Gordon Guyatt

Publications of Gordon Guyatt

• Formatting modifications in GRADE evidence profiles improved guideline panelists comprehension and accessibility to information. A randomized trial.

  Authors: Per Olav Vandvik, Nancy Santesso, Elie A Akl, John You, Sohail Mulla, Frederick A Spencer, Bradley C Johnston, Jan Brozek, Julia Kreis, Linn Brandt, Qi Zhou, Holger S Schunemann, Gordon Guyatt

  Journal of clinical epidemiology. 05/2012;

  OBJECTIVE: To determine the effects of formatting alternatives in Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence profiles on guideline panelists' preferences,OBJECTIVE: To determine the effects of formatting alternatives in Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence profiles on guideline panelists' preferences, comprehension, and accessibility. STUDY DESIGN AND SETTING: We randomized 116 antithrombotic therapy guideline panelists to review one of two table formats with four formatting alternatives. After answering relevant questions, panelists reviewed the other format and reported their preferences for specific formatting alternatives. RESULTS: Panelists (88 of 116 invited [76%]) preferred presentation of study event rates over no study event rates (median 1 [interquartile range (IQR) 1] on 1-7 scale), absolute risk differences over absolute risks (median 2 [IQR 3]), and additional information in table cells over footnotes (median 1 [IQR 2]). Panelists presented with time frame information in the tables, and not only in footnotes, were more likely to correctly answer questions regarding time frame (58% vs. 11%, P<0.0001), and those presented with risk differences and not absolute risks were more likely to correctly interpret confidence intervals for absolute effects (95% vs. 54%, P<0.0001). Information was considered easy to find, easy to comprehend, and helpful in making recommendations regardless of table format (median 6, IQR 0-1). CONCLUSION: Panelists found information in GRADE evidence profiles accessible. Correct comprehension of some key information was improved by providing additional information in table and presenting risk differences.

• GRADE guidelines 11-making an overall rating of confidence in effect estimates for a single outcome and for all outcomes.

  Authors: Gordon Guyatt, Andrew D Oxman, Shahnaz Sultan, Jan Brozek, Paul Glasziou, Pablo Alonso-Coello, David Atkins, Regina Kunz, Victor Montori, Roman Jaeschke, David Rind, Philipp Dahm, Elie A Akl, Joerg Meerpohl, Gunn Vist, Elise Berliner, Susan Norris, Yngve Falck-Ytter, Holger J Schünemann

  Journal of clinical epidemiology. 04/2012;

  GRADE requires guideline developers to make an overall rating of confidence in estimates of effect (quality of evidence-high, moderate, low, or very low) for each important or critical outcome. GRADEGRADE requires guideline developers to make an overall rating of confidence in estimates of effect (quality of evidence-high, moderate, low, or very low) for each important or critical outcome. GRADE suggests, for each outcome, the initial separate consideration of five domains of reasons for rating down the confidence in effect estimates, thereby allowing systematic review authors and guideline developers to arrive at an outcome-specific rating of confidence. Although this rating system represents discrete steps on an ordinal scale, it is helpful to view confidence in estimates as a continuum, and the final rating of confidence may differ from that suggested by separate consideration of each domain. An overall rating of confidence in estimates of effect is only relevant in settings when recommendations are being made. In general, it is based on the critical outcome that provides the lowest confidence.

• Reflections on meta-analyses involving trials stopped early for benefit: Is there a problem and if so, what is it?

  Authors: Dirk Bassler, Victor M Montori, Matthias Briel, Paul Glasziou, Stephen D Walter, Tim Ramsay, Gordon Guyatt

  Statistical methods in medical research. 12/2011;

  We review controversies associated with randomized controlled trials (RCTs) stopped early for apparent benefit (truncated RCTs or tRCTs) and present our groups' perspective. Long-established theory,We review controversies associated with randomized controlled trials (RCTs) stopped early for apparent benefit (truncated RCTs or tRCTs) and present our groups' perspective. Long-established theory, simulations and recent empirical evidence demonstrate that tRCTs will on average overestimate treatment effects, and this overestimation may be large, particularly when tRCTs have small number of events. Theoretical considerations and simulations demonstrate that on average, meta-analyses of RCTs with appropriate stopping rules will lead to only trivial overestimation of treatment effects. However, tRCTs will disproportionally contribute to meta-analytic estimates when tRCTs occur early in the sequence of trials with few subsequent studies, publication of nontruncated RCTs is delayed, there is publication bias, or tRCTs result in a 'freezing' effect in which 'correcting' trials are never undertaken. To avoid applying overestimates of effect to clinical decision-making, clinicians should view the results of individual tRCTs with small sample sizes and small number of events with skepticism. Pooled effects from meta-analyses including tRCTs are likely to overestimate effect when there is a substantial difference in effect estimates between the tRCTs and the nontruncated RCTs, and in which the tRCTs have a substantial weight in the meta-analysis despite themselves having a relatively small number of events. Such circumstances call for sensitivity analyses omitting tRCTs.

