Showing papers by "Gordon H. Guyatt published in 2001"

Users' Guides to the Medical Literature

Abstract: Medical practice is constantly changing. The rate of change is accelerating, and physicians can be forgiven if they often find it dizzying. How can physicians learn about new information and innovations, and decide how (if at all) they should modify their practice? Possible sources include summaries from the medical literature (review articles, practice guidelines, consensus statements, editorials, and summary articles in "throwaway" journals); consultation with colleagues who have special expertise; lectures; seminars; advertisements in medical journals; conversations with representatives from pharmaceutical companies; and original articles in journals and journal supplements. Each of these sources of information might be valuable, though each is subject to its own particular biases. 1,2 Problems arise when, as is often the case, these sources of information provide different suggestions about patient care. See also p 2093. Without a way of critically appraising the information they receive, clinicians are relatively helpless in deciding what new information

Intention-to-treat principle

Abstract: In deciding if a treatment is likely to work in an individual patient, clinicians need to know the effect of the intervention in patients who take the treatment as prescribed. However, participants in clinical trials may not adhere to the protocol, or clinicians may recommend withdrawal of the study

Treatment of open fractures of the shaft of the tibia

Abstract: We have systematically reviewed the effect of alternative methods of stabilisation of open tibial fractures on the rates of reoperation, and the secondary outcomes of nonunion, deep and superficial infection, failure of the implant and malunion by the analysis of 799 citations on the subject, identified from computerised databases. Although 68 proved to be potentially eligible, only eight met all criteria for inclusion. Three investigators independently graded the quality of each study and extracted the relevant data. One study (n = 56 patients) suggested that the use of external fixators significantly decreased the requirement for reoperation when compared with fixation with plates. The use of unreamed nails, compared with external fixators (five studies, n = 396 patients), reduced the risk of reoperation, malunion and superficial infection. Comparison of reamed with unreamed nails showed a reduced risk of reoperation (two studies, n = 132) with the reamed technique. An indirect comparison between reamed nails and external fixators also showed a reduced risk of reoperation (two studies) when using nails. We have identified compelling evidence that unreamed nails reduced the incidence of reoperations, superficial infections and malunions, when compared with external fixators. The relative merits of reamed versus unreamed nails in the treatment of open tibial fractures remain uncertain.

The attributable mortality and length of intensive care unit stay of clinically important gastrointestinal bleeding in critically ill patients

Abstract: Objective To estimate the mortality and length of stay in the intensive care unit (ICU) attributable to clinically important gastrointestinal bleeding in mechanically ventilated critically ill patients. Design Three strategies were used to estimate the mortality attributable to bleeding in two multicentre databases. The first method matched patients who bled with those who did not (matched cohort), using duration of ICU stay prior to the bleed, each of six domains of the Multiple Organ Dysfunction Score (MODS) measured 3 days prior to the bleed, APACHE II score, age, admitting diagnosis, and duration of mechanical ventilation. The second approach employed Cox proportional hazards regression to match bleeding and non-bleeding patients (model-based matched cohort). The third method, instead of matching, derived estimates based on regression modelling using the entire population (regression method). Three parallel analyses were conducted for the length of ICU stay attributable to clinically important bleeding. Setting Sixteen Canadian university-affiliated ICUs. Patients A total of 1666 critically ill patients receiving mechanical ventilation for at least 48 hours. Measurements We prospectively collected data on patient demographics, APACHE II score, admitting diagnosis, daily MODS, clinically important bleeding, length of ICU stay, and mortality. Independent adjudicators determined the occurrence of clinically important gastrointestinal bleeding, defined as overt bleeding in association with haemodynamic compromise or blood transfusion. Results Of 1666 patients, 59 developed clinically important gastrointestinal bleeding. The mean APACHE II score was 22.9 ± 8.6 among bleeding patients and 23.3 ± 7.7 among non-bleeding patients. The risk of death was increased in patients with bleeding using all three analytic approaches (matched cohort method: relative risk [RR] = 2.9, 95% confidence interval (CI) = 1.6–5.5; model-based matched cohort method: RR = 1.8, 95% CI = 1.1–2.9; and the regression method: RR = 4.1, 95% CI = 2.6–6.5). However, this was not significant for the adjusted regression method (RR = 1.0, 95% CI = 0.6–1.7). The median length of ICU stay attributable to clinically important bleeding for these three methods, respectively, was 3.8 days (95% CI = –0.01 to 7.6 days), 6.7 days (95% CI = 2.7–10.7 days), and 7.9 days (95% CI = 1.4–14.4 days). Conclusions Clinically important upper gastrointestinal bleeding has an important attributable morbidity and mortality, associated with a RR of death of 1–4 and an excess length of ICU stay of approximately 4–8 days.

