Jin-Qiu Yuan

Comparative Effectiveness and Safety of Oral Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction: A Systematic Review and Network Meta-analysis

CONTEXT Phosphodiesterase type 5 inhibitors (PDE5-Is) are currently the first-line therapy for erectile dysfunction (ED), but available studies investigating the comparative effects of different PDE5-Is are limited. OBJECTIVE To compare the efficacy and safety of different classes of oral PDE5-Is for ED. EVIDENCE ACQUISITION A systematic search was performed in PubMed, Cochrane Library, and Embase to identify randomized controlled trials that compared different PDE5-Is or PDE5-Is with a placebo for ED. The methodological quality of included studies was appraised with the Cochrane Collaboration bias appraisal tool, and the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation system. EVIDENCE SYNTHESIS A total of 118 trials (31 195 individuals) were included. There was no major difference in the results between the traditional meta-analysis and the network meta-analysis. Network meta-analysis demonstrated that PDE5-Is were superior to placebo to improve erectile function. Compared with tadalafil (relative risk [RR]: 0.61; 95% confidence interval [CI], 0.33-0.90) and vardenafil (RR: 0.63; 95% CI, 0.35-0.92), avanafil was less effective on Global Assessment Questionnaire question 1. Tadalafil was more effective than vardenafil (mean difference [MD]: 1.49; 95% CI, 0.50-2.50) and udenafil (MD: -1.84; 95% CI, -3.31 to -0.33) as measured by the erectile function domain of the International Index of Erectile Function. For all efficacy outcomes, the absolute effects and the rank tests indicated that tadalafil and vardenafil were the most effective agents. After adjusting for dosage, the conclusion remained the same. Safety analysis showed there was no major difference among different agents. CONCLUSIONS In recommended doses, oral PDE5-Is are more effective than placebo for ED, and tadalafil seems to be the most effective agent, followed by vardenafil. PDE5-Is are generally safe and well tolerated, and there is no major difference on the safety profile.

Concordant analysis of KRAS, BRAF, PIK3CA mutations, and PTEN expression between primary colorectal cancer and matched metastases

Current data on the concordance of KRAS, BRAF, PIK3CA mutation status or PTEN expression status between primary tumors and metastases in colorectal cancer (CRC) are conflicting. We conducted a systematic review and meta-analysis to examine concordance and discordance of the status of these four biomarkers between primary tumors and corresponding metastases in CRC patients. The biomarker status in primary tumors was used as the reference standard. Concordance data for KRAS, BRAF, PIK3CA and PTEN were provided by 43, 16, 9 and 7 studies, respectively. The pooled concordance rate was 92.0% (95% CI: 89.7%–93.9%) for KRAS, 96.8% (95% CI: 94.8%–98.0%) for BRAF, 93.9% (95% CI: 89.7%–96.5%) for PIK3CA and 71.7% (95% CI: 57.6%–82.5%) for PTEN. The pooled false positive and false negative rates for KRAS were 9.0% (95% CI: 6.5%–12.4%) and 11.3% (95% CI: 8.0%–15.8%), respectively. KRAS, BRAF and PIK3CA mutations are highly concordant between primary tumors and corresponding metastases in CRC, but PTEN loss is not. Nine percent of patients with wild-type KRAS in primary tumors who received anti-EGFR treatment had mutant KRAS in metastases, while 11.3% patients with mutant KRAS primary tumors had wild-type KRAS in the metastases. These 11.3% patients currently do not receive potentially beneficial anti-EGFR treatment.

Gemcitabine plus erlotinib for advanced pancreatic cancer: a systematic review with meta-analysis.

