Abstract Background To determine whether individual statins had differing effects on insulin sensitivity (IS) in patients without pre-existing diabetes mellitus. Methods A systematic literature ...search of MEDLINE, EMBASE and Cochrane CENTRAL was conducted through December 2008. Trials were included if they compared pravastatin, atorvastatin, rosuvastatin or simvastatin to placebo/control, excluded patients with diabetes, and reported data on insulin sensitivity/resistance. IS data was pooled and evaluated as standardized mean differences (SMDs) and 95% confidence interval (CI) using a random-effects model. Results 16 studies ( n = 1146) were included, with patients receiving pravastatin in three trials ( n = 164), atorvastatin in five trials ( n = 315), rosuvastatin in five trials ( n = 419), and simvastatin in five trials ( n = 369). When pooled as a class, statins had no significant impact on IS as compared with placebo/control SMD −0.084 (95% CI −0.210 to 0.042); p = 0.19. Pravastatin was found to significantly improved IS SMD 0.342 (95% CI 0.032–0.621); p = 0.03, whereas simvastatin significantly worsened IS SMD −0.321 (95% CI −0.526 to −0.117); p = 0.03. Conclusions Statins do not appear to demonstrate a ‘class effect’ on IS in patients without diabetes. Differences between individual statins likely exist that may partially explain the findings of previously conducted meta-analyses examining the impact of statins on the development of diabetes.
Acute ischemic strokes are associated with poor outcomes and high health care burden. Evidence exists evaluating the use of neurothrombectomy devices in patients receiving currently recommended ...treatments that may have limited efficacy.
To describe the state of the evidence supporting use of neurothrombectomy devices in the treatment of acute ischemic stroke.
MEDLINE, SCOPUS, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Web of Science were searched, without language restrictions, from their inception through May 2010. The MEDLINE and Cochrane Central Register of Controlled Trials searches were updated through November 2010.
Two independent investigators screened citations for human studies of any design or case series or case reports of patients with an acute ischemic stroke that evaluated a neurothrombectomy device and reported at least 1 clinical effectiveness outcome or harm.
Using standardized protocols, 2 independent investigators extracted information about study characteristics and outcomes, and a third reviewer resolved disagreement.
87 articles met eligibility criteria, including 18 prospective single-group studies, 7 noncomparative retrospective studies, and 62 case series or case reports. Two U.S. Food and Drug Administration (FDA)-cleared devices, the MERCI Retriever (Concentric Medical, Mountain View, California) (40%) and the Penumbra System (Penumbra, Alameda, California) (9%), represented a large portion of the available data. All prospective and retrospective studies provided data on successful recanalization with widely varying rates (43% to 78% with the MERCI Retriever and 83% to 100% with the Penumbra System). Rates of harms, including symptomatic (16 studies; 0% to 10% with the MERCI Retriever and 0% to 11% with the Penumbra System) or asymptomatic (13 studies; 28% to 43% and 1% to 30%, respectively) intracranial hemorrhage and vessel perforation or dissection (11 studies; 0% to 7% and 0% to 5%, respectively), also varied by device. Predictors of harm included older age, history of stroke, and higher baseline stroke severity scores, whereas successful recanalization was the sole predictor of good outcomes.
Most available data are from single-group, noncomparative studies. In addition, the patient population most likely to benefit from these devices is undetermined.
Currently available neurothrombectomy devices offer intriguing treatment options in patients with acute ischemic stroke. Future trials should use a randomized design, with adequate power to show equivalency or noninferiority between competing strategies or devices, and strive to identify populations that are most likely to benefit from use of neurothrombectomy devices.
Agency for Healthcare Research and Quality.
