Showing papers by "Gordon H. Guyatt published in 2002"

Methods to explain the clinical significance of health status measures.

Abstract: One can classify ways to establish the interpretability of quality-of-life measures as anchor based or distribution based. Anchor-based measures require an independent standard or anchor that is itself interpretable and at least moderately correlated with the instrument being explored. One can further classify anchor-based approaches into population-focused and individual-focused measures. Population-focused approaches are analogous to construct validation and rely on multiple anchors that frame an individual's response in terms of the entire population (eg, a group of patients with a score of 40 has a mortality of 20%). Anchors for population-based approaches include status on a single item, diagnosis, symptoms, disease severity, and response to treatment. Individual-focused approaches are analogous to criterion validation. These methods, which rely on a single anchor and establish a minimum important difference in change in score, require 2 steps. The first step establishes the smallest change in score that patients consider, on average, to be important (the minimum important difference). The second step estimates the proportion of patients who have achieved that minimum important difference. Anchors for the individual-focused approach include global ratings of change within patients and global ratings of differences between patients. Distribution-based methods rely on expressing an effect in terms of the underlying distribution of results. Investigators may express effects in terms of between-person standard deviation units, within-person standard deviation units, and the standard error of measurement. No single approach to interpretability is perfect. Use of multiple strategies is likely to enhance the interpretability of any particular instrument.

Users' guides to the medical literature : a manual for evidence-based clinical practice

Abstract: The #1 guide to the principles and clinical applications of evidence-based medicine is better than ever! No other resource helps clinicians to put key evidence-based medicine protocols into daily clinical practice better than Users' Guides to the Medical Literature. An instant classic in its first edition, this detailed, yet highly readable reference demystifies the statistical, analytical, and clinical principles of evidence-based medicine, giving you a hands-on, practical resource that no other text can match. Readers will learn how to distinguish solid medical evidence from poor medical evidence, devise the best search strategies for each clinical question, critically appraise the medical literature, and optimally tailor evidence-based medicine for each patient. The third edition of this landmark resource is now completely revised and refreshed throughout, with expanded coverage of both basic and advanced issues in using evidence-based medicine in clinical practice. Completely updated with new medical studies, new chapters, and new methods for applying EBM principles to patient care Contributors represent the world's most prominent assembly of EBM experts Covers both basic principles and clinical application

Post-randomisation exclusions: the intention to treat principle and excluding patients from analysis

Abstract: When is it legitimate to exclude randomised patients from the analysis of data in clinical trials? Basing their analysis on the desirability of minimising bias and random error, the authors consider the circumstances when it may be possible to exclude patients, even in an intention to treat trial

Meta-analyses of Therapies for Postmenopausal Osteoporosis. IX: Summary of Meta-Analyses of Therapies for Postmenopausal Osteoporosis

Abstract: This section summarizes the results of the seven systematic reviews of osteoporosis therapies published in this series [calcium, vitamin D, hormone replacement therapy (HRT), alendronate, risedronate, raloxifene, and calcitonin] and systematic reviews of etidronate and fluoride we have published elsewhere. We highlight the methodological strengths and weaknesses of the individual studies, and summarize the effects of treatments on the risk of vertebral and nonvertebral fractures and on bone density, including effects in different patient subgroups. We provide an estimate of the expected impact of antiosteoporosis interventions in prevention and treatment populations using the number needed to treat (NNT) as a reference. In addition to the evidence, judgements about the relative weight that one places on weaker and stronger evidence, attitudes toward uncertainty, circumstances of patients' and societal values or preferences will, and should, play an important role in decision-making regarding anti-osteoporosis therapy.

Interventions to reduce unintended pregnancies among adolescents: systematic review of randomised controlled trials

Abstract: Objective: To review the effectiveness of primary prevention strategies aimed at delaying sexual intercourse, improving use of birth control, and reducing incidence of unintended pregnancy in adolescents. Data sources: 12 electronic bibliographic databases, 10 key journals, citations of relevant articles, and contact with authors. Study selection: 26 trials described in 22 published and unpublished reports that randomised adolescents to an intervention or a control group (alternate intervention or nothing). Data extraction: Two independent reviewers assessed methodological quality and abstracted data. Data synthesis: The interventions did not delay initiation of sexual intercourse in young women (pooled odds ratio 1.12; 95% confidence interval 0.96 to 1.30) or young men (0.99; 0.84 to 1.16); did not improve use of birth control by young women at every intercourse (0.95; 0.69 to 1.30) or at last intercourse (1.05; 0.50 to 2.19) or by young men at every intercourse (0.90; 0.70 to 1.16) or at last intercourse (1.25; 0.99 to 1.59); and did not reduce pregnancy rates in young women (1.04; 0.78 to 1.40). Four abstinence programmes and one school based sex education programme were associated with an increase in number of pregnancies among partners of young male participants (1.54; 1.03 to 2.29). There were significantly fewer pregnancies in young women who received a multifaceted programme (0.41; 0.20 to 0.83), though baseline differences in this study favoured the intervention. Conclusions: Primary prevention strategies evaluated to date do not delay the initiation of sexual intercourse, improve use of birth control among young men and women, or reduce the number of pregnancies in young women.

