Dexmedetomidine effect on delirium in elderly patients undergoing general anesthesia: A protocol for systematic review and meta-analysis

Background:Delirium is a common postoperative complication. Many studies have found that dexmedetomidine is associated with a reduced incidence of postoperative delirium (POD). This meta-analysis aimed to analyze the effects of dexmedetomidine on POD incidence among elderly patients undergoing general anesthesia.Methods:We searched 4 electronic databases (i.e., Pubmed, Embase, Cochrane, and Web of Science) from inception to November 30, 2020, for randomized controlled trials that evaluated the effects of dexmedetomidine in preventing the occurrence of POD in elderly patients (aged ≥60 years). The study protocol was registered in PROSPERO (CRD42020192114).Results:14 studies with 4173 patients showed that dexmedetomidine was significantly associated with a decreased POD incidence among elderly patients (relative risk [RR] = 0.58; 95% confidence interval [CI] = 0.44–0.76). The incidence of POD was significantly reduced in the noncardiac surgery group (RR 0.51; 95% CI 0.37–0.72), when dexmedetomidine was applied during the postoperative period (RR = 0.53; 95% CI = 0.40–0.70), and in patients received low-doses (RR = 0.54; 95% CI = 0.34–0.87) and normal-doses (RR = 0.59; 95% CI = 0.42–0.83). There were no significant differences in POD incidence in the cardiac surgery group (RR = 0.71; 95% CI = 0.45–1.11), and when dexmedetomidine was applied during the intra- (RR = 0.55; 95% CI = 0.29–1.01) or perioperative period (RR = 0.95; 95% CI = 0.64–1.40).Conclusions:Our meta-analysis suggests that dexmedetomidine may significantly reduce POD incidence in elderly noncardiac surgery patients and when applied during the postoperative period, in addition, both low- and normal-doses of dexmedetomidine may reduce POD incidence. However, its use in cardiac surgery patients and during the intra- or perioperative period may have no significant effects on POD incidence.     

Perioperative omega-3 fatty acids for liver surgery: A meta-analysis of randomized controlled trials

Introduction:The effect of perioperative omega-3 fatty acids for liver surgery remained controversial. We conducted a systematic review and meta-analysis to explore the influence of omega-3 fatty acids versus placebo in patients undergoing liver surgery.Methods:We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through May 2020, and included randomized controlled trials (RCTs) assessing the effect of omega-3 fatty acids versus placebo for liver surgery. This meta-analysis was performed using the random-effect model.Results:Five RCTs were included in the meta-analysis. Overall, compared with control group for liver surgery, omega-3 fatty acids were associated with substantially reduced incidence of infection (odd ratio [OR]=0.56; 95% confidence interval [CI] =0.34–0.91; P = .02), but revealed no remarkable influence on complications (OR = 0.60; 95% CI = 0.29–1.24; P = .17), mortality (OR = 0.76; 95% CI = 0.06–9.37; P = .83), liver failure (OR = 0.72; 95% CI = 0.10 to 5.00; P = 0.74), biliary leakage (OR=1.24; 95% CI = 0.41 to 3.76; P = .70), bleeding (OR = 1.76; 95% CI = 0.63–4.95; P = .28), or ileus (OR = 0.39; 95% CI = 0.07–2.05; P = .27).Conclusion:Perioperative omega-3 fatty acids may be beneficial to reduce the incidence of infection after liver surgery.     

The comparison of ketamine with tramadol for postoperative pain relief on children following adenotonsillectomy or tonsillectomy: A meta-analysis of randomized controlled trials

Introduction:The comparison of ketamine with tramadol for pain control remains controversial in pediatric adenotonsillectomy or tonsillectomy. We conduct a systematic review and meta-analysis to explore the efficacy of ketamine vs tramadol for pain relief in children following adenotonsillectomy or tonsillectomy.Methods:We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through October 2019 for randomized controlled trials (RCTs) assessing the effect of ketamine vs tramadol for pediatric adenotonsillectomy or tonsillectomy. This meta-analysis is performed using the random-effects model.Results:Six RCTs are included in the meta-analysis. Overall, compared to ketamine group for pediatric adenotonsillectomy or tonsillectomy, tramadol is associated with substantially lower CHEOPS at 1 h (SMD = 1.56; 95% CI = 0.20–2.92; P = .02; low quality) and longer first time of additional pain medication (SMD = −0.47; 95% CI = −0.74 to −0.19; P = .0008; low quality), but demonstrates no obvious effect on CHEOPS at 6 h (SMD = 0.51; 95% CI = −1.17 to 2.19; P = .55; low quality), sedation scale at 1 h (SMD = −0.80; 95% CI = −3.07 to 1.48; P = .49; low quality) or additional pain medication (RR = 1.31; 95% CI = 0.85–2.02; P = .23; moderate quality).Conclusions:Tramadol may be better to alleviate the postoperative pain after pediatric adenotonsillectomy or tonsillectomy.     