Abstract Purpose We wanted to determine the association between consumption of barley and changes in plasma lipids in healthy and hypercholesterolemic men and women. Methods A systematic literature ...search was conducted from the earliest possible date through January 2008. Trials were included in the analysis if they were randomized controlled trials of barley that reported efficacy data on at least 1 lipid endpoint. A DerSimonian and Laird random-effects model was used in calculating the weighted mean difference (WMD) and its 95% confidence interval (CI). Statistical heterogeneity was addressed using the I statistic. Visual inspection of funnel plots, Egger's weighted regression statistics, and the trim and fill method were used to assess for publication bias. Results We found 8 trials (n = 391 patients) of 4 to 12 weeks' duration evaluating the lipid-reducing effects of barley. The use of barley significantly lowered total cholesterol (weighted mean difference WMD, −13.38 mg/dL; 95% CI, −18.46 to −8.31 mg/dL), low-density lipoprotein (LDL) cholesterol (WMD, −10.02 mg/dL; 95% CI, −14.03 to −6.00 mg/dL) and triglycerides (WMD, −11.83 mg/dL; 95% CI, −20.12 to −3.55 mg/dL) but did not appear to significantly alter high-density lipoprotein (HDL) cholesterol ( P = .07). Conclusion Barley-derived β-glucan appears to beneficially affect total cholesterol, LDL-cholesterol, and triglycerides, but not HDL-cholesterol.
In order to determine the impact of garlic on total cholesterol (TC), TAG levels, as well as LDL and HDL, and establish if any variables have an impact on the magnitude of this effect, a ...meta-analysis was conducted. A systematic literature search of MEDLINE, CINAHL and the Cochrane Database from the earliest possible date through to November 2007 was conducted to identify randomised, placebo-controlled trials of garlic that reported effects on TC, TAG concentrations, LDL or HDL. The weighted mean difference of the change from baseline (with 95 % CI) was calculated as the difference between the means in the garlic groups and the control groups using a random-effects model. Subgroup and sensitivity analyses were performed to determine the effects on type, brand and duration of garlic therapy as well as baseline TC and TAG levels, the use of dietary modification, and study quality on the meta-analysis's conclusions. Twenty-nine trials were included in the analysis. Upon meta-analysis garlic was found to significantly reduce TC ( - 0.19; 95 % CI - 0.33, - 0.06 mmol/l) and TAG ( - 0.11; 95 % CI - 0.19, - 0.06 mmol/l) but exhibited no significant effect on LDL or HDL. There was a moderate degree of statistical heterogeneity for the TC and TAG analyses. Garlic reduces TC to a modest extent, an effect driven mostly by the modest reductions in TAG, without appreciable LDL lowering or HDL elevation. Higher baseline line TC levels and the use of dietary modification may alter the effect of garlic on these parameters. Future studies should be conducted evaluating the impact of adjunctive garlic therapy with fibrates or statins on TAG concentrations.
Abstract Background Plant sterols and stanols are plant steroids with a similar chemical structure and cellular function to human cholesterol, and are recommended as dietary modifiers of serum ...lipids. Plant sterols have a higher degree of absorption than plant stanols, suggesting differential efficacy between the two. Design A meta-analysis of randomized controlled trials was performed to summarize direct comparisons between the effect of plant sterols vs plant stanols on serum lipid levels in healthy patients and patients with hypercholesterolemia. Methods A systematic literature search of MEDLINE, EMBASE, Cochrane CENTRAL, and the Natural Medicines Comprehensive Database was conducted from January 1950 through January 2009. Trials were included in the analysis if they were randomized controlled trials evaluating the effect of plant sterols vs plant stanols in healthy patients or patients with hypercholesterolemia who reported efficacy data on total, low-density lipoprotein, and high-density lipoprotein cholesterols or triglycerides. The weighted mean difference (WMD) of the change from baseline (in mg/dL) with 95% confidence interval was calculated as the difference between the means in the plant sterol and plant stanol groups using a random-effects model. Results Fourteen studies (n=531 patients) met the inclusion criteria. Upon meta-analysis, the results showed that there is no statistically or clinically significant difference between plant sterols and plant stanols in their abilities to modify total cholesterol (WMD −1.11 mg/dL −0.0286 mmol/L, 95% confidence interval CI −4.12 to 1.90, P =0.47), low-density lipoprotein cholesterol (WMD −0.35 mg/dL −0.0091 mmol/L, 95% CI −2.98 to 2.28, P =0.79), high-density lipoprotein cholesterol (WMD −0.28 mg/dL –0.00073 mmol/L, 95% CI −1.18 to 0.62, P =0.54), or triglycerides (WMD −1.80 mg/dL −0.0203 mmol/L, 95% CI −6.80 to 3.21, P =0.48). Conclusions Plant sterols and plant stanols do not have statistically or clinically relevant differing effects on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride levels. The selection of plant sterols vs plant stanols should then be based on potential differences in safety parameters and further study is required to elucidate such differences.