• Screening and prevention of venous thromboembolism in critically ill patients: a decision analysis and economic evaluation.

  Authors: Sachin Sud, Nicole Mittmann, Deborah J Cook, William Geerts, Brian Chan, Peter Dodek, Michael K Gould, Gordon Guyatt, Yaseen Arabi, Robert A Fowler

  American journal of respiratory and critical care medicine. 08/2011; 184(11):1289-98.

  Venous thromboembolism is difficult to diagnose in critically ill patients and may increase morbidity and mortality. To evaluate the cost-effectiveness of strategies to reduce morbidity from venousVenous thromboembolism is difficult to diagnose in critically ill patients and may increase morbidity and mortality. To evaluate the cost-effectiveness of strategies to reduce morbidity from venous thromboembolism in critically ill patients. A Markov decision analytic model to compare weekly compression ultrasound screening (screening) plus investigation for clinically suspected deep vein thrombosis (DVT) (case finding) versus case finding alone; and a hypothetical program to increase adherence to DVT prevention. Probabilities were derived from a systematic review of venous thromboembolism in medical-surgical intensive care unit patients. Costs (in 2010 $US) were obtained from hospitals in Canada, Australia, and the United States, and the medical literature. Analyses were conducted from a societal perspective over a lifetime horizon. Outcomes included costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios. In the base case, the rate of proximal DVT was 85 per 1,000 patients. Screening resulted in three fewer pulmonary emboli than case-finding alone but also two additional bleeding episodes, and cost $223,801 per QALY gained. In sensitivity analyses, screening cost less than $50,000 per QALY only if the probability of proximal DVT increased from a baseline of 8.5-16%. By comparison, increasing adherence to appropriate pharmacologic thromboprophylaxis by 10% resulted in 16 fewer DVTs, one fewer pulmonary emboli, and one additional heparin-induced thrombocytopenia and bleeding event, and cost $27,953 per QALY gained. Programs achieving increased adherence to best-practice venous thromboembolism prevention were cost-effective over a wide range of program costs and were robust in probabilistic sensitivity analyses. Appropriate prophylaxis provides better value in terms of costs and health gains than routine screening for DVT. Resources should be targeted at optimizing thromboprophylaxis.

• GRADE guidelines 6. Rating the quality of evidence--imprecision.

  Authors: Gordon H Guyatt, Andrew D Oxman, Regina Kunz, Jan Brozek, Pablo Alonso-Coello, David Rind, P J Devereaux, Victor M Montori, Bo Freyschuss, Gunn Vist, Roman Jaeschke, John W Williams, Mohammad Hassan Murad, David Sinclair, Yngve Falck-Ytter, Joerg Meerpohl, Craig Whittington, Kristian Thorlund, Jeff Andrews, Holger J Schünemann

  Journal of clinical epidemiology. 08/2011; 64(12):1283-93.

  GRADE suggests that examination of 95% confidence intervals (CIs) provides the optimal primary approach to decisions regarding imprecision. For practice guidelines, rating down the quality ofGRADE suggests that examination of 95% confidence intervals (CIs) provides the optimal primary approach to decisions regarding imprecision. For practice guidelines, rating down the quality of evidence (i.e., confidence in estimates of effect) is required if clinical action would differ if the upper versus the lower boundary of the CI represented the truth. An exception to this rule occurs when an effect is large, and consideration of CIs alone suggests a robust effect, but the total sample size is not large and the number of events is small. Under these circumstances, one should consider rating down for imprecision. To inform this decision, one can calculate the number of patients required for an adequately powered individual trial (termed the "optimal information size" [OIS]). For continuous variables, we suggest a similar process, initially considering the upper and lower limits of the CI, and subsequently calculating an OIS. Systematic reviews require a somewhat different approach. If the 95% CI excludes a relative risk (RR) of 1.0, and the total number of events or patients exceeds the OIS criterion, precision is adequate. If the 95% CI includes appreciable benefit or harm (we suggest an RR of under 0.75 or over 1.25 as a rough guide) rating down for imprecision may be appropriate even if OIS criteria are met.