Users' Guides to the Medical Literature: Essentials of Evidence-Based Clinical Practice

Abstract: "Users' Guide to the Medical Literature: Essentials of Evidence-Based Clinical Practice" will help you develop the core knowledge you need to take control of the medical literature - to uncover the relevant information, assess its validity and determine whether it applies to your patient. The pocketsized Essentials is succinct yet thorough in its exposition of the concepts, making it the ideal text to tote along on the wards. Affordably priced, the book offers: a thorough, comprehensive and clinician-friendly evidence-based medicine toolkit; why framing the right question is so important; how to find and distinguish between strong and weak evidence; what's needed to critically appraise the best evidence; how to weigh the risks and benefits that precede medical management decisions; how to individualize evidence to each patient; and, a CD-ROM to enable intuitive, nonlinear learning experiences in coordination with the text.Also available is the "Manual for Evidence-Based Clinical Practice", which together with "Essentials of Evidence-Based Clinical Practice" provide the most detailed yet clinical-friendly exposition of the concepts necessary to use the medical literature to solve patient problems.

Development of a self-reported Chronic Respiratory Questionnaire (CRQ-SR)

Abstract: BACKGROUND The Chronic Respiratory Questionnaire (CRQ) is an established measure of health status for chronic obstructive pulmonary disease (COPD). It has been found to be reproducible and sensitive to change, but as an interviewer led questionnaire is very time consuming to administer. A study was undertaken to develop a self-reported version of the CRQ (CRQ-SR) and to compare the results of this questionnaire with the conventional interviewer led CRQ (CRQ-IL). METHODS Fifty two patients with moderate to severe COPD participated in the study. Subjects completed the CRQ-SR 1 week after completing the CRQ-IL, and a further CRQ-SR was administered 1 week later. For patients in group A (n=27) the dyspnoea provoking activities that they had previously selected were transcribed onto the second CRQ-SR, while patients in group B (n=25) were not informed of their previous dyspnoea provoking activities when they completed the second CRQ-SR. To assess the short term reproducibility and reliability of the CRQ-SR it was then administered twice at an interval of 7–10 days to a further group of 21 patients. The CRQ-IL was not administered. Longer term reproducibility was examined in 39 stable patients who completed the CRQ-SR at initial assessment and then again 7 weeks later. RESULTS Mean scores per dimension, mean differences, and limits of agreement are given for each dimension in the comparison of the two questionnaires. There were no statistically significant differences between the CRQ-IL and CRQ-SR in the mastery and fatigue dimensions (p>0.05). A statistically significant difference between the two scores was found in the dyspnoea dimension (p=0.006) and the emotional function dimension (p=0.04), but these differences were well within the minimum clinically important threshold. No statistically significant difference in the mean dyspnoea score was seen between groups A and B. The CRQ-SR was found to be reproducible both in the short term and after the longer period of 7 weeks, with no statistically or clinically significant differences in any dimension. Test-retest reliability was found to be high in each dimension, both in the short and longer term. CONCLUSIONS The CRQ-SR is a reproducible, reliable, and stable measure of health status. It compares well with the CRQ-IL but cannot be used interchangeably. The main advantage of the CRQ-SR over the CRQ-IL is that is quick to administer, reducing assessment time and hence cost.

