Shelley R. Salpeter

Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women

Aim:  To quantify the effects of hormone‐replacement therapy (HRT) on components of the metabolic syndrome in postmenopausal women.

Brief report: Coronary heart disease events associated with hormone therapy in younger and older women. A meta-analysis.

AbstractOBJECTIVE: To assess the effect of hormone therapy (HT) on coronary heart disease (CHD) events in younger and older postmenopausal women. DESIGN: A comprehensive database search identified randomized-controlled trials of HT of at least 6 months’ duration that reported CHD events, defined as myocardial infarction or cardiac death. MEASUREMENTS: The pooled odds ratios (ORs) for CHD events were reported separately for younger and older women, defined as participants with mean time from menopause of less than or greater than 10 years, or mean age less than or greater than 60 years. MAIN RESULTS: Pooled data from 23 trials, with 39,049 participants followed for 191,340 patient-years, showed that HT significantly reduced CHD events in younger women (OR 0.68 [confidence interval (C I), 0.48 to 0.96]), but not in older women (OR 1.03 [CI, 0.91 to 1.16]). Hormone therapy reduced events in younger women compared with older women (OR 0.66 [CI, 0.46 to 0.95]). In older women, HT increased events in the first year (OR 1.47 [CI, 1.12 to 1.92]), then reduced events after 2 years (OR 0.79 [CI, 0.67 to 0.93]). CONCLUSIONS: Hormone therapy reduces the risk of CHD events in younger postmenopausal women. In older women, HT increases, then decreases risk over time.

Cardioselective β-Blockers in Patients with Reactive Airway Disease: A Meta-Analysis