• [The validity and sensitivity to change of the Spanish self-administered version of the chronic respiratory questionnaire (CRQ-SAS)].

  Authors: Laura Vigil, M Rosa Güell, Fátima Morante, Elena López De Santamaría, Francesca Sperati, Gordon Guyatt, Holger Schünemann

  Archivos de bronconeumología. 07/2011; 47(7):343-9.

  The interviewer-administered chronic respiratory questionnaire (CRQ-IA) is widely used and has demonstrated excellent properties for measuring health-related quality of life (HRQL) in patients withThe interviewer-administered chronic respiratory questionnaire (CRQ-IA) is widely used and has demonstrated excellent properties for measuring health-related quality of life (HRQL) in patients with chronic obstructive pulmonary disease (COPD). However, the self-administered version (CRQ-SAS) in Spanish has not been validated. The aim of this trial was to evaluate the validity and the sensitivity of the Spanish version of the CRQ-SAS in patients with COPD. We randomized 40 patients with COPD (33 treated with pulmonary rehabilitation and 7 with liquid oxygen therapy) to one of the two methods of administration of CRQ (SAS vs. IA) both before and 8 weeks after the treatment. In addition, patients completed the SF-36 questionnaire, pulmonary function tests, and six-minute walk test. The CRQ-SAS demonstrated good longitudinal construct validity on all domains with a range of correlations, for the change scores, between 0.46 (P=.05) and 0.71 (P=.01). Regarding sensitivity to change, we observed a minimal clinically significant change in most domains (fatigue 0.71 [P=.02], emotional factor 0.62 [P=.04], control of the disease 0.83 [P=.06]). The Spanish version of CRQ-SAS is valid for evaluating HRQL in COPD patients. The correlations of the CRQ-SAS with other tools provide construct validity and show good sensitivity to change.

• Economic evaluation of reamed versus unreamed intramedullary nailing in patients with closed and open tibial fractures: results from the study to prospectively evaluate reamed intramedullary nails in patients with tibial fractures (SPRINT).

  Authors: Matthias Briel, Sheila Sprague, Diane Heels-Ansdell, Gordon Guyatt, Mohit Bhandari, Gordon Blackhouse, David Sanders, Emil Schemitsch, Marc Swiontkowski, Paul Tornetta, Stephen D Walter, Ron Goeree

  Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research. 06/2011; 14(4):450-7.

  Recently, results from the large, randomized study to prospectively evaluate reamed intramedullary nails in patients with tibial fractures (SPRINT) trial suggested a benefit for reamed intramedullaryRecently, results from the large, randomized study to prospectively evaluate reamed intramedullary nails in patients with tibial fractures (SPRINT) trial suggested a benefit for reamed intramedullary nail insertion in patients with closed tibial shaft fractures largely based on cost-neutral autodynamizations and a potential advantage for unreamed intramedullary nailing in open fractures. We performed an economic evaluation to compare resource use and effectiveness of reamed and unreamed intramedullary nailing using a cost-utility analysis. We calculated quality-adjusted life years (QALYs) for each patient from a self-administered health utility index 3 questionnaire for the first 12 months following the intramedullary nailing. A convenience sample of 235 SPRINT patients provided data on costs associated with health care resource utilization. All costs are reported in Canadian dollars for the 2008 financial year. We found incremental effects of -0.017 (95% confidence interval [CI] -0.021-0.058) and -0.002 (95% CI -0.060-0.062) QALYs for patients treated with reamed compared with unreamed intramedullary nails in closed and open fractures, respectively. The incremental costs for reamed compared with unreamed intramedullary nailing were $51 Canadian dollars (95% CI -$2298-$2400) in closed tibial fractures and $2546 Canadian dollars (95%CI -$1773-$6864) in open tibial fractures. Unreamed nailing dominated reamed nailing for both closed and open tibial fractures; however, the cost and the utility results had high variability. Our economic analysis from a governmental perspective suggests small differences in both cost and effectiveness with large uncertainty between reamed and unreamed intramedullary nailing.

