Showing papers by "Gordon H. Guyatt published in 2010"

Higher vs Lower Positive End-Expiratory Pressure in Patients With Acute Lung Injury and Acute Respiratory Distress Syndrome: Systematic Review and Meta-analysis

Abstract: Context Trials comparing higher vs lower levels of positive end-expiratory pressure (PEEP) in adults with acute lung injury or acute respiratory distress syndrome (ARDS) have been underpowered to detect small but potentially important effects on mortality or to explore subgroup differences. Objectives To evaluate the association of higher vs lower PEEP with patient-important outcomes in adults with acute lung injury or ARDS who are receiving ventilation with low tidal volumes and to investigate whether these associations differ across prespecified subgroups. Data Sources Search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (1996-January 2010) plus a hand search of conference proceedings (2004-January 2010). Study Selection Two reviewers independently screened articles to identify studies randomly assigning adults with acute lung injury or ARDS to treatment with higher vs lower PEEP (with low tidal volume ventilation) and also reporting mortality. Data Extraction Data from 2299 individual patients in 3 trials were analyzed using uniform outcome definitions. Prespecified effect modifiers were tested using multivariable hierarchical regression, adjusting for important prognostic factors and clustering effects. Results There were 374 hospital deaths in 1136 patients (32.9%) assigned to treatment with higher PEEP and 409 hospital deaths in 1163 patients (35.2%) assigned to lower PEEP (adjusted relative risk [RR], 0.94; 95% confidence interval [CI], 0.86-1.04; P = .25). Treatment effects varied with the presence or absence of ARDS, defined by a value of 200 mm Hg or less for the ratio of partial pressure of oxygen to fraction of inspired oxygen concentration (P = .02 for interaction). In patients with ARDS (n = 1892), there were 324 hospital deaths (34.1%) in the higher PEEP group and 368 (39.1%) in the lower PEEP group (adjusted RR, 0.90; 95% CI, 0.81-1.00; P = .049); in patients without ARDS (n = 404), there were 50 hospital deaths (27.2%) in the higher PEEP group and 44 (19.4%) in the lower PEEP group (adjusted RR, 1.37; 95% CI, 0.98-1.92; P = .07). Rates of pneumothorax and vasopressor use were similar. Conclusions Treatment with higher vs lower levels of PEEP was not associated with improved hospital survival. However, higher levels were associated with improved survival among the subgroup of patients with ARDS.

Effect of early surgery after hip fracture on mortality and complications: systematic review and meta-analysis

Abstract: Background: Guidelines exist for the surgical treatment of hip fracture, but the effect of early surgery on mortality and other outcomes that are important for patients remains unclear. We conducted a systematic review and meta-analysis to determine the effect of early surgery on the risk of death and common postoperative complications among elderly patients with hip fracture. Methods: We searched electronic databases (including MEDLINE and EMBASE), the archives of meetings of orthopedic associations and the bibliographies of relevant articles and questioned experts to identify prospective studies, published in any language, that evaluated the effects of early surgery in patients undergoing procedures for hip fracture. Two reviewers independently assessed methodologic quality and extracted relevant data. We pooled data by means of the DerSimonian and Laird random-effects model, which is based on the inverse variance method. Results: We identified 1939 citations, of which 16 observational studies met our inclusion criteria. These studies had a total of 13 478 patients for whom mortality data were complete (1764 total deaths). Based on the five studies that reported adjusted risk of death (4208 patients, 721 deaths), irrespective of the cut-off for delay (24, 48 or 72 hours), earlier surgery (i.e., within the cut-off time) was associated with a significant reduction in mortality (relative risk [RR] 0.81, 95% confidence interval [CI] 0.68–0.96, p = 0.01). Unadjusted data indicated that earlier surgery also reduced in-hospital pneumonia (RR 0.59, 95% CI 0.37–0.93, p = 0.02) and pressure sores (RR 0.48, 95% CI 0.34–0.69, p Interpretation: Earlier surgery was associated with a lower risk of death and lower rates of postoperative pneumonia and pressure sores among elderly patients with hip fracture. These results suggest that reducing delays may reduce mortality and complications.

Is a subgroup effect believable? Updating criteria to evaluate the credibility of subgroup analyses

Abstract: How can we tell the difference between spurious and real subgroup effects? This article identifies new criteria and proposes a checklist for judging the credibility of subgroup analyses

Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis.

