospital17
TL;DR: This document provides European Respiratory Society/American Thoracic Society and ERS/ATS evidence-based recommendations for the use of noninvasive ventilation in acute respiratory failure based on the most current literature.
Abstract: Noninvasive mechanical ventilation (NIV) is widely used in the acute care setting for acute respiratory failure (ARF) across a variety of aetiologies. This document provides European Respiratory Society/American Thoracic Society recommendations for the clinical application of NIV based on the most current literature. The guideline committee was composed of clinicians, methodologists and experts in the field of NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology for each actionable question. The GRADE Evidence to Decision framework in the guideline development tool was used to generate recommendations. A number of topics were addressed using technical summaries without recommendations and these are discussed in the supplementary material. This guideline committee developed recommendations for 11 actionable questions in a PICO (population–intervention–comparison–outcome) format, all addressing the use of NIV for various aetiologies of ARF. The specific conditions where recommendations were made include exacerbation of chronic obstructive pulmonary disease, cardiogenic pulmonary oedema, de novo hypoxaemic respiratory failure, immunocompromised patients, chest trauma, palliation, post-operative care, weaning and post-extubation. This document summarises the current state of knowledge regarding the role of NIV in ARF. Evidence-based recommendations provide guidance to relevant stakeholders.
University of California, San Francisco1, San Francisco VA Medical Center2, University of Colorado Denver3, McMaster University4, University of North Carolina at Chapel Hill5, Icahn School of Medicine at Mount Sinai6, Erasmus University Medical Center7, University of Washington8, Kingston General Hospital9
TL;DR: A multidisciplinary Delphi panel developed a consensus definition for ACP for adults that can be used to inform implementation and measurement of ACP clinical, research, and policy initiatives.
UNICEF1, University of Toronto2, Harvard University3, Yale University4, University of Hong Kong5, Li Ka Shing Faculty of Medicine, University of Hong Kong6, University of California, Berkeley7, McMaster University8, University of Southampton9, Purdue University10, Columbia University11, New York University12, University of Missouri–St. Louis13, Aga Khan University14
TL;DR: In this paper, the authors provide a comprehensive updated analysis of early childhood development interventions across the five sectors of health, nutrition, education, child protection, and social protection, concluding that to make interventions successful, smart, and sustainable, they need to be implemented as multi-sectoral intervention packages anchored in nurturing care.
TL;DR: This Users’ Guide will help clinicians understand the available metrics for assessing discrimination, calibration, and the relative performance of different prediction models to help clinicians make optimal use of existing prediction models.
Abstract: Accurate information regarding prognosis is fundamental to optimal clinical care. The best approach to assess patient prognosis relies on prediction models that simultaneously consider a number of prognostic factors and provide an estimate of patients' absolute risk of an event. Such prediction models should be characterized by adequately discriminating between patients who will have an event and those who will not and by adequate calibration ensuring accurate prediction of absolute risk. This Users' Guide will help clinicians understand the available metrics for assessing discrimination, calibration, and the relative performance of different prediction models. This article complements existing Users' Guides that address the development and validation of prediction models. Together, these guides will help clinicians to make optimal use of existing prediction models.
TL;DR: This paper has presented and compared several low-cost and non-invasive health and activity monitoring systems that were reported in recent years and compatibility of several communication technologies as well as future perspectives and research challenges in remote monitoring systems will be discussed.
Abstract: Life expectancy in most countries has been increasing continually over the several few decades thanks to significant improvements in medicine, public health, as well as personal and environmental hygiene. However, increased life expectancy combined with falling birth rates are expected to engender a large aging demographic in the near future that would impose significant burdens on the socio-economic structure of these countries. Therefore, it is essential to develop cost-effective, easy-to-use systems for the sake of elderly healthcare and well-being. Remote health monitoring, based on non-invasive and wearable sensors, actuators and modern communication and information technologies offers an efficient and cost-effective solution that allows the elderly to continue to live in their comfortable home environment instead of expensive healthcare facilities. These systems will also allow healthcare personnel to monitor important physiological signs of their patients in real time, assess health conditions and provide feedback from distant facilities. In this paper, we have presented and compared several low-cost and non-invasive health and activity monitoring systems that were reported in recent years. A survey on textile-based sensors that can potentially be used in wearable systems is also presented. Finally, compatibility of several communication technologies as well as future perspectives and research challenges in remote monitoring systems will be discussed.