Meta-Analyses of Therapies for Postmenopausal Osteoporosis

Abstract: III. Risedronate Ann Cranney, MD, MSc; Peter Tugwell, MD, MSc; Jonathan Adachi, MD; Bruce Weaver, MSc; Nicole Zytaruk, RN; Alexandra Papaioannou, MD; Vivian Robinson, MSc, Beverley Shea, BScN, MSc; George Wells, PhD; Gordon Guyatt, MD, MSc; the Osteoporosis Methodology Group; and the Osteoporosis Research Advisory Group IV. Raloxifene Ann Cranney, MD, MSc; Peter Tugwell, MD, MSc; Nicole Zytaruk, RN; Vivian Robinson, MSc; Bruce Weaver, MSc; Jonathan Adachi, MD; George Wells, PhD; Beverley Shea, BScN, MSc; Gordon Guyatt, MD, MSc; the Osteoporosis Methodology Group; and the Osteoporosis Research Advisory Group

Clinical expertise in the era of evidence-based medicine and patient choice.

Abstract: You are caring for a 68 year old man who has hypertension (intermittently controlled) with a remote gastrointestinal bleed and non-valvular atrial fibrillation (NVAF) for 3 months, and an enlarged left atrium (so cardioversion is unlikely). The patient has no history of stroke or transient ischaemic attack. His father experienced a debilitating stroke several years ago and when he learns that his atrial fibrillation places him at higher risk for a stroke, he is visibly distressed. The concepts of evidence-based medicine are evolving as limitations of early models are addressed. In this editorial, we present a new model for evidence-based clinical decision making based on patients' circumstances, patients' preferences and actions, and best research evidence, with a central role for clinical expertise to integrate these components. Traditionally, clinicians have been credited with clinical acumen according to their skills in making a diagnosis and prescribing or administering a treatment. The advent of major investments in biomedical research, leading to new and better tests and treatments, has spurred the development of critical appraisal of the medical literature and evidence-based medicine,1 and application of current best evidence from healthcare research is now an expected adjunct to clinical acumen. Initially, evidence-based medicine focused mainly on determining the best research evidence relevant to a clinical problem or decision and applying that evidence to resolve the issue. This early formulation de-emphasised traditional determinants of clinical decisions, including physiological rationale and individual clinical experience. Subsequent versions of evidence-based decision making have emphasised that research evidence alone is not an adequate guide to action. Rather, clinicians must apply their expertise to assess the patient's problem and must also incorporate the research evidence and the patient's preferences or values before making a management recommendation (figure 1).2 Figure 1 Early model of the key elements for evidence-based clinical decisions Figure …

II. Meta-Analysis of Alendronate for the Treatment of Postmenopausal Women

Abstract: Objective To review the effect of alendronate on bone density and fractures in postmenopausal women. Data source We searched MEDLINE, EMBASE, Current Contents, and the Cochrane Controlled trials registry from 1980 to 1999, and we examined citations of relevant articles and proceedings of international meetings. Study selection We included 11 trials that randomized women to alendronate or placebo and measured bone density for at least 1 yr. Data extraction For each trial, three independent reviewers assessed the methodological quality and abstracted data. Data synthesis The pooled relative risk (RR) for vertebral fractures in patients given 5 mg or more of alendronate was 0.52 [95% confidence interval (CI), 0.43-0.65]. The RR of nonvertebral fractures in patients given 10 mg or more of alendronate was 0.51 (95% CI 0.38-0.69), an appreciably greater effect than for the 5 mg dose. We found a similar reduction in RR across nonvertebral fracture types; in particular, RR reductions for fractures traditionally thought to be "osteoporotic," such as hip and forearm, were very similar to RR reductions for "nonosteoporotic" fractures. Individual studies showed similar results, reflected in the P values of the test of heterogeneity (P = 0.99 for vertebral and 0.88 for nonvertebral fractures). Alendronate produced positive effects on the percentage change in bone density, which increased with both dose and time. After 3 yr of treatment with 10 mg of alendronate or more, the pooled estimate of the difference in percentage change between alendronate and placebo was 7.48% (95% CI 6.12-8.85) for the lumbar spine (2-3 yr), 5.60% (95% CI 4.80-6.39) for the hip (3-4 yr), 2.08% (95% CI 1.53-2.63) for the forearm (2-4 yr), and 2.73% (95% CI 2.27-3.20) for the total body (3 yr). Heterogeneity of the treatment effect of alendronate was not consistently explained by any of our a priori hypotheses; in particular, the effect was very similar in prevention and treatment studies. The pooled RR for discontinuing medication due to adverse effects for 5 mg or greater of alendronate was 1.15 (95% CI 0.93-1.42). The pooled RR for discontinuing medication due to gastro-intestinal (GI) side effects for 5 mg or greater was 1.03 (0.81-1.30, P = 0.83), and the pooled RR for GI adverse effects with continuation of medication was 1.03 (0.98 to 1.07) P = 0.23. Conclusions Alendronate increases bone density in both early postmenopausal women and those with established osteoporosis while reducing the rate of vertebral fracture over 2-3 yr of treatment. Reductions in nonvertebral fractures are evident among postmenopausal women without prevalent fractures and have bone mineral density (BMD) levels below the World Health Organization threshold for osteoporosis. The impact on fractures appears consistent across all fracture types, casting doubt on traditional distinctions between osteoporotic and nonosteoporotic fractures.