Context Although -blockers improve clinical outcomes in many patients with cardiovascular disease, clinicians sometimes avoid these agents in patients with concomitant lung disease because they fear precipitation of acute bronchospasm. Contribution This meta-analysis of 29 randomized trials shows that cardioselective-blockers (1-blockers), given for a few days to a few weeks, do not significantly worsen pulmonary function or respiratory symptoms and do not lead to increased use of inhalers in patients with mild to moderate reactive (reversible) airway disease. Cautions The studies in this meta-analysis were short, evaluated only cardioselective -blockers, and did not include patients with severe or irreversible airway disease. The Editors -Adrenergic blocking agents, or -blockers, are indicated in the management of angina pectoris, myocardial infarction, hypertension, congestive heart failure, cardiac arrhythmia, and thyrotoxicosis and are given to reduce perioperative complications (1-13). Despite clear evidence of the effectiveness and mortality benefit of these drugs, clinicians are often hesitant to administer them in patients with some common conditions for fear of adverse reactions (14-17). Many patients with reactive airway disease, with or without a chronic obstructive component, have concomitant conditions such as hypertension or cardiac arrhythmias, which necessitate the use of -blockers. However, review articles and practice guidelines usually list asthma and chronic obstructive pulmonary disease (COPD) as contraindications to -blocker use, citing cases of acute bronchospasm during administration of noncardioselective -blockers (6, 10, 18-22). Cardioselective -blockers, or 1-blockers, have greater than 20 times more affinity for 1 receptors than for 2 receptors and in theory should pose much less risk for bronchoconstriction (23). We used data from randomized, blinded, placebo-controlled trials to evaluate the effect of cardioselective 1-blockers on respiratory function in patients with reactive airway disease (defined as asthma or COPD with a reversible obstructive component). We also sought to evaluate the respiratory response to 2-agonists administered after 1-blockers or after placebo in the same participants. This analysis has already been published as a review in the Cochrane Library (24). Methods Patients We chose to evaluate only patients with documented reactive airway disease because these patients are thought to be particularly susceptible to the adverse respiratory effects of -blockers. Patients with COPD are generally at greater risk for ischemic heart disease than are patients with asthma and thus may benefit more from the use of -blockers. This study evaluates a subgroup of patients with a documented chronic obstructive component of disease but was not designed to make recommendations about patients with COPD. A recent meta-analysis evaluated the use of cardioselective -blockers in patients with COPD, given as a single dose or as continued treatment (25). Pooled data from 19 trials demonstrated no adverse effect on FEV1 or respiratory symptoms for 1-blockers compared to placebo, even in patients with severe chronic airway obstruction. Search Strategy A search was performed to identify all relevant published clinical trials that addressed the effects of cardioselective -blockers on airway function in patients with reactive airway disease. Two investigators jointly developed strategies with the help of an information service librarian and the Cochrane Airways Group Trial Search Coordinator. The EMBASE, MEDLINE, and CINAHL databases were searched comprehensively to identify all relevant clinical trials in humans published between 1966 and May 2001. The search was performed by using the Cochrane Airways Group registry to identify randomized, blinded, placebo-controlled trials of reactive airways disease. Terms used in the search were asthma*, bronchial hyperreactivity*, respiratory sounds*, wheez*, obstructive lung disease* and obstructive airway disease*. Trials of -blockers were sought by using the terms adrenergic antagonist*, sympatholytic* and adrenergic receptor block*. Trials were not excluded on the basis of language. The search was further augmented by scanning references of identified articles, reviews, and abstracts at clinical symposia. Study Selection Two investigators independently evaluated studies for inclusion. In choosing articles, investigators were blinded to results but not to journal, author, or institution of studies. The observed interrater agreement for the assessment of inclusion was calculated as a percentage. For all clinical trials identified from the search, investigators determined whether the -blocker used was cardioselective and whether it was considered to have intrinsic sympathomimetic activity (1, 26-36). Studies were evaluated if intravenous or oral cardioselective -blockers were administered as a single dose or as continued treatment lasting 3 days or longer. Single-dose trials were included if 1) FEV1 at rest was reported, either as liters or as a percentage of the normal predicted value at baseline and at follow-up; 2) 2-agonists were withheld for at least 8 hours before initial FEV1 measurement; 3) patients were not selected on the basis of previous response to -blockers; 4) the study was randomized, placebo-controlled, and single- or double-blinded; and 5) only patients with documented reactive airway disease were included. Reactive airway disease was demonstrated by a mean increase of at least 15% in FEV1 in response to 2-agonist, response to methacholine challenge, or presence of asthma as defined by the American Thoracic Society (37). Crossover trials were included if different interventions were administered in random order. We decided a priori that inclusion criteria 3, 4, and 5 would be applied to trials of continued treatment. Studies of continued treatment were included if they did not report FEV1 but instead evaluated the amount of 2-agonist use and respiratory symptoms compared with placebo. Trials were also included if 2-agonists were not withheld during the trial. Assessment of Validity The methodologic quality of each trial was assessed according to the following factors: 1) Was the study randomized? If so, was the randomization procedure adequate, and was allocation concealed? 2) Were the patients and people administering the treatment blinded to the intervention? 3) Were withdrawals and dropouts described, and was the analysis performed on an intention-to-treat basis? On the basis of these criteria, studies were broadly subdivided as all quality criteria met (A), one or more quality criteria only partially met (B), or one or more criteria not met (C). Clinical trials that did not meet criteria for inclusion but gave information on FEV1 response to cardioselective -blockers in patients with reactive airway disease were analyzed separately and used in a sensitivity analysis. These included studies that were not placebo-controlled; did not document asthma criteria; did not give baseline FEV1 data; or, for single-dose studies, did not withhold 2-agonists for 8 hours before measurements. Study Characteristics The main intervention of interest was intravenous or oral cardioselective -blockers versus placebo, given as a single dose or as continued treatment. Administration of a 2-agonist, intravenously or by inhalation, after the study medication or after placebo was also studied. Each 1-blocker used was classified into one of two categories: 1-blockers without intrinsic sympathomimetic activity, and 1-blockers with intrinsic sympathomimetic activity. Data Extraction Two investigators independently extracted data on change in mean group FEV1 in response to placebo or study drug; response of FEV1 to 2-agonist administered after placebo or study drug; symptoms reported during the trial, such as wheezing, dyspnea, or exacerbation of asthma; and, for trials of continued treatment, weekly use of inhaled short-acting 2-agonists. Data Synthesis The ratio of the lowest group FEV1 value after administration of study drug to baseline FEV1 was measured for placebo and active treatment and was recorded as the percentage change from baseline. The placebo response was then subtracted from the treatment response to obtain the net treatment effect, reported as a percentage of the baseline FEV1 value. For response to 2-agonists given after treatment or placebo, the new baseline value was the mean group FEV1 value obtained after study drug but before 2-agonist administration. The net treatment effect was estimated by calculating the ratio of FEV1 measured after agonist administration to the new baseline value for both placebo and active treatment and then subtracting the placeboagonist response from the treatmentagonist response. Whenever possible, the SD for the net treatment effect was calculated from individual-patient data or P values and was then used to derive the SDs for the analysis. Some trials provided SDs for treatment response and placebo response separately. For trials that reported no information on SDs, the average SD was obtained from trials that provided such data, calculated separately for placebo, treatment, and -agonist responses. Sensitivity analyses were performed to evaluate the effect of including these trials by using the lowest and highest available SD in place of the pooled SD and also by excluding these trials from the analysis. The Appendix Table shows the method used to obtain SDs for each trial. The mean treatment effects were pooled to obtain a weighted average of the study means using the fixed-effects model for continuous outcomes (38, 39). Confidence intervals with 95% significance were obtained for the pooled study means. The analysis was performed by using Meta View 4.1 (Cochrane Library software [Update Software, Oxford, United Kingdom]). Results for respiratory symptoms were measured as a risk difference by subtractin

