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Gordon Guyatt

Publications and source records attributed to Gordon Guyatt.

87 records · Page 5Linked to original sources
PubMed2002

Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women.

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.

Alendronate↗
PubMed2002

Meta-analyses of therapies for postmenopausal osteoporosis. III. Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis.

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 2.5 mg or more of risedronate was 0.64 [95% confidence interval (CI) 0.54, 0.77]. The pooled RR of nonvertebral fractures in patients given 2.5 mg or more of risedronate was 0.73 (95% CI 0.61, 0.87). 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 2.5-mg dose. The pooled estimate of the difference in percentage change between 5 mg risedronate and placebo after the final year of treatment (1.5-3 yr) was 4.54% (95% CI 4.12, 4.97) for the lumbar spine, and 2.75% (95% CI 2.32, 3.17) 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.

Etidronic Acid↗
PubMed2002

Meta-analyses of therapies for postmenopausal osteoporosis. IV. Meta-analysis of raloxifene for the prevention and treatment of postmenopausal osteoporosis.

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.

Female↗
PubMed2002

Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women.

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.

Estrogen Replacement Therapy↗
PubMed2002

Meta-analyses of therapies for postmenopausal osteoporosis. VI. Meta-analysis of calcitonin for the treatment of postmenopausal osteoporosis.

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.

Calcitonin↗
PubMed2002

Meta-analyses of therapies for postmenopausal osteoporosis. VII. Meta-analysis of calcium supplementation for the prevention of postmenopausal osteoporosis.

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.

Calcium↗
PubMed2002

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

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.

Female↗
PubMed2002

Meta-analyses of therapies for postmenopausal osteoporosis. IX: Summary of meta-analyses of therapies for postmenopausal osteoporosis.

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.

Bone Density↗
PubMed2002

Effect of air filtration systems on asthma: a systematic review of randomized trials.

STUDY OBJECTIVES: To systematically review the evidence of randomized trials evaluating the effects of residential air filtration systems on patients with asthma. DATA SOURCES: We searched for published and unpublished studies using MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Collaboration. We reviewed all reference lists for additional articles of relevance, and contacted experts in the field and air filter manufacturers. STUDY SELECTION: We identified 10 relevant randomized controlled trials that examined the influence of a residential air filtration system on patients with asthma. DATA EXTRACTION: In duplicate and independently, we abstracted data on the methodologic quality, population, intervention, and outcomes. DATA SYNTHESIS: Five of 10 studies enrolled adults only. One study included children only. The sample size ranged from 9 to 45 participants in each study, for a total of 216 patients across all studies. Two studies reported a statistically significant decrease in airway responsiveness associated with air filter utilization. Air filters were associated with significantly lower total symptom scores (weighted mean difference of 0.47; 95% confidence interval [CI], 0.69 to 0.25) on a 10-point scale, and lower sleep disturbance score (weighted mean difference of 0.93; 95% CI, 1.44 to 0.42); however, heterogeneity of results weakens the inferences from these trials. Air filtration systems were not associated with any differences in medication use or morning peak expiratory flow values. None of these trials employed validated scales to measure clinical symptoms or quality of life. CONCLUSIONS: Among patients with allergies and asthma, use of air filters is associated with fewer symptoms. Rigorous sufficiently powered randomized clinical trials are needed to more precisely define the influence of air filtration on health-related quality of life and symptom control for asthmatic patients.

Air Conditioning↗
PubMedDate not supplied

Effect of coronary artery bypass graft surgery on older women's health-related quality of life.

OBJECTIVE: The purpose of this study was to determine if health-related quality of life (HRQL) improves after coronary artery bypass graft (CABG) surgery in older women. DESIGN: The study design was longitudinal observational. SETTING: The study took place in a tertiary-care teaching hospital in Hamilton, Ontario, Canada. PATIENTS: Study participants included 34 women 61 years or older who had elective or urgent CABG surgery for the first time. OUTSOME MEASURES: The 2 measures of HRQL were the Medical Outcomes Study Short Form-36 and the Feeling Thermometer (FT). The Short Form-36 is composed of 8 subscales that are summarized into the Physical and the Mental Composite Scores. The FT is a utility measure that rates patients' preferences for different health states. RESULTS: HRQL of older women was improved after CABG surgery: 7.79 points in the physical composite scores (P = .001), 7.26 in the mental composite scores (P = .008), and 29.77 points in the FT scores (P < .001). Age was a predictor of HRQL, with older women demonstrating poorer physical and better mental HRQL 3 months after the operation. CONCLUSIONS: HRQL of older women is improved significantly as early as 3 months after CABG surgery.

Aged↗
PubMedDate not supplied

Number needed to treat in cardiac rehabilitation.

Clinicians, patients, and health policy-makers must judge whether healthcare interventions are worth the side effects, inconvenience, and costs. The number needed to treat (NNT) provides an estimate of the number of patients who need to be treated to attain an additional favorable outcome, or to prevent an additional adverse outcome, and is the reciprocal of the absolute risk reduction. The closer the NNT is to 1.0-meaning that every patient who is treated achieves a benefit-the more effective the treatment. Traditionally, mortality has been considered a primary outcome measure of the effectiveness of cardiac rehabilitation and, if the event rates in two groups (ie, rehabilitation and usual care) are known, the absolute risk reduction can be calculated and the NNT estimated. Mortality data were derived from three meta-analyses of cardiac rehabilitation trials: one published in 1988 (n = 3614), one in 1989 (n = 4247), and one in 2001 (n = 7683). The respective estimated NNT for mortality in the meta-analyses were 32, 46, and 72 (95% confidence intervals [95% CI] 19, 1403). Improved exercise tolerance and patient-perceived health-related quality of life (HRQL) are also considered important and attainable outcomes of cardiac rehabilitation but are continuous, not dichotomous, variables. If the minimal important difference for a continuous outcome is known, then the proportions of patients who improve, remain the same, or deteriorate can be determined and the NNT estimated. Exercise tolerance and HRQL data from two randomized controlled trials of 8 weeks of rehabilitation after myocardial infarction, the Cardiac Rehabilitation in Advanced Age trial (CR-AGE; n = 270) and the McMaster Early Rehabilitation Study (MERS; n = 201) were used to estimate the NNT. In CR-AGE, the improvement in exercise tolerance was significantly greater in the rehabilitation than usual care group and the estimated NNT was 5 (95% CI 3, 13). The generic global HRQL score increased significantly in CR-AGE with rehabilitation with an estimated NNT of 12 (95% CI 5, 26) but, as the subscale group differences were not significant, the NNT was not estimated. The NNT for exercise tolerance was not estimated in MERS, as the group difference was not significant. On the other hand, specific HRQL scores in MERS increased significantly with rehabilitation giving an estimated NNT for global HRQL of 6 (95% CI 3, 21) and 6 to 10 for the HRQL sub-scales. The data and the estimated NNT from the meta-analyses of cardiac rehabilitation in large numbers of patients suggest a limited mortality effect, probably reflecting current cardiology practice. The estimated NNT from the two trials with relatively small numbers of patients suggest inconsistent exercise tolerance effects and a relatively short duration for improved HRQL. Along with the classic reporting scales, information about clinical and laboratory variables, and patient preferences, the NNT is a useful additional measure of effectiveness that provides both clinicians and patients with information about the impact of cardiac rehabilitation as secondary prevention therapy.

Exercise Tolerance↗