Sagar S Makanji

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.

Almonds have a neutral effect on serum lipid profiles: a meta-analysis of randomized trials.

Almond consumption may be associated with improvements in serum lipid profiles. The aim was to evaluate the influence of almonds on lipid parameters to help define the role of almonds as a lipid modulator. MEDLINE, EMBASE, Cochrane CENTRAL, and the Natural Medicines Comprehensive Database were searched through July 2008, with no language restrictions, for randomized controlled trials of almonds in human patients that reported efficacy data on at least one of the following endpoints: total, low-density lipoprotein (LDL), or high-density lipoprotein (HDL) cholesterol, triglycerides, or the LDL:HDL ratio. A manual search of references from primary or review articles was performed to identify additional relevant trials. Five randomized, controlled trials (totaling 142 participants) met all inclusion criteria. Upon meta-analysis, almond consumption ranging from 25 to 168 g/day significantly lowered total cholesterol [weighted mean difference -6.95 mg/dL (95% confidence interval [CI] -13.12 to -0.772) (-0.18 mmol/L [95% CI -0.34 to -0.02])] and showed a strong trend toward reducing LDL cholesterol [weighted mean difference -5.79 mg/dL (95% CI -11.2 to 0.00) (-0.15 mmol/L [95% CI -0.29 to 0.00])]. No significant effect on HDL cholesterol, triglycerides, or LDL:HDL ratio was found. No statistical heterogeneity was observed for any analysis (I2=0% for all). Review of funnel plots and the Eggers weighted regression statistic P values suggested a low likelihood of publication bias in all analyses (P>0.25 for all). Almond consumption may decrease total cholesterol and does not significantly affect LDL or HDL cholesterol, triglycerides, or the LDL:HDL ratio. The current body of randomized trials does not support the ingestion of almonds solely for their lipid modifying effects. Both the lipid modulating effects and the safety/tolerability of almonds should be further investigated through the conduction of larger randomized, double-blinded trials of longer duration. Such studies might focus specifically on whether the efficacy of almonds as a lipid modulator varies by dose or comorbidity.

Targeting the endocannabinoid system in treating brain disorders.

Recent cannabinoid research has a primary focus on developing therapeutics against human diseases. Many studies on cannabinoids indicate important progress for protection against several neurodegenerative disorders. Agonists of cannabinoid receptors activate signalling pathways in the brain that are linked to neuronal repair and cell maintenance, and endogenous ligands can also activate neuroprotective responses. These endocannabinoids are bioactive fatty acid amides and esters that are synthesised in the brain and include arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol. Endocannabinoids are released in response to pathogenic events, thus representing a potential compensatory repair mechanism. Enhancing this on-demand action of endocannabinoids is a strategy with which to promote endogenous repair signalling. For such enhancement, considerable work has gone into modulating the availability of endocannabinoids by blocking the processes of their deactivation. The targets include the anandamide-hydrolysing enzyme fatty acid amide hydrolase, the carrier-mediated anandamide transport system and 2-arachidonoyl glycerol-deactivating enzyme monoacylglycerol lipase. The activity of endocannabinoids is terminated through transport and degradation and, accordingly, selective inhibitors of these processes effectively exploit the protective nature of cannabinergic responses. This review highlights recent studies implicating the endocannabinoid system in neuroprotection against different disorders of the CNS.

Effect of Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers on the Frequency of Post-Cardiothoracic Surgery Atrial Fibrillation:

