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Sunnybrook Health Sciences Centre

HealthcareToronto, Ontario, Canada
About: Sunnybrook Health Sciences Centre is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Breast cancer. The organization has 7689 authors who have published 15236 publications receiving 523019 citations. The organization is also known as: Sunnybrook.


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Journal ArticleDOI
TL;DR: An ethical framework for pandemic influenza planning was developed with expertise from clinical, organisational and public health ethics and validated through a stakeholder engagement process and will require re-evaluation and refinement.
Abstract: Planning for the next pandemic influenza outbreak is underway in hospitals across the world. The global SARS experience has taught us that ethical frameworks to guide decision-making may help to reduce collateral damage and increase trust and solidarity within and between health care organisations. Good pandemic planning requires reflection on values because science alone cannot tell us how to prepare for a public health crisis. In this paper, we present an ethical framework for pandemic influenza planning. The ethical framework was developed with expertise from clinical, organisational and public health ethics and validated through a stakeholder engagement process. The ethical framework includes both substantive and procedural elements for ethical pandemic influenza planning. The incorporation of ethics into pandemic planning can be helped by senior hospital administrators sponsoring its use, by having stakeholders vet the framework, and by designing or identifying decision review processes. We discuss the merits and limits of an applied ethical framework for hospital decision-making, as well as the robustness of the framework. The need for reflection on the ethical issues raised by the spectre of a pandemic influenza outbreak is great. Our efforts to address the normative aspects of pandemic planning in hospitals have generated interest from other hospitals and from the governmental sector. The framework will require re-evaluation and refinement and we hope that this paper will generate feedback on how to make it even more robust.

251 citations

Journal ArticleDOI
TL;DR: The surprise question performs poorly to modestly as a predictive tool for death, with worse performance in noncancer illness, and further studies are needed to develop accurate tools for patients with palliative care needs.
Abstract: BACKGROUND: The surprise question — “Would I be surprised if this patient died in the next 12 months?” — has been used to identify patients at high risk of death who might benefit from palliative care services. Our objective was to systematically review the performance characteristics of the surprise question in predicting death. METHODS: We searched multiple electronic databases from inception to 2016 to identify studies that prospectively screened patients with the surprise question and reported on death at 6 to 18 months. We constructed models of hierarchical summary receiver operating characteristics (sROCs) to determine prognostic performance. RESULTS: Sixteen studies (17 cohorts, 11 621 patients) met the selection criteria. For the outcome of death at 6 to 18 months, the pooled prognostic characteristics were sensitivity 67.0% (95% confidence interval [CI] 55.7%–76.7%), specificity 80.2% (73.3%–85.6%), positive likelihood ratio 3.4 (95% CI 2.8–4.1), negative likelihood ratio 0.41 (95% CI 0.32–0.54), positive predictive value 37.1% (95% CI 30.2%–44.6%) and negative predictive value 93.1% (95% CI 91.0%–94.8%). The surprise question had worse discrimination in patients with noncancer illness (area under sROC curve 0.77 [95% CI 0.73–0.81]) than in patients with cancer (area under sROC curve 0.83 [95% CI 0.79–0.87; p = 0.02 for difference]). Most studies had a moderate to high risk of bias, often because they had a low or unknown participation rate or had missing data. INTERPRETATION: The surprise question performs poorly to modestly as a predictive tool for death, with worse performance in noncancer illness. Further studies are needed to develop accurate tools to identify patients with palliative care needs and to assess the surprise question for this purpose.

251 citations

Journal ArticleDOI
TL;DR: 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 were tested.
Abstract: 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). Each patient assigned to receive amphotericin B was also randomly assigned to receive fluconazole or flucytosine as a partner drug. After induction treatment, all the patients received fluconazole consolidation therapy and were followed to 10 weeks. Results A total of 721 patients underwent randomization. Mortality in the oral-regimen, 1-week amphoterici...

