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.

Beyond journal clubs

Abstract: Incorporating evidence-based medicine (EBM) into clinical practice is an important competency that residency training must address. Residency program directors, and the clinical educators who work with them, should develop curricula to enhance residents' capacity for independent evidence-based practice. In this article, the authors argue that residency programs must move beyond journal club formats to promote the practice of EBM by trainees. The authors highlight the limitations of journal club, and suggest additional curricular approaches for an integrated EBM curriculum. Helping residents become effective evidence users will require a sustained effort on the part of residents, faculty, and their educational institutions.

Risedronate for the prevention and treatment of postmenopausal osteoporosis.

Abstract: BACKGROUND Postmenopausal osteoporosis results in an increased susceptibility to low-trauma fractures due to reduced bone volume and microarchitectural deterioration. Risedronate, a third generation bisphosphonate, has been shown in multiple clinical trials to reduce fracture risk and improve bone mineral density in postmenopausal women with osteoporosis. First and second generation bisphosphonates are known to have gastrointestinal side-effects and risedronate may be better tolerated. OBJECTIVES To systematically review the efficacy of risedronate on bone density, and fracture reduction in postmenopausal women. SEARCH STRATEGY The Cochrane Controlled Trials Registry Medline, and Current Contents were searched from 1990 - 2001. The electronic search was supplemented by handsearching four osteoporosis journals and their conference proceedings, as well as contacting content experts and industry sources for unpublished data. SELECTION CRITERIA We included eight trials that randomised women to risedronate or an alternative (placebo or calcium and /or vitamin D) and measured bone mineral density for at least one year. DATA COLLECTION AND ANALYSIS For each trial three independent reviewers assessed the methodological quality and abstracted data. Data was extracted for outcomes of fracture, bone mineral density and adverse events. The more conservative random effects model was used to pool data. The quality of trials was assessed according to the Jadad five-point scale. MAIN RESULTS Both vertebral and non-vertebral fractures were statistically and clinically reduced with risedronate. Eleven out of one hundred women who received risedronate had a vertebral fracture compared to 17 out of one hundred of those who received an alternative treatment (pooled relative risk for vertebral fractures of 0.64 (95% CI 0.52 - 0.77). Three percent of participants who received risedronate had a non-vertebral fracture compared to 4.6% of those who received an alternative treatment (pooled relative risk for nonvertebral fractures of 0.73 (95% CI 0.61 - 0.87). The weighted mean difference for the percent change from baseline for bone mineral density with 5 mg daily for lumbar spine, femoral neck and trochanter was 4.54% (95%CI 4.12 - 4.97), p<0.01; 2.75% (95% CI 2.32 - 3.17), p<0.01; and 4.38% (95% CI 3.51 - 5.25), p<0.01 respectively. REVIEWER'S CONCLUSIONS There is good evidence for the efficacy of risedronate in the reduction of both vertebral and non-vertebral fractures. In addition, there is evidence from randomized trials that risedronate is able to achieve this without increasing risk for overall withdrawals due to adverse effects.

Total Hip Arthroplasty Versus Hemiarthroplasty for Displaced Femoral Neck Fracture: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Abstract: Background Hip fractures are a leading cause of disability worldwide, with displaced femoral neck fractures being of particular concern. A recent meta-analysis reported that total hip arthroplasty (THA) was superior to hemiarthroplasty (HA) in terms of reoperations, but inferior in terms of dislocations. However, publication of 4 additional randomized controlled trials that enrolled nearly 1,780 additional patients merits an updated meta-analysis. Methods We conducted a literature search of 4 databases to identify randomized controlled trials comparing THA and HA in patients with displaced femoral neck fractures. For patient-reported outcomes, the minimally important difference informed calculation of risk differences. We performed a subgroup analysis to address the possible impact of risk of bias and performed meta-regression to assess the possible impact of duration of follow-up. Results Sixteen studies that enrolled 3,084 patients randomized to undergo THA (n = 1,521) or HA (n = 1,563) proved eligible. There were no significant differences between the 2 groups in terms of the revision rate at up to 5 years of follow-up or functional outcome at up to 3 years. Health-related quality of life was superior in the THA group (mean difference [MD] = 0.05, 95% confidence interval [CI] = 0.02 to 0.07, minimally important difference, 0.145). There was no significant difference between the groups in terms of dislocation or periprosthetic fracture incidence. Operative time was significantly shorter in the HA group (MD = 22 minutes, 95% CI = 9 to 35 minutes). Analyses addressing risk of bias and length of follow-up did not reveal subgroup differences. Certainty of evidence for all outcomes was rated as moderate. Conclusions The best evidence showed, with moderate certainty, that HA and THA likely result in similar revision rate, function, mortality, periprosthetic fracture, and dislocation at up to 5 years, with a small, possibly unimportant benefit in health-related quality of life with THA. More specifically, the improvements are well below established cutoffs for clinical importance. Almost half of all patients were from a single large randomized controlled trial, although the results were consistent across the studies. In addition, HA likely results in a clinically unimportant reduction in operative time. Level of evidence Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Evidence-based practice is not synonymous with delivery of uniform health care.