Analgesic comparison of dezocine plus propofol versus fentanyl plus propofol for gastrointestinal endoscopy: A meta-analysis

Introduction:As the adjunctive anesthesia to propofol, both dezocine and fentanyl showed some potential for gastrointestinal endoscopy. This meta-analysis aimed to compare their efficacy and safety.Methods:PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of dezocine versus fentanyl for the anesthesia of patients undergoing gastrointestinal endoscopy were included.Results:Five RCTs involving 677 patients were included in the meta-analysis. Overall, compared with fentanyl plus propofol for gastrointestinal endoscopy, dezocine plus propofol resulted in the reduction in propofol dose(mean difference [MD] = −11.72; 95% confidence interval [CI] = −22.83 to −0.61; P = .04), awakening time (std. MD = −1.79; 95% CI = −3.31 to −0.27; P = .02) and hypopnea (risk ratio [RR] = 0.16; 95% CI = 0.06–0.41; P = .0002), but had no remarkable effect on induction time (MD = 1.20; 95% CI = −0.98 to 3.39; P = .28), postoperative pain score (MD = −0.38; 95% CI = −1.00 to 0.24; P = .24), nausea or vomiting (RR = 0.45; 95% CI = 0.10–1.98; P = .29).Conclusion:Dezocine plus propofol may be better for the anesthesia of gastrointestinal endoscopy than fentanyl plus propofol.     

Monotherapy with mirabegron had a better tolerance than the anticholinergic agents on overactive bladder: A systematic review and meta-analysis

Background:We conducted this meta-analysis to explore the tolerance of monotherapy with mirabegron (50 mg) on an overactive bladder, compared with a common dosage of anticholinergic agents.Materials and methods:A comprehensive search for all randomized controlled trials that evaluated the safety of mirabegron and anticholinergic agents on overactive bladder was performed, and we searched the Cochrane Central Register of Controlled trials databases, Pubmed, Embase, and relevant trials from 2013.02 to 2019.10.Results:Eight studies included 5500 patients with treatment of monotherapy on overactive bladder were identified. The total number of treatment-emergent adverse events had no significantly difference between two monotherapies (RR = 0.88 95%CI: 0.76–1.01; P = .08); however, patients would have a better tolerance with mirabegron (50 mg) in adverse events of dry mouth (RR = 0.42; 95%CI: 0.33–0.53; P < .01) and tachycardia (RR = 0.52; 95%CI: 0.29–0.94; P = .03); and there were no significant differences between two groups in hypertension (RR = 1.02; 95%CI: 0.80–1.30; P = .90), constipation (RR = 0.91; 95%CI: 0.65–1.26; P = 0.57), blurred vision (RR = 1.03; 95%CI: 0.60–1.77; P = 0.92), and urinary tract infection (RR = 0.90; 95%CI: 0.70–1.16; P = .41).Conclusions:Treatment-emergent adverse events in patients with overactive bladder who underwent monotherapy of mirabegron (50 mg) or the anticholinergic agents had no significant differences, but mirabegron has a better tolerance in the aspect of dry mouth and tachycardia.     

Integrative treatment of herbal medicine with western medicine on coronary artery lesions in children with Kawasaki disease

