Gordon H. Guyatt

Bio: Gordon H. Guyatt is an academic researcher from McMaster University. The author has contributed to research in topics: Randomized controlled trial & Evidence-based medicine. The author has an hindex of 231, co-authored 1620 publications receiving 228631 citations. Previous affiliations of Gordon H. Guyatt include Memorial Sloan Kettering Cancer Center & Cayetano Heredia University.

Preadmission antithrombotic treatment and stroke severity in patients with atrial fibrillation and acute ischaemic stroke: an observational study.

Abstract: Summary Background Vitamin K antagonists (eg, warfarin) substantially reduce the risk of ischaemic stroke in patients with atrial fibrillation. Additionally, therapeutic anticoagulation at time of acute stroke admission might reduce in-hospital mortality and disability. We assessed the association between preadmission antithrombotic treatment and initial stroke severity, neurological deterioration, major vascular events during hospital stay, and death or disability at discharge in patients with acute ischaemic stroke and atrial fibrillation. Methods We identified consecutive patients with acute ischaemic stroke and atrial fibrillation, admitted to 11 hospitals in Ontario, Canada, from the Registry of the Canadian Stroke Network (2003–05). Logistic regression was used to assess the association between antiplatelet treatment, subtherapeutic warfarin treatment (admission international normalised ratio [INR] 7) and severe stroke (CNS ≤7). Disability was measured with the modified-Rankin scale (mRS) and was categorised into strokes associated with no or mild-moderate dependency (mRS 0–3) and with severe dependency or death (mRS 4–6). Results Of 948 patients, 306 (32%) were not on antithrombotic treatment, 292 (31%) were receiving antiplatelet treatment, 238 (25%) were receiving warfarin with a subtherapeutic INR, and 112 (12%) were receiving warfarin with a therapeutic INR on admission. Compared with those not receiving antithrombotic therapy, antiplatelet therapy (odds ratio 0·7; 95% CI 0·5–0·995) and therapeutic warfarin (0·4; 0·2–0·6) were associated with a reduction in severe stroke at admission. Therapeutic warfarin was also associated with a reduction in the odds of severe disability or death at discharge (0·5; 0·3–0·9). Interpretation Therapeutic warfarin is associated with reduced severity of ischaemic stroke at presentation and reduced disability or death at discharge in patients with atrial fibrillation. Antiplatelet treatment is associated with a more modest reduction than warfarin in baseline stroke severity.

The impact of prophylactic dexamethasone on nausea and vomiting after laparoscopic cholecystectomy: a systematic review and meta-analysis.

Abstract: Objective: To determine the impact of prophylactic corticosteroid administration on postoperative nausea, vomiting, pain and complications in patients undergoing laparoscopic cholecystectomy. Data Sources: We searched 4 bibliographic databases, conference proceedings, reference lists of articles and textbooks, and contacted experts in the field of anesthesia and hepatobiliary surgery. Review Methods: We evaluated the methodologic quality of trials and extracted data regarding baseline characteristics, interventions, and outcomes. We pooled results from the studies using a random-effects model, evaluated the degree of heterogeneity, and explored potential explanations for heterogeneity. Results: Seventeen trials met eligibility criteria and provided high quality evidence regarding steroid effectiveness. Irrespective of the co-interventions (other antiemetic medications), dexamethasone reduced the incidence of nausea (RR 0.59, 95% CI, 0.48–0.72), vomiting (RR 0.41, 95% CI, 0.30–0.55), and postoperative nausea or vomiting (RR 0.55, 95% CI, 0.44–0.67) relative to placebo. Dexamethasone also seemed to reduce the severity of postoperative pain (Ratio of Means 0.87, 95% CI, 0.78–0.98), although substantial unexplained heterogeneity was present (I2 90.4%). The incidence of headache and dizziness was similar between groups. Conclusions: Prophylactic dexamethasone decreases the incidence of nausea and vomiting after LC relative to placebo and may decrease the severity of postoperative pain. Dexamethasone does not increase the incidence of headaches or dizziness. Surgeons should consider administering prophylactic corticosteroids to patients undergoing laparoscopic cholecystectomy, particularly those at high risk of postoperative nausea and vomiting.

An emerging consensus on grading recommendations

Abstract: Clinical practice guidelines have improved in quality over the past 10 years by adhering to a few basic principles, such as conducting thorough systematic reviews of relevant evidence and grading the recommendations and the quality of the underlying evidence. The large number of systems of measuring the quality of evidence and recommendations that have emerged are, however, confusing.1 The mission of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) working group is to help resolve the confusion among the different systems of rating evidence and recommendations. The group has wide representation from many organisations including the Agency for Healthcare Research and Quality in the US, the National Institute for Clinical Excellence for England and Wales, and the World Health Organization. Developing a new uniform rating system is challenging because all systems have limitations and because many organisations have invested a great deal of time and effort to develop their rating systems and are understandably reluctant to adopt a new system. The GRADE working group first published the results of its work in 2004 in the BMJ.2 A simpler, clinically oriented description will soon be published.3 GRADE has taken care to ensure its suggested system is simple to use and applicable to a wide variety of clinical recommendations that span the full spectrum of medical specialties and clinical care. The GRADE system classifies recommendations in 1 of 2 levels—strong and weak—and quality of evidence into 1 of 4 levels—high, moderate, low, and very low. Evidence based on randomised controlled trials (RCTs) begins with a top rating on GRADE’s 4 level quality of evidence classification (table …

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

Abstract: David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.

Abstract: Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field,1,2 and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research,3 and some health care journals are moving in this direction.4 As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews. Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in 4 leading medical journals in 1985 and 1986 and found that none met all 8 explicit scientific criteria, such as a quality assessment of included studies.5 In 1987, Sacks and colleagues6 evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in 6 domains. Reporting was generally poor; between 1 and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement.7 In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials.8 In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1). Box 1 Conceptual issues in the evolution from QUOROM to PRISMA

Measuring inconsistency in meta-analyses

Abstract: Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice? Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis. Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4 Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted? A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …

Bias in meta-analysis detected by a simple, graphical test

Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure

Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.

Abstract: This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.