TL;DR: High carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality.
Memorial Sloan Kettering Cancer Center1, University of California, Los Angeles2, Yale University3, Fox Chase Cancer Center4, Johns Hopkins University5, Duke University6, University of Texas Southwestern Medical Center7, University of Washington8, McMaster University9, Princess Margaret Cancer Centre10, University of Ottawa11, Bristol-Myers Squibb12
TL;DR: The primary outcome was safety and tolerability, assessed in all treated patients, and data from the latter two cohorts, which were considered potentially suitable for further clinical development, are presented.
Abstract: Summary Background Nivolumab has shown improved survival in the treatment of advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy. We assessed the safety and activity of combination nivolumab plus ipilimumab as first-line therapy for NSCLC. Methods The open-label, phase 1, multicohort study (CheckMate 012) cohorts reported here were enrolled at eight US academic centres. Eligible patients were aged 18 years or older with histologically or cytologically confirmed recurrent stage IIIb or stage IV, chemotherapy-naive NSCLC. Patients were randomly assigned (1:1:1) by an interactive voice response system to receive nivolumab 1 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks, nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 12 weeks, or nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks until disease progression, unacceptable toxicities, or withdrawal of consent. Data from the latter two cohorts, which were considered potentially suitable for further clinical development, are presented in this report; data from the other cohort (as well as several earlier cohorts) are described in the appendix. The primary outcome was safety and tolerability, assessed in all treated patients. This ongoing study is registered with ClinicalTrials.gov, number NCT01454102. Findings Between May 15, 2014, and March 25, 2015, 78 patients were randomly assigned to receive nivolumab every 2 weeks plus ipilimumab every 12 weeks (n=38) or nivolumab every 2 weeks plus ipilimumab every 6 weeks (n=40). One patient in the ipilimumab every-6-weeks cohort was excluded before treatment; therefore 77 patients actually received treatment (38 in the ipilimumab every-12-weeks cohort; 39 in the ipilimumab every-6-weeks cohort). At data cut-off on Jan 7, 2016, 29 (76%) patients in the ipilimumab every-12-weeks cohort and 32 (82%) in the ipilimumab every-6-weeks cohort had discontinued treatment. Grade 3–4 treatment-related adverse events occurred in 14 (37%) patients in the ipilimumab every-12-weeks cohort and 13 (33%) patients in the every-6-weeks cohort; the most commonly reported grade 3 or 4 treatment-related adverse events were increased lipase (three [8%] and no patients), pneumonitis (two [5%] and one [3%] patients), adrenal insufficiency (one [3%] and two [5%] patients), and colitis (one [3%] and two [5%] patients). Treatment-related serious adverse events were reported in 12 (32%) patients in the ipilimumab every-12-weeks cohort and 11 (28%) patients in the every-6-weeks cohort. Treatment-related adverse events (any grade) prompted treatment discontinuation in four (11%) patients in the every-12-weeks cohort and five (13%) patients in the every-6-weeks cohort. No treatment-related deaths occurred. Confirmed objective responses were achieved in 18 (47% [95% CI 31–64]) patients in the ipilimumab every-12-weeks cohort and 15 (38% [95% CI 23–55]) patients in the ipilimumab every-6-weeks cohort; median duration of response was not reached in either cohort, with median follow-up times of 12·8 months (IQR 9·3–15·5) in the ipilimumab every-12-weeks cohort and 11·8 months (6·7–15·9) in the ipilimumab every-6-weeks cohort. In patients with PD-L1 of 1% or greater, confirmed objective responses were achieved in 12 (57%) of 21 patients in the ipilimumab every-12-weeks cohort and 13 (57%) of 23 patients in the ipilimumab every-6-weeks cohort. Interpretation In NSCLC, first-line nivolumab plus ipilimumab had a tolerable safety profile and showed encouraging clinical activity characterised by a high response rate and durable response. To our knowledge, the results of this study are the first suggestion of improved benefit compared with anti-PD-1 monotherapy in patients with NSCLC, supporting further assessment of this combination in a phase 3 study. Funding Bristol-Myers Squibb.
TL;DR: In emergency situations, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran.
