Ripple Talati

Neurothrombectomy devices for the treatment of acute ischemic stroke: state of the evidence

BACKGROUND 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. PURPOSE To describe the state of the evidence supporting use of neurothrombectomy devices in the treatment of acute ischemic stroke. DATA SOURCES 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. STUDY SELECTION 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. DATA EXTRACTION Using standardized protocols, 2 independent investigators extracted information about study characteristics and outcomes, and a third reviewer resolved disagreement. DATA SYNTHESIS 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. LIMITATIONS Most available data are from single-group, noncomparative studies. In addition, the patient population most likely to benefit from these devices is undetermined. CONCLUSION 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. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

The Effects of Barley-Derived Soluble Fiber on Serum Lipids

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 I2 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.

The effect of adding plant sterols or stanols to statin therapy in hypercholesterolemic patients: systematic review and meta-analysis.

Objective: To characterize the effect of plant sterols/stanols on serum lipids in hypercholesterolemic patients on concurrent statin therapy, we conducted a meta-analysis of randomized controlled trials. Methods: A systematic literature search of MEDLINE, EMBASE, Cochrane CENTRAL, and the Natural Medicines Comprehensive Database was conducted from the earliest possible date through May 2008. Trials were included in the analysis if they were randomized controlled trials evaluating the use of plant sterols/stanols in combination with statins in hypercholesterolemic patients that reported efficacy data on total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides. The weighted mean difference (WMD) of the change from baseline (in mg/dL) with 95% confidence interval (CI) was calculated as the difference between the mean in the plant sterol/stanol groups and the control groups, using a random-effects model. Results: Eight studies (n  =  306 patients) met the inclusion criteria. Upon meta-analysis, the use of plant sterols/stanols in combination with statin therapy significantly lowered total cholesterol (WMD, −14.01 mg/dL [95% CI, −18.66 to −9.37], p < 0.0001) and LDL cholesterol (WMD, −13.26 mg/dL [95% CI, −17.34 to −9.18], p < 0.0001) but not HDL cholesterol or triglycerides. Conclusions: Based upon the current literature, we can only say that plant sterols/stanols, when administered in addition to statins, favorably affect total and LDL cholesterol with 95% confidence. Randomized trials examining the impact of plant sterols/stanols in combinatation with statins on patient morbidity and mortality are needed.

The Comparative Efficacy of Plant Sterols and Stanols on Serum Lipids: A Systematic Review and Meta-Analysis

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 impact of garlic on lipid parameters: a systematic review and meta-analysis

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-analysiss 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.

Adding a dopamine agonist to preexisting levodopa therapy vs. levodopa therapy alone in advanced Parkinson's disease: a meta analysis.

Background:  To perform a meta analysis of randomised placebo‐controlled trials evaluating the use of dopamine agonist (DA) or placebo to preexisting levodopa therapy for the treatment of advanced Parkinson’s disease (PD). We focused on clinically important efficacy [Unified Parkinson’s Disease Rating Scale (UPDRS) activities of daily living (ADL) and motor scores as well as change in ‘off’ time and levodopa dose] and safety outcomes (withdrawal because of adverse drug events (ADEs), dyskinesias, hallucinations and mortality).

Recombinant Human Growth Hormone in the Treatment of Patients With Cystic Fibrosis

CONTEXT: 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. OBJECTIVE: To review the effectiveness of rhGH in the treatment of patients with CF. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Efficacy and Safety of Innovator versus Generic Drugs in Patients with Epilepsy: A Systematic Review

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.

Intravenous magnesium sulfate enhances the ability of dofetilide to successfully cardiovert atrial fibrillation or flutter: results of the Dofetilide and Intravenous Magnesium Evaluation

AIMS A previous study found that the adjunctive use of intravenous magnesium sulfate with ibutilide could increase the odds of a patient chemically cardioverting from atrial fibrillation (AF) or flutter (AFL) to normal sinus rhythm (NSR) by 78%. Whether or not intravenous magnesium has the same effect on dofetilides ability to chemically cardiovert patients from AF/AFL to NSR is not known. METHODS AND RESULTS This was a retrospective cohort evaluation of consecutive eligible patients receiving dofetilide for chemical cardioversion of AF or AFL at a single institution. All AF or AFL patients received dofetilide according to the institutions standard protocol, which required patients to remain as an inpatient for a minimum of 3 days or 6 doses after the initiation of dofetilide therapy. Patients receiving any dose of intravenous magnesium starting on the same day as dofetilide constituted the treatment group. Controls received dofetilide, but no intravenous magnesium any time prior to chemical cardioversion. Patients underwent continuous electrocardiographic monitoring throughout their hospital admission. Multivariable logistic regression analysis was used to determine the impact of intravenous magnesium on dofetilides efficacy. A total of 160 patients in persistent AF or AFL (mean age 66.6 +/- 11.0 years, 70.0% male, 30.0% in AF or AFL >15 days, 54.4% hypertension, 37.5% heart failure, 16.3% valvular disease, 16.3% previous myocardial infarction, and baseline serum magnesium levels 2.1 +/- 0.26 mg/dL) and receiving dofetilide (mean dose 428 +/- 118 microg/dose) were included in this analysis. The overall chemical cardioversion rate with dofetilide irrespective of adjunctive intravenous magnesium utilization was 41.9%. The concurrent administration of intravenous magnesium (n = 50) was associated with a 107% increased odds of successful chemical cardioversion [adjusted odds ratio: 2.07 (95% confidence intervals: 1.00-4.33)] compared with those who did not receive magnesium (n = 110). Only one case of torsade de pointes occurred in the no magnesium group during the index hospital admission. CONCLUSION Concurrent use of intravenous magnesium is associated with an enhanced ability of dofetilide to successfully convert AF or AFL.

Benefits and risks associated with β-blocker prophylaxis in noncardiac surgery

PURPOSE The benefits and risks associated with use of beta-blocker prophylaxis in noncardiac surgery (NCS) are described. SUMMARY 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. CONCLUSION 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.