Meta-Analysis of Randomized and Controlled Treatment Trials for Achalasia

Pharmacological therapy, botulinum toxin injection, pneumatic dilatation, and surgical myotomy are the primary therapeutic modalities for achalasia, for which laparoscopic myotomy is recommended as state-of-the-art therapy. However, its efficacy and safety remain unclear compared with other approaches in the treatment of achalasia. We searched electronic databases (MEDLINE, EMBASE, Cochrane Central Registry of Controlled Trials, LILACS-Latin American, Caribbean health science literature, and Science Citation Index Expanded) for randomized controlled trials to evaluate which therapeutic measures are temporary and reversible and which measures are definitive and effective by pooling data including remission rate, relapse rate, complications, and adverse effects. Seventeen studies with 761 patients met our inclusion criteria. There was better remission rate in pneumatic dilation than in botulinum toxin injection for initial intervention [relative risk (RR) 2.20, 95% confidence interval (CI) 1.51–3.20], Pneumatic dilation had lower relapse rate than did botulinum toxin injection (RR 0.12, 95% CI 0.04–0.32). Compared with pneumatic dilation, laparoscopic myotomy further increased remission rate (RR 1.48, 95% CI 1.48–1.87), and reduced clinical relapse rate (RR 0.14, 95% CI 0.04–0.58), and there was no difference in complication rate (RR 1.48, 95% CI 0.37–5.99). Based on limited randomized and controlled trials, laparoscopic myotomy is the preferred method for patients with achalasia. Future trials should investigate whether laparoscopic myotomy combined with different modalities of fundoplication is superior to isolated laparoscopic myotomy.     

A Meta-Analysis of Randomized Controlled Trials on Antiplatelet Agents Versus Placebo/Control for Treating Peripheral Artery Disease

Effect of aspirin (antiplatelet agents) in patients with peripheral artery disease (PAD) was still controversial. Varying studies reported varying results. Therefore, we did this meta-analysis to investigate if aspirin could reduce cardiovascular events in patients with PAD.A comprehensive literature search (PubMed, CCTR, Embase, Web of Science, CNKI, CBM-disc, and relevant websites) was conducted from 1990 to September 2014. The key search terms (“aspirin,” “PAD,” “peripheral arterial occlusive diseases,” and “claudication”) produced 9 high-quality randomized controlled trials (RCTs) of aspirin versus placebo/control. Mantel–Haenszel random-effects model was used to analysis of the 9 RCTs. The primary outcome was the cardiovascular events.Nine RCTs, composed of 9526 patients (4786 aspirin-treated and 4740 placebo or control-treated patients), were meta-analyzed. The results indicated that compared to placebo/control, aspirin could not significantly reduce the cardiovascular events (OR = 0.81, 95% CI = 0.56–1.15). Moreover, aspirin could not produce better effect on prevention of nonfatal myocardial infarction (OR = 0.98, 95% CI = 0.52–1.84), nonfatal stroke (OR = 0.89, 95% CI = 0.69–1.14), cardiovascular death (OR = 0.97, 95% CI = 0.68–1.38), any death (OR = 1.05, 95% CI = 0.85–1.30), and major bleeding (OR = 1.16, 95% CI = 0.82–1.65) than placebo/control. But aspirin, as monotherapy therapy, did significantly reduce the risk of nonfatal stroke (OR = 0.42, 95% CI = 0.21–0.84).Aspirin, as monotherapy or combination therapy, did not result in a significant decrease in the cardiovascular events. But aspirin, as monotherapy therapy, did significantly reduce the risk of nonfatal stroke. Our conclusion might help clinicians in clinical treating PAD. Future studies are needed to draw firm conclusions about the clinical benefit and risks of aspirin and other antiplatelet agents.     

Steroid Injection and Nonsteroidal Anti-inflammatory Agents for Shoulder Pain: A PRISMA Systematic Review and Meta-Analysis of Randomized Controlled Trials