Abstract: Context Theory and simulation suggest that randomized controlled trials (RCTs) stopped early for benefit (truncated RCTs) systematically overestimate treatment effects for the outcome that precipitated early stopping. Objective To compare the treatment effect from truncated RCTs with that from meta-analyses of RCTs addressing the same question but not stopped early (nontruncated RCTs) and to explore factors associated with overestimates of effect. Data Sources Search of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify truncated RCTs up to January 2007; search of MEDLINE, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects to identify systematic reviews from which individual RCTs were extracted up to January 2008. Study Selection Selected studies were RCTs reported as having stopped early for benefit and matching nontruncated RCTs from systematic reviews. Independent reviewers with medical content expertise, working blinded to trial results, judged the eligibility of the nontruncated RCTs based on their similarity to the truncated RCTs. Data Extraction Reviewers with methodological expertise conducted data extraction independently. Results The analysis included 91 truncated RCTs asking 63 different questions and 424 matching nontruncated RCTs. The pooled ratio of relative risks in truncated RCTs vs matching nontruncated RCTs was 0.71 (95% confidence interval, 0.65-0.77). This difference was independent of the presence of a statistical stopping rule and the methodological quality of the studies as assessed by allocation concealment and blinding. Large differences in treatment effect size between truncated and nontruncated RCTs (ratio of relative risks Conclusions Truncated RCTs were associated with greater effect sizes than RCTs not stopped early. This difference was independent of the presence of statistical stopping rules and was greatest in smaller studies.

Beyond Mortality: Future Clinical Research in Acute Lung Injury

Abstract: Mortality in National Heart, Lung and Blood Institute-sponsored clinical trials of treatments for acute lung injury (ALI) has decreased dramatically during the past two decades. As a consequence, design of such trials based on a mortality outcome requires ever-increasing numbers of patients. Recognizing that advances in clinical trial design might be applicable to these trials and might allow trials with fewer patients, the National Heart, Lung and Blood Institute convened a workshop of extramural experts from several disciplines. The workshop assessed the current state of clinical research addressing ALI, identified research needs, and recommended: (1) continued performance of trials evaluating treatments of patients with ALI; (2) development of strategies to perform ALI prevention trials; (3) observational studies of patients without ALI undergoing prolonged mechanical ventilation; and (4) development of a standardized format for reporting methods, endpoints, and results of ALI trials.

The Vexing Problem of Guidelines and Conflict of Interest: A Potential Solution

Abstract: Issues of financial and intellectual conflict of interest in clinical practice guidelines have raised increasing concern. Professional organizations have responded by more rigorous regulation of conflict of interest. Nevertheless, tension remains between the competing goals of optimizing guideline quality by using the experience and insight of experts and ensuring that financial and intellectual conflicts of interest do not influence recommendations. The executive committee of the American College of Chest Physicians' Antithrombotic Guidelines has developed a strategy comprising 3 innovative aspects to address this tension: First, place equal emphasis on intellectual and financial conflicts and provide explicit criteria for both; second, a methodologist without important conflicts of interest should have primary responsibility for each chapter; and third, experts with important financial or intellectual conflicts of interest can collect and interpret evidence, but only panel members without important conflicts can be involved in developing the recommendation for a specific question. These strategies may help to achieve the benefits of expert input without conflicts of interest influencing recommendations.

Prevalence and underdiagnosis of chronic obstructive pulmonary disease among patients at risk in primary care