Abstract: BackgroundIdarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. MethodsWe performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time. Secondary end points included the restoration of hemostasis and safety measures. ResultsA total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted thrombin time or the ecarin clotting time. In group A, 137 patients (45.5%) presented ...
Harvard University1, Medical University of Vienna2, Institut Jules Bordet3, University of St. Gallen4, Kantonsspital St. Gallen5, Institut Gustave Roussy6, Memorial Sloan Kettering Cancer Center7, Karolinska Institutet8, University of Bordeaux9, University of North Carolina at Chapel Hill10, Queen Mary University of London11, Charité12, Marmara University13, Mount Sinai Hospital, Toronto14, Ludwig Maximilian University of Munich15, University of Michigan16, National Taiwan University17, University of Ulm18, National Institutes of Health19, Gdańsk Medical University20, Sahlgrenska University Hospital21, Baylor College of Medicine22, University of Toronto23, Netherlands Cancer Institute24, Paracelsus Private Medical University of Salzburg25, Fudan University26, The Royal Marsden NHS Foundation Trust27, Kyoto University28, Institute of Cancer Research29, University of Milan30, McMaster University31
TL;DR: The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer, and recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence.
University of Toronto1, University of Düsseldorf2, German Cancer Research Center3, University of Pittsburgh4, Ontario Institute for Cancer Research5, Seoul National University6, University of Warsaw7, University of Lyon8, Mayo Clinic9, The Chinese University of Hong Kong10, Johns Hopkins University11, University of Alabama at Birmingham12, Fred Hutchinson Cancer Research Center13, University of Washington14, University of California, San Francisco15, McMaster University16, Hamilton Health Sciences17, Vanderbilt University18, University of Colorado Denver19, Semmelweis University20, Erasmus University Rotterdam21, University of Ulsan22, Kitasato University23, Mexican Social Security Institute24, Masaryk University25, Emory University26, University of Debrecen27, University of Naples Federico II28, Washington University in St. Louis29, McGill University30, Montreal Children's Hospital31, Virginia Commonwealth University32, Chonnam National University33, University of Queensland34, University of Calgary35, University of São Paulo36, University of Cincinnati37, University of Arkansas for Medical Sciences38, The Catholic University of America39, University of California, Los Angeles40, University of Sydney41, Kumamoto University42, Saint Louis University43, Case Western Reserve University44
TL;DR: Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes.
Guy's and St Thomas' NHS Foundation Trust1, John Radcliffe Hospital2, University of Nottingham3, Brigham and Women's Hospital4, ISMETT5, Banaras Hindu University6, Newton Wellesley Hospital7, Madras Institute of Orthopaedics and Traumatology8, University of the West Indies9, University of Michigan10, Sahlgrenska University Hospital11, Queen Mary University of London12, Aga Khan University13, University of Manchester14, Virginia Commonwealth University15, University of Padua16, Changi General Hospital17, King's College London18, Southampton General Hospital19, Texas Tech University Health Sciences Center20, McMaster University21, University Hospital Waterford22, Turku University Hospital23, University of Mainz24, Bezmialem Foundation University25, Colchester Hospital University NHS Foundation Trust26, Kent State University27, Guy's Hospital28, Cairo University29, Children's of Alabama30
TL;DR: The development of the STROCSS guideline (Strengthening the Reporting of Cohort Studies in Surgery), consisting of a 17-item checklist, is described and it is hoped its use will increase the transparency and reporting quality of such studies.
VU University Medical Center1, University of Southern California2, Max Planck Society3, McMaster University4, University of Adelaide5, University of California, Irvine6, Erasmus University Rotterdam7, Delft University of Technology8, Erasmus University Medical Center9, German Center for Neurodegenerative Diseases10, Greifswald University Hospital11, University of Münster12, University of Marburg13, University of Queensland14, QIMR Berghofer Medical Research Institute15, Queensland University of Technology16, Virginia Commonwealth University17, University of Göttingen18, University Hospital Heidelberg19, University of Sydney20, Otto-von-Guericke University Magdeburg21, Trinity College, Dublin22, University of Regensburg23, University Medical Center Groningen24, Leiden University Medical Center25, University of Melbourne26, University of Texas Health Science Center at Houston27, Charité28, University of Bonn29, University of Lübeck30, University Medical Center Freiburg31, Stanford University32, University of Calgary33, Warneford Hospital34, Royal Edinburgh Hospital35, University of Edinburgh36, University of Bern37, Cardiff University38, Leibniz Institute for Neurobiology39, University of Tübingen40, Tomsk State University41, Mental Health Research Institute42, Siberian State Medical University43
TL;DR: In this article, the authors present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD.