Advantages and possible risks associated with steroid injection compared with nonsteroidal anti-inflammatory drugs (NSAIDs) for shoulder pain are not fully understood.To compare the efficiency and safety of steroid injection versus NSAIDs for patients with shoulder pain.PubMed, Embase, and the Cochrane Library were searched through July 2015.Study eligibility criteria, participants, and interventions: randomized controlled trials (RCTs) that assessed steroid injection versus NSAIDs for patients with shoulder pain.Study appraisal and synthesis methods: predefined primary efficacy outcome was functional improvement; and secondary efficacy outcomes included pain relief and complications. Relative risks (RRs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model accounting for clinical heterogeneity.Eight RCTs involving 465 participants were included in the meta-analysis. Five trials compared steroid injection with oral NSAIDs, and 3 compared steroids injection with NSAIDs injection. Compared with steroid injection, oral NSAIDs were less effective in 4 or 6 weeks for functional improvement (SMD 0.61; 95% CI, 0.08–1.14; P = 0.01), while there was no significant difference in pain relief (SMD 0.45; 95% CI, −0.50–1.40; P < 0.00001) or complication rate (RR 1.10; 95% CI, 0.26–4.58; P = 0.29). Meta-analysis was not performed for NSAIDs injection due to considerable heterogeneity. Conflicting results were observed in favor of either steroid or NSAIDs injection.Not all diseases that can lead to shoulder pain were included, detailed intervention protocols were inconsistent across studies, and some estimated data were input into comparison while some data were lost, which could exert an influence on pooled results.Steroid injection, compared with oral NSAIDs, provides slightly more improvement in shoulder function without superiority in pain relief or risk of complications at 4 to 6 weeks.Treatment decision should be made based on diseases. NSAIDs injection might be a treatment method for shoulder pain.     

Transcatheter Aortic Valve Replacement in Low-Risk Patients: A Meta-Analysis of Randomized Controlled Trials

IntroductionTranscatheter aortic valve replacement (TAVR) has become the standard treatment option for patients with symptomatic severe aortic stenosis (AS) with high surgical risk and a reasonable option for intermediate surgical risk as an alternative to surgical aortic valve replacement (SAVR). The role of TAVR in lower risk patients is less established but has been the focus of recent randomized controlled trials (RCTs). We performed a meta-analysis of RCTs to assess TAVR outcomes among low surgical risk patients.Methods and resultsSystematic search of RCTs was done using PubMed, EMBASE, and Cochrane Library databases. Statistical analysis was performed with RevMan v5.3 software using a random effects model to report risk ratio (RR) with 95% confidence interval (CI). A total of three RCTs including 2698 patients (1375 TAVR and 1323 SAVR) were analyzed. Compared to SAVR, TAVR was not associated with all-cause mortality [RR 0.86 (95% CI 0.61–1.19); P = 0.36; I² = 8%] or stroke [RR 0.82 (0.48–1.43); P = 0.49; I² = 42%]. However, TAVR was significantly associated with lower risk of acute kidney injury [RR 0.27 (0.13–0.54); P = 0.0002; I² = 0%], new-onset atrial fibrillation [RR 0.26 (0.18–0.39); P < 0.00001; I² = 80%], and life-threatening or disabling bleeding [RR 0.35 (0.22–0.55); P < 0.00001; I² = 57%], but a higher risk of moderate-severe paravalvular leak [RR 4.40 (1.22–15.86); P = 0.02; I² = 26%] and permanent pacemaker insertion [RR 2.73 (1.41–5.28); P = 0.003; I² = 83%].ConclusionsThere is no difference in all-cause mortality or stroke between TAVR and SAVR, but TAVR is associated with lower risk of other perioperative complications except for moderate-severe paravalvular leak and the need for permanent pacemaker implantation.     

Drug-Eluting Versus Bare-Metal Stents in Older Patients: A Meta-Analysis of Randomized Controlled Trials

BackgroundDespite the high prevalence of ischemic heart disease in older patients, there is a substantial lack of evidence to guide clinical decision-making in this population. Hence, we performed a meta-analysis to determine the safety and efficacy of percutaneous coronary intervention (PCI) with drug-eluting stents (DES) versus bare-metal stents (BMS).MethodsElectronic databases were searched for randomized trials comparing DES with BMS in patients ≥70 years-old. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included different ischemic and bleeding events. Subgroup analyses for dual-antiplatelet therapy (DAPT) duration were conducted.ResultsWe included 7 trials with a total of 5449 patients. The use of DES compared with BMS was associated with a significant reduction in MACE (odds ratio [OR]:0.76; 95% confidence interval [CI]:0.62–0.93; P = 0.007) with no increased risk of bleeding events (OR: 1.07; 95% CI: 0.89–1.27; P = 0.48). However, longer duration of DAPT (>6 months) for the DES group increased bleeding events (OR: 1.52; 95% CI: 1.05–2.20; P = 0.03). In contrast, shorter DAPT showed persistent efficacy in reducing MACE in DES-treated patients with no increased bleeding events (OR: 0.72; 95% CI: 0.60–0.87; P < 0.01 and OR: 1.01; 95% CI: 0.84–1.22; P = 0.89, respectively).ConclusionsIn older patients who had undergone PCI, DES showed superior efficacy in reducing MACE with no increased risk of bleeding compared with BMS. Persistent MACE reduction was evident with shorter DAPT durations in DES-treated patients.SummaryThis meta-analysis of randomized clinical trials demonstrated that drug-eluting stents were associated with a significant reduction in major adverse cardiovascular events with no increased risk of bleeding compared with bare-metal stents. The risk of bleeding was high with longer dual antiplatelet therapy duration for patients who underwent DES placement. However, short duration of dual antiplatelet therapy substantially reduced major adverse cardiovascular events with no increased bleeding risk.     

