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.

Users' Guides to the Medical Literature XIV. How to Decide on the Applicability of Clinical Trial Results to Your Patient

Abstract: You are the attending physician on duty when a poor, 45-year-old man presents to the emergency department of a general hospital in the Philippines. He has severe chest pain for 2 hours, associated with clammy perspiration. Physical examination reveals a blood pressure of 110/70 mm Hg, a pulse rate of 92 beats per minute, a normal first heart sound, and clear lungs. An electrocardiogram discloses 3-mm ST-segment elevation in the inferior leads. As intravenous lines are placed, and the patient is prepared for admission to the coronary care department, you consider whether you should offer this patient a thrombolytic agent. Though your response is that the impecunious patient cannot afford the treatment, you ponder the right course of action in a richer patient. As your duty ends that night, you resolve to prepare forthenextpatientadmittedforanacute myocardial infarction (MI) by retrieving the best evidence on the use of thrombolytics.

Stress Ulcer Prophylaxis in Critically Ill Patients Resolving Discordant Meta-Analyses

Abstract: Purpose. —To resolve discrepancies in previous systematic overviews and provide estimates of the effect of stress ulcer prophylaxis on gastrointestinal bleeding, pneumonia, and mortality in critically ill patients. Data Identification. —Computerized search of published and unpublished research, bibliographies, pharmaceutical and personal files, and conference abstract reports. Study Selection. —Independent review of 269 articles identified 63 relevant randomized trials for inclusion. Data Abstraction. —We made independent, duplicate assessment of the methodologic quality, population, intervention, and outcomes of each trial. Results. —The source of discrepancies between prior meta-analyses included incomplete identification of relevant studies, differential inclusion of non—English language and nonrandomized trials, different definitions of bleeding, provision of additional information through direct correspondence with authors, and different statistical methods. The current overview demonstrates that prophylaxis with histamine2-receptor antagonists decreases the incidence of overt gastrointestinal bleeding (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.42 to 0.79) and clinically important bleeding (OR, 0.44; 95% CI, 0.22 to 0.88). There is a trend toward decreased overt bleeding when antacids are compared with no therapy (OR, 0.66; 95% CI, 0.37 to 1.17). Histamine2-receptor antagonists and antacids are associated with a trend toward lower clinically important bleeding rates than sucralfate is. There is a trend toward an increased risk of pneumonia associated with histamine2-receptor antagonists as compared with no prophylaxis (OR, 1.25; 95% CI, 0.78 to 2.00). Sucralfate is associated with a lower incidence of nosocomial pneumonia when compared with antacids (OR, 0.80; 95% CI, 0.56 to 1.15) and histamine2-receptor antagonists (OR, 0.77; 95% CI, 0.60 to 1.01). Sucralfate is also associated with a reduced mortality rate (OR, 0.73; 95% CI, 0.54 to 0.97) relative to antacids and to histamine2-receptor antagonists (OR, 0.83; 95% CI, 0.63 to 1.09). Conclusions. —Our results emphasize the need for registries to include all randomized trials and demonstrate the importance of explicit methodology for systematic reviews. There is strong evidence of reduced clinically important gastrointestinal bleeding with histamine2-receptor antagonists. Sucralfate may be as effective in reducing bleeding as gastric pH—altering drugs and is associated with lower rates of pneumonia and mortality. However, the data are insufficient to determine the net effect of sucralfate compared with no prophylaxis. (JAMA. 1996;275:308-314)

Surveillance and prevention of major perioperative ischemic cardiac events in patients undergoing noncardiac surgery: a review