Physicians' and patients' choices in evidence based practice

Abstract: Acriticism directed at evidence based medicine is that it ties the hands of practitioners and robs patients of their personal choices in reaching a decision about optimal care.1 There are many barriers to implementing health research in practice,2–4 but, conceptually at least, tying clinical hands and robbing patients of their choices are not among them. Rather, patients' preferences were incorporated into the first model of evidence based medicine5 and their importance has been underscored in a recent revision, depicted in the figure. In this figure, clinical decisions must include consideration of, firstly, the patient's clinical and physical circumstances to establish what is wrong and what treatment options are available. Secondly, the latter need to be …

Clinical expertise in the era of evidence-based medicine and patient choice

Abstract: You are caring for a 68 year old man who has hypertension (intermittently controlled) with a remote gastrointestinal bleed and non-valvular atrial fibrillation (NVAF) for 3 months, and an enlarged left atrium (so cardioversion is unlikely). The patient has no history of stroke or transient ischaemic attack. His father experienced a debilitating stroke several years ago and when he learns that his atrial fibrillation places him at higher risk for a stroke, he is visibly distressed. The concepts of evidence-based medicine are evolving as limitations of early models are addressed. In this editorial, we present a new model for evidence-based clinical decision making based on patients' circumstances, patients' preferences and actions, and best research evidence, with a central role for clinical expertise to integrate these components. Traditionally, clinicians have been credited with clinical acumen according to their skills in making a diagnosis and prescribing or administering a treatment. The advent of major investments in biomedical research, leading to new and better tests and treatments, has spurred the development of critical appraisal of the medical literature and evidence-based medicine,1 and application of current best evidence from healthcare research is now an expected adjunct to clinical acumen. Initially, evidence-based medicine focused mainly on determining the best research evidence relevant to a clinical problem or decision and applying that evidence to resolve the issue. This early formulation de-emphasised traditional determinants of clinical decisions, including physiological rationale and individual clinical experience. Subsequent versions of evidence-based decision making have emphasised that research evidence alone is not an adequate guide to action. Rather, clinicians must apply their expertise to assess the patient's problem and must also incorporate the research evidence and the patient's preferences or values before making a management recommendation (figure 1).2 Figure 1 Early model of the key elements for evidence-based clinical decisions Figure …

VII. Meta-Analysis of Calcium Supplementation for the Prevention of Postmenopausal Osteoporosis

Abstract: Objective To summarize controlled trials examining the effect of calcium on bone density and fractures in postmenopausal women. Data source We searched MEDLINE and EMBASE up to 1998 and the Cochrane Controlled Register up to 2000, and we examined citations of relevant articles and proceedings of international meetings. We contacted osteoporosis investigators to identify additional studies, and primary authors for unpublished data. Study selection We included 15 trials (1806 patients) that randomized postmenopausal women to calcium supplementation or usual calcium intake in the diet and reported bone mineral density of the total body, vertebral spine, hip, or forearm, or recorded the number of fractures, and followed patients for at least 1 yr. Data extraction For each trial, three independent reviewers assessed the methodological quality and extracted data. Data synthesis We found calcium to be more effective than placebo in reducing rates of bone loss after two or more years of treatment. The pooled difference in percentage change from baseline was 2.05% [95% confidence interval (CI) 0.24-3.86] for total body bone density, 1.66% (95% CI 0.92-2.39) for the lumbar spine, 1.64% (95% CI 0.70-2.57) for the hip, and 1.91% (95% CI 0.33-3.50) for the distal radius. The relative risk (RR) of fractures of the vertebrae was 0.77, with a wide CI (95% CI 0.54-1.09); the RR for nonvertebral fractures was 0.86 (95% CI 0.43-1.72). Conclusions Calcium supplementation alone has a small positive effect on bone density. The data show a trend toward reduction in vertebral fractures, but do not meaningfully address the possible effect of calcium on reducing the incidence of nonvertebral fractures.

V. Meta-Analysis of the Efficacy of Hormone Replacement Therapy in Treating and Preventing Osteoporosis in Postmenopausal Women

Abstract: Objective To review the effect of hormone replacement therapy (HRT) on bone density and fractures in postmenopausal women. Data source We searched MEDLINE and EMBASE from 1966 to 1999, the Cochrane Controlled Register, citations of relevant articles, and proceedings of international meetings for eligible randomized controlled trials. We contacted osteoporosis investigators to identify additional studies, and primary authors for unpublished data. Study selection We included 57 studies that randomized postmenopausal women to HRT or a control (placebo or calcium/vitamin D) and were of at least 1 yr in duration. Seven of these studies reported fractures. Data abstraction For each study, three independent reviewers assessed the methodological quality and abstracted the data. Data synthesis HRT showed a trend toward reduced incidence of vertebral fractures [relative risk (RR) 0.66, 95% confidence interval (CI) 0.41-1.07; 5 trials] and nonvertebral fractures (RR 0.87, 95% CI 0.71-1.08; 6 trials). HRT had a consistent effect on bone mineral density (BMD) at all sites. The difference between HRT and control in the percent change in bone density at 2 yr was 6.76 (5.83, 7.89; 21 trials) at the lumbar spine and 4.53 (3.68, 5.36; 14 trials) and 4.12 (3.45, 4.80; 9 trials) at the forearm and femoral neck, respectively. Conclusions HRT has a consistent, favorable and large effect on bone density at all sites. The data show a nonsignificant trend toward a reduced incidence in vertebral and nonvertebral fractures.