Relation of distribution- and anchor-based approaches in interpretation of changes in health-related quality of life.

Abstract: Background Approaches to interpretation of quality of life changes in clinical trials have fallen into two camps: those that rely on the distribution of changes and the Effect Size (ES), and those that use some external anchor, such as patient judgments of change, which is then used to compute a Minimally Important Difference (MID), the proportion benefiting from treatment, p(B), and the Number Needed to Treat (NNT). Objective To examine the relationship between the ES and p(B), and the impact of the MID on this relationship. Methods Simulation was used based on a normal distribution to compute the proportion of patients benefiting in both parallel group and crossover designs, for various values of the ES and the MID. The agreement of the simulation with empirical data from four studies of asthma and respiratory disease was assessed. The effect of skewness in the distributions of change scores on the relationship between ES and p(B) was also examined. Results The simulation showed a near-linear relationship between ES and p(B), which was nearly independent of the value of the MID. Agreement of the simulation with the empirical data were excellent. Although the curves differed for crossover and parallel group designs, the general form was similar. Introducing moderate skew into the distributions had minimal impact on the relationship. Conclusions The proportion of patients who will benefit from treatment can be directly estimated from the ES, and is nearly independent of the choice of MID. Effect size and anchor based approaches provide equivalent information in this situation.

Physician interpretations and textbook definitions of blinding terminology in randomized controlled trials.

Abstract: Context When clinicians assess the validity of randomized controlled trials (RCTs), they commonly evaluate the blinding status of individuals in the RCT. The terminology authors often use to convey blinding status (single, double, and triple blinding) may be open to various interpretations. Objective To determine physician interpretations and textbook definitions of RCT blinding terms.

New strategies for clinical trials in patients with sepsis and septic shock.

Abstract: OBJECTIVE: The difficulty in identifying new treatment modalities that significantly reduce the mortality and morbidity rates associated with sepsis has highlighted the need to reevaluate the approach to clinical trial design. The United Kingdom Medical Research Council convened an International Working Party to address these issues. DATA SOURCES: The subject areas that were to be the focus of discussion were identified by the co-chairs, and group leaders were nominated. Preconference reading material was circulated to group members. STUDY SELECTION AND DATA EXTRACTION: Small-group discussion fed into an iterative process of feedback from plenary sessions, followed by the formulation of recommendations. Finally, each working group prepared a summary of its recommendations and these are reported herein. DATA SYNTHESIS: There were five key recommendations. First, investigators should no longer rely solely on the American College of Chest Physicians/Society of Critical Care Medicine definitions of sepsis or sepsis syndrome as the basis of trial entry. Entry criteria should be based on three principles: a) All patients should have infection; b) there should be evidence of a pathologic process that represents a biologically plausible target for the proposed intervention, for example, an abnormal circulating level of a biological marker pertinent to the study drug; and c) patients should fall into an appropriate category of severity (usually severe sepsis). Second, investigators should use a scoring system for organ dysfunctions that has been validated and that can be incorporated into all sepsis studies; agreement on the use of a single system would simplify comparisons between studies. Third, the primary outcome measure generally should be mortality rates, but under appropriate circumstances major morbidities could be considered as primary end points. Regardless of choice of the duration to primary end point, patients should be followed for > or =90 days. Fourth, sample size needs to be based on a realistic assessment of achievable effect size based on knowledge of the at-risk population. Fifth, subgroups should be few in number and should be defined a priori on the basis of variables present before randomization. CONCLUSIONS: Important changes in several aspects of trial design may improve the quality of clinical studies in sepsis and maximize the chance of identifying effective therapeutic agents.

A meta-analysis of etidronate for the treatment of postmenopausal osteoporosis.