Mortality Associated with Hormone Replacement Therapy in Younger and Older Women: A Meta-analysis

OBJECTIVE: To assess mortality associated with hormone replacement in younger and older postmenopausal women.DESIGN: A comprehensive search of medline, cinahl, and embase databases was performed to identify randomized controlled trials of hormone replacement therapy from 1966 to September 2002. The search was augmented by scanning selected journals through April 2003 and references of identified articles. Randomized trials of greater than 6 months’ duration were included if they compared hormone replacement with placebo or no treatment, and reported at least 1 death.MEASUREMENTS: Outcomes measured were total deaths and deaths due to cardiovascular disease, cancer, or other causes. Odds ratios (OR) for total and cause-specific mortality were reported separately for trials with mean age of participants less than and greater than 60 years at baseline.MAIN RESULTS: Pooled data from 30 trials with 26,708 participants showed that the OR for total mortality associated with hormone replacement was 0.98 (95% confidence interval [CI], 0.87 to 1.12). Hormone replacement reduced mortality in the younger age group (OR, 0.61; CI, 0.39 to 0.95), but not in the older age group (OR, 1.03; CI, 0.90 to 1.18). For all ages combined, treatment did not significantly affect the risk for cardiovascular or cancer mortality, but reduced mortality from other causes (OR, 0.67; CI, 0.51 to 0.88).CONCLUSIONS: Hormone replacement therapy reduced total mortality in trials with mean age of participants under 60 years. No change in mortality was seen in trials with mean age over 60 years.