Background This study aims to comprehensively summarize the currently available evidences on the efficacy and safety of gemcitabine plus erlotinib for treating advanced pancreatic cancer. Methodology/Principal Findings PubMed, EMBASE, The Cochrane Library and abstracts of recent major conferences were systematically searched to identify relevant publications. Studies that were conducted in advanced pancreatic cancer patients treated with gemcitabine plus erlotinib (with or without comparison with gemcitabine alone) and reporting objective response rate, disease control rate, progression-free survival, time-to-progression, overall survival, 1-year survival rate and/or adverse events were included. Data on objective response rate, disease control rate, 1-year survival rate and adverse events rate, respectively, were combined mainly by using Meta-Analyst software with a random-effects model. Data on progression-free survival, time-to-progression and overall survival were summarized descriptively. Sixteen studies containing 1,308 advanced pancreatic cancer patients treated with gemcitabine plus erlotinib were included. The reported median progression-free survival (or time-to-progression), median overall survival, 1-year survival rates, objective response rates and disease control rates were 2–9.6 months, 5–12.5 months, 20%–51%, 0%–28.6% and 25.0%–83.3%, respectively. The weighted 1-year survival rate, objective response rate and disease control rate based on studies reporting robust results were 27.9%, 9.1% and 57.0%, respectively. According to the studies with relevant data, the incidences of total and severe adverse events were 96.3% and 62.9%, respectively. The most frequently reported adverse events were leucopenia, rash, diarrhea, vomitting, neutropenia, thrombocytopenia, anaemia, stomatitis, drug-induced liver injury, fatigue and fever. Compared with gemcitabine alone, the progression-free survival and overall survival with gemcitabine plus erlotinib were significantly longer, but there were also more deaths and interstitial lung disease-like syndrome related to this treatment. Conclusions/Significance Gemcitabine plus erlotinib represent a new option for the treatment of advanced pancreatic cancer, with mild but clinically meaningful additive efficacy compared with gemcitabine alone. Its safety profile is generally acceptable, although careful management is needed for some specific adverse events.

The efficacy and safety of alpha-1 blockers for benign prostatic hyperplasia: an overview of 15 systematic reviews

Abstract Objective: A great number of clinical trials and systematic reviews have evaluated the efficacy and safety of α1 blockers for benign prostatic hyperplasia (BPH). We carried out an overview of reviews to provide an up-to-date summary of evidence regarding the efficacy and safety between different α1 blockers for BPH. Research design and methods: PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical Literature Database and VIP were searched for eligible studies. Direct evidence was analyzed narratively. We used a random-effects model within a Bayesian framework to calculate indirect estimates if no direct evidence existed. The GRADE approach was used in summarizing conclusions. Results: A total of 15 systematic reviews involving five α1 blockers met the inclusion criteria. Direct evidence demonstrated that α1 blockers were superior to placebo in reducing urinary symptom scores and improving peak urinary flow PUF. Doxazosin could significantly reduce urinary symptom scores compared with tamsulosin mean difference (MD −1.60, 95% CI −1.80 to −1.40) and alfuzosin (MD1.7, 95% CI 0.76–1.64). Indirect evidence suggested that the urinary symptom score and PUF at endpoint in men treated with naftopidil were similar to those treated with other α1 blockers. α1 Blockers generally lead to more adverse effects compared with placebo, and those caused by terazosin were more frequent than others. Conclusions: α1 Blockers are more effective than placebo for BPH, doxazosin and tamsulosin seem to be more effective than other α1 blockers. The adverse effects caused by α1 blockers are generally mild and well-tolerated.

Systematic review with network meta-analysis: comparative effectiveness and safety of strategies for preventing NSAID-associated gastrointestinal toxicity.

Many strategies are used to prevent nonsteroidal anti‐inflammatory drug (NSAID)‐associated gastrointestinal toxicity, but the comparative effectiveness remains unclear.

Blood as a Substitute for Tumor Tissue in Detecting EGFR Mutations for Guiding EGFR TKIs Treatment of Nonsmall Cell Lung Cancer: A Systematic Review and Meta-Analysis.