Effect of Music on Patients Undergoing Colonoscopy: A Meta-Analysis of Randomized Controlled Trials

Purpose Music has been utilized as a therapeutic tool during colonoscopy, but various randomized controlled trials (RCTs) have been inconsistent. We conducted a meta-analysis to analyze the effect of music on patients undergoing colonoscopy. Patients and Methods Multiple medical databases were searched (12/06). Only RCTs on adult subjects that compared music versus no music during colonoscopy were included. Meta-analysis was analyzed for total procedure time, dose of sedative medications (midazolam and mepiridine), and patients’ pain scores, experience, and willingness to repeat the same procedure in the future. Results Eight studies (N = 712) met the inclusion criteria. Patients’ overall experience scores (P < 0.01) were significantly improved with music. No significant differences were noted for patients’ pain scores (P = 0.09), mean doses of midazolam (P = 0.10), mean doses of meperidine (P = 0.23), procedure times (P = 0.06), and willingness to repeat the same procedure in future (P = 0.10). Conclusions Music improves patients’ overall experience with colonoscopy.     

Effect of Probiotics on Blood Lipid Concentrations: A Meta-Analysis of Randomized Controlled Trials

Previous clinical studies have reported mixed results regarding the effect of probiotics on lipid metabolism. Therefore, we conducted a meta-analysis of randomized controlled trials to quantify the direction and magnitude of the potential effect of probiotics on blood lipid concentrations.Eligible studies were randomized, placebo-controlled trials whose interventions were probiotic products containing live bacteria. The studies reported net changes in lipid profiles (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides) and their associated standard deviations (or the data to calculate them). The probiotic products did not contain prebiotics or other active ingredients, and the full article was accessible in English.The pooled mean net change in lipid profiles and 95% confidence intervals (95% CIs) were calculated. Q statistics and I² were calculated to examine heterogeneity. Potential sources of heterogeneity were investigated via subgroup and sensitivity analyses, and publication biases were estimated.A total of 30 randomized controlled trials with 1624 participants (828 in intervention groups and 796 in placebo groups) were included in this analysis. Subjects treated with probiotics demonstrated reduced total cholesterol and LDL cholesterol compared to control subjects by 7.8 mg/dL (95% CI: −10.4, −5.2) and 7.3 mg/dL (95% CI: −10.1, −4.4), respectively. There was no significant effect of probiotics on HDL cholesterol or triglycerides. The effect of probiotics on total cholesterol and LDL cholesterol depended on a variety of factors. The significant effects were greater for higher baseline total cholesterol levels, longer treatment durations, and certain probiotic strains. In addition, these associations seem stronger in studies supported by probiotics companies.The studies included in this meta-analysis showed significant heterogeneity as indicated by the Q statistics and I². In addition, industry sponsorship may affect study findings.These results suggest that the use of probiotics may improve lipid metabolism by decreasing total and LDL cholesterol concentrations. However, both the efficacy of probiotics for cholesterol lowering and safety should be investigated further in well-designed clinical trials.     