Abstract: Background: People with known risk factors for chronic obstructive pulmonary disease (COPD) are important targets for screening and early intervention. We sought to measure the prevalence of COPD among such individuals visiting a primary care practitioner for any reason. We also evaluated the accuracy of prior diagnosis or nondiagnosis of COPD and identified associated clinical characteristics. Methods: We recruited patients from three primary care sites who were 40 years or older and had a smoking history of at least 20 pack-years. Participants were asked about respiratory symptoms and underwent postbronchodilator spirometry. COPD was defined as a ratio of forced expiratory volume in the first second of expiration to forced vital capacity (FEV 1 /FVC) of less than 0.7 and an FEV 1 of less than 80% predicted. Results: Of the 1459 patients who met the study criteria, 1003 (68.7%) completed spirometry testing. Of these, 208 were found to have COPD, for a prevalence of 20.7% (95% confidence interval 18.3%–23.4%). Of the 205 participants with COPD who completed the interview about respiratory symptoms before spirometry, only 67 (32.7%) were aware of their diagnosis before the study. Compared with patients in whom COPD had been correctly diagnosed before the study, those in whom COPD had been over-diagnosed or undiagnosed were similar in terms of age, sex, current smoking status and number of visits to a primary care practitioner because of a respiratory problem. Interpretation: Among adult patients visiting a primary care practitioner, as many as one in five with known risk factors met spirometric criteria for COPD. Underdiagnosis of COPD was frequent, which suggests a need for greater screening of at-risk individuals. Knowledge of the prevalence of COPD will help plan strategies for disease management.

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.

Efficacy and safety of finasteride therapy for androgenetic alopecia: a systematic review.

Abstract: Context Androgenetic alopecia is the most common form of alopecia in men. Objective To determine the efficacy and safety of finasteride therapy for patients with androgenetic alopecia. Data Sources MEDLINE, EMBASE, CINAHL, Cochrane Registers, and LILACS were searched for randomized controlled trials reported in any language that evaluated the efficacy and safety of finasteride therapy in comparison to treatment with placebo in adults with androgenetic alopecia. Study Selection and Data Extraction Two reviewers independently evaluated eligibility and collected the data, including assessment of methodological quality (Jadad score). Outcome measures included patient self-assessment, hair count, investigator clinical assessment, global photographic assessment, and adverse effects at short term (≤12 months) and long term (≥24 months). Heterogeneity was explored by testing a priori hypotheses. Data Synthesis Twelve studies fulfilled the eligibility criteria (3927 male patients), 10 of which demonstrated a Jadad score of 3 or more. The proportion of patients reporting an improvement in scalp hair was greater with finasteride therapy than with placebo treatment in the short term (relative risk [RR], 1.81 [95% confidence interval (CI), 1.42-2.32]; I 2 , 64%) and in the long term (RR, 1.71 [95% CI, 1.15-2.53]; I 2 , 16%); both results were considered to have moderate-quality evidence. The number needed to treat for 1 patient to perceive himself as improved was 5.6 (95% CI, 4.6-7.0) in the short term and 3.4 (95% CI, 2.6-5.1) in the long term. Moderate-quality evidence suggested that finasteride therapy increased the mean hair count from baseline in comparison to placebo treatment, expressed as a percentage of the initial count in each individual, at short term (mean difference [MD], 9.42% [95% CI, 7.95%-10.90%]; I 2 , 50%) and at long term (MD, 24.3% [95% CI, 17.92%-30.60%]; I 2 , 0%). Also, the proportion of patients reported as improved by investigator assessment was greater in the short term (RR, 1.80 [95% CI, 1.43-2.26]; number needed to treat, 3.7 [95% CI, 3.2-4.3]; I 2 , 82%) (moderate-quality evidence). Moderate-quality evidence suggested an increase in erectile dysfunction (RR, 2.22 [95% CI, 1.03-4.78]; I 2 , 1%; number needed to harm, 82.1 [95% CI, 56-231]) and a possible increase in the risk of any sexual disturbances (RR, 1.39 [95% CI, 0.99-1.95]; I 2 , 0%). The risk of discontinuing treatment because of sexual adverse effects was similar to that of placebo (RR, 0.88 [95% CI, 0.51-1.49]; I 2 , 5%) (moderate-quality evidence). Conclusion Moderate-quality evidence suggests that daily use of oral finasteride increases hair count and improves patient and investigator assessment of hair appearance, while increasing the risk of sexual dysfunction.

How to Use an Article About Quality Improvement

Abstract: Quality improvement (QI) attempts to change clinician behavior and, through those changes, lead to improved patient outcomes. The methodological quality of studies evaluating the effectiveness of QI interventions is frequently low. Clinicians and others evaluating QI studies should be aware of the risk of bias, should consider whether the investigators measured appropriate outcomes, should be concerned if there has been no replication of the findings, and should consider the likelihood of success of the QI intervention in their practice setting and the costs and possibility of unintended effects of its implementation. This article complements and enhances existing Users' Guides that address the effects of interventions—Therapy, Harm, Clinical Decision Support Systems, and Summarizing the Evidence guides—with an emphasis on issues specific to QI studies. Given the potential for widespread implementation of QI interventions, there is a need for robust study methods in QI research.