III. Meta-Analysis of Risedronate for the Treatment of Postmenopausal Osteoporosis

Abstract: Objective: To review the effect of risedronate on bone density and fractures in postmenopausal women Data Sources: We searched MEDLINE from 1966 to the end of 2000 and examined citations of relevant articles and the proceedings of international osteoporosis meetings Study Selection: We included eight randomized, placebo-controlled trials of postmenopausal women receiving risedronate or placebo with a follow-up of at least one year and providing data on bone density or fracture rate Data Extraction: For each trial, two independent reviewers assessed the methodological quality and abstracted data Data Synthesis: The major methodological limitation of the trials was the loss to follow-up, which was over 20% in most trials and over 35% in the largest study However, the magnitude of the treatment effect was unrelated to loss to follow-up, and in one of the largest trials, more high-risk patients were lost to follow-up in the control than in the treatment group The pooled relative risk (RR) for vertebral fractures in women given 25 mg or more of risedronate was 064 [95% confidence interval (CI) 054, 077] The pooled RR of nonvertebral fractures in patients given 25 mg or more of risedronate was 073 (95% CI 061, 087) Risedronate produced positive effects on the percentage change in bone density of the lumbar spine, combined forearm, and femoral neck that were generally larger with the 5-mg daily dose than with cyclical administration or the 25-mg dose The pooled estimate of the difference in percentage change between 5 mg risedronate and placebo after the final year of treatment (15-3 yr) was 454% (95% CI 412, 497) for the lumbar spine, and 275% (95% CI 232, 317) at the femoral neck Conclusions: Risedronate substantially reduces the risk of both vertebral and nonvertebral fractures This fracture reduction is accompanied by an increase in bone density of the lumbar spine and femoral neck in both early postmenopausal women and those with established osteoporosis

Meta-analyses of therapies for postmenopausal osteoporosis. VIII: Meta-analysis of the efficacy of vitamin D treatment in preventing osteoporosis in postmenopausal women.

Abstract: OBJECTIVE To review the effect of vitamin D on bone density and fractures in postmenopausal women. DATA SOURCE We searched MEDLINE and EMBASE from 1966 to 1999 and examined citations of relevant articles and proceedings of international meetings. We contacted osteoporosis investigators and primary authors to identify additional studies and to obtain unpublished data. STUDY SELECTION We included 25 trials that randomized women to standard or hydroxylated vitamin D with or without calcium supplementation or a control and measured bone density or fracture incidence for at least 1 yr. DATA EXTRACTION For each trial, three independent reviewers assessed the methodological quality and abstracted data. DATA SYNTHESIS Vitamin D reduced the incidence of vertebral fractures [relative risk (RR) 0.63, 95% confidence interval (CI) 0.45-0.88, P < 0.01) and showed a trend toward reduced incidence of nonvertebral fractures (RR 0.77, 95% CI 0.57-1.04, P = 0.09). Most patients in the trials that evaluated vertebral fractures received hydroxylated vitamin D, and most patients in the trials that evaluated nonvertebral fractures received standard vitamin D. Hydroxylated vitamin D had a consistently larger impact on bone density than did standard vitamin D. For instance, total body differences in percentage change between hydroxylated vitamin D and control were 2.06 (0.72, 3.40) and 0.40 (-0.25, 1.06) for standard vitamin D. At the lumbar spine and forearm sites, hydroxylated vitamin D doses above 50 microg yield larger effects than lower doses. Vitamin D resulted in an increased risk of discontinuing medication in comparison to control as a result of either symptomatic adverse effects or abnormal laboratory results (RR 1.37, 95% CI 1.01-1.88), an effect that was similar in trials of standard and hydroxylated vitamin D. CONCLUSIONS Vitamin D decreases vertebral fractures and may decrease nonvertebral fractures. The available data are uninformative regarding the relative effects of standard and hydroxylated vitamin D.

Treatment of acute Achilles tendon ruptures: a systematic overview and metaanalysis.

Abstract: A quantitative systematic review of randomized and quasirandomized trials was conducted to determine the effect of surgical versus conservative treatment of acute Achilles tendon ruptures on rates of rerupture. Secondary outcomes included deep infection rates, return to normal function, and minor complaints. A search of computerized databases was conducted to locate clinical studies published from 1969 to 2000. Additional studies were located through hand searches of major orthopaedic journals, bibliographies of major orthopaedic texts, and personal files. Of the 273 citations initially identified, 11 proved potentially eligible, and six met all eligibility criteria. Three investigators independently graded study quality and abstracted relevant data. Among the studies, surgical repair revealed a significant reduction in the risk of rerupture when compared with conservative treatment. Alternatively, the risk of infection with surgical repair was significantly increased. Pooled analysis of studies did not reveal any difference in the risk of minor complaints or return to normal function between surgical repair and conservatively treated groups. Surgical treatment significantly reduces the risk of Achilles tendon rerupture, but increases the risk of infection, when compared with conservative therapy. Wide confidence intervals around the estimates of risk reduction suggest a large trial is needed to establish risks and benefits.