Abstract: The aim of the study was to review the effect of etidronate on bone density and fractures in postmenopausal women. We searched MEDLINE from 1966 to 1998, examined citations of relevant articles, and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies, primary authors, and pharmaceutical industry sources for unpublished data. We included 13 trials that randomized women to etidronate or an alternative (placebo or calcium and/or vitamin D) and measured bone density for at least 1 year. For each trial, three independent reviewers assessed the methodologic quality and abstracted data. The data suggested a reduction in vertebral fractures with a pooled relative risk of 0.63 (95% CI 0.44 to 0.92). There was no effect on nonvertebral fractures (relative risk 0.99, (95% CI 0.69 to 1.42). Etidronate, relative to control, increased bone density after 1–3 years of treatment in the lumbar spine by 4.06% (95% CI 3.12 to 5.00), in the femoral neck by 2.35% (95% CI 1.66 to 3.04) and in the total body by 0.97% (95% CI 0.39 to 1.55). Effects were larger at 4 years, though the number of patients followed much smaller. Etidronate increases bone density in the lumbar spine and femoral neck for up to 4 years. The pooled estimates of fracture reduction with etidronate suggest a reduction in vertebral fractures, but no effect on nonvertebral fractures.

Surgeons' preferences for the operative treatment of fractures of the tibial shaft. An international survey.

Abstract: There are more potential treatments for tibial fractures and more potential complications of those treatments than there are for any other type of fracture. The American Academy of Orthopaedic Surgeons recently reviewed malpractice claims to identify the procedures and diagnoses that have most commonly resulted in legal action. Among all orthopaedic conditions, fractures of the tibia and fibula ranked second with regard to the total number of patient malpractice claims, accounting for over thirty million dollars in indemnity1. The National Center for Health Statistics reported that more than 490,000 fractures of the tibia and fibula occur each year in the United States2. Although many tibial fractures may be managed nonoperatively, fractures for which nonoperative treatment has failed, open fractures, fractures with an associated compartment syndrome, and high-energy fractures require operative stabilization3. Surgical options include external fixation, plate fixation, and intramedullary nailing with or without reaming. Although there is a consensus among orthopaedic surgeons with regard to the optimal treatment of fractures of the femoral shaft, the appropriate treatment of closed and open tibial fractures remains controversial. Meta-analyses that include randomized trials provide the best evidence regarding the results of operative treatment of fractures of the tibial shaft4-7. In our meta-analysis6, one randomized trial8, involving fifty-six patients, showed a significant reduction in the rate of reoperation after external fixation compared with the rate after the use of plates (relative risk reduction, 87%; 95% confidence interval, 46% to 97%). Other trials showed that nailing without reaming resulted in a significant reduction in the risk of reoperation compared with the risk after external fixation (relative risk reduction, 49%; 95% confidence interval, 31% to 63%). Nailing with reaming reduced the risk of nonunion of closed and open fractures of the …

Colloid use for fluid resuscitation: evidence and spin.

Abstract: In this issue, Wilkes and Navickis present a meta-analysis of albumin versus crystalloids in critically ill patients. This meta-analysis has many strengths, but its weaknesses may limit the inferen...

User's guide to the orthopaedic literature: how to use an article about a surgical therapy.

Abstract: Summary We suggest a three-step approach when using an article from the surgical literature to guide your patient care: (1) assess whether the study can provide valid results, (2) review the results, and (3) consider how the results might be applied to your patient. Randomization, concealment, intention-to-treat analysis, similarity of patients for known prognostic factors, blinding of patients and outcome assessors, and completeness of follow-up are important guides to study validity. The 95% confidence interval around the treatment effect is a measure of precision. Consider whether all of the clinically important outcomes were reported and whether the likely benefits of treatment outweigh the potential harm and costs.

International approaches to the prescription of long-term oxygen therapy.