• The GRADE approach and Bradford Hill's criteria for causation.

  Authors: Holger Schünemann, Suzanne Hill, Gordon Guyatt, Elie A Akl, Faruque Ahmed

  Journal of epidemiology and community health. 05/2011; 65(5):392-5.

  This article describes how the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the quality of evidence and strength of recommendations considers theThis article describes how the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the quality of evidence and strength of recommendations considers the Bradford Hill criteria for causation and how GRADE may relate to questions in public health. A primary concern in public health is that evidence from non-randomised studies may provide a more adequate or best available measure of a public health strategy's impact, but that such evidence might be graded as lower quality in the GRADE framework. GRADE, however, presents a framework that describes both criteria for assessing the quality of research evidence and the strength of recommendations that includes considerations arising from the Bradford Hill criteria. GRADE places emphasis on recommendations and in assessing quality of evidence; GRADE notes that randomisation is only one of many relevant factors. This article describes how causation may relate to developing recommendations and how the Bradford Hill criteria are considered in GRADE, using examples from the public health literature with a focus on immunisation.

• Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study.

  Authors: P J Devereaux, Denis Xavier, Janice Pogue, Gordon Guyatt, Alben Sigamani, Ignacio Garutti, Kate Leslie, Purnima Rao-Melacini, Sue Chrolavicius, Homer Yang, Colin Macdonald, Alvaro Avezum, Luc Lanthier, Weijiang Hu, Salim Yusuf

  Annals of internal medicine. 04/2011; 154(8):523-8.

  Each year, millions of patients worldwide have a perioperative myocardial infarction (MI) after noncardiac surgery. To examine the characteristics and short-term outcome of perioperative MI. CohortEach year, millions of patients worldwide have a perioperative myocardial infarction (MI) after noncardiac surgery. To examine the characteristics and short-term outcome of perioperative MI. Cohort study. (ClinicalTrials.gov registration number: NCT00182039) 190 centers in 23 countries. 8351 patients included in the POISE (PeriOperative ISchemic Evaluation) trial. Four cardiac biomarker or enzyme assays were measured within 3 days of surgery. The definition of perioperative MI included either autopsy findings of acute MI or an elevated level of a cardiac biomarker or enzyme and at least 1 of the following defining features: ischemic symptoms, development of pathologic Q waves, ischemic changes on electrocardiography, coronary artery intervention, or cardiac imaging evidence of MI. Within 30 days of random assignment, 415 patients (5.0%) had a perioperative MI. Most MIs (74.1%) occurred within 48 hours of surgery; 65.3% of patients did not experience ischemic symptoms. The 30-day mortality rate was 11.6% (48 of 415 patients) among patients who had a perioperative MI and 2.2% (178 of 7936 patients) among those who did not (P < 0.001). Among patients with a perioperative MI, mortality rates were elevated and similar between those with (9.7%; adjusted odds ratio, 4.76 [95% CI, 2.68 to 8.43]) and without (12.5%; adjusted odds ratio, 4.00 [CI, 2.65 to 6.06]) ischemic symptoms. Cardiac markers were measured only until day 3 after surgery, and additional asymptomatic MIs may have been missed. Most patients with a perioperative MI will not experience ischemic symptoms. Data suggest that routine monitoring of troponin levels in at-risk patients is needed after surgery to detect most MIs, which have an equally poor prognosis regardless of whether they are symptomatic or asymptomatic.

• Dalteparin versus unfractionated heparin in critically ill patients.

  Authors: Deborah Cook, Maureen Meade, Gordon Guyatt, Stephen Walter, Diane Heels-Ansdell, Theodore E Warkentin, Nicole Zytaruk, Mark Crowther, William Geerts, D Jamie Cooper, Shirley Vallance, Ismael Qushmaq, Marcelo Rocha, Otavio Berwanger, Nicholas E Vlahakis

  The New England journal of medicine. 04/2011; 364(14):1305-14.