A lack of consensus in the assessment of fracture healing among orthopaedic surgeons

Abstract: BackgroundThe assessment of fracture healing is both a clinically relevant and frequently used outcome measure following lower extremity trauma. However, it remains uncertain whether there is a consensus in the assessment of fracture healing among orthopaedic surgeons. Variability in the assessment

A systematic review and meta-analysis of studies comparing mortality rates of private for-profit and private not-for-profit hospitals

Abstract: Background: Canadians are engaged in an intense debate about the relative merits of private for-profit versus private not-for-profit health care delivery. To inform this debate, we undertook a systematic review and meta-analysis of studies comparing the mortality rates of private for-profit hospitals and those of private not-for-profit hospitals. Methods: We identified studies through an electronic search of 11 bibliographical databases, our own files, consultation with experts, reference lists, PubMed and SciSearch. We masked the study results before determining study eligibility. Our eligibility criteria included observational studies or randomized controlled trials that compared private for-profit and private not-for-profit hospitals. We excluded studies that evaluated mortality rates in hospitals with a particular profit status that subsequently converted to the other profit status. For each study, we calculated a relative risk of mortality for private for-profit hospitals relative to private not-for-profit hospitals and pooled the studies of adult populations that included adjustment for potential confounders (e.g., teaching status, severity of illness) using a random effects model. Results: Fifteen observational studies, involving more than 26 000 hospitals and 38 million patients, fulfilled the eligibility criteria. In the studies of adult populations, with adjustment for potential confounders, private for-profit hospitals were associated with an increased risk of death (relative risk [RR] 1.020, 95% confidence interval [CI] 1.003–1.038; p = 0.02). The one perinatal study with adjustment for potential confounders also showed an increased risk of death in private for-profit hospitals (RR 1.095, 95% CI 1.050–1.141; p < 0.0001). Interpretation: Our meta-analysis suggests that private for-profit ownership of hospitals, in comparison with private not-for-profit ownership, results in a higher risk of death for patients.

VI. Meta-Analysis of Calcitonin for the Treatment of Postmenopausal Osteoporosis

Abstract: Objective: To review the effect of calcitonin on bone density and fractures in postmenopausal women. Data Source: We searched MEDLINE and EMBASE from 1966 to 2000 and examined citations of relevant articles and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies and primary authors for unpublished data. Study Selection: We included 30 studies that randomized women to calcitonin or an alternative (placebo or calcium and/or vitamin D) and measured bone density or fracture incidence for at least 1 yr. Data Extraction: For each trial, three independent reviewers assessed the methodological quality and abstracted data. Data Synthesis: Calcitonin reduced the incidence of vertebral fractures, with a pooled relative risk (RR) of 0.46 [95% confidence interval (CI) 0.25-0.87, P = 0.02, n = 1404, 4 trials]. However, the RR from the one relatively large randomized controlled trial (RCT) was 0.79 (95% CI 0.62-1.00, P = 0.05, n = 1108). For nonvertebral fractures, the pooled RR was 0.52 (95% CI 0.22-1.23, P = 0.14, n = 1481, 3 trials). Once again, the single large trial showed a less impressive effect than the smaller trials (RR 0.80, 95% CI 0.59-1.09, P = 0.16, n = 1245). For bone density of the lumbar spine, the pooled weekly dose of 250 to 2800 IU per week resulted in significant increase in the weighted mean difference (WMD) of 3.74 (2.04-5.43, P < 0.01, n = 2260, 24 trials). The combined forearm showed a similar effect, with a WMD of 3.02 (95% CI 0.98-5.07, P < 0.01, n = 468, 9 trials). At the femoral neck, the pooled weighted mean difference showed a nonsignificant trend toward benefit, WMD 3.80 (95% CI-0.32-7.91, P = 0.07, 9 trials, n = 513). Methodologically weaker studies tended to show greater effects on bone density, and the lumbar spine results suggested the possibility of publication bias. Conclusions: Calcitonin likely increases bone density in postmenopausal women predominantly at the lumbar spine and forearm for weekly doses of greater than 250 IU, although the true effect may be smaller than the pooled estimate would suggest. Calcitonin likely reduces the risk of vertebral fracture; its effect on nonvertebral fracture remains uncertain.

Family impact of child oral and oro-facial conditions.