Background:Kawasaki disease (KD) is a major cause of coronary artery lesions (CALs) in children. Approximately 10% to 20% of children treated with intravenous immunoglobulin are intravenous immunoglobulin-resistant. This study evaluated the efficacy and safety of adding herbal medicine to conventional western medicines versus conventional western medicines alone for CALs in children with KD.Methods:This study searched 9 electronic databases until August 31, 2021. The inclusion criteria were the randomized controlled trials (RCTs) that assessed the CALs in children with KD and compared integrative treatment with conventional western treatments. Two authors searched independently for RCTs, including eligible articles that fulfilled the inclusion criteria, extracted data, and assessed the methodological quality using the Cochrane risk of bias tool. Meta-analysis was conducted using Cochrane Collaboration''s Review Manager 5.4 software. The effect size was presented as the risk ratio (RR), and the fixed-effect models were used to pool the results.Results:The finally selected 12 studies included a total of 1030 KD patients. According to a meta-analysis, the integrative treatment showed better results than the conventional treatment in the CAL prevalence rate (RR = 2.00; 95% confidence interval [CI], 1.49–2.71; P < .00001), CAL recovery rate (RR = 1.27; 95% CI, 1.05–1.54; P = .02), and total effective rate (RR = 1.17; 95% CI, 1.11–1.23; P < .00001). Only 2 studies referred to the safety of the treatment. The asymmetrical funnel plot of the CAL prevalence rate indicated the possibility of potential publication bias.Conclusions:This review found the integrative treatment to be more effective in reducing the CAL prevalence rate and increasing the CAL recovery rate and total effective rate in KD patients than conventional western treatment. However, additional well-designed RCTs will be needed further to compensate restrictions of insufficient trials on safety, methodological quality, and publication bias.     

Maintenance treatment of combination with bevacizumab vs single agent for advanced non-squamous non-small cell lung cancer: A systematic review and meta-analysis

Background:When the patients of advanced non-squamous non-small cell lung cancer (NSCLC) have achieved remission by induction therapy, it is controversial that combination with bevacizumab is used as maintenance therapy. Pemetrexed is a classic drug for maintenance therapy, is bevacizumab the superiority to pemetrexed is also unclear. This meta-analysis aims to evaluate the effectiveness and safety of advanced non-squamous NSCLC in the maintenance treatment.Method:From the establishment as of December 6, 2020, PubMed, Embase, and Cochrane electronic databases were searched and the American Society of Clinical Oncology, European Society of Medical Oncology, and National Comprehensive Cancer Network databases in the past 10 years. The application of combination with bevacizumab, pemetrexed was studied in clinical trials of maintenance treatment for advanced NSCLC. The extracted data include progression-free survival (PFS), overall survival (OS), and grade 3–4 adverse events (AE).Results:Seven clinical trials we screened, 6 were phase III RCTs, and a cohort trial, including 3298 patients. Compared with bevacizumab and pemetrexed, PFS of combination with bevacizumab was significantly improved (hazard ratio [HR] = 0.71, 95% confidence interval [CI] = 0.65–0.77, P < .00001), but OS was not improved (HR = 0.93, 95% CI = 0.85–1.01, P = .10). Compared with bevacizumab and pemetrexed, no significant difference of PFS (HR = 0.87, 95% CI = 0.69–1.09, P = .21), and OS (HR = 0.87, 95% CI = 0.72–1.05, P = .15) was found. A higher incidence of grade 3–4 AE occurred in combination with bevacizumab (odds ratio = 1.63, 95% CI = 1.35–1.97, P < .00001).Conclusions:PFS was significantly improved in patients with advanced non-squamous NSCLC who use bevacizumab combination with single-agent as maintenance treatment, but it does not translate into the advantages of OS; compared with bevacizumab, no PFS and OS benefits were found. A higher incidence of grade 3–4 AE occurred in combination with bevacizumab than pemetrexed and bevacizumab.     

Influence of ketamine versus fentanyl on pain relief for pediatric orthopedic emergencies: A meta-analysis of randomized controlled studies

Introduction:The comparison of ketamine with fentanyl for pain control of pediatric orthopedic emergencies remains controversial. We conduct a systematic review and meta-analysis to explore the influence of ketamine versus fentanyl on pain management among pediatric orthopedic emergencies.Methods:We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through September 2020 for randomized controlled trials assessing the effect of ketamine versus fentanyl on pain management for pediatric orthopedic emergencies.Results:Five randomized controlled trials are included in the meta-analysis. Overall, compared with fentanyl for pediatric orthopedic emergencies, ketamine led to similar change in pain scores at 15 to 20 minutes (standard mean difference = -0.05; 95% confidence interval [CI] = -0.38 to 0.28; P = .77) and 30 minutes (standard mean difference = 0.11; 95% CI = -0.20 to 0.42; P = .49), as well as rescue analgesia (RR = 0.90; 95% CI = 0.54 to 1.51; P = .69), but revealed the increase in nausea/vomiting (RR = 2.65; 95% CI = 1.13 to 6.18; P = .02) and dizziness (RR = 3.83; 95% CI = 1.38 to 10.60; P = .01).Conclusions:Ketamine may be similar to fentanyl in terms of the analgesic efficacy for pediatric orthopedic emergencies.     