Meta-analysis: Metformin Treatment in Persons at Risk for Diabetes Mellitus

PURPOSE We performed a meta-analysis of randomized controlled trials to assess the effect of metformin on metabolic parameters and the incidence of new-onset diabetes in persons at risk for diabetes. METHODS We performed comprehensive English- and non-English-language searches of EMBASE, MEDLINE, and CINAHL databases from 1966 to November of 2006 and scanned selected references. We included randomized trials of at least 8 weeks duration that compared metformin with placebo or no treatment in persons without diabetes and evaluated body mass index, fasting glucose, fasting insulin, calculated insulin resistance, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and the incidence of new-onset diabetes. RESULTS Pooled results of 31 trials with 4570 participants followed for 8267 patient-years showed that metformin reduced body mass index (-5.3%, 95% confidence interval [CI], -6.7--4.0), fasting glucose (-4.5%, CI, -6.0--3.0), fasting insulin (-14.4%, CI, -19.9--8.9), calculated insulin resistance (-22.6%, CI, -27.3--18.0), triglycerides (-5.3%, CI, -10.5--0.03), and low-density lipoprotein cholesterol (-5.6%, CI, -8.3--3.0%), and increased high-density lipoprotein cholesterol (5.0%, CI, 1.6-8.3) compared with placebo or no treatment. The incidence of new-onset diabetes was reduced by 40% (odds ratio 0.6; CI, 0.5-0.8), with an absolute risk reduction of 6% (CI, 4-8) during a mean trial duration of 1.8 years. CONCLUSION Metformin treatment in persons at risk for diabetes improves weight, lipid profiles, and insulin resistance, and reduces new-onset diabetes by 40%. The long-term effect on morbidity and mortality should be assessed in future trials.