  The effects of thromboprophylaxis with low-molecular-weight heparin, as compared with unfractionated heparin, on venous thromboembolism, bleeding, and other outcomes are uncertain in critically illThe effects of thromboprophylaxis with low-molecular-weight heparin, as compared with unfractionated heparin, on venous thromboembolism, bleeding, and other outcomes are uncertain in critically ill patients. In this multicenter trial, we tested the superiority of dalteparin over unfractionated heparin by randomly assigning 3764 patients to receive either subcutaneous dalteparin (at a dose of 5000 IU once daily) plus placebo once daily (for parallel-group twice-daily injections) or unfractionated heparin (at a dose of 5000 IU twice daily) while they were in the intensive care unit. The primary outcome, proximal leg deep-vein thrombosis, was diagnosed on compression ultrasonography performed within 2 days after admission, twice weekly, and as clinically indicated. Additional testing for venous thromboembolism was performed as clinically indicated. Data were analyzed according to the intention-to-treat principle. There was no significant between-group difference in the rate of proximal leg deep-vein thrombosis, which occurred in 96 of 1873 patients (5.1%) receiving dalteparin versus 109 of 1873 patients (5.8%) receiving unfractionated heparin (hazard ratio in the dalteparin group, 0.92; 95% confidence interval [CI], 0.68 to 1.23; P=0.57). The proportion of patients with pulmonary emboli was significantly lower with dalteparin (24 patients, 1.3%) than with unfractionated heparin (43 patients, 2.3%) (hazard ratio, 0.51; 95% CI, 0.30 to 0.88; P=0.01). There was no significant between-group difference in the rates of major bleeding (hazard ratio, 1.00; 95% CI, 0.75 to 1.34; P=0.98) or death in the hospital (hazard ratio, 0.92; 95% CI, 0.80 to 1.05; P=0.21). In prespecified per-protocol analyses, the results were similar to those of the main analyses, but fewer patients receiving dalteparin had heparin-induced thrombocytopenia (hazard ratio, 0.27; 95% CI, 0.08 to 0.98; P=0.046). Among critically ill patients, dalteparin was not superior to unfractionated heparin in decreasing the incidence of proximal deep-vein thrombosis. (Funded by the Canadian Institutes of Health Research and others; PROTECT ClinicalTrials.gov number, NCT00182143.).

• GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables.

  Authors: Gordon Guyatt, Andrew D Oxman, Elie A Akl, Regina Kunz, Gunn Vist, Jan Brozek, Susan Norris, Yngve Falck-Ytter, Paul Glasziou, Hans DeBeer, Roman Jaeschke, David Rind, Joerg Meerpohl, Philipp Dahm, Holger J Schünemann

  Journal of clinical epidemiology. 04/2011; 64(4):383-94.

  This article is the first of a series providing guidance for use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system of rating quality of evidence and gradingThis article is the first of a series providing guidance for use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system of rating quality of evidence and grading strength of recommendations in systematic reviews, health technology assessments (HTAs), and clinical practice guidelines addressing alternative management options. The GRADE process begins with asking an explicit question, including specification of all important outcomes. After the evidence is collected and summarized, GRADE provides explicit criteria for rating the quality of evidence that include study design, risk of bias, imprecision, inconsistency, indirectness, and magnitude of effect. Recommendations are characterized as strong or weak (alternative terms conditional or discretionary) according to the quality of the supporting evidence and the balance between desirable and undesirable consequences of the alternative management options. GRADE suggests summarizing evidence in succinct, transparent, and informative summary of findings tables that show the quality of evidence and the magnitude of relative and absolute effects for each important outcome and/or as evidence profiles that provide, in addition, detailed information about the reason for the quality of evidence rating. Subsequent articles in this series will address GRADE's approach to formulating questions, assessing quality of evidence, and developing recommendations.

• PROphylaxis for ThromboEmbolism in Critical Care Trial protocol and analysis plan.

  Authors: Deborah Cook, Maureen Meade, Gordon Guyatt, Stephen D Walter, Diane Heels-Ansdell, William Geerts, Theodore E Warkentin, D Jamie Cooper, Nicole Zytaruk, Shirley Vallance, Otavio Berwanger, Marcelo Rocha, Ismael Qushmaq, Mark Crowther

  Journal of critical care. 04/2011; 26(2):223.e1-9.