Abstract: THIS IS THE SECOND OF 2 ARTICLES EVALUATING cardiac events in patients undergoing noncardiac surgery. Unrecognized myocardial infarctions (MIs) are common, and up to 50% of perioperative MIs may go unrecognized if physicians rely only on clinical signs or symptoms. In this article, we summarize the evidence regarding monitoring strategies for perioperative MI in patients undergoing noncardiac surgery. Perioperative troponin measurements and 12-lead electrocardiograms can detect clinically silent MIs and provide independent prognostic information. Currently, there are no standard diagnostic criteria for perioperative MIs in patients undergoing noncardiac surgery. We propose diagnostic criteria that reflect the unique features of perioperative MIs. Finally, we review the evidence for perioperative prophylactic cardiac interventions. There is encouraging evidence that some perioperative interventions (e.g., β-blockers, α2-adrenergic agonists, statins) may prevent major cardiac ischemic events, but firm conclusions await the results of large definitive trials. The best evidence does not support a management strategy of preoperative coronary revascularization before noncardiac surgery.

Randomized Controlled Trials of Surgical Interventions

Abstract: Background and Objectives: Surgical trials pose many methodological challenges often not present in trials of medical interventions. If not properly accounted for, these challenges may introduce significant biases and threaten the validity of the results. Methods: We systematically reviewed the significance of randomized controlled trials in the evaluation of surgical interventions, discussed the methodological challenges encountered in designing and conducting randomized controlled trials of surgical treatments, and proposed possible solutions to overcome these challenges. Conclusions: Many barriers and issues of surgical trials affecting internal validity can be overcome with proper methodology, and in most cases these issues do not restrict their conduct. Researchers should consider their research question carefully and design a surgical trial that contains features appropriate for the question. In doing so, they must ensure that the trial is valid, feasible, and affordable—a difficult feat, but one well worth the challenge. (Ann Surg 2010;251: 409‐416) R andomized controlled trials (RCTs) are the most rigorous method of determining whether a cause and effect relationship exists between treatment and outcome. Most surgical research takes the form of retrospective case series, often with a small number of patients. 1,2 Furthermore, surgical treatments are half as likely to be based on RCT evidence than are medical therapies. 3,4 If RCTs are difficult to conduct rigorously in an area, the methodology is more likely to be faulty, and the results may then be misleading. Surgical trials pose many methodological challenges often not present in trials of medical interventions. If not properly accounted for, these challenges may introduce significant biases and threaten the validity of the results. The objectives of this article are to review the significance of RCTs in the evaluation of surgical interventions, discuss some of the methodological challenges encountered in designing and conducting RCTs of surgical treatments, and propose possible solutions to overcome these challenges.

Internet Versus Mailed Questionnaires: A Controlled Comparison (2)

Abstract: BACKGROUND: Low response rates among surgeons can threaten the validity of surveys. Internet technologies may reduce the time, effort, and financial resources needed to conduct surveys. OBJECTIVE: We investigated whether using Web-based technology could increase the response rates to an international survey. METHODS: We solicited opinions from the 442 surgeon–members of the Orthopaedic Trauma Association regarding the treatment of femoral neck fractures. We developed a self-administered questionnaire after conducting a literature review, focus groups, and key informant interviews, for which we used sampling to redundancy techniques. We administered an Internet version of the questionnaire on a Web site, as well as a paper version, which looked similar to the Internet version and which had identical content. Only those in our sample could access the Web site. We alternately assigned the participants to receive the survey by mail (n=221) or an email invitation to participate on the Internet (n=221). Non-respondents in the mail arm received up to three additional copies of the survey, while non-respondents in the Internet arm received up to three additional requests, including a final mailed copy. All participants in the Internet arm had an opportunity to request an emailed Portable Document Format (PDF) version. RESULTS: The Internet arm demonstrated a lower response rate (99/221, 45%) than the mail questionnaire arm (128/221, 58%) (absolute difference 13%, 95% confidence interval 4%-22%, P<0.01). CONCLUSIONS: Our Internet-based survey to surgeons resulted in a significantly lower response rate than a traditional mailed survey. Researchers should not assume that the widespread availability and potential ease of Internet-based surveys will translate into higher response rates. [J Med Internet Res 2004;6(4):e39]

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.