Systematic Review: The Effects of Growth Hormone on Athletic Performance

The use of human growth hormone to improve athletic performance has recently received worldwide attention. This practice, often called sports doping, is banned by most professional sports leagues and associations, including the International Olympic Committee, Major League Baseball, and the National Football League (13). However, a wide range of athletes, including those from baseball (46), cycling (7, 8), and track and field (5, 9), have been implicated in or have confessed to illicit growth hormone use. The Mitchell report (10) recently identified 89 Major League Baseball players who allegedly used performance-enhancing drugs, and some of these players have subsequently admitted to using growth hormone (11, 12). Part of the attraction of using growth hormone as a performance enhancer has been that its use is difficult to detect. The World Anti-Doping Agency, whose formation stemmed from the widely publicized doping scandal of the 1998 Tour de France (13), first used a blood test to detect exogenous growth hormone during the 2004 Olympic Games in Athens. However, according to the World Anti-Doping Agency, there have been no test-confirmed positive cases for growth hormone doping in professional or Olympic athletes (14), probably because of the limited availability and implementation of this test. Although growth hormone is reportedly used to enhance athletic performance and has been called the most anabolic substance known (15), its efficacy for this purpose is not well established. Some have suggested that growth hormone is a wonder drug (16) that results in ripped muscle (17) and provides stamina-increasing properties (18). Exogenous growth hormone therapy in growth hormonedeficient adults (that is, those with growth hormone deficiency due to hypothalamic or pituitary defects) results in increased lean mass and decreased fat mass (19), and comparable body composition changes are seen in healthy elderly adults who receive growth hormone (20). Some experts, however, have suggested that the strength-enhancing properties of growth hormone among healthy adults have been exaggerated (15). Serious side effects, including diabetes, hepatitis, and acute renal failure, may occur in athletes using high-dose growth hormone (21). Furthermore, the use of growth hormone for athletic enhancement is not approved by the U.S. Food and Drug Administration, and the distribution of growth hormone for this purpose is illegal in the United States (22). We performed a systematic review of randomized, controlled trials to determine the effects of growth hormone therapy on athletic performance in healthy, physically fit, young adults. Our primary aim was to evaluate the effects of growth hormone on body composition, strength, basal metabolism, and exercise capacity. In addition, we sought to synthesize the evidence on adverse events associated with growth hormone in the healthy young and assess the quality of the published literature. Methods Literature Searches In consultation with 2 research librarians, we developed individual search strategies to identify potentially relevant studies from the MEDLINE, EMBASE, SPORTDiscus, and Cochrane Collaboration databases. We sought English-language reports indexed through 11 October 2007 with keywords including growth hormone and randomized, controlled trial (Appendix Table 1). We searched bibliographies of retrieved articles for additional studies. Appendix Table 1. Search Strategy Study Selection We sought randomized, controlled trials, including crossover trials, that compared growth hormone therapy with no growth hormone therapy. We included studies that 1) evaluated at least 5 participants, 2) enrolled only community-dwelling participants, 3) assessed participants with a mean or median age between 13 and 45 years, and 4) provided data on at least 1 clinical outcome of interest. We excluded studies that 1) focused solely on evaluating growth hormone secretagogues, 2) explicitly included patients with any comorbid medical condition, or 3) evaluated growth hormone as treatment for a specific illness (for example, adult growth hormone deficiency or fibromyalgia). Data Abstraction One author reviewed the titles and abstracts of articles identified through our search and retrieved potentially relevant studies. An endocrinologist and a physician with training in meta-analytic techniques separately reviewed the retrieved studies and abstracted data independently onto pretested abstraction forms. We resolved abstraction differences by repeated review and consensus. If a study did not present data necessary for analysis or mentioned results but did not present data, we requested additional data from study authors. If data were presented graphically, we used the graph-digitizing program DigitizeIt, version 1.5 (Share It, Braunschweig, Germany), to abstract data from the graph (23). If multiple studies presented findings from the same cohort, we used these data only once in our analysis. We abstracted 4 types of data from each study: participant characteristics (for example, age, sex, body mass index, baseline maximum oxygen uptake [VO2max]), study interventions (for example, dose, route, frequency, and duration of growth hormone therapy), study quality (for example, quality of randomization and blinding) (24, 25), and clinical outcomes. We included studies that provided data on at least 1 of the following clinical outcomes: body composition (for example, body weight, lean body mass, fat mass), strength (for example, biceps or quadriceps strength), basal metabolism (for example, resting energy expenditure, basal metabolic rate, heart rate, respiratory exchange ratio, or respiratory quotient), exercise capacity (for example, exercising lactate levels, exercising respiratory exchange ratio or respiratory quotient, maximum inspiratory pressure, bicycling speed, and VO2max), or adverse events. Because the terms lean body mass and fat-free mass are typically used interchangeably in the literature, we report fat-free mass and lean body mass data as a single category of lean body mass. Similarly, we report resting energy expenditure and basal metabolic rate as a single category of basal metabolic rate. Quantitative Data Synthesis To describe key study characteristics, we computed mean values weighted by the number of participants in the trial. To evaluate the effects of growth hormone on body composition and strength, we computed a change score for each clinical outcome for both the treatment and control groups as the value of the outcome at trial end minus the value of the outcome at trial start. We used these change scores to calculate the weighted mean difference and standard mean difference (26) effect sizes. The weighted mean difference is reported in the same units as the clinical outcome of interest, thereby facilitating clinical interpretation. Because our outcomes were similar for both methods, we present only the outcomes from the weighted mean difference method. For studies that did not report the variance of an outcome at trial end minus the value at trial start, we calculated it as the sum of the trial-start and trial-end variances minus twice the covariance (20, 27). Because trial-start data were not available for most of the studies reporting basal metabolic outcomes, we compared trial-end results between treatment and control groups for these outcomes. We combined studies by using random-effects models (2628) because of potential interstudy heterogeneity. The considerable variability in exercise protocols used in the included studies reporting exercise capacity outcomes made pooling these results inappropriate. Instead, we provide a narrative, qualitative assessment of exercise capacity outcomes and report their associated published P values. The variability in reporting adverse events among included studies also made a quantitative meta-analysis of these outcomes inappropriate. Instead, we calculated the proportions of adverse events among participants who received and did not receive growth hormone in studies that reported or evaluated for each adverse event. We performed sensitivity analyses and assessed interstudy heterogeneity to evaluate the robustness of our results. We removed each study individually to evaluate that studys effect on the summary estimates. We assessed publication bias by constructing funnel plots and calculated the number of unpublished studies required to statistically significantly change our results (28). We assessed heterogeneity among study results for each of the summary effects by calculating the Q statistic (and associated P value) and I 2 statistic (26, 2830). We evaluated heterogeneity through predetermined subgroup analysis that stratified studies by duration of treatment. We performed analyses by using Stata software, version 9.1 (Stata, College Station, Texas); SPSS, version 15.0 (SPSS, Chicago); and Comprehensive Meta-Analysis, version 2 (Biostat, Englewood, New Jersey). We considered P values less than 0.05 (2-tailed) to indicate statistically significant differences. Role of the Funding Source The authors were supported in part or fully by the Agency for Healthcare Research and Quality, Santa Clara Valley Medical Center, the U.S. Department of Veteran Affairs, Stanford University Medical Center, Stanford University, Genentech, the National Science Foundation, and the Evidence-Based Medicine Center of Excellence of Pfizer. These funding sources had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. Results The Figure summarizes the results of our literature searches. We reviewed 7599 titles from the MEDLINE, EMBASE, SPORTDiscus, and the Cochrane Collaboration databases. From our search, we reviewed 252 abstracts in detail and retrieved 56 articles for full-text evaluation.