AbstractTumor tissues are often absent or insufficient for testing epidermal growth factor receptor (EGFR) mutations to guide EGFR tyrosine kinase inhibitors (TKIs) treatment of patients with nonsmall cell lung cancer (NSCLC).We conducted this systematic review and meta-analysis to assess whether blood can be used as a substitute for tumor tissue in detecting EGFR mutations.MEDLINE, EMBASE, and the Cochrane Library were searched for studies that provided data to estimate the accuracy of blood testing against tissue testing in NSCLC patients and/or those directly compared the efficacy of EGFR TKIs in EGFR mutant and wild-type patients according to sources of specimens.Sensitivity, specificity, and concordance rate were used as measures of the accuracy. Risk ratio (RR) for objective response and hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) were used as measures for treatment efficacy. We combined the effects by using the fixed-effects model unless there was evidence of heterogeneity, in which case a random-effects mode was used.This systematic review included 25 studies with 2605 patients. The pooled overall sensitivity, specificity, and concordance rate were 0.61, 0.90, and 0.79, respectively. Serum showed lower sensitivity (0.56 vs 0.65) but higher specificity (0.95 vs 0.85) and higher concordance (0.86 vs 0.74) than plasma. EGFR mutations (exon 19 or 21) in blood were significantly associated with objective response (RR: 4.08; 95% confidence interval [CI] 2.48–6.70), PFS (HR: 0.72; 95% CI 0.64–0.80), and OS (HR: 0.71; 95% CI 0.50–0.99). Importantly, the association of the mutations with the 3 clinical outcomes for serum was similar to that for tumor tissue and higher than that for plasma.Blood, in particular serum, is a good substitute when tumor tissue is absent or insufficient for testing EGFR mutations to guide EGFR TKIs treatment in patients with NSCLC. EGFR mutation positivity in blood could be used to recommend EGFR TKIs treatment, but the absence of blood positivity should not necessarily be construed with confirmed negativity.

Systematic review and meta-analysis of application of fibrin sealant after liver resection

Abstract Background: Fibrin sealant (FS) has been increasingly used on the raw surface after liver resection but its clinical value has not been established to date. The aim of this study was to evaluate the efficacy and safety of the employment of FS after liver resection. Methods: PubMed, Cochrane Library, Embase, CNKI, CBM and VIP were searched for randomized trials comparing the effect of FS with no FS or any other intervention for patients undergoing liver resection. Primary outcomes included time to hemostasis, hemostatic success, amount of drainage and drainage duration. Results: Eleven randomized controlled trials were included. Meta-analysis suggested that the amount of drainage (standard mean difference −0.30; 95% confidence interval [CI] −0.82 to 0.23) and drainage duration (mean difference [MD] −0.46, 95% CI −0.61 to −1.53) were similar between FS group and no FS group. Compared with topical hemostatic agents, FS could significantly reduce time to hemostasis (MD −208.46, 95% CI −228.22 to −188.70) and increase hemostasis success rate (relative risk 1.35, 95% CI 1.17 to 1.57). Two trials compared FS with argon beam coagulation (ABC), which both suggested that FS could significantly decrease the time to hemostasis. Conclusions: This study demonstrated a modest benefit of FS over no FS, topical hemostatic agents and ABC in controlling intraoperative bleeding from the raw liver surface after liver resection. But there is no evidence that FS is beneficial to patients in reducing amount of drainage and drainage duration.