The analgesic efficacy of pregabalin for shoulder arthroscopy: A meta-analysis of randomized controlled trials

Introduction:The efficacy of pregabalin for pain management of shoulder arthroscopy remains controversial. We conduct this meta-analysis to explore the influence of pregabalin versus placebo on the postoperative pain intensity of shoulder arthroscopy.Methods:We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through November 2019 for randomized controlled trials assessing the effect of pregabalin versus placebo on pain control of shoulder arthroscopy. This meta-analysis was performed using the random-effect model.Results:Three randomized controlled trials were included in the meta-analysis. Overall, compared with control group for shoulder arthroscopy, pregabalin remarkably decreased pain scores at 0 to 1 hour (Std. MD = −0.57; 95% CI = −1.04 to −0.09; P = .02) and 12 hours (Std. MD = −0.37; 95% CI = −0.72 to −0.02; P = .04), as well as analgesic consumption (Std. MD = −1.84; 95% CI = −2.24 to −1.44; P < .00001), but showed no notable influence on pain scores at 24 hours (Std. MD = −0.54; 95% CI = −1.47 to 0.38; P = .25), nausea or vomiting (RR = 0.84; 95% CI = 0.53–1.33; P = .45), dizziness (RR = 1.14; 95% CI = 0.89–1.47; P = .30).Conclusions:Pregabalin may benefit to pain control after shoulder arthroscopy.     

The Efficacy and Toxicity of Paclitaxel Plus S-1 Compared With Paclitaxel Plus 5-Fu for Advanced Gastric Cancer: A PRISMA Systematic Review and Meta-analysis of Randomized Controlled Trials

The standard treatment for patients with advanced gastric cancer (AGC) is still a matter of debate. The chemotherapy regimen of paclitaxel (PTX) combined with S-1 has been used to treat AGC or metastatic gastric cancer.We conducted a meta-analysis to compare oral S-1 and infusional 5-fluorouracil (5-FU) to determine which agent was more efficacious and less toxic in combination with PTX. A systematic review with a meta-analysis was performed. PubMed, EmBase, the Cochrane Central Register of Controlled Trials, and the China National Knowledge Infrastructure databases were searched to select randomized controlled trials (RCTs) comparing PTX plus S-1 and PTX plus 5-FU in patients with AGC.Three RCTs were eligible and 352 patients were analyzed. PTX plus S-1 increased the disease control rate (risk ratio [RR] = 1.14, 95% confidence interval [CI] = 1.00–1.30, P = 0.04) and reduced the progressive disease rate (RR = 0.62, 95% CI] = 0.39–0.98, P = 0.04) compared with PTX plus 5-FU. There was a significant decrease in nausea (RR = 0.60, 95% CI = 0.43–0.82, P = 0.001) and vomiting (RR = 0.55, 95% CI = 0.33–0.91, P = 0.02) in patients treated with PTX plus S-1.PTX plus S-1 was associated with almost equivalent safety and a lower progressive disease rate compared with PTX plus 5-FU. PTX plus S-1 is a good alternative strategy for patients who cannot tolerate a continuous intravenous infusion.     

Association of the VEGFR2 single nucleotide polymorphism rs2305948 with glioma risk

Background:Many studies have reported a relationship between the vascular endothelial growth factor receptor 2 single nucleotide polymorphism (SNP) rs2305948 and glioma, but their conclusions have been controversial. A meta-analysis was performed to assess the association between rs2305948 and glioma susceptibility.Methods:Inclusion criteria and a strategy for screening of original literature were created. Eligible articles on the correlation between the SNP rs2305948 and glioma were identified in the PubMed, Embase, Web of Science, Cochrane Library, CNKI and Wanfang databases. After extracting the data, Stata 12. 0 software was used to perform statistical analysis under 5 genetic models and to calculate the combined odds ratio (OR) value and its 95% confidence interval (CI).Results:Four case-control studies including 1595 cases and 1657 controls were entered into the study. The overall analysis showed that no obvious association existed between rs2305948 and glioma risk (allele: OR = 1.20, 95% CI = 0.93–1.54, P = .162; dominant: OR = 1.17, 95% CI = 0.93–1.46, P = .174; recessive: OR = 1.72, 95% CI = 0.94–3.15, P = .076; heterozygous: OR = 1.11, 95% CI = 0.94–1.30, P = .226; homozygous: OR = 1.74, 95% CI = 0.92–3.29, P = .088). The subgroup analysis suggested that the SNP rs2305948 was related to glioma susceptibility under allele, dominant, recessive and homozygote models in the Asian population (allele: OR = 1.34, 95% CI = 1.16–1.55, P < .001; recessive: OR = 2.24, 95% CI = 1.49–3.36, P < .001; homozygous: OR = 2.32, 95% CI = 1.54–3.50, P < .001).Conclusion:The vascular endothelial growth factor receptor 2 rs2305948 gene polymorphism may be related to glioma susceptibility in the Asian population. However, the association is not clear in non-Asian populations, for which there has been less research.     