Impact of More Restrictive Blood Transfusion Strategies on Clinical Outcomes: A Meta-analysis and Systematic Review

BACKGROUND There is accumulating evidence that restricting blood transfusions improves outcomes, with newer trials showing greater benefit from more restrictive strategies. We systematically evaluated the impact of various transfusion triggers on clinical outcomes. METHODS The MEDLINE database was searched from 1966 to April 2013 to find randomized trials evaluating a restrictive hemoglobin transfusion trigger of <7 g/dL, compared with a more liberal trigger. Two investigators independently extracted data from the trials. Outcomes evaluated included mortality, acute coronary syndrome, pulmonary edema, infections, rebleeding, number of patients transfused, and units of blood transfused per patient. Extracted data also included information on study setting, design, participant characteristics, and risk for bias of the included trials. A secondary analysis evaluated trials using less restrictive transfusion triggers, and a systematic review of observational studies evaluated more restrictive triggers. RESULTS In the primary analysis, pooled results from 3 trials with 2364 participants showed that a restrictive hemoglobin transfusion trigger of <7 g/dL resulted in reduced in-hospital mortality (risk ratio [RR], 0.74; confidence interval [CI], 0.60-0.92), total mortality (RR, 0.80; CI, 0.65-0.98), rebleeding (RR, 0.64; CI, 0.45-0.90), acute coronary syndrome (RR, 0.44; CI, 0.22-0.89), pulmonary edema (RR, 0.48; CI, 0.33-0.72), and bacterial infections (RR, 0.86; CI, 0.73-1.00), compared with a more liberal strategy. The number needed to treat with a restrictive strategy to prevent 1 death was 33. Pooled data from randomized trials with less restrictive transfusion strategies showed no significant effect on outcomes. CONCLUSIONS In patients with critical illness or bleed, restricting blood transfusions by using a hemoglobin trigger of <7 g/dL significantly reduces cardiac events, rebleeding, bacterial infections, and total mortality. A less restrictive transfusion strategy was not effective.

Cardioselective beta-blockers for chronic obstructive pulmonary disease: a meta-analysis.

Beta-blocker therapy has a mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to assess the effect of cardioselective beta-blockers on respiratory function of patients with COPD. Comprehensive searches were performed of the EMBASE, MEDLINE and CINAHL databases from 1966 to May 2001, and identified articles and related reviews were scanned. Randomised, blinded, controlled trials that studied the effects of cardioselective beta-blockers on the forced expiratory volume in 1 s (FEV1) or symptoms in patients with COPD were included in the analysis. Interventions studied were the administration of beta-blocker, given either as a single dose or for longer duration, and the use of beta2-agonist given after the study drug. Outcomes measured were the change in FEV1 from baseline and the number of patients with respiratory symptoms. Eleven studies of single-dose treatment and 8 of continued treatment were included. Cardioselective beta-blockers produced no significant change in FEV1 or respiratory symptoms compared to placebo, given as a single dose (-2.05% [95% CI, -6.05% to 1.96%]) or for longer duration (-2.55% [CI, -5.94% to 0.84]), and did not significantly affect the FEV1 treatment response to beta2-agonists. Subgroup analyses revealed no significant change in results for those participants with severe chronic airways obstruction or for those with a reversible obstructive component. In conclusion, cardioselective beta-blockers given to patients with COPD do not produce a significant reduction in airway function or increase the incidence of COPD exacerbations. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta-blockers should be considered for patients with COPD.