  This article reports the preparatory studies as well as the design, implementation, and a priori analysis plans of PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) beforeThis article reports the preparatory studies as well as the design, implementation, and a priori analysis plans of PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) before dissemination of results. PROphylaxis for ThromboEmbolism in Critical Care Trial (NCT00182143) is a randomized, stratified, concealed international trial comparing subcutaneous injection of unfractionated heparin (UFH) 5000 IU or the low-molecular weight heparin (LMWH) dalteparin 5000 IU once daily plus once-daily placebo for the duration of the intensive care unit stay. The objective of PROTECT is to examine, among medical-surgical critically ill patients, the effect of the LMWH vs heparin on the primary outcome of proximal leg deep vein thrombosis (DVT) and the following secondary outcomes: DVT elsewhere, pulmonary embolism, any venous thromboembolism (DVT or pulmonary embolism), the composite of venous thromboembolism or death, bleeding, and heparin-induced thrombocytopenia. Patients are followed up to death or hospital discharge. Venous thromboembolism events were included after intensive care unit discharge. All patients, families, clinicians, research personnel, and the trial biostatistician are blind to allocation. We describe the pilot work, large trial methodology, implementation methods, and the analytic plan. Patient recruitment is complete, but 2 patients remain in the hospital. The rigorous design of PROTECT suggests that the risk of systematic error will be low. The sample size suggests that the risk of random error will be low. PROTECT will be the largest investigator-initiated peer-review funded thromboprophylaxis trial in critical care in the world. If PROTECT shows that LMWH is more effective than UFH, this trial will change practice in that LMWH may be the anticoagulant thromboprophylaxis of choice for this population. If the results show that UFH is as effective or more effective than LMWH, intensivists in many parts of the world may continue to use UFH, whereas those currently using LMWH may reconsider and change to use UFH. Unfavorable consequences such as major bleeding, ease of use, and the costs of complications will also factor into such decisions.

• Fluid lavage of open wounds (FLOW): a multicenter, blinded, factorial pilot trial comparing alternative irrigating solutions and pressures in patients with open fractures.

  Authors: Bradley Petrisor, Xin Sun, Mohit Bhandari, Gordon Guyatt, Kyle J Jeray, Sheila Sprague, Stephanie Tanner, Emil Schemitsch, Parag Sancheti, Jeff Anglen, Paul Tornetta, Michael Bosse, Susan Liew, Stephen Walter

  The Journal of trauma. 03/2011; 71(3):596-606.

  Open fractures are an important source of morbidity and are associated with delayed union, nonunion, and infection. Preventing infection through meticulous irrigation and debridement is an importantOpen fractures are an important source of morbidity and are associated with delayed union, nonunion, and infection. Preventing infection through meticulous irrigation and debridement is an important goal in management, and different lavage fluids and irrigation techniques (e.g., high- or low-pressure lavage) have been described for this purpose. However, there are a limited number of randomized trials comparing irrigating solutions or irrigating technique. We compared the use of castile soap versus normal saline and high- versus low-pressure pulsatile lavage on the rates of reoperations and complications in patients with open fracture wounds. We conducted a multicenter, blinded, randomized 2 × 2 factorial pilot trial of 111 patients in whom an open fracture wound was treated with either castile soap solution or normal saline and either high- or low-pressure pulsatile lavage. The primary composite outcome of reoperation, measured at 12 months after initial operative procedure, included infection, wound healing problems, and nonunion. Planned reoperations were not included. Secondary outcomes included all infection, all wound healing problems, and nonunion as well as functional outcomes scores (EuroQol-5 dimensions and short form-12). Eighty-nine patients completed the 1-year follow-up. Among all patients, 13 (23%) in the castile soap group and 13 (24%) in the saline group had a primary outcome event (hazard ratio, 0.91, 95% confidence interval: 0.42-2.00, p = 0.52). Sixteen patients (28%) in the high-pressure group and 10 patients (19%) in the low-pressure group had a primary outcome event (hazard ratio 0.55, 95% confidence interval: 0.24-1.27, p = 0.17). Functional outcome scores showed no significant differences at any time point between groups. The fluid lavage of open wounds pilot randomized controlled trial demonstrated the possibility that the use of low pressure may decrease the reoperation rate for infection, wound healing problems, or nonunion. We have demonstrated the desirability and feasibility of a definitive trial examining the effects of alternative irrigation approaches.

• Essay for the CIHR/CMAJ award: impact of the Perioperative Ischemic Evaluation (POISE) trial.

  Authors: Philip J Devereaux, Gordon Guyatt, Homer Yang, Salim Yusuf

  CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 03/2011; 183(6):E351-3.

• Vasopressor administration and sepsis: a survey of Canadian intensivists.