Abstract: While there is broad agreement about who should receive long-term oxygen therapy (LTOT), there is little information available on how clinicians should decide on the oxygen prescription itself, at rest, during sleep and during exercise. The authors describe the results of an international survey that was undertaken to compare how respirologists prescribed oxygen. A questionnaire was sent to 100 respirologists in each of seven countries. The questionnaire identified whether resting flow rates were derived in a standard manner or by individualized patient testing. Test targets were ascertained for rest, exercise and sleep, as was the percentage of time that each test target had to reach for the test to be accepted. The majority of respondents individualized the oxygen prescription at rest (81%). Resting arterial oxygen saturation (Sa,O2) was most commonly targeted at 90-91%. The approach to night prescription varied (p<0.001). Respirologists in Canada and the USA increased the resting Sa,O2 by 1-2 L x min(-1) during sleep, while those in Spain used the resting (awake) flow for the night prescription (62%). Respirologists in the Netherlands, France, and Italy individualized the night prescription more frequently. Although oxygen during exercise was individualized in most countries (74%), significant differences remained among countries (p<0.001). The majority of respirologists (62%) aimed to achieve an Sa,O2 of 90-91% during exercise, while 70% of all respirologists tried to achieve the desired Sa,O2 for 90% of the test. There were substantial differences among countries as to how the oxygen prescription was written. This survey highlights the need for multicentre studies that improve the effectiveness of long-term oxygen therapy utilization.

Agreement between Alternative Classifications of Acute Respiratory Distress Syndrome

Abstract: To examine the agreement between two classifications of acute respiratory distress syndrome (ARDS) that are used interchangeably in clinical practice and clinical research, we classified 118 patients taking part in a randomized trial with respect to the presence of ARDS using the North American–European Consensus Committee (NAECC) and the Lung Injury Severity Score (LISS) criteria. The incidence of ARDS using NAECC criteria was 55.1% (95% confidence interval, 46.1% to 64.1%), and using the LISS criteria 61.9% (95% confidence interval, 53.1% to 70.6%). The p value on the difference between these proportions was 0.07. Raw agreement, chance-corrected agreement (kappa), and chance-independent agreement (phi) on the study occurrence of ARDS using the two classifications were, respectively, 0.73 (95% CI, 0.65 to 0.81), 0.46 (95% CI, 0.32 to 0.61), and 0.63 (95% CI, 0.41 to 0.79). No single component of either index contributed to disagreement to an appreciably greater extent than other components. Baseline char...

Digitalis for treatment of congestive heart failure in patients in sinus rhythm

Abstract: Background: Digitalis glycosides have been in clinical use in the treatment of congestive heart failure (CHF) for more than 200 years. In recent years several trials have been conducted to address concerns about efficacy and toxicity. Although a systematic review of the literature was published in 1990, an update is required to include more current trials. Objectives: To examine the effectiveness of digitalis glycosides in treating CHF in patients with normal sinus rhythm. To examine the effect of digitalis in patients taking diuretics, angiotensin converting enzyme inhibitors, and beta-blockers; patients with varying severity and duration of disease; patients with prior exposure to digitalis versus no prior exposure; and patients with "CHF due to systolic dysfunction" versus "CHF with preserved systolic function". Search strategy: The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library Issue 4 2008, MEDLINE (1966 to November 2008), EMBASE (1990 to November 2008) and Dissertation Abstracts (to November 2008) were searched. Annual meeting abstracts of the American Heart Association, American College of Cardiology, and European Society of Cardiology were also searched from 1996 to November 2008. In addition, reference lists provided by the pharmaceutical industry (GlaxoSmithKline) were searched. Selection criteria: Included were randomized placebo-controlled trials of 20 or more adult patients of either sex with symptomatic CHF who were studied for seven weeks or more. Excluded were trials in which the prevalence of atrial fibrillation was 2% or greater, or in which any arrhythmia that might compromise cardiac function or any potentially reversible cause of CHF such as acute ischemic heart disease or myocarditis was present. Data collection and analysis: Articles selected from the searches described above were evaluated as a joint effort of the coauthors. The staff of the Cochrane Heart Group ran searches on the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE. Main results: Thirteen studies (7896 participants) meeting the defined criteria were identified, and major endpoints of mortality, hospitalization, and clinical status, based respectively upon 8, 4, and 12 of these selected studies, were recorded and analyzed. The data show that there is no evidence of a difference in mortality between treatment and control groups, whereas digitalis therapy is associated with a lower rate of hospitalization and of clinical deterioration. The largest study showed a significant rise in other cardiac deaths, possibly due to arrhythmias. However collectively these findings were based on studies done before beta-blockers became widely used to treat CHF. Authors' conclusions: The literature indicates that digitalis may have a useful role in the treatment of patients with CHF who are in normal sinus rhythm. New trials are needed to elucidate the importance of digitalis dosage, and its usefulness in the era of beta-blockers.