Antibiotic Prophylaxis of Bacterial Infections in Cirrhotic Inpatients: a Meta-Analysis of Randomized Controlled Trials

Background: Antibiotic prophylaxis has been reported to decrease bacterial infections and fatality rates in inpatients with cirrhosis. We performed a systematic review to evaluate the efficacy of antibiotic prophylaxis in inpatients with cirrhosis, regardless of the underlying risk factors that led to hospital admission. Methods: A comprehensive literature search strategy was performed including the Cochrane Library, Embase, Medline, a manual search of bibliographic references, and contacting the authors of each included trial. We included any randomized clinical trial comparing different types of antibiotic prophylaxis with placebo or no intervention in inpatients with cirrhosis. Two reviewers independently applied the selection criteria to all identified references, appraised the methodological quality of each trial and extracted the relevant data. Relative risks and 95% confidence intervals were estimated using the fixed effect model. A test of heterogeneity and a funnel plot were performed and an intention-to-treat approach was used for the outcome measures. Results: Nineteen randomized trials were identified, 13 of which were included in the review. A significant beneficial effect on mortality (RR: 0.70; 95% CI: 0.56, 0.89) and prevention of bacterial infections (RR: 0.39; 95% CI: 0.32, 0.48) was observed, regardless of the underlying risk factors. Few adverse events were reported and there was no heterogeneity between studies. We identified a funnel plot asymmetry for the included trials. Conclusions: Antibiotic prophylaxis for inpatients with cirrhosis is efficacious in reducing the number of deaths and bacterial infections regardless of the underlying risk factors.     

Efficacy of Probiotics in Irritable Bowel Syndrome: A Meta-Analysis of Randomized,Controlled Trials

Purpose  This study was designed to evaluate whether probiotics improve symptoms in patients with irritable bowel syndrome. Methods  PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for studies that investigated the efficacy of probiotics in the management of irritable bowel syndrome. Clinical improvement was the key outcome of interest. Data were searched within the time period of 1966 through September 2007. Results  Eight randomized, placebo-controlled, clinical trials met our criteria and were included in the analysis. Pooling of eight trials for the outcome of clinical improvement yielded a significant relative risk of 1.22 (95 percent confidence interval, 1.07–1.4; P = 0.0042). Conclusions  Probiotics may improve symptoms of irritable bowel syndrome and can be used as supplement to standard therapy.     

Prophylactic Corticosteroids Do Not Prevent Post-ERCP Pancreatitis: A Meta-Analysis of Randomized Controlled Trials

Background: Data regarding the use of corticosteroids for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis are conflicting. The aim of this meta-analysis was to compare corticosteroids with placebo for prevention of post-ERCP pancreatitis. Methods: Multiple databases including MEDLINE, EMBASE, Cochrane controlled trials register, the Cochrane Library, Science Citation Index, Google Scholar and Google updated to June 2007 were searched to retrieve the relevant randomized controlled trials. Primary outcome measure was post-ERCP pancreatitis. Results: Six randomized controlled trials involving 2,448 patients were identified. The analysis showed that corticosteroids did not prevent post-ERCP pancreatitis (OR 1.13:95% CI [0.88,1.46]). Subsequent sensitivity and subgroup analyses according to different criteria all confirmed these results. Conclusions: Based on available evidence, prophylactic corticosteroids do not reduce the incidence of post-ERCP pancreatitis.     

Selexipag in Patients With Pulmonary Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Despite the availability of treatments for all subgroups of pulmonary hypertension (PH), the prognosis for PH remains poor. This systematic review and meta-analysis aimed to determine the efficacy and safety of selexipag in patients with PH. A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of PH with selexipag, compared with placebo or blank, were reviewed. Studies were pooled to weighted mean differences (WMDs) and risk ratios (RRs), with 95% confidence intervals (CIs). Selexipag was safe and significantly improved hospitalization for worsening of PH, WHO FC, mPAP, NT-proBNP, and cardiac index in patients with PH. Selexipag should be considered in patients with pulmonary arterial hypertension or chronic thromboembolic PH.     

Efficacy and Safety of Topiramate for Essential Tremor: A Meta-Analysis of Randomized Controlled Trials

Essential tremor (ET) is the most common movement disorder that is frequently treated by propranolol or primidone. However, 30% of patients with ET do not respond to either propranolol or primidone. The objective of this study was to assess the efficacy and safety of topiramate for ET.We searched the MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for relevant randomized controlled trials on the effects of topiramate for ET. A meta-analysis technique was applied to estimate the efficacy and safety of topiramate. The primary outcome was the change in the Fahn–Tolosa–Marin tremor rating scale (TRS). The secondary outcomes included the respective change in the location, motor tasks/function and function disability scores, and adverse events.We included 3 randomized controlled trials with a total of 294 participants. Topiramate was significantly better than placebo in reducing TRS of patients with ET (mean difference [MD] −8.58, 95% confidence interval [CI] −15.46 to −1.70). Changes from the scales of upper limb tremor severity (MD −5.12, 95% CI −7.79 to −2.45), motor tasks/function (MD −5.07, 95% CI −7.12 to −3.03), and functional disability (MD −4.72, 95% CI −6.77 to −2.67) were significantly greater with topiramate than with placebo. More participants taking topiramate experienced adverse events leading to withdrawal than those taking placebo (risk difference 19%, 95% CI 11%–27%).There is consistent evidence supporting the efficacy of topiramate in treating ET; however, a significant proportion of participants withdrew due to its adverse effects.     