  Authors: Francois Lamontagne, Deborah J Cook, Neill K J Adhikari, Matthias Briel, Mark Duffett, Michelle E Kho, Karen E A Burns, Gordon Guyatt, Alexis F Turgeon, Qi Zhou, Maureen O Meade

  Journal of critical care. 03/2011; 26(5):532.e1-7.

  Patients with septic shock often receive intravenous vasopressor infusions, with little evidence available to guide their titration. We surveyed Canadian intensivists to document self-reportedPatients with septic shock often receive intravenous vasopressor infusions, with little evidence available to guide their titration. We surveyed Canadian intensivists to document self-reported vasopressor titration strategies for patients with septic shock. We identified Canadian intensivists caring for adult patients by merging membership lists of 3 Canadian critical care associations. We invited respondents to complete a scenario-based questionnaire to understand triggers for vasopressor use, target blood pressure values, and the influence of chronic comorbidities and acute illnesses on vasopressor prescription. Sixty-three percent of eligible intensivists completed our survey. Most respondents (82.6%) would frequently or always administer vasopressor therapy for isolated hypotension but not for other isolated signs of organ failure (such as elevated serum lactate or low urine output). Respondents defined low blood pressure using mean arterial pressure (83.7%) and aimed for higher values when resuscitating a patient with multiple organ failure. Chronic comorbidities and acute concurrent illnesses had variable effects on stated vasopressor prescription. Norepinephrine (94.8%) was the preferred first-line vasopressor. Self-reported vasopressor use for the treatment of septic shock is relatively uniform among Canadian intensivists; however, practice is variable in patients with chronic comorbidities or acute concurrent illnesses.

• Is a subgroup claim believable? A user's guide to subgroup analyses in the surgical literature.

  Authors: Xin Sun, Diane Heels-Ansdell, Stephen D Walter, Gordon Guyatt, Sheila Sprague, Mohit Bhandari, David Sanders, Emil Schemitsch, Paul Tornetta, Marc Swiontkowski

  The Journal of bone and joint surgery. American volume. 02/2011; 93(3):e8.

• Prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurement after noncardiac surgery: a systematic review and meta-analysis.

  Authors: Michael Levy, Diane Heels-Ansdell, Rajesh Hiralal, Mohit Bhandari, Gordon Guyatt, Salim Yusuf, Deborah Cook, Juan Carlos Villar, Matthew McQueen, Edward McFalls [......] John Sear, Pierre Foex, Wendy Lim, Giora Landesberg, Gilles Godet, Don Poldermans, Francesca Bursi, Miklos D Kertai, Neera Bhatnagar, P J Devereaux

  Anesthesiology. 02/2011; 114(4):796-806.

  There is uncertainty regarding the prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurements after noncardiac surgery. The current study undertook a systematic reviewThere is uncertainty regarding the prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurements after noncardiac surgery. The current study undertook a systematic review and meta-analysis. The study used six search strategies and included noncardiac surgery studies that provided data from a multivariable analysis assessing whether a postoperative troponin or creatine kinase muscle and brain isoenzyme measurement was an independent predictor of mortality or a major cardiovascular event. Independent investigators determined study eligibility and abstracted data in duplicate. Fourteen studies, enrolling 3,318 patients and 459 deaths, demonstrated that an increased troponin measurement after surgery was an independent predictor of mortality (odds ratio [OR] 3.4, 95% confidence interval [CI] 2.2-5.2), but there was substantial heterogeneity (I(2) = 56%). The independent prognostic capabilities of an increased troponin value after surgery in the 10 studies that assessed intermediate-term (≤ 12 months) mortality was an OR = 6.7 (95% CI 4.1-10.9, I(2) = 0%) and in the 4 studies that assessed long-term (more than 12 months) mortality was an OR = 1.8 (95% CI 1.4-2.3, I(2) = 0%; P < 0.001 for test of interaction). Four studies, including 1,165 patients and 202 deaths, demonstrated an independent association between an increased creatine kinase muscle and brain isoenzyme measurement after surgery and mortality (OR 2.5, 95% CI 1.5-4.0, I(2) = 4%). An increased troponin measurement after surgery is an independent predictor of mortality, particularly within the first year; limited data suggest an increased creatine kinase muscle and brain isoenzyme measurement also predicts subsequent mortality. Monitoring troponin measurements after noncardiac surgery may allow physicians to better risk stratify and manage their patients.

• Italian version of Qualiveen-30: cultural adaptation of a neurogenic urinary disorder-specific instrument.