The benefits and risks associated with use of beta-blocker prophylaxis in noncardiac surgery (NCS) are described.
Perioperative beta-blockade is recommended by the American College of Cardiology and ...the American Heart Association for use in patients already on beta-blockers or in high-risk patients undergoing NCS to reduce myocardial ischemia and myocardial infarction (MI); however, the recommendations are not as clear for patients undergoing intermediate- or low-risk NCS. Numerous trials have evaluated the effect of perioperative beta-blockers on MI, stroke, bradycardia, hypotension, overall mortality, and cardiovascular mortality in patients undergoing NCS. Several trials suggest that dosing, patient population, type of NCS, genetic polymorphisms, and type of anesthesia may be important in determining the benefits and risks of perioperative beta-blockade in these patients. In the meta-analyses evaluating beta-blockers in NCS, the balance of benefits to harms associated with aggressive perioperative beta-blocker therapy was not favorable. However, the largest, most recent trial drove the meta-analyses results and has some methodological caveats and limitations that must be considered. Recent meta-analyses have found that the use of beta-blockers reduces the rate of MI but increases the frequency of stroke, and these MIs and strokes can occur with differing severities.
Perioperative use of beta-blockers in NCS can protect against postoperative MI but increases the risk of stroke, severe hypotension, and severe bradycardia. Although less common, the strokes are severe, and the troubling trend toward increasing cardiovascular and total mortality precludes the recommendation for their use in patients not previously treated with beta-blockers.
Patients with ischemic heart disease and preserved ventricular function experience considerable morbidity and mortality despite standard medical therapy.
To compare benefits and harms of using ...angiotensin-converting enzyme (ACE) inhibitors, angiotensin II-receptor blockers (ARBs), or combination therapy in adults with stable ischemic heart disease and preserved ventricular function.
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (earliest date, July 2009) were searched without language restrictions.
Two independent investigators screened citations for trials of at least 6 months' duration that compared ACE inhibitors, ARBs, or combination therapy with placebo or active control and reported any of several clinical outcomes.
Using standardized protocols, 2 independent investigators extracted information about study characteristics and rated the quality and strength of evidence. Disagreement was resolved by consensus.
41 studies met eligibility criteria. Moderate- to high-strength evidence (7 trials; 32 559 participants) showed that ACE inhibitors reduce the relative risk (RR) for total mortality (RR, 0.87 95% CI, 0.81 to 0.94) and nonfatal myocardial infarction (RR, 0.83 CI, 0.73 to 0.94) but increase the RR for syncope (RR, 1.24 CI, 1.02 to 1.52) and cough (RR, 1.67 CI, 1.22 to 2.29) compared with placebo. Low-strength evidence (1 trial; 5926 participants) suggested that ARBs reduce the RR for the composite end point of cardiovascular mortality, nonfatal myocardial infarction, or stroke (RR, 0.88 CI, 0.77 to 1.00) but not for the individual components. Moderate-strength evidence (1 trial; 25 620 participants) showed similar effects on total mortality (RR, 1.07 CI, 0.98 to 1.16) and myocardial infarction (RR, 1.08 CI, 0.94 to 1.23) but an increased risk for discontinuations because of hypotension (P < 0.001) and syncope (P = 0.035) with combination therapy compared with ACE inhibitors alone.
Many studies either did not assess or did not report harms in a systematic manner. Many studies did not adequately report benefits or harms by various patient subgroups.
Adding an ACE inhibitor to standard medical therapy improves outcomes, including reduced risk for mortality and myocardial infarctions, in some patients with stable ischemic heart disease and preserved ventricular function. Less evidence supports a benefit of ARB therapy, and combination therapy seems no better than ACE inhibitor therapy alone and increases harms.
Agency for Healthcare Research and Quality.