Abstract: – Objectives: The aim of this study was to develop and evaluate the Family Impact Scale, a measure of the family impact of child oral and oro-facial disorders. This formed one component of the Child Oral Health Quality of Life Instrument©. Methods: The scale was developed using a process described by Guyatt et al. (1987) and Juniper et al. (1996). An item pool was developed using a review of existing child health status and family impact questionnaires, interviews with 41 parents–caregivers of children with paedodontic, orthodontic and oro-facial conditions and discussions with dental specialists. The resulting pool of 21 items was used in an item impact study in which 93 parents–caregivers provided data on the frequency and importance of these items. The 14 items identified most frequently or rated the most important were selected for the final questionnaire. The discriminant and construct validity and internal consistency reliability of this 14-item scale were assessed in a study of 266 parents–caregivers from the three clinical groups. Seventy-nine of these participants completed a second copy of the questionnaire to facilitate assessment of test–retest reliability. Results: Family Impact Scale scores ranged from 0 to 33, indicating that the measure was sensitive to variations in family impact. Floor effects were minimal with only 10.2% of subjects having a score of zero and there were no ceiling effects, that is, subjects with maximum scores. Almost three-quarters of parents–caregivers reported some family impact ‘sometimes’ or ‘often/everyday’ over the previous 3 months. Impact on parental or family activities of this frequency was reported by 53.0%, impact on parental emotions by 44.0%, conflict in the family by 31.6% and financial difficulties by 31.2%. The measure and its component items were reasonably good at discriminating between the three clinical groups included in the study and showed good construct validity. It had excellent internal consistency reliability with a Cronbach's alpha of 0.83 and was reproducible for parent–caregivers who reported that their child's condition was stable (ICC = 0.80). Conclusions: The study provides some data to suggest that child oral and oro-facial conditions have a pervasive impact on the family. The Family Impact Scale had good technical properties. Its evaluative properties need to be tested in longitudinal studies.

Clinical expertise in the era of evidence-based medicine and patient choice (editorial)

Abstract: Scenario You are caring for a 68 year old man who has hypertension (intermittently controlled) with a remote gastrointestinal bleed and non-valvular atrial fibrillation (NVAF) for 3 months, and an enlarged left atrium (so cardioversion is unlikely). The patient has no history of stroke or transient ischaemic attack. His father experienced a debilitating stroke several years ago and when he learns that his atrial fibrillation places him at higher risk for a stroke, he is visibly distressed.

An observational study of orthopaedic abstracts and subsequent full-text publications.

Abstract: Background: Research abstracts are frequently referenced in orthopaedic textbooks and influence orthopaedic care. However, little is known about the quality of information provided in the abstracts, the frequency of publication of complete papers after presentation of abstracts, or any discrepancies between abstracts and published papers. The objective of this study was to determine the quality of information provided in orthopaedic abstracts, rates of publication of full-text articles after presentation of abstracts, predictors of publication of full-text articles, and consistency between abstracts and full-text articles. Methods: We retrieved all abstracts from the 1996 scientific program of the sixty-third Annual Meeting of the American Academy of Orthopaedic Surgeons. For each abstract, we recorded the completeness of reporting and key features of the study design, conduct, analysis, and interpretation. A computerized Medline and PubMed search established whether the abstract had been followed by publication of a full-text article. Finally, we evaluated the consistency of reporting between abstracts and final publications. Results: The program included 465 abstracts, 66% of which were on prognostic studies. All abstracts described the study design, and 70.7% of the designs were observational. Key methodological issues were reported in less than half of the abstracts, and information on data analysis was reported in <15%. One hundred and fifty-nine (34%) of the 465 abstracts were followed by publication of a full-text article. The mean time to publication (and standard deviation) was 17.6 ±; 12 months (range, one to fifty-six months). Inconsistencies between the abstract and the full-text article included the primary outcome measure, which differed 14% of the time, and the results, which differed 19% of the time. Conclusions: Two-thirds of the orthopaedic abstracts in this sample were not followed by publication of a full-text paper. The overall quality of reporting in abstracts proved inadequate, and inconsistencies between the final published paper and the original abstract occurred frequently. The routine use of abstracts as a guide to orthopaedic practice needs to be reconsidered.

Can we individualize the ‘number needed to treat’? An empirical study of summary effect measures in meta-analyses

Abstract: Background Meta-analyses summarize the magnitude of treatment effect using a number of measures of association, including the odds ratio (OR), risk ratio (RR), risk difference (RD) and/or number needed to treat (NNT). In applying the results of a meta-analysis to individual patients, some textbooks of evidence-based medicine advocate individualizing NNT, based on the RR and the patient's expected event rate (PEER). This approach assumes constant RR but no empirical study to date has examined the validity of this assumption. Methods We randomly selected a subset of meta-analyses from a recent issue of the Cochrane Library (1998, Issue 3). When a meta-analysis pooled more than three randomized controlled trials (RCT) to produce a summary measure for an outcome, we compared the OR, RR and RD of each RCT with the corresponding pooled OR, RR and RD from the meta-analysis of all the other RCT. Using the conventional P-value of 0.05, we calculated the percentage of comparisons in which there were no statistically significant differences in the estimates of OR, RR or RD, and refer to this percentage as the 'concordance rate'. Results For each effect measure, we made 1843 comparisons, extracted from 55 meta-analyses. The random effects model OR had the highest concordance rate, closely followed by the fixed effects model OR and random effects model RR. The minimum concordance rate for these indices was 82%, even when the baseline risk differed substantially. The concordance rates for RD, either fixed effects or random effects model, were substantially lower (54-65%). Conclusions The fixed effects OR, random effects OR and random effects RR appear to be reasonably constant across different baseline risks. Given the interpretational and arithmetic ease of RR, clinicians may wish to rely on the random effects model RR and use the PEER to individualize NNT when they apply the results of a meta-analysis in their practice.