Improving the interpretation of quality of life evidence in meta-analyses: the application of minimal important difference units

Abstract: Systematic reviews of randomized trials that include measurements of health-related quality of life potentially provide critical information for patient and clinicians facing challenging health care decisions. When, as is most often the case, individual randomized trials use different measurement instruments for the same construct (such as physical or emotional function), authors typically report differences between intervention and control in standard deviation units (so-called "standardized mean difference" or "effect size"). This approach has statistical limitations (it is influenced by the heterogeneity of the population) and is non-intuitive for decision makers. We suggest an alternative approach: reporting results in minimal important difference units (the smallest difference patients experience as important). This approach provides a potential solution to both the statistical and interpretational problems of existing methods.

Cautionary tales in the interpretation of clinical studies involving older persons

Abstract: The care of patients 65 years or older presents a challenge for evidence-based medicine. Such patients are underrepresented in clinical trials, are more vulnerable to treatment-induced harm, and often are unable to fully participate in treatment decisions. We outline several cautionary themes in the interpretation of clinical studies of therapeutic interventions involving older persons as they apply to processes of everyday clinical decision making. In particular, we focus on issues of study design and quality of evidence, choice of outcome measures, missing outcome data, assessment of potential harm, quantifying treatment effects in individual patients (and adjusting these for effect modifiers and reduced life expectancy), eliciting patient values and preferences, prioritizing therapeutic goals and selection of treatments, and assisting patients in adhering to agreed therapeutic regimens.

Assessing disease activity in ulcerative colitis: patients or their physicians?

Abstract: Background: We aimed to determine the optimal approach to assess disease activity (i.e., biological inflammation) in ulcerative colitis (UC) by comparing patients' and physicians' rating of the disease. Methods: This was a prospective, multicenter, double-cohort study. The first cohort was composed of 94 children with UC (parent proxy when required) and their physicians who provided independent clinical report and global assessment of disease, rated on a 100 mm visual analog scale. Constructs of disease activity (including mucosal inflammation, laboratory tests, Mayo score, and the Pediatric UC Activity Index), were scored by an independent blinded physician and used to compare validity of the assessment. Of the 94 children, 43 were seen at a follow-up visit and provided a global rating of change in disease activity. To ascertain whether age influences assessment accuracy, a second cohort of 86 adult UC patients were analyzed in a similar way. Results: In both cohorts the physician global assessment had higher correlations with all constructs of disease activity than did the patient' global assessment (for colonoscopic score r = 0.76 vs. r = 0.29, P = 0.002). Even with abdominal pain, a subjective item, the physician's rating had higher correlation than the patient's rating. Similarly, the physician rating of change better reflected change in disease activity than that of the patient rating. Conclusions: For indirect measurement of biological activity on the basis of symptoms and signs, clinician assessments are superior to those of patients. Patient assessments, physician assessments, and direct measurement of disease activity provide complementary information in clinical research. (Inflamm Bowel Dis 2009)

Systematic review of reviews including animal studies addressing therapeutic interventions for sepsis.

Abstract: Objective:Certain methodologic features of animal experiments such as random assignment have been found to reduce the risk of bias. Because animal research sometimes informs clinical practice, explicit acknowledgment of the risk of bias and clinical relevance cultivates realistic expectations on the

An instrument to assess quality of life in relation to nutrition: item generation, item reduction and initial validation