Rosuvastatin Treatment for Preventing Contrast-Induced Acute Kidney Injury After Cardiac Catheterization: A Meta-Analysis of Randomized Controlled Trials

We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the protective effects of rosuvastatin on contrast-induced acute kidney injury (CI-AKI) and major adverse cardiovascular events (MACEs) in patients undergoing cardiac catherization.PubMed, MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Central RCTs were searched for RCTs from inception to May 2015, to compare rosuvastatin for preventing CI-AKI with placebo treatment in patients undergoing cardiac catherization.Five RCTs with a total of 4045 patients involving 2020 patients pretreated with rosuvastatin and 2025 control patients were identified and analyzed. Patients treated with rosuvastatin had a 51% lower risk of CI-AKI compared with the control group based on a fixed-effect model (OR = 0.49, 95% CI = 0.37–0.66, P < 0.001), and showed a trend toward a reduced risk of MACEs (OR = 0.62, 95% CI = 0.36–1.07, P = 0.08). A subgroup analysis showed that studies with Jadad score ≥3 showed a significant reduction of CI-AKI (OR = 0.53, 95% CI, 0.38–0.73, P < 0.001). However, the risk of CI-AKI did not significantly differ in the studies with Jadad score <3 (OR = 0.54, 95% CI, 0.13–2.24, P = 0.40). In addition, the rosuvastatin treatment showed no effect for preventing CI-AKI in patients with chronic kidney disease (CKD) undergoing elective cardiac catherization (I² = 0%, OR = 0.81, 95% CI = 0.41–1.61, P = 0.55).This updated meta-analysis demonstrated that preprocedural rosuvastatin treatment could significantly reduce the incidence of CI-AKI, with a trend toward a reduced risk of MACEs in patients undergoing cardiac catheterization. However, rosuvastatin treatment did not seem to be effective for preventing CI-AKI in CKD patients undergoing elective cardiac catheterization.     

Traditional herbal medicine combined with first-line platinum-based chemotherapy for advanced non-small-cell lung cancer: A PRISMA-compliant systematic review and meta-analysis

Background:Non-small-cell lung cancer (NSCLC) is a major health burden in many countries. This review aimed to evaluate the efficacy of traditional herbal medicine (THM) combined with first-line platinum-based chemotherapy (PBCT) for the treatment of advanced NSCLC.Methods:From inception to April 2021, relevant studies were retrieved from 9 electronic databases. Randomized controlled trials (RCTs) comparing survival outcomes of THM + PBCT treatment with PBCT treatment in patients with advanced NSCLC were reviewed. The risk of bias was evaluated using the Cochrane Risk of Bias Tool. Overall survival, 1-year survival, progression-free survival or time to progression, tumor response rate, and adverse effects were analyzed.Results:Sixteen RCTs comprising 1445 patients were included. The meta-analysis indicated that THM + PBCT treatment, compared to PBCT alone, could improve overall survival (median survival ratio = 1.24, 95% confidence intervals [CI] [1.11, 1.39], P < .001), progression-free survival/time to progression (median survival ratio = 1.22, 95% CI [1.09, 1.37], P < .001), and the 1-year survival rate (risk ratio [RR] = 1.56, 95% CI [1.31, 1.86], P < .001). THM + PBCT also led to a higher tumor response rate (RR = 1.39, 95% CI [1.22, 1.59], P < .001) and lower incidence of thrombocytopenia (RR = 0.72, 95% CI [0.56, 0.92], P = .009) and nausea/vomiting (RR = 0.35, 95% CI [0.21, 0.57], P < .001), while there was no significant effect observed on leukopenia (RR = 0.68, 95% CI [0.34, 1.36], P = .27).Conclusion:THM, when used in combination with PBCT, might increase survival and the tumor response rate while decreasing the side effects caused by chemotherapy in patients with advanced NSCLC. However, considering the limited methodological qualities of the included trials, more rigorous RCTs are needed.     