Regular Versus As-Needed Short-Acting Inhaled β -Agonist Therapy for Chronic Obstructive Pulmonary Disease

Abstract: Regular short-acting inhaled β -agonist therapy is of uncertain benefit in patients with chronic obstructive pulmonary disease (COPD). We conducted a randomized, concealed, double-blind, placebo-controlled crossover trial in two periods, each of 3-mo duration, involving 53 patients with a smoking history of > 20 pack-years, an FEV1 of < 70% predicted, and an FEV1/VC ratio of < 0.7 after inhalation of 200 μ g albuterol. All patients received regular ipratropium bromide at 20 μ g per puff in 2 puffs four times daily, beclomethasone at 250 μ g per puff or equivalent corticosteroid in 2 puffs twice daily, and open-label inhaled albuterol as needed. Interventional therapy consisted of regular inhaled albuterol (100 μ g per puff, in 2 puffs four times daily) versus placebo. Patients used twice as much active albuterol in the regular use period (mean: 8.07 puffs of coded and 4.68 puffs of open-label medication; total: 12.75 puffs daily) than during the as-needed period (mean: 6.34 puffs of open-label albuterol d...

Traffic-Related Fatalities Among Older Drivers and Passengers Past and Future Trends

Abstract: PURPOSE OF THE STUDY: This study was initiated to forecast the number of older drivers and passengers who may be fatally injured in traffic crashes in future years. DESIGN AND METHODS: The study was based on data from the U.S. Fatality Analysis Reporting System covering the period from 1975 to 1998. Projections were based on least squares regression models. RESULTS: About 35,000 drivers and passengers died in traffic crashes each year from 1975 to 1998. Older adults (65 and older) accounted for 10% of all fatalities in 1975, 17% in 1998, and a projected 27% by 2015, the same proportion predicted for drivers and passengers aged younger than 30. On the basis of these projections, the number of fatally injured women and men aged 65 and older will increase respectively by 373% and 271% between 1975 and 2015. IMPLICATIONS: If current trends continue, the number of fatalities among older drivers and passengers and those aged younger than 30, may be equivalent early in this century. These projections call for further research into conditions that may lead to crashes involving older drivers and for the development and implementation of initiatives to curb traffic-related fatalities among older adults. Language: en

Evidence-based medicine in anesthesiology.

Abstract: By making the clinical decision making process explicit, conscious, and science based, we may avoid confusing opinion with evidence. EBM may help sharpen our critical appraisal skills and thus improve the way we practice, teach, and conduct research. Nevertheless, EBM will need to supplement rather than substitute for other approaches to patient care and teaching. EBM may better incorporate patients' values into clinical decision making, and this may be especially important in anesthesiology, where we are in need of valid evidence about important clinical issues such as preoperative testing and postoperative analgesia. By incorporating valid scientific evidence and patients' values into clinical decision making, we may improve patient outcomes. Outside of internal medicine, the literature suggesting that the practice of EBM improves outcomes is sparse, though increasing. Future studies to critically evaluate the practice of EBM in anesthesiology and critical care would be helpful.