Abstract: It is arguable that modification of diet, given its potential for positive health outcomes, should be widely advocated and adopted. However, food intake, as a basic human need, and its modification may be accompanied by sensations of both pleasure and despondency and may consequently affect to quality of life (QoL). Thus, the feasibility and success of dietary changes will depend, at least partly, on whether potential negative influences on QoL can be avoided. This is of particular importance in the context of dietary intervention studies and in the development of new food products to improve health and well being. Instruments to measure the impact of nutrition on quality of life in the general population, however, are few and far between. Therefore, the aim of this project was to develop an instrument for measuring QoL related to nutrition in the general population. We recruited participants from the general population and followed standard methodology for quality of life instrument development (identification of population, item selection, n = 24; item reduction, n = 81; item presentation, n = 12; pretesting of questionnaire and initial validation, n = 2576; construct validation n = 128; and test-retest reliability n = 20). Of 187 initial items, 29 were selected for final presentation. Factor analysis revealed an instrument with 5 domains. The instrument demonstrated good cross-sectional divergent and convergent construct validity when correlated with scores of the 8 domains of the SF-36 (ranging from -0.078 to 0.562, 19 out of 40 tested correlations were statistically significant and 24 correlations were predicted correctly) and good test-retest reliability (intra-class correlation coefficients from 0.71 for symptoms to 0.90). We developed and validated an instrument with 29 items across 5 domains to assess quality of life related to nutrition and other aspects of food intake. The instrument demonstrated good face and construct validity as well as good reliability. Future work will focus on the evaluation of longitudinal construct validity and responsiveness.

Determinants of knowledge gain in evidence-based medicine short courses: an international assessment

Abstract: Background: Health care professionals worldwide attend courses and workshops to learn evidence-based medicine (EBM), but evidence regarding the impact of these educational interventions is conflicting and of low methodologic quality and lacks generalizability. Furthermore, little is known about determinants of success. We sought to measure the effect of EBM short courses and workshops on knowledge and to identify course and learner characteristics associated with knowledge acquisition. Methods: Health care professionals with varying expertise in EBM participated in an international, multicentre before– after study. The intervention consisted of short courses and workshops on EBM offered in diverse settings, formats and intensities. The primary outcome measure was the score on the Berlin Questionnaire, a validated instrument measuring EBM knowledge that the participants completed before and after the course. Results: A total of 15 centres participated in the study and 420 learners from North America and Europe completed the study. The baseline score across courses was 7.49 points (range 3.97–10.42 points) out of a possible 15 points. The average increase in score was 1.40 points (95% confidence interval 0.48–2.31 points), which corresponded with an effect size of 0.44 standard deviation units. Greater improvement in scores was associated (in order of greatest to least magnitude) with active participation required of the learners, a separate statistics session, fewer topics, less teaching time, fewer learners per tutor, larger overall course size and smaller group size. Clinicians and learners involved in medical publishing improved their score more than other types of learners; administrators and public health professionals improved their score less. Learners who perceived themselves to have an advanced knowledge of EBM and had prior experience as an EBM tutor also showed greater improvement than those who did not. Interpretation: EBM course organizers who wish to optimize knowledge gain should require learners to actively participate in the course and should consider focusing on a small number of topics, giving particular attention to statistical concepts.

A survey evaluating surgeons’ peri-operative usage of acetyl-salicylic acid (ASA) and their willingness to enroll their patients in a perioperative ASA randomized controlled trial

Abstract: Purpose: Major cardiovascular complications associated with noncardiac surgery represent a substantial population health problem for which there are no established efficacious and safe prophylactic interventions. Acetyl-salicylic acid (ASA) represents a promising intervention. The objective of this study was to determine surgeons’ perioperative usage of ASA, and if they would enrol their patients in a perioperative ASA randomized controlled trial (RCT). Methods: Cross-sectional survey of all practicing Canadian general, orthopedic, and vascular surgeons. Our mailed, self-administered survey asked surgeons to consider only their patients who were at risk of a major perioperative cardiovascular complication. Results: The response rate was 906/1854 (49%). For patients taking ASA chronically, there was marked variability regarding ASA continuation prior to surgery amongst the general and orthopedic surgeons, whereas 76% of vascular surgeons continued ASA in 81-100% of their patients. For patients not taking ASA chronically, approaches to starting ASA prior to surgery were variable amongst the vascular surgeons, whereas 70% of general and 82% of orthopaedic surgeons did not start ASA. For patients taking ASA chronically, 73% of general surgeons, 70% of orthopaedic surgeons, and 36% of vascular surgeons would allow at least 40% of their patients to participate in a perioperative RCT comparing stopping versus continuing ASA. For patients not taking ASA chronically, most general (76%), orthopaedic (67%), and vascular (51%) surgeons would allow at least 40% of their patients to participate in a perioperative RCT comparing starting ASA versus placebo. Conclusion: This national survey demonstrates that perioperative ASA usage as reported by surgeons is variable, identifying the need for, and community interest in, a large perioperative ASA trial.