Background: A recent meta-analysis demonstrated that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) reduce the incidence of new-onset atrial fibrillation by nearly 50%. However, the ability of ACE inhibitors or ARBs to prevent post-cardiothoracic surgery (CTS) atrial fibrillation, when used postoperatively, has yet to be evaluated. Objective: To evaluate the impact of postoperative ACE inhibitor or ARB use on the incidence of post-CTS atrial fibrillation. Methods: We performed a retrospective cohort study of propensity score matched patients who underwent CTS at a single institution from January 2004 through December 2005. Patients who received either an ACE inhibitor or an ARB within 24 hours of surgery were propensity score matched for common predictors of post-CTS atrial fibrillation (age >70 y, preoperative digoxin use, postoperative β-blocker or amiodarone use, β-blockor intolerance, valve surgery, male sex, and history of diabetes mellitus, smoking, chronic obstructive pulmonary disease, prior cardiothoracic surgery) in a 1:1 ratio with patients who did not receive an ACE inhibitor or an ARB. Multivariate logistic regression was used to generate adjusted odds ratios to minimize the impact of baseline confounders. Results: A total of 1469 patients underwent CTS during the study evaluation period. Postoperatively, 188 received an ACE inhibitor or an ARB and were matched to 188 control patients. Mean ± SD age of matched patients was 68.1 ± 11.8 years, 66% were men, 42% underwent valve surgery, and 69% and 35% received postoperative β-blockade and amiodarone, respectively. Patients who received an ACE inhibitor or an ARB did not experience a significant reduction in post-CTS atrial fibrillation compared with control patients (adjusted OR 0.95; 95% CI 0.57 to 1.56; p = 0.83). Conclusions: In this evaluation, postoperative ACE inhibitor or ARB use was not associated with a reduction in post-CTS atrial fibrillation. A study of preoperative, longer-term ACE inhibitor and/or ARB therapy is needed to determine the benefits of that strategy.

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.

Comparative Effectiveness of Low-Molecular-Weight Heparins versus Other Anticoagulants in Major Orthopedic Surgery: A Systematic Review and Meta-analysis

To evaluate the comparative efficacy and safety of low‐molecular‐weight heparins (LMWHs) versus other anticoagulants as venous thromboembolism prophylaxis in major orthopedic surgery.

Prolonged Versus Standard-Duration Venous Thromboprophylaxis in Major Orthopedic Surgery: A Systematic Review

BACKGROUND The optimal duration of thromboprophylaxis after major orthopedic surgery is unclear. PURPOSE To compare the benefits and harms of prolonged versus standard-duration thromboprophylaxis after major orthopedic surgery in adults. DATA SOURCES Cochrane Central Register of Controlled Trials and Scopus from 1980 to July 2011 and MEDLINE from 1980 through November 2011, without language restrictions. STUDY SELECTION Randomized trials reporting thromboembolic or bleeding outcomes that compared prolonged (≥21 days) with standard-duration (7 to 10 days) thromboprophylaxis. DATA ABSTRACTION Two independent reviewers abstracted data and rated study quality and strength of evidence. DATA SYNTHESIS Eight randomized, controlled trials (3 good-quality and 5 fair-quality) met the inclusion criteria. High-strength evidence showed that compared with standard-duration therapy, prolonged prophylaxis resulted in fewer cases of pulmonary embolism (PE) (5 trials; odds ratio [OR], 0.14 [95% CI, 0.04 to 0.47]; absolute risk reduction [ARR], 0.8%), asymptomatic deep venous thrombosis (DVT) (4 trials; relative risk [RR], 0.48 [CI, 0.31 to 0.75]; ARR, 5.8%), symptomatic DVT (4 trials; OR, 0.36 [CI, 0.16 to 0.81]; ARR, 1.5%), and proximal DVT (6 trials; RR, 0.29 [CI, 0.16 to 0.52]; ARR, 7.1%). Moderate-strength evidence showed fewer symptomatic objectively confirmed episodes of venous thromboembolism (4 trials; RR, 0.38 [CI, 0.19 to 0.77]; ARR, 5.7%), nonfatal PE (4 trials; OR, 0.13 [CI, 0.03 to 0.54]; ARR, 0.7%), and DVT (7 trials; RR, 0.37 [CI, 0.21 to 0.64]; ARR, 12.1%) with prolonged prophylaxis. High-strength evidence showed more minor bleeding events with prolonged prophylaxis (OR, 2.44 [CI, 1.41 to 4.20]; absolute risk increase, 6.3%), and insufficient evidence from 1 trial on hip fracture surgery suggested more surgical-site bleeding events (OR, 7.55 [CI, 1.51 to 37.64]) with prolonged prophylaxis. LIMITATIONS Data relevant to knee replacement or hip fracture surgery were scant and insufficient. Most trials had few events; the strength of evidence ratings that were used may not adequately capture uncertainty in such situations. CONCLUSION Prolonged prophylaxis decreases the risk for venous thromboembolism, PE, and DVT while increasing the risk for minor bleeding in patients undergoing total hip replacement.

Comparative effectiveness of combined pharmacologic and mechanical thromboprophylaxis versus either method alone in major orthopedic surgery: a systematic review and meta-analysis.