Abstract Objective Systematic reviewers often use a “best evidence” approach to address the key questions, but what is meant by “best” is often unclear. The goal of this project was to create a ...decision framework for “best evidence” approaches to increase transparency in systematic reviews. Study Design and Setting The project was separated into three areas: 1) inclusion criteria, 2) evidence prioritization strategies, and 3) evaluative approaches. This commentary focuses only on the second task. The full report is available on the Effective Healthcare Web site of the Agency for Healthcare Research and Quality. Results The four identified strategies were as follows: 1) Use only the single best study; 2) Use the best set of studies; 3) Same as 2, but also consider whether the evidence permits a conclusion; and 4) Same as 3, but also consider the overall strength of the evidence. Simpler strategies (such as #1) are less likely to produce false conclusions, but are also more likely to yield insufficient evidence (possibly because of imprecise data). Conclusion Systematic reviewers routinely prioritize evidence in numerous ways. This document provides a conceptual construct to enhance the transparency of systematic reviewers' decisions.
Generic antiepileptic drugs achieve blood concentrations similar to those of innovator drugs in healthy volunteers, but their comparative effectiveness has not been well evaluated. Thus, we assessed ...the efficacy, tolerability, and safety of innovator versus generic antiepileptic drugs. We searched the MEDLINE database, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science for studies that evaluated innovator and generic antiepileptic drugs in patients with epilepsy and reported data on prespecified outcomes. We extracted data on study design, interventions, quality criteria, study population, baseline characteristics, and outcomes. Compared with initiation of innovator antiepileptic drugs, initiation of generic antiepileptic drugs did not significantly alter seizure occurrence (relative risk RR 0.87, 95% confidence interval CI 0.64–1.18; strength of evidence: low) or frequency (standardized mean difference 0.03, 95% CI −0.08–0.14; strength of evidence: low), withdrawals due to lack of efficacy (RR 1.02, 95% CI 0.41–2.54; strength of evidence: low) or adverse events (RR 0.79, 95% CI 0.28–2.20; strength of evidence: low), pharmacokinetic concentrations (maximum, minimum, or area under the curve strength of evidence: low), or a myriad of adverse events (strength of evidence: low or insufficient) in clinical trials. In qualitatively evaluated observational studies, switching between forms of antiepileptic drug (innovator to generic, generic to generic) may increase the risk of hospitalization (strength of evidence: low), hospital stay duration (strength of evidence: low), and a composite end point of medical service utilization (strength of evidence: insufficient) but may not increase outpatient service utilization (strength of evidence: low). Data are limited predominantly to carbamazepine, phenytoin, and valproic acid. Clinical trials are limited by small sample size, short‐term nature, and lack of specification of A‐rated generic products (generics that the United States Food and Drug Administration has deemed bioequivalent to the innovator drug). Observational trials lack full accounting for confounders and have inherent limitations. With a low strength of evidence, it appears that initiating an innovator or generic antiepileptic drug will provide similar efficacy, tolerability, and safety but that switching from one form to the other may be associated with more hospitalizations and longer hospital stays.
Recombinant human growth hormone (rhGH) improves growth in patients with growth hormone deficiency or idiopathic short stature. Its role in patients with cystic fibrosis (CF) is unclear.
To review ...the effectiveness of rhGH in the treatment of patients with CF.
Medline and the Cochrane Central Register of Controlled Trials were searched from the earliest date through April 2010. Randomized controlled trials, observational studies, systematic reviews/meta-analyses, or case reports were included if rhGH therapy was administered to patients with CF and data on prespecified harms, intermediate outcomes, or final health outcomes were reported. When applicable, end points were pooled by using a random-effects model. The overall body of evidence was graded for each outcome as insufficient, low, moderate, or high.
Ten unique controlled trials (n = 312) and 8 observational studies (n = 58) were included. On quantitative synthesis of controlled trials, several markers of pulmonary function, anthropometrics, and bone mineralization were significantly improved versus control. Results of single-arm observational studies for the aforementioned outcomes were generally supportive of findings in clinical trials. There is insufficient evidence to determine the effect of rhGH on intravenous antibiotic use during therapy, pulmonary exacerbations, health-related quality-of-life, bone consequences, or total mortality, but moderate evidence suggests that rhGH therapy reduces the rate of hospitalization versus control.
rhGH improved almost all intermediate measures of pulmonary function, height, and weight in patients with CF. Improvements in bone mineral content are also promising. However, with the exception of hospitalizations, the benefits on final health outcomes cannot be directly determined at this time.
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