Association between Directly Observed Therapy and Treatment Outcomes in Multidrug-Resistant Tuberculosis: A Systematic Review and Meta-Analysis

Background Multidrug-resistant tuberculosis (MDR-TB) represents a major obstacle towards successful TB control. Directly observed therapy (DOT) was recommended by WHO to improve adherence and treatment outcomes of MDR-TB patients, however, the effectiveness of DOT on treatment outcomes of MDR-TB patients was mixed in previous studies. We conducted this systematic review and meta-analysis to assess the association between DOT and treatment outcomes and to examine the impact of different DOT providers and DOT locations on successful treatment outcomes in MDR-TB patients. Methods We searched studies published in English between January 1970 and December 2015 in major electronic databases. Two reviewers independently screened articles and extracted information of DOT, treatment success rate and other characteristics of studies. Random effects model was used to calculate the pooled treatment success rate and 95% confidence interval (CI). Sub-group analyses were conducted to access factors associated with successful treatment outcomes. Results A total of 31 articles 7,466 participants were included. Studies reporting full DOT (67.4%, 95% CI: 61.4–72.8%) had significantly higher pooled treatment success rates than those reporting self-administration therapy (46.9%, 95% CI: 41.4–52.4%). No statistically difference was found among DOT provided by healthcare providers (65.8%, 95% CI: 55.7–74.7%), family members (72.0%, 95% CI: 31.5–93.5%) and private DOT providers (69.5%, 95% CI: 57.0–79.7%); and neither did we find significantly difference on pooled treatment success rates between patients having health facility based DOT (70.5%, 95% CI: 61.5–78.1%) and home-based DOT (68.4%, 95% CI: 51.5–81.5%). Conclusion Providing DOT for a full course of treatment associated with a higher treatment success rate in MDR-TB patients.

The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis

Objectives Estimate the epidermal growth factor receptor (EGFR) mutation prevalence in all non-small cell lung cancer (NSCLC) patients and patient subgroups. Results A total of 456 studies were included, reporting 30,466 patients with EGFR mutation among 115,815 NSCLC patients. The overall pooled prevalence for EGFR mutations was 32.3% (95% CI 30.9% to 33.7%), ranging from 38.4% (95% CI: 36.5% to 40.3%) in China to 14.1% (95% CI: 12.7% to 15.5%) in Europe. The pooled prevalence of EGFR mutation was higher in females (females vs. males: 43.7% vs. 24.0%; OR: 2.7, 95% CI: 2.5 to 2.9), non-smokers (non-smokers vs. past or current smokers: 49.3% vs. 21.5%; OR: 3.7, 95% CI: 3.4 to 4.0), and patients with adenocarcinoma (adenocarcinoma vs. non-adenocarcinoma: 38.0% vs. 11.7%; OR: 4.1, 95% CI: 3.6 to 4.8). Materials and Methods PubMed, EMBASE, and the Cochrane Library were searched to June 2013. Eligible studies reported EGFR mutation prevalence and the association with at least one of the following factors: gender, smoking status and histology. Random-effects models were used to pool EGFR mutation prevalence data. Conclusion This study provides the exact prevalence of EGFR mutations in different countries and NSCLC patient subgroups.

Methodological quality of meta-analyses on treatments for chronic obstructive pulmonary disease: a cross-sectional study using the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool

Background:Meta-analysis (MA) of randomised trials is considered to be one of the best approaches for summarising high-quality evidence on the efficacy and safety of treatments. However, methodological flaws in MAs can reduce the validity of conclusions, subsequently impairing the quality of decision making.Aims:To assess the methodological quality of MAs on COPD treatments.Methods:A cross-sectional study on MAs of COPD trials. MAs published during 2000–2013 were sampled from the Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effect. Methodological quality was assessed using the validated AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool.Results:Seventy-nine MAs were sampled. Only 18% considered the scientific quality of primary studies when formulating conclusions and 49% used appropriate meta-analytic methods to combine findings. The problems were particularly acute among MAs on pharmacological treatments. In 48% of MAs the authors did not report conflict of interest. Fifty-eight percent reported harmful effects of treatment. Publication bias was not assessed in 65% of MAs, and only 10% had searched non-English databases.Conclusions:The methodological quality of the included MAs was disappointing. Consideration of scientific quality when formulating conclusions should be made explicit. Future MAs should improve on reporting conflict of interest and harm, assessment of publication bias, prevention of language bias and use of appropriate meta-analytic methods.