Bayesian Meta-analysis of Hormone Therapy and Mortality in Younger Postmenopausal Women

BACKGROUND There is uncertainty over the risks and benefits of hormone therapy. We performed a Bayesian meta-analysis to evaluate the effect of hormone therapy on total mortality in younger postmenopausal women. This analysis synthesizes evidence from different sources, taking into account varying views on the issue. METHODS A comprehensive search from 1966 through January 2008 identified randomized controlled trials of at least 6 months duration that evaluated hormone therapy in women with mean age <60 years and reported at least one death, and prospective observational cohort studies that evaluated the relative risk of mortality associated with hormone therapy after adjustment for confounding variables. RESULTS The results were synthesized using a hierarchical random-effects Bayesian meta-analysis. The pooled results from 19 randomized trials, with 16,000 women (mean age 55 years) followed for 83,000 patient-years, showed a mortality relative risk of 0.73 (95% credible interval 0.52-0.96). When data from 8 observational studies were added to the analysis, the resultant relative risk was 0.72 (credible interval 0.62-0.82). The posterior probability that hormone therapy reduces total mortality in younger women is almost 1. CONCLUSIONS The synthesis of data using Bayesian meta-analysis indicates a reduction in mortality in younger postmenopausal women taking hormone therapy compared with no treatment. This finding should be interpreted taking into account the potential benefits and harms of hormone therapy.

Meta-analysis: Anticholinergics, but not β-agonists, reduce severe exacerbations and respiratory mortality in COPD

BACKGROUND: Anticholinergics and β2-agonists have generally been considered equivalent choices for bronchodilation in chronic obstructive pulmonary disease (COPD).OBJECTIVE: To assess the safety and efficacy of anticholinergics and β2-agonists in COPD.DESIGN: We comprehensively searched electronic databases from 1966 to December 2005, clinical trial websites, and references from selected reviews. We included randomized controlled trials of at least 3 months duration that evaluated anticholinergic or β2-agonist use compared with placebo or each other in patients with COPD.MEASUREMENTS: We evaluated the relative risk (RR) of exacerbations requiring withdrawal from the trial, severe exacerbations requiring hospitalization, and deaths attributed to a lower respiratory event.RESULTS: Pooled results from 22 trials with 15,276 participants found that anticholinergic use significantly reduced severe exacerbations (RR 0.67, confidence interval [CI] 0.53 to 0.86) and respiratory deaths (RR 0.27, CI 0.09 to 0.81) compared with placebo. β2-Agonist use did not affect severe exacerbations (RR 1.08, CI 0.61 to 1.95) but resulted in a significantly increased rate of respiratory deaths (RR 2.47, CI 1.12 to 5.45) compared with placebo. There was a 2-fold increased risk for severe exacerbations associated with β2-agonists compared with anticholinergics (RR 1.95, CI 1.39 to 2.93). The addition of β2-agonist to anticholinergic use did not improve any clinical outcomes.CONCLUSION: Inhaled anticholinergics significantly reduced severe exacerbations and respiratory deaths in patients with COPD, while β2-agonists were associated with an increased risk for respiratory deaths. This suggests that anticholinergics should be the bronchodilator of choice in patients with COPD, and β2-agonists may be associated with worsening of disease control.