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Institution

St. Joseph's Healthcare Hamilton

HealthcareHamilton, Ontario, Canada
About: St. Joseph's Healthcare Hamilton is a healthcare organization based out in Hamilton, Ontario, Canada. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 1539 authors who have published 2746 publications receiving 87423 citations.


Papers
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Journal ArticleDOI
Adam J. Bass1, Vesteinn Thorsson2, Ilya Shmulevich2, Sheila Reynolds2  +254 moreInstitutions (32)
11 Sep 2014-Nature
TL;DR: A comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project is described and a molecular classification dividing gastric cancer into four subtypes is proposed.
Abstract: Gastric cancer was the world’s third leading cause of cancer mortality in 2012, responsible for 723,000 deaths1. The vast majority of gastric cancers are adenocarcinomas, which can be further subdivided into intestinal and diffuse types according to the Lauren classification2. An alternative system, proposed by the World Health Organization, divides gastric cancer into papillary, tubular, mucinous (colloid) and poorly cohesive carcinomas3. These classification systems have little clinical utility, making the development of robust classifiers that can guide patient therapy an urgent priority. The majority of gastric cancers are associated with infectious agents, including the bacterium Helicobacter pylori4 and Epstein–Barr virus (EBV). The distribution of histological subtypes of gastric cancer and the frequencies of H. pylori and EBV associated gastric cancer vary across the globe5. A small minority of gastric cancer cases are associated with germline mutation in E-cadherin (CDH1)6 or mismatch repair genes7 (Lynch syndrome), whereas sporadic mismatch repair-deficient gastric cancers have epigenetic silencing of MLH1 in the context of a CpG island methylator phenotype (CIMP)8. Molecular profiling of gastric cancer has been performed using gene expression or DNA sequencing9–12, but has not led to a clear biologic classification scheme. The goals of this study by The Cancer Genome Atlas (TCGA) were to develop a robust molecular classification of gastric cancer and to identify dysregulated pathways and candidate drivers of distinct classes of gastric cancer.

4,583 citations

Journal ArticleDOI
TL;DR: A detailed examination of the key aspects of pilot studies for phase III trials including the general reasons for conducting a pilot study, the relationships between pilot studies, proof-of-concept studies, and adaptive designs, and some suggestions on how to report the results of pilot investigations using the CONSORT format.
Abstract: Pilot studies for phase III trials - which are comparative randomized trials designed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas. Also commonly know as "feasibility" or "vanguard" studies, they are designed to assess the safety of treatment or interventions; to assess recruitment potential; to assess the feasibility of international collaboration or coordination for multicentre trials; to increase clinical experience with the study medication or intervention for the phase III trials. They are the best way to assess feasibility of a large, expensive full-scale study, and in fact are an almost essential pre-requisite. Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies. The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including: 1) the general reasons for conducting a pilot study; 2) the relationships between pilot studies, proof-of-concept studies, and adaptive designs; 3) the challenges of and misconceptions about pilot studies; 4) the criteria for evaluating the success of a pilot study; 5) frequently asked questions about pilot studies; 7) some ethical aspects related to pilot studies; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format.

2,365 citations

Journal ArticleDOI
TL;DR: In an unselected birth cohort, more than one in four children had wheezing that persisted from childhood to adulthood or that relapsed after remission, suggesting that outcomes in adult asthma may be determined primarily in early childhood.
Abstract: Background The outcome of childhood asthma in adults has been described in high-risk cohorts, but few population-based studies have reported the risk factors for persistence and relapse. Methods We assessed children born from April 1972 through March 1973 in Dunedin, New Zealand, repeatedly from 9 to 26 years of age with questionnaires, pulmonary-function tests, bronchial-challenge testing, and allergy testing. Results By the age of 26 years, 51.4 percent of 613 study members with complete respiratory data had reported wheezing at more than one assessment. Eighty-nine study members (14.5 percent) had wheezing that persisted from childhood to 26 years of age, whereas 168 (27.4 percent) had remission, but 76 (12.4 percent) subsequently relapsed by the age of 26. Sensitization to house dust mites predicted the persistence of wheezing (odds ratio, 2.41; P=0.001) and relapse (odds ratio, 2.18; P=0.01), as did airway hyperresponsiveness (odds ratio for persistence, 3.00; P<0.001; odds ratio for relapse, 3.03; P...