250 citations

Journal ArticleDOI
TL;DR: Limited evidence from observational data suggest that TEG®/ROTEM® tests diagnose early trauma coagulopathy and may predict blood-product transfusion and mortality in trauma.
Abstract: The understanding of coagulopathies in trauma has increased interest in thromboelastography (TEG®) and thromboelastometry (ROTEM®), which promptly evaluate the entire clotting process and may guide blood product therapy. Our objective was to review the evidence for their role in diagnosing early coagulopathies, guiding blood transfusion, and reducing mortality in injured patients. We considered observational studies and randomized controlled trials (MEDLINE, EMBASE, and Cochrane databases) to February 2014 that examined TEG®/ROTEM® in adult trauma patients. We extracted data on demographics, diagnosis of early coagulopathies, blood transfusion, and mortality. We assessed methodologic quality by using the Newcastle-Ottawa scale (NOS) for observational studies and QUADAS-2 tool for diagnostic accuracy studies. Fifty-five studies (12,489 patients) met inclusion criteria, including 38 prospective cohort studies, 15 retrospective cohort studies, two before-after studies, and no randomized trials. Methodologic quality was moderate (mean NOS score, 6.07; standard deviation, 0.49). With QUADAS-2, only three of 47 studies (6.4%) had a low risk of bias in all domains (patient selection, index test, reference standard and flow and timing); 37 of 47 studies (78.8%) had low concerns regarding applicability. Studies investigated TEG®/ROTEM® for diagnosis of early coagulopathies (n = 40) or for associations with blood-product transfusion (n = 25) or mortality (n = 24). Most (n = 52) were single-center studies. Techniques examined included rapid TEG® (n =12), ROTEM® (n = 18), TEG® (n = 23), or both TEG® and rapid TEG® (n = 2). Many TEG®/ROTEM® measurements were associated with early coagulopathies, including some (hypercoagulability, hyperfibrinolysis, platelet dysfunction) not assessed by routine screening coagulation tests. Standard measures of diagnostic accuracy were inconsistently reported. Many abnormalities predicted the need for massive transfusion and death, but predictive performance was not consistently superior to routine tests. One observational study suggested that a ROTEM® -based transfusion algorithm reduced blood-product transfusion, but TEG®/ROTEM®-based resuscitation was not associated with lower mortality in most studies. Limited evidence from observational data suggest that TEG®/ROTEM® tests diagnose early trauma coagulopathy and may predict blood-product transfusion and mortality in trauma. Effects on blood-product transfusion, mortality, and other patient-important outcomes remain unproven in randomized trials.

250 citations

Journal ArticleDOI
TL;DR: 800 mg tarenflurbil twice per day was well tolerated for up to 24 months of treatment, with evidence of a dose-related effect on measures of daily activities and global function in patients with mild to moderate AD.
Abstract: Summary Background The amyloid-β peptide Aβ 42 has been implicated in the pathogenesis of Alzheimer's disease (AD). We aimed to test the effects of tarenflurbil, a selective Aβ 42 -lowering agent (SALA), on cognition and function in patients with mild to moderate AD. Methods 210 patients living in the community who had a mini-mental state examination (MMSE) score of 15–26 were randomly assigned to receive tarenflurbil twice per day (400 mg [n=69] or 800 mg [n=70]) or placebo (n=71) for 12 months in a phase II, multicentre, double-blind study. Primary efficacy outcomes were the AD assessment scale cognitive subscale (ADAS-cog), the Alzheimer's Disease Cooperative Study activities of daily living scale (ADCS-ADL), and the clinical dementia rating sum of boxes (CDR-sb). In a 12-month extended treatment phase, patients who had received tarenflurbil continued to receive the same dose, and patients who had received placebo were randomly assigned to tarenflurbil at 800 mg or 400 mg twice per day. Primary efficacy analyses were done by intention to treat. This trial is registered with Health Canada (084527) and the Medicines and Healthcare products Regulatory Agency in the UK (20365/0001/A 69316). Findings A prespecified interaction analysis revealed that patients with mild AD (baseline MMSE 20–26) and moderate AD (baseline MMSE 15–19) responded differently to tarenflurbil in the ADAS-cog and the ADCS-ADL (p≥0·10); therefore, these groups were analysed separately. Patients with mild AD in the 800 mg tarenflurbil group had lower rates of decline than did those in the placebo group in activities of daily living (ADCS-ADL difference in slope 3·98 [95% CI 0·33 to 7·62] points per year, effect size [reduction from placebo decline rate] 46·4%, Cohen's d 0·45; p=0·033) and global function (CDR-sb difference −0·80 [−1·57 to −0·03] points per year, effect size 35·7%, Cohen's d 0·42; p=0·042); slowing of cognitive decline did not differ significantly (ADAS-cog difference −1·36 [−4·07 to 1·36] points per year, effect size 33·7%, Cohen's d 0·20; p=0·327). In patients with moderate AD, 800 mg tarenflurbil twice per day had no significant effects on ADCS-ADL and ADAS-cog and had a negative effect on CDR-sb (−52%, Cohen's d −1·08; p=0·003). The most common adverse events were diarrhoea (in seven, nine, and five patients in the 800 mg, 400 mg, and placebo groups, respectively), nausea (in seven, seven, and four patients), and dizziness (in five, nine, and four patients). Patients with mild AD who were in the 800 mg tarenflurbil group for 24 months had lower rates of decline for all three primary outcomes than did patients who were in the placebo group for months 0–12 and a tarenflurbil group for months 12–24 (all p Interpretation 800 mg tarenflurbil twice per day was well tolerated for up to 24 months of treatment, with evidence of a dose-related effect on measures of daily activities and global function in patients with mild AD. Funding Myriad Pharmaceuticals.

249 citations


Authors

Showing all 7765 results

NameH-indexPapersCitations
Gordon B. Mills1871273186451
David A. Bennett1671142109844
Bruce R. Rosen14868497507
Robert Tibshirani147593326580
Steven A. Narod13497084638
Peter Palese13252657882
Gideon Koren129199481718
John B. Holcomb12073353760
Julie A. Schneider11849256843
Patrick Maisonneuve11858253363
Mitch Dowsett11447862453
Ian D. Graham11370087848
Peter C. Austin11265760156
Sandra E. Black10468151755
Michael B. Yaffe10237941663
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202324
2022103
20211,627
20201,385
20191,171
20181,044