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Gagliardi A.R.,Toronto General Research Institute | Alhabib S.,King Abdullah University of Science and Technology
Implementation Science | Year: 2015

Background: There is currently no reliable way to choose strategies that are appropriate for implementing guidelines facing different barriers. This study examined trends in guideline implementation by topic over a 10-year period to explore whether and how strategies may be suitable for addressing differing barriers. Methods: A scoping systematic review was performed. MEDLINE and EMBASE were searched from 2004 to 2013 for studies that evaluated the implementation of guidelines on arthritis, diabetes, colorectal cancer and heart failure. Data on study characteristics, reason for implementation (new guideline or quality improvement), implementation strategy used, rationale for selecting that strategy and reported impact were extracted and summarized. Interventions were mapped against a published taxonomy of guideline implementation strategies. Results: The search resulted in 1,709 articles; 156 were retrieved and 127 were excluded largely because they did not evaluate guideline implementation, leaving 32 eligible for review (4 arthritis, 3 colorectal cancer, 21 diabetes, 4 heart failure). Six of 7 randomized trials and 8 of 25 observational studies had a low risk of bias. Most studies promoted guideline use for quality improvement (78.0%). Few studies rationalized strategy choice (18.8%). Most employed multiple approaches and strategies, most often educational meetings and print material for professionals or patients. Few studies employed organizational, financial or regulatory approaches. Strategies employed that were unique to the published taxonomy included professional (print material, tailoring guidelines, self-audit training or material) and patient strategies (education, counselling, group interaction, print material, reminders). Most studies achieved positive impact (87.5%). This did not appear to be associated with guideline topic, use of theory or barrier assessment, or number or type of implementation approaches and strategies. Conclusions: While few studies were eligible, limiting insight on how to choose implementation strategies that address guideline-specific barriers, this review identified other important findings. Education for professionals or patients and print material were the most commonly employed strategies for translating guidelines to practice. Mapping of strategies onto the published taxonomy identified gaps in guideline implementation that represent opportunities for future research and expanded the taxonomy. © 2015 Gagliardi and Alhabib; licensee BioMed Central.

Galligan C.L.,Toronto General Research Institute
Rheumatology (Oxford, England) | Year: 2010

RA is a common, relapsing autoimmune disease primarily affecting the joints. Fibroblast-like synovial (FLS) cells are thought to be responsible for pannus formation and secretion of factors that recruit leucocytes to affected joints, thereby promoting bone and cartilage destruction. Fibrocytes are multipotent circulating stem cells that may have a role in RA pathogenesis, perhaps as the precursors of the FLS cells, or by regulating FLS cell function. We utilized multidimensional phospho-specific flow cytometry to characterize the activation status of peripheral blood (PB) fibrocytes derived from human RA patients at different stages of disease and from mice with CIA. Human PB fibrocytes from RA patients exhibited phosporylation activation of the p44/42 and p38 MAP kinases (MAPKs), and STAT3 (signal transducer and activator of transcription) and STAT-5 early in disease, within the first year of diagnosis. Similarly, in murine CIA, an increase in the total number of PB phosphoSTAT5-positive fibrocytes was observed at early time points in disease. Notably, in the affected paws of mice with CIA, we identified an increased number of fibrocytes, in contrast to the paws of control mice. These data suggest that activated fibrocytes may influence the disease process in RA and may serve as surrogate markers for disease in the PB of affected patients.

Stewart D.E.,Toronto General Research Institute
New England Journal of Medicine | Year: 2011

A 24-year-old married woman presents with a 1-month history of diminished concentration and interest, insomnia, fatigue, tearfulness, and depressed mood. She is 10 weeks pregnant, stopped working 3 weeks ago, and mostly stays in bed. Two years ago, she was successfully treated briefly with sertraline at a daily dose of 50 mg for depression after a suicide attempt. She reports that she wants to continue the pregnancy and says that she does not feel suicidal. What would you advise? Copyright © 2011 Massachusetts Medical Society.

Markle J.G.,Rockefeller University | Fish E.N.,Toronto General Research Institute | Fish E.N.,University of Toronto
Trends in Immunology | Year: 2014

The significant contributions of sex to an immune response, specifically in the context of the sex bias observed in susceptibility to infectious and autoimmune diseases and their pathogenesis, have until recently, largely been ignored and understudied. This review highlights recent findings related to sex-specific factors that provide new insights into how sex determines the transcriptome, the microbiome, and the consequent immune cell functional profile to define an immune response. Unquestionably, accumulating data confirm that sex matters and must be a consideration when decisions around therapeutic intervention strategies are developed. © 2013 Elsevier Ltd.

Jin T.,Toronto General Research Institute
Endocrine Reviews | Year: 2016

The role of the Wnt signaling pathway in metabolic homeostasis has drawn our intensive attention, especially after the genome-wide association study discovery that certain polymorphisms of its key effector TCF7L2 are strongly associated with the susceptibility to type 2 diabetes. For a decade, great efforts have been made in determining the function of TCF7L2 in various metabolic organs, which have generated both considerable achievements and disputes. In this review, I will briefly introduce the canonical Wnt signaling pathway, focusing on its effector -catenin/TCF, including emphasizing the bidirectional feature of TCFs and -catenin posttranslational modifications. I will then summarize the observations on the association between TCF7L2 polymorphisms and type 2 diabetes risk. The main content, however, is on the intensive functional exploration of the metabolic role of TCF7L2, including the disputes generated on determining its role in the pancreas and liver with various transgenicmouselines. Finally, I will discuss those achievements and disputes and presentmyfuture perspectives. © 2016 by the Endocrine Society.

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