To evaluate the comparative efficacy and safety of combination pharmacologic and mechanical venous thromboembolism (VTE) prophylaxis versus either method alone in major orthopedic surgery.

Are the risk factors listed in warfarin prescribing information associated with anticoagulation-related bleeding? A systematic literature review

Warfarin significantly reduces thromboembolic risk, but perceptions of associated bleeding risk limit its use. The evidence supporting the association between bleeding and individual patient risks factors is unclear. This systematic review aims to determine the strength of evidence supporting an accentuated bleeding risk when patients with risk factors listed in the warfarin prescribing information are prescribed the drug. A systematic literature search of MEDLINE and Cochrane CENTRAL was conducted to identify studies reporting multivariate relationships between prespecified covariates and the risk of bleeding in patients receiving warfarin. The prespecified covariates were identified based on patient characteristics for bleeding listed in the warfarin package insert. Each covariate was evaluated for its association with specific types of bleeding. The quality of individual evaluations was rated as ‘good’, ‘fair’ or ‘poor’ using methods consistent with those recommended by the Agency for Healthcare Research and Quality (AHRQ). Overall strength of evidence was determined using the Grading of Recommendations Assessment, Development (GRADE) criteria and categorised as ‘insufficient’, ‘very low’, ‘low’, ‘moderate’ or ‘high’. Thirty‐four studies, reporting 134 multivariate evaluations of the association between a covariate and bleeding risk were identified. The majority of evaluations had a low strength of evidence for the association between covariates and bleeding and none had a high strength of evidence. Malignancy and renal insufficiency were the only two covariates that had a moderate strength of evidence for their association with major and minor bleeding respectively. The associations between covariates listed in the warfarin prescribing information and increased bleeding risk are not well supported by the medical literature.

Systematic review: comparative effectiveness of adjunctive devices in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention of native vessels

BackgroundDuring percutaneous coronary intervention (PCI), dislodgement of atherothrombotic material from coronary lesions can result in distal embolization, and may lead to increased major adverse cardiovascular events (MACE) and mortality. We sought to systematically review the comparative effectiveness of adjunctive devices to remove thrombi or protect against distal embolization in patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI of native vessels.MethodsWe conducted a systematic literature search of Medline, the Cochrane Database, and Web of Science (January 1996-March 2011), http://www.clinicaltrials.gov, abstracts from major cardiology meetings, TCTMD, and CardioSource Plus. Two investigators independently screened citations and extracted data from randomized controlled trials (RCTs) that compared the use of adjunctive devices plus PCI to PCI alone, evaluated patients with STEMI, enrolled a population with 95% of target lesion(s) in native vessels, and reported data on at least one pre-specified outcome. Quality was graded as good, fair or poor and the strength of evidence was rated as high, moderate, low or insufficient. Disagreement was resolved through consensus.Results37 trials met inclusion criteria. At the maximal duration of follow-up, catheter aspiration devices plus PCI significantly decreased the risk of MACE by 27% compared to PCI alone. Catheter aspiration devices also significantly increased the achievement of ST-segment resolution by 49%, myocardial blush grade of 3 (MBG-3) by 39%, and thrombolysis in myocardial infarction (TIMI) 3 flow by 8%, while reducing the risk of distal embolization by 44%, no reflow by 48% and coronary dissection by 70% versus standard PCI alone. In a majority of trials, the use of catheter aspiration devices increased procedural time upon qualitative assessment.Distal filter embolic protection devices significantly increased the risk of target revascularization by 39% although the use of mechanical thrombectomy or embolic protection devices did not significantly impact other final health outcomes. Distal balloon or any embolic protection device increased the achievement of MBG-3 by 61% and 20% and TIMI3 flow by 11% and 6% but did not significantly impact other intermediate outcomes versus control. Upon qualitative analysis, all device categories, with exception of catheter aspiration devices, appear to significantly prolong procedure time compared to PCI alone while none appear to significantly impact ejection fraction. Many of the final health outcome and adverse event evaluations were underpowered and the safety of devices overall is unclear due to insufficient amounts of data.ConclusionsIn patients with STEMI, for most devices, few RCTs evaluated final health outcomes over a long period of follow-up. Due to insufficient data, the safety of these devices is unclear.