Glutamine Supplementation in Intensive Care Patients: A Meta-Analysis of Randomized Clinical Trials

The role of glutamine (GLN) supplementation in critically ill patients is controversial. Our aim was to analyze its potential effect in patients admitted to intensive care unit (ICU).We performed a systematic literature review through Medline, Embase, Pubmed, Scopus, Ovid, ISI Web of Science, and the Cochrane-Controlled Trials Register searching for randomized clinical trials (RCTs) published from 1983 to 2014 and comparing GLN supplementation to no supplementation in patients admitted to ICU. A random-effect meta-analysis for each outcome (hospital and ICU mortality and rate of infections) of interest was carried out. The effect size was estimated by the risk ratio (RR).Thirty RCTs were analyzed with a total of 3696 patients, 1825 (49.4%) receiving GLN and 1859 (50.6%) no GLN (control groups). Hospital mortality rate was 27.6% in the GLN patients and 28.6% in controls with an RR of 0.93 (95% CI = 0.81–1.07; P = 0.325, I² = 10.7%). ICU mortality was 18.0 % in the patients receiving GLN and 17.6% in controls with an RR of 1.01 (95% CI = 0.86–1.19; P = 0.932, I² = 0%). The incidence of infections was 39.7% in GLN group versus 41.7% in controls. The effect of GLN was not significant (RR = 0.88; 95% CI = 0.76–1.03; P = 0.108, I² = 56.1%).These results do not allow to recommend GLN supplementation in a generic population of critically ills. Further RCTs are needed to explore the effect of GLN in more specific cohort of patients.     

Therapeutic efficacy and safety of Kangfuxin in combination with rabeprazole in the treatment of peptic ulcer: A systematic review and meta-analysis

Background:Kangfuxin (KFX), a well-known Chinese patent medicine which extracted from Periplaneta americana, is widely used as an adjuvant in the treatment of peptic ulcers (PUs) with proton pump inhibitors (PPIs) such as rabeprazole, in China. However, no clear consensus has been reached on the efficacy for PU treatment.Methods:We searched in 7 electronic databases to find randomized controlled trials (RCTs) completed before May 31, 2020 to explore the clinical efficiency of KFX plus rabeprazole in the treatment of PU. Risk ratio (RR) corresponding to 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by both Egger''s and Begg''s tests. Statistical analyses were performed using RevMan 5.4 and Stata version 10.0.Results:Twenty-five RCTs, comprising 2555 PU patients, were included in this study. Meta-analysis showed that, when compared with rabeprazole-based treatment alone, KFX plus rabeprazole significantly improved the healing rate (RR = 1.34, 95% CI 1.25–1.44) and overall response rate of ulcers (RR = 1.16, 95% CI 1.13–1.20), alleviated the clinical symptoms of PU (RR = 1.14, 95% CI 1.08–1.21), and reduced the recurrence of PU (RR = 0.38, 95% CI 0.24–0.61) without an increase in the occurrence of adverse events (RR = 0.92, 95% CI 0.66–1.28).Conclusion:Our study suggests that KFX combined with rabeprazole showed positive therapeutic effects and is safe for treating PU, which may provide more reliable evidence for the clinical use of KFX in the treatment of PU.     

Low-Dose Versus Standard Dose of Bacillus Calmette-Guerin in the Treatment of Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis

Whether low-dose Bacillus Calmette-Guerin (BCG) treatment can reduce the side effects while maintaining efficacy for patients with nonmuscle invasive bladder cancer (NMIBC) is controversial.To investigate whether low-dose BCG treatment can reduce the side effects while maintaining efficacy for patients with NMIBC when compared with standard-dose BCG treatment.A comprehensive literature search of PubMed, EMBASE, CINAHL, LILACS, and CENTRAL databases was conducted to identify relevant randomized controlled trials (RCT) or quasi-randomized controlled trials (qRCT) that have assessed the efficacy of low- and standard-dose BCG therapy for patients with NMIBC. Systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis Criteria.Six RCTs and 2 qRCTs were eligible for meta-analysis. Low-dose BCG instillation was not inferior to reduce the risk of bladder tumor recurrence (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.00–1.31; P = 0.05), meanwhile no difference was found regarding tumor progression (HR = 1.08; 95%CI, 0.83–1.42; P = 0.57). However, low-dose BCG provided a significantly lower incidence of overall side effects (RR = 0.75; 95%CI, 0.60–0.94; P = 0.01), systemic side effects (RR = 0.57; 95%CI, 0.34–0.97; P = 0.04), severe side effects (RR = 0.52; 95%CI, 0.36–0.74; P = 0.0003), and withdrawal due to BCG toxicity (RR = 0.49; 95%CI, 0.26–0.91; P = 0.02). In contrast, local side effects were comparable between low- and standard-dose arms (RR = 0.89; 95%CI, 0.73–1.08; P = 0.24).Low-dose BCG instillation significantly reduces the incidence of overall side effects, especially severe and systemic symptoms in patients with NMIBC, while the oncological control efficacy of low-dose BCG is not inferior to standard-dose BCG. Further studies with stratification using different risk factors at randomization are required to assess whether the efficacy of low-dose BCG is comparable to standard dose BCG for different risk of patients.PROSPERO registration No CRD42014014871 (www.crd.york.ac.uk/prospero/).     

Association of interleukin-6 gene polymorphisms with the risk of hepatocellular carcinoma: An up-to-date meta-analysis

Background:This study was aimed to evaluate the association between interleukin-6 (IL-6) gene polymorphisms and the risk of hepatocellular carcinoma (HCC) in a meta-analysis.Methods:A literature search was performed for case-control studies published during May, 1993 to May, 2020 focusing on IL-6 gene polymorphisms (–174G > C, –572G > C, and –597G > A) and HCC susceptibility by using PubMed, Cochrane Database, EMBASE, Web of science, and China National Knowledge Infrastructure. From 128 full-text articles, 11 were included in this meta-analysis. I² index was used to assess heterogeneity and Newcastle-Ottawa Scale was utilized for quality assessment.Results:For IL-6 –174G > C polymorphism, in codominant (GG vs CC: odds ratios [OR] = 2.78, 95% confidence intervals [CI] = 1.25–6.19, P = .01, I² = 16%) and recessive (GG+GC vs CC: OR = 2.76, 95% CI = 1.29–5.90, P = .009, I² = 3%) models, IL-6 –174G>C polymorphism was significantly associated with the risk of HCC. In dominant (GG vs CC+GC: OR = 1.80, 95% CI = 0.92–3.54, P = .09, I² = 86%) and allele (G vs C: OR = 1.49, 95% CI = 0.95–2.32, P = .08, I² = 68%) models, IL-6 –174G>C polymorphism had no impact on the risk of HCC. However, in non-Italian Caucasian population, IL-6 –174G>C polymorphism was significantly related to the occurrence of HCC in both dominant (GG vs CC+GC: OR = 3.26, 95% CI = 2.29–4.65, P < .00001, I² = 0%) and allele (G vs C: OR = 2.48, 95% CI = 1.48–4.15, P = .0006) models. Such correlations also could be observed when healthy individuals were selected as controls. For IL-6 –572G>C and –597G>A polymorphisms, no significant association was observed in all models, regardless of the source of control and population subgroups. No publication bias could be calculated when Begg and Egger tests were employed.Conclusion:This meta-analysis indicated that IL-6 –174G>C polymorphism was significantly related with the risk for HCC, especially in non-Italian Caucasian population. No significant association was observed for the correlation between IL-6 –572G>C and –597G>A polymorphisms and HCC susceptibility.     

Efficacy and safety of sacubitril-valsartan in patients with heart failure: a systematic review and meta-analysis of randomized clinical trials: A PRISMA-compliant article