  Authors: Véronique Bonniaud, Dianne Bryant, Claudio Pilati, Mauro Menarini, Marcello Lamartina, Gordon Guyatt, Giulio Del Popolo

  Neurourology and urodynamics. 02/2011; 30(3):354-9.

  Qualiveen-30 is a neurological urinary disorder (UD)-specific health-related quality of life (HRQL) instrument, recommended in the European Association of Urology guideline 2008. The objective is toQualiveen-30 is a neurological urinary disorder (UD)-specific health-related quality of life (HRQL) instrument, recommended in the European Association of Urology guideline 2008. The objective is to complete the cultural adaptation of Qualiveen-30 into Italian. One hundred and twenty eight Italian-speaking spinal cord injury (SCI) patients completed Qualiveen-30 and the SF-12 physical and mental component (PC and MC) at enrollment and 4 weeks later. At follow-up, patients also made global ratings of change (GRC) in urinary HRQL (GRC). Qualiveen-30 proved reliable (intraclass correlation coefficients of four domains: 0.77-0.90). Correlations with SF-12 and GRC were generally consistent with our a priori predictions. Qualiveen-30 domains showed weak-to-moderate cross-sectional correlations with SF-12 scores (0.31-0.45 PC and 0.28-0.45 MC). Correlations between changes in Qualiveen-30 scores and in SF-12-PC scores were weak or absent. Correlations between changes in Qualiveen-30 scores and in SF-12-MC scores were weak to moderate (0.25-0.38). Relationships between change in Qualiveen-30 and GRC were moderate to strong (0.48-0.56). The responsiveness was excellent, similar to the original form (SMR: 1.76-2.31). Minimally important difference values in the four domains varied from 0.34 to 0.47. Italian Qualiveen-30 is a reliable, valid, and responsive measure of UD-related HRQL in SPI patients. Investigators can be confident of the Qualiveen-30 questionnaire's ability in distinguishing between patients in a cross-sectional survey, as well as in measuring within-subject changes over time in clinical trials in French, English, and Italian.

• The number of patients and events required to limit the risk of overestimation of intervention effects in meta-analysis--a simulation study.

  Authors: Kristian Thorlund, Georgina Imberger, Michael Walsh, Rong Chu, Christian Gluud, Jørn Wetterslev, Gordon Guyatt, Philip J Devereaux, Lehana Thabane

  PloS one. 01/2011; 6(10):e25491.

  Meta-analyses including a limited number of patients and events are prone to yield overestimated intervention effect estimates. While many assume bias is the cause of overestimation, theoreticalMeta-analyses including a limited number of patients and events are prone to yield overestimated intervention effect estimates. While many assume bias is the cause of overestimation, theoretical considerations suggest that random error may be an equal or more frequent cause. The independent impact of random error on meta-analyzed intervention effects has not previously been explored. It has been suggested that surpassing the optimal information size (i.e., the required meta-analysis sample size) provides sufficient protection against overestimation due to random error, but this claim has not yet been validated. We simulated a comprehensive array of meta-analysis scenarios where no intervention effect existed (i.e., relative risk reduction (RRR) = 0%) or where a small but possibly unimportant effect existed (RRR = 10%). We constructed different scenarios by varying the control group risk, the degree of heterogeneity, and the distribution of trial sample sizes. For each scenario, we calculated the probability of observing overestimates of RRR>20% and RRR>30% for each cumulative 500 patients and 50 events. We calculated the cumulative number of patients and events required to reduce the probability of overestimation of intervention effect to 10%, 5%, and 1%. We calculated the optimal information size for each of the simulated scenarios and explored whether meta-analyses that surpassed their optimal information size had sufficient protection against overestimation of intervention effects due to random error. The risk of overestimation of intervention effects was usually high when the number of patients and events was small and this risk decreased exponentially over time as the number of patients and events increased. The number of patients and events required to limit the risk of overestimation depended considerably on the underlying simulation settings. Surpassing the optimal information size generally provided sufficient protection against overestimation. Random errors are a frequent cause of overestimation of intervention effects in meta-analyses. Surpassing the optimal information size will provide sufficient protection against overestimation.

• Guidelines and Conflicts of Interest.

  Authors: Gordon Guyatt, Holger Schünemann, Elie Akl

  Annals of internal medicine. 09/2010; 153(6):422.