The Placebo Response in Randomized Trials in Nonalcoholic Steatohepatitis Simply Explained

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Complete Revascularization in Patients With STEMI and Multi-Vessel Disease: A Meta-Analysis of Randomized Controlled Trials

BackgroundPercutaneous coronary intervention (PCI) is the treatment of choice for ST-elevation myocardial infarction (STEMI). However, efficacy of complete vs culprit only revascularization in patients with STEMI and multivessel disease remains unclear.MethodsWe searched PubMed/MEDLINE, and Cochrane library. The primary endpoint was major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), repeat revascularization, stroke, major bleeding, and contrast induced nephropathy. Estimates were calculated as random effects hazard ratios (HRs) with 95% confidence intervals (CI).ResultsTwelve trials with 7592 patients were included. There was a significantly lower risk of MACE [HR 0.61; 95% CI (0.43–0.60); p = 0.0009; I² = 72%], cardiovascular mortality [HR 0.74; 95% CI (0.56–0.99); p = 0.04; I² = 2%], and repeat revascularization [HR 0.43; 95% CI (0.31–0.59); p < 0.00001; I² = 67%] in patients treated with complete compared with culprit-only revascularization. There was no statistically significant difference in MI [HR 0.77; 95% CI (0.52–1.12); p = 0.17; I² = 49%], all-cause mortality [HR 0.86; 95% CI (0.65–1.13); p = 0.28; I² = 14%], heart failure [HR 0.82 95% CI (0.51–1.32); p = 0.42; I² = 26%], major bleeding [HR 1.07; 95% CI (0.66–1.75); p = 0.78; I² = 25%], stroke [HR 0.67; 95% CI (0.24–1.89); p = 0.45; I² = 54%], or contrast induced nephropathy, although higher contrast volumes were used in the complete revascularization group [HR 1.22; 95% CI (0.78–1.92); p = 0.39; I² = 0%].ConclusionComplete revascularization was associated with a significantly lower risk of MACE, cardiovascular mortality, and repeat revascularization compared with culprit-only revascularization. These results suggest complete revascularization with PCI following STEMI and multivessel disease should be considered.     

Mavacamten Treatment for Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy, yet pharmacological therapy has been unchanged for decades until the recent introduction of mavacamten, a first-in-class cardiac myosin inhibitor. We assessed the efficacy and safety of mavacamten in HCM. To date, only 3 randomized controlled trials (RCTs) compared the outcomes of mavacamten vs placebo for HCM. We used a fixed effects model to calculate risk ratios (RRs) with 95% confidence intervals (CIs). The primary composite endpoint (PCE) was defined as either ≥1.5 mL/kg/min increase in peak oxygen consumption (pVO2) with ≥1 New York Heart Association functional class (NYHA-FC) improvement or ≥3.0 mL/kg/min increase in pVO2 without worsening of NYHA-FC. Secondary outcomes included ≥1 NYHA-FC improvement, septal reduction therapy (SRT) or guideline eligible for SRT, ≥1 serious adverse event (SAE), ≥1 treatment emergency adverse event (TEAE), atrial fibrillation (AF), and nonsustained ventricular tachycardia (NSVT). Three RCTs (n = 422, mean follow-up 24 weeks) were included. Compared to placebo, mavacamten achieved higher rates of PCE (RR 1.92; 95% CI 1.28-2.88; P = 0.002) and ≥1 NYHA-FC improvement (RR 2.10; 95% CI 1.66-2.67; P < 0.00001) and lower rates of SRT or guideline eligible for SRT (RR 0.29; 95% CI 0.22-0.39; P < 0.00001). There were no differences between both groups in ≥1 SAE, AF, and NSVT, however mavacamten had higher rates of ≥1 TEAE. In patients with HCM, mavacamten helps improve pVO2 and NYHA-FC and reduces SRT but may be associated with TEAE. Further research is warranted to evaluate the efficacy, safety, and long-term outcomes of mavacamten.