Evaluating the Teaching of Evidence-Based Medicine

Abstract: AN INCREASING NUMBER OF MEDICAL SCHOOLS AND residency programs are instituting curricula for teaching the principles and practice of evidencebased medicine (EBM). For example, 95% of US internal medicine residency programs have journal clubs and 37% of US and Canadian internal medicine residencies have time dedicated for EBM. Curricula based on EBM are increasingly popular in residency programs in other specialties, including family medicine, pediatrics, obstetrics/ gynecology, and surgery. Despite the widespread teaching of EBM, however, most of what is known about the outcomes of evidence-based curricula relies on observational data. Although evaluation of the quality of research evidence is a core competency of EBM, the quantity and quality of the evidence for effectively teaching EBM are poor. Ironically, if one were to develop guidelines for how to teach EBM based on these results, they would be based on the lowest level of evidence. There are several reasons why the quality of the evidence for teaching EBM is so weak. Many of these problems are related to the limitations in educational research in general. First, quantitative research methods may be inadequate to capture the complexity of an educational system. Second, students and residents change frequently, making it difficult to retain a consistent sample. Third, the time allotted for a given intervention may be brief in the context of the overall medical curriculum. Fourth, educational institutions may be hesitant to pay students as research participants or to allocate them to unproved educational interventions. Fifth, because most educational interventions are unique to specific institutions, assessment of their effectiveness is usually limited by small sample sizes. Furthermore, even if such interventions could be instituted across multiple institutions, the problems of standardization and cointervention would be particularly challenging. Sixth, perhaps because they are simplest to measure, the most frequently reported outcomes are subjective variables such as satisfaction or self-reported changes in attitudes or knowledge, rather than more important assessments of objectively measured clinical skills or improved patient outcomes. Finally, granting agencies do not give priority to educational investigations, making it difficult to undertake definitive multicenter studies. Educators who have struggled to evaluate educational interventions will find these issues all too familiar. With the increasing prevalence of EBM teaching, however, highquality evidence is more important than ever. Assessment of EBM teaching has also presented some unique problems. For instance, we originally defined evidence-based practice in terms of 4 basic competencies: (1) recognition of a patient problem and construction of a structured clinical question; (2) ability to efficiently and effectively search the medical literature to retrieve the best available evidence to answer the clinical question; (3) critical appraisal of the evidence; and (4) integration of the evidence with all aspects of individual patient decision making to determine the best clinical care for the patient. Although these 4 skills were the most commonly reported curricular objectives in 99 internal medicine residencies that teach EBM, almost all the research on EBM education has focused exclusively on the third item: teaching critical appraisal skills. Examining this literature may yield useful insights into the difficulties of EBM educational research. Since critical appraisal skills involve the ability to differentiate strong from weak research methods, one might expect that this research would be of relatively high quality. In fact, most of these studies are methodologically weak. Using broad criteria to identify any reports of a graduate (residency) EBM curricula, Green identified 18 reports published between 1980 and 1997. Of these, 72% used a traditional journal club format to teach critical appraisal skills. Only 7 of the 18 studies evaluated the effectiveness of their intervention. Five of these 7 studies compared intervention with control (only 1 with randomized design); only 2 of 7 studies used any blinding. Of these 5 controlled studies, 2 used a validated outcome measure to evaluate critical appraisal skills. Measurement of behavioral change relied on self-report in all 5 studies, and none examined patient outcomes. Most reports did not evaluate their intervention

Interobserver and intraobserver variation in the assessment of the healing of tibial fractures after intramedullary fixation

Abstract: The reliability of the radiological assessment of the healing of tibial fractures remains undetermined. We examined the inter- and intraobserver agreement of the healing of such fractures among four orthopaedic trauma surgeons who, on two separate occasions eight weeks apart, independently assessed the radiographs of 30 patients with fractures of the tibial shaft which had been treated by intramedullary fixation. The radiographs were selected from a database to represent fractures at various stages of healing. For each radiograph, the surgeon scored the degree of union, quantified the number of cortices bridged by callus or with a visible fracture line, described the extent and quality of the callus, and provided an overall rating of healing. The interobserver chance-corrected agreement using a quadratically weighted kappa (κ) statistic in which values of 0.61 to 0.80 represented substantial agreement were as follows: radiological union scale (κ = 0.60); number of cortices bridged by callus (κ = 0.75); number of cortices with a visible fracture line (κ = 0.70); the extent of the callus (κ = 0.57); and general impression of fracture healing (κ = 0.67). The intraobserver agreement of the overall impression of healing (κ = 0.89) and the number of cortices bridged by callus (κ = 0.82) or with a visible fracture line (κ = 0.83) was almost perfect. There are no validated scales which allow surgeons to grade fracture healing radiologically. Among those examined, the number of cortices bridged by bone appears to be a reliable, and easily measured radiological variable to assess the healing of fractures after intramedullary fixation.

Comparison of mortality between private for-profit and private not-for-profit hemodialysis centers: a systematic review and meta-analysis.