Abstract: Current clinical practice is characterized by substantial variation in delivery of health care for the same conditions.1 In turn, clinical variation is considered one of the major drivers of ever-increasing health care costs1 contributing to the estimated 30% of inappropriate or wasteful health care.2 Perhaps as a natural response to this unsatisfactory situation, a widespread and influential school of thought has emerged contending that greater uniformity of clinical practice is desirable.1,3 Advocates maintain that by achieving uniformity in care, practice variation can be decreased, in turn leading to large cost reductions. The suggested mechanism to achieve uniformity in part involves clinician adherence to practice guidelines, which is seen as synonymous with evidence-based practice.3 In this Viewpoint, we explain that this position is based on a misunderstanding of trustworthy guidelines4 and that striving for uniformity of practice as an end is misguided. The first limitation in the drive for uniformity is a failure to appreciate the need for guidelines that achieve a high standard of trustworthiness.4 Flawed guidelines, particularly those that offer strong recommendations when only weak recommendations are warranted, are unlikely to facilitate optimal practice. Advocates for uniformity should highlight the distinction between flawed vs trustworthy guidelines and ensure that only the latter are seen as a guide for clinical practice.4,5 Uniformity of practice means that patients with a similar presentation of underlying condition, severity, and circumstances will receive the same treatment— that is, they will all receive or not receive particular diagnostic tests, medications, or surgical procedures. There are circumstances in which such uniformity is desirable. In particular, when clinicians are confident in the estimates of the effects of health interventions on all outcomes of importance to patients (ie, high-quality evidence is available), the desirable consequences of the one management strategy clearly outweigh its undesirable consequences, and the relative importance patients place on the key outcomes (ie, their values and preferences) are similar across patients. That the recommended intervention is not overly costly, is highly feasible, is acceptable to clinicians and patients, and reduces health disparities further strengthens the case for uniformity of clinical practice. There are many, indeed the majority of, situations in which clinicians and patients make management decisions of importance, but these conditions are not met. For example, the American Board of Internal Medicine’s Choosing Wisely campaign has identified 135 health interventions in which evidence suggests equivalence but not superiority to other options in terms of benefits, harms, and costs.6 Studies directly addressing the relevant questions may not have been undertaken, or if they have, they may be small, poorly designed or implemented, show inconsistent results, be limited by publication bias, or have enrolled idiosyncratic populations of questionable applicability. In these cases, the confidence in the estimate of effects will often be low or very low. In addition, if values and preferences differ widely across patients (which is often if not uniformly the case), the right decision for one patient may be the wrong decision for another. For example, Montori et al7 illustrated how recent guidelines by the American College of Cardiology and the American Heart Association for the use of statins for primary prevention of heart disease do not mandate uniform practice—some patients informed about cardiovascular disease risk reduction will choose the recommended course of action and use statins, but others will not. Organizations that produce guidelines should distinguish between situations in which confidence in effect estimates is high and the balance between desirable and undesirable consequences is clear and when these conditions do not exist. In the former situation the guideline will include strong, definitive recommendations that often warrant uniformity of practice. In the latter, they will issue weak (conditional or contingent) recommendations. The recommended course of action will be right for many patients, but not right for all.5 In this scenario, uniformity of practice will not be appropriate. For example, administration of at least 1 antiplatelet agent and a statin for patients who have experienced a myocardial infarction; a β-blocker and an angiotensin-converting enzyme inhibitor for patients with systolic heart failure; corticosteroids for patients experiencing asthma exacerbation; and curative chemotherapy for patients with large cell lymphoma all warrant strong recommendations. These situations therefore warrant uniform practice, other than in exceptional situations such as drug allergy or severe comorbidities. In each case, clinicians should have high confidence in estimates of effect and in the desirable consequences of the intervention being much greater than the undesirable consequences. In contrast, use of anticoagulants for low-risk patients with atrial fibrillation; indefinite anticoagulation for patients with unprovoked venous thromboembolism; use of corticosteroids for patients with idiopathic pulmonary fibrosis; and chemotherapy for patients with advanced non–small cell lung cancer warrant weak recommendations. In these instances, in which clinicians have either low confidence in VIEWPOINT

Confidence in life-support decisions in the intensive care unit: A survey of healthcare workers

Abstract: ObjectiveTo examine the relationship between intensive care unit (ICU) healthcare workers' confidence and their decision to withdraw life support.DesignCross-sectional survey of Canadian intensivists, ICU housestaff, and bedside nurses. Respondents chose the level of care (from comfort measures only

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.