Abstract: The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.
TL;DR: It is found that, when maintained under germ-free conditions, mice do not display an age-related increase in circulating pro-inflammatory cytokine levels, suggesting that aging-associated microbiota promote inflammation and that reversing these age- related microbiota changes represents a potential strategy for reducing age-associated inflammation and the accompanying morbidity.
TL;DR: Benralizumab showed significant, clinically relevant benefits, as compared with placebo, on oral glucocorticoid use and exacerbation rates and without a sustained effect on the forced expiratory volume in 1 second (FEV1).
Abstract: BackgroundMany patients with severe asthma rely on oral glucocorticoids to manage their disease We investigated whether benralizumab, a monoclonal antibody directed against the alpha subunit of the interleukin-5 receptor that significantly reduces the incidence of asthma exacerbations, was also effective as an oral glucocorticoid–sparing therapy in patients relying on oral glucocorticoids to manage severe asthma associated with eosinophilia MethodsIn a 28-week randomized, controlled trial, we assessed the effects of benralizumab (at a dose of 30 mg administered subcutaneously either every 4 weeks or every 8 weeks [with the first three doses administered every 4 weeks]) versus placebo on the reduction in the oral glucocorticoid dose while asthma control was maintained in adult patients with severe asthma The primary end point was the percentage change in the oral glucocorticoid dose from baseline to week 28 Annual asthma exacerbation rates, lung function, symptoms, and safety were assessed ResultsOf 3
Tufts University1, Karolinska University Hospital2, University of Texas MD Anderson Cancer Center3, Universitaire Ziekenhuizen Leuven4, City of Hope National Medical Center5, McMaster University6, Jichi Medical University7, University of Chicago8, Fred Hutchinson Cancer Research Center9, University of Pennsylvania10, Merck & Co.11, University of Würzburg12
TL;DR: Letermovir prophylaxis resulted in a significantly lower risk of clinically significant CMV infection than placebo, and the frequency and severity of adverse events were similar in the two groups overall.
Abstract: BackgroundCytomegalovirus (CMV) infection remains a common complication after allogeneic hematopoietic-cell transplantation. Letermovir is an antiviral drug that inhibits the CMV–terminase complex. MethodsIn this phase 3, double-blind trial, we randomly assigned CMV-seropositive transplant recipients, 18 years of age or older, in a 2:1 ratio to receive letermovir or placebo, administered orally or intravenously, through week 14 after transplantation; randomization was stratified according to trial site and CMV disease risk. Letermovir was administered at a dose of 480 mg per day (or 240 mg per day in patients taking cyclosporine). Patients in whom clinically significant CMV infection (CMV disease or CMV viremia leading to preemptive treatment) developed discontinued the trial regimen and received anti-CMV treatment. The primary end point was the proportion of patients, among patients without detectable CMV DNA at randomization, who had clinically significant CMV infection through week 24 after transplanta...
The Centre for Applied Genomics1, Google2, University of Toronto3, McGill University4, University of Alberta5, McMaster University6, Dalhousie University7, Queen's University8, University of Western Ontario9, Autism Speaks10, University of Illinois at Chicago11, University of Washington12, Trinity College, Dublin13, Vanderbilt University14, Newcastle University15, Boston Children's Hospital16, Utrecht University17, University of California, San Diego18, Memorial University of Newfoundland19, Children's Hospital of Eastern Ontario20, Stanford University21, Centre for Addiction and Mental Health22, Drexel University23
TL;DR: Se sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal that identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability.
Abstract: We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertions and deletions or copy number variations per ASD subject. We identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (P = 6 × 10-4). In 294 of 2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried copy number variations and/or chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD.
TL;DR: This report summarizes and builds upon some of the key concepts in the symposium “The Microbiome: Development, Stress, and Disease” within the context of how microbiota might influence the neurobiology of stress.