Abstract: ContextPrivate for-profit and private not-for-profit dialysis facilities provide the majority of hemodialysis care in the United States. There has been extensive debate about whether the profit status of these facilities influences patient mortality.ObjectiveTo determine whether a difference in adjusted mortality rates exists between hemodialysis patients receiving care in private for-profit vs private not-for-profit dialysis centers.Data SourcesWe searched 11 bibliographic databases, reviewed our own files, and contacted experts in June 2001–January 2002. In June 2002, we also searched PubMed using the "related articles" feature, SciSearch, and the reference lists of all studies that fulfilled our eligibility criteria.Study SelectionWe included published and unpublished observational studies that directly compared the mortality rates of hemodialysis patients in private for-profit and private not-for-profit dialysis centers and provided adjusted mortality rates. We masked the study results prior to determining study eligibility, and teams of 2 reviewers independently evaluated the eligibility of all studies. Eight observational studies that included more than 500 000 patient-years of data fulfilled our eligibility criteria.Data ExtractionTeams of 2 reviewers independently abstracted data on study characteristics, sampling method, data sources, and factors controlled for in the analyses. Reviewers resolved disagreements by consensus.Data SynthesisThe studies reported data from January 1, 1973, through December 31, 1997, and included a median of 1342 facilities per study. Six of the 8 studies showed a statistically significant increase in adjusted mortality in for-profit facilities, 1 showed a nonsignificant trend toward increased mortality in for-profit facilities, and 1 showed a nonsignificant trend toward decreased mortality in for-profit facilities. The pooled estimate, using a random-effects model, demonstrated that private for-profit dialysis centers were associated with an increased risk of death (relative risk, 1.08; 95% confidence interval, 1.04-1.13; P<.001). This relative risk suggests that there are annually 2500 (with a plausible range of 1200-4000) excessive premature deaths in US for-profit dialysis centers.ConclusionsHemodialysis care in private not-for-profit centers is associated with a lower risk of mortality compared with care in private for-profit centers.

Assessing Clinical Significance in Measuring Oncology Patient Quality of Life: Introduction to the Symposium, Content Overview, and Definition of Terms

Abstract: The Clinical Significance Consensus Meeting Group of the Symposium on the Clinical Significance of Quality-of-Life Measures in Cancer Patients produced 6 articles regarding the clinical significance of quality of life (QOL) assessments in oncology. The 6 articles deal with the methods used to date: group-vs-individual clinical significance; single items vs summated scores; patient, clinician, and population perspectives; assessment of changes over time; and communication of results. The articles were produced by a team of 30 QOL research experts assembled in a consensus writing meeting held at the Mayo Clinic, Rochester, Minn, October 6 and 7, 2000. This introduction describes the need for the articles, definitions of key terms, and plans for the future. It is hoped that this series of articles will serve as a resource for individuals conducting cancer QOL research and for clinicians considering incorporation of QOL assessment in the treatment of patients with neoplastic diseases. A secondary goal is to stimulate further discussion and research in the interpretation of QOL assessments.

IV. Meta-Analysis of Raloxifene for the Prevention and Treatment of Postmenopausal Osteoporosis

Abstract: A. Abstract Objective: To review the effect of raloxifene on bone density and fractures in postmenopausal women. Data Source: We searched MEDLINE from 1966 to 2000 and examined citations of relevant articles and the proceedings of international osteoporosis meetings. Study Selection: We included seven trials that randomized women to raloxifene or placebo, with both groups receiving similar calcium and vitamin D supplementation, and measured bone density for at least one year. Data Extraction: For each trial, three independent reviewers abstracted the data and assessed the methodological quality using a validated tool. Data Synthesis: Data from one large dominating trial suggest a reduction in vertebral fractures with a relative risk (RR) of 0.60 [95% confidence interval (CI) 0.50 – 0.70, P 0.01]. The RR of nonvertebral fractures in patients given 60 mg or more of raloxifene in the larger study was 0.92 (95% CI 0.79 –1.07, P 0.27). Raloxifene resulted in positive effects on the percentage change in bone density, which increased over time and was independent of dose. At the final year, point estimates and 95% CIs for the differences in percent change in bone density (95% CI) between raloxifene and placebo groups were 1.33 (95% CI 0.37–2.30) for total body, 2.51 (95% CI 2.21–2.82) for lumbar spine, 2.05 (95% CI 0.71–3.39) for combined forearm, and 2.11 (95% CI 1.68 –2.53) for combined hip (P 0.01 at all four sites). Results were similar across studies, and formal tests of heterogeneity did not approach conventional statistical significance. Raloxifene slightly increased rates of withdrawal from therapy as a result of adverse effects (RR 1.15, 95% CI 1.00 – 1.33, P 0.05). The pooled RR was significant for hot flashes 1.46 (95% CI 1.23–1.74, P 0.01) and nonsignificant for leg cramps 1.64 (95% CI 0.84 –3.20, P 0.15). Conclusion: Raloxifene increases bone density, and the effect increases over 2 yr. The data suggest a positive impact of raloxifene on vertebral fractures. There was little effect of raloxifene on nonvertebral fractures. B. Background