Background:To investigate the efficacy and safety of sacubitril-valsartan in patients with heart failure, relevant randomized clinical trials (RCTs) were analyzed.Methods:We used Cochrane Library, PubMed web of science, CNKI, VIP, Medline, ISI Web of Science, CBMdisc, and Wanfang database to conduct a systematic literature research. A fixed-effects model was used to evaluate the standardized mean differences (SMDs) with 95% confidence intervals. We conducted sensitivity analysis and analyzed publication bias to comprehensively estimate the efficacy and safety of sacubitril-valsartan in patients with heart failure.Results:Among 132 retrieved studies, 5 relevant RCTs were included in the meta-analysis. The result showed that left ventricular ejection fraction (LVEF) was improved after sacubitril-valsartan in patients with heart failure, with an SMD (95% CI of 1.1 [1.01, 1.19] and P < .00001 fixed-effects model). Combined outcome indicators showed that, combined outcome indicators showed that, compared with control group, the left ventricular volume index (LAVI) (WMD = −2.18, 95% CI [−3.63, −0.74], P = .003), the E/e’ (WMD = −1.01, 95% CI [−1.89, −0.12], P = .03), the cardiovascular death (RR = 0.89, 95% CI [0.83, 0.96], P = .003], and the rehospitalization rate of heart failure (RR = 0.83, 95% CI [0.78, 0.88], P < .01) decreased more significantly, but it had no effect on renal function (WMD = 0.74, 95% CI [0.54, 1.01], P = .06).Conclusions:The present meta-analysis suggested that sacubitril-valsartan may improve the cardiac function of heart failure. Given the limited number of included studies, additional large sample-size RCTs are required to determine the long-term effect of cardiac function of sacubitril-valsartan in patients with heart failure.     

Overexpression of MMP14 predicts the poor prognosis in gastric cancer: Meta-analysis and database validation

Background:Plenty of studies have showed matrix metalloproteinase 14 (MMP14) expression might be associated with the prognosis of gastric cancer (GC). However, no definite conclusion has been obtained for the contradictory results.Methods:We searched PubMed, Web of science, Embase, and Cochrane library for eligible studies. The association between MMP14 expression and prognostic outcomes of GC was evaluated. Hazard ratio (HR) and 95% confidence interval (CI) were integrated to show the effect of MMP14 expression on the overall survival (OS) or recurrence-free survival (RFS). Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to validate the association of MMP14 expression with OS or RFS in GC. A brief bioinformatics analysis was also performed to determine the prognostic role of MMP14 expression in GC.Results:High MMP14 expression was associated with shorter OS compared to low MMP14 expression in GC (HR = 1.95, P < .01). Patients with high MMP14 expression tended to have worse differentiation (P = .03), deeper tumor invasion (P < .01), earlier lymph node metastasis (P < .01), earlier distant metastasis (P < .01) and more advanced clinical stage (P < .01) compared to those with low MMP14 expression. The data from TCGA and GEO showed MMP14 was overexpressed in tumor tissues compared to normal tissues (P < .05), and high MMP14 expression was significantly related to shorter OS (HR = 1.70, 95% CI = 1.32–2.20, P < .01) and RFS (HR = 1.45, 95% CI = 1.15–1.83, P < .01) compared to low MMP14 expression in GC. Expression of MMP14 was linked to functional networks involving the biological process, metabolic process, response to stimulus, cell communication and so on. Functional network analysis suggested that MMP14 regulated the protein digestion and absorption, extracellular matrix receptor interaction, focal adhesion, ribosome, spliceosome, and so on.Conclusion:High MMP14 expression was associated with worse prognosis of GC compared to low MMP14 expression. MMP14 expression could serve as a prognostic factor and potential therapeutic target of GC.     

The effect and safety of ropinirole in the treatment of Parkinson disease: A systematic review and meta-analysis

Background:It is necessary to conduct a meta-analysis of the clinical randomized controlled trials (RCTs) on ropinirole in the treatment of Parkinson disease (PD), to explore the effects and safety of ropinirole, and to provide a theoretical basis for clinically safe and rational drug use.Methods:RCTs on the effectiveness and safety of ropinirole in the treatment of PD were searched. We searched Dutch medical literature database, Pubmed, Cochrane Library, China National Knowledge Infrastructure, Wanfang Knowledge Service Platform up to December 15, 2020. The Cochrane risk bias assessment tool was used to evaluate the quality of the included literature, and the RevMan5.3 software was used for meta-analysis.Results:A total of 12 RCTs with 3341 patients were included. The changes of Parkinson Disease Rating Scale Part II score (mean difference = –2.23, 95% confidence interval [CI] –2.82 to –1.64) and Parkinson Disease Rating Scale Part III scores (mean difference = –4.93, 95%CI –5.25 to –4.61) in the ropinirole group was significantly lower than that in the control group. The incidence of dizziness (odd risk [OR] = 1.85, 95%CI 1.50–2.28), nausea (OR = 2.17, 95%CI 1.81–2.59), vomiting (OR = 2.73, 95%CI 1.47–5.09), and lethargy (OR = 2.19, 95%CI 1.39–3.44) in the ropinirole group was significantly higher than that in the control group (all P < .