1,265 citations

Journal ArticleDOI
TL;DR: This work has shown that the presence of gut microbiota regulates the set point for hypothalamic‐pituitary‐adrenal (HPA) axis activity, and the role intestinal microbiota may play in communication between these two systems is increasing.
Abstract: Background There is increasing interest in the gut-brain axis and the role intestinal microbiota may play in communication between these two systems. Acquisition of intestinal microbiota in the immediate postnatal period has a defining impact on the development and function of the gastrointestinal, immune, neuroendocrine and metabolic systems. For example, the presence of gut microbiota regulates the set point for hypothalamic-pituitary-adrenal (HPA) axis activity. Methods We investigated basal behavior of adult germ-free (GF), Swiss Webster female mice in the elevated plus maze (EPM) and compared this to conventionally reared specific pathogen free (SPF) mice. Additionally, we measured brain mRNA expression of genes implicated in anxiety and stress-reactivity. Key Results Germ-free mice, compared to SPF mice, exhibited basal behavior in the EPM that can be interpreted as anxiolytic. Altered GF behavior was accompanied by a decrease in the N-methyl-D-aspartate receptor subunit NR2B mRNA expression in the central amygdala, increased brain-derived neurotrophic factor expression and decreased serotonin receptor 1A (5HT1A) expression in the dentate granule layer of the hippocampus. Conclusions & Inferences We conclude that the presence or absence of conventional intestinal microbiota influences the development of behavior, and is accompanied by neurochemical changes in the brain.

1,129 citations

Journal ArticleDOI
TL;DR: The consistency of reports of interactions with azole antibiotics, macrolides, quinolones, nonsteroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors, selective serotonin reuptake inhibitors, omeprazole, lipid-lowering agents, amiodarone, and fluorouracil suggests that coadministration with warfarin should be avoided or closely monitored.
Abstract: Background Warfarin is a highly efficacious oral anticoagulant, but its use is limited by a well-founded fear of bleeding. Drug and food interactions are frequently cited as causes of adverse events with warfarin. We provide an updated systematic overview of the quality, clinical effect, and importance of these reported interactions. Data Sources MEDLINE, TOXLINE, IPA, and EMBASE databases from October 1993 to March 2004. Database searches combined the keyword warfarin with drug interactions , herbal medicines , Chinese herbal drugs , and food-drug interactions . Study Selection Eligible articles contained original reports of warfarin drug or food interactions in human subjects. Non-English articles were included if sufficient information could be abstracted. Data Extraction Reports were rated independently by 2 investigators for interaction direction, clinical severity, and quality of evidence. Quality of evidence was based on previously validated causation criteria and study design. Data Synthesis Of 642 citations retrieved, 181 eligible articles contained original reports on 120 drugs or foods. Inter-rater agreement was excellent, with weighted κ values of 0.84 to 1.00. Of all reports, 72% described a potentiation of warfarin’s effect and 84% were of poor quality, 86% of which were single case reports. The 31 incidents of clinically significant bleeding were all single case reports. Newly reported interactions included celecoxib, rofecoxib, and herbal substances, such as green tea and danshen. Conclusions The number of drugs reported to interact with warfarin continues to expand. While most reports are of poor quality and present potentially misleading conclusions, the consistency of reports of interactions with azole antibiotics, macrolides, quinolones, nonsteroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors, selective serotonin reuptake inhibitors, omeprazole, lipid-lowering agents, amiodarone, and fluorouracil, suggests that coadministration with warfarin should be avoided or closely monitored. More systematic study of warfarin drug interactions in patients is urgently needed.

1,080 citations


Authors

Showing all 1545 results

NameH-indexPapersCitations
Gordon H. Guyatt2311620228631
Deborah J. Cook173907148928
Ming-Sound Tsao11468365660
Mark Crowther11167652415
Paul M. O'Byrne10460556520
Michael Walsh10296342231
David L. Streiner10160448863
Jonathan D. Adachi9658931641
Michael H. Boyle9537530791
Jack Gauldie9335231189
Flávio Kapczinski9262530471
Roman Jaeschke9124081517
John Bienenstock8942629118
Malcolm R. Sears8637530802
Stephen M. Collins8632025646
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20235
20229
2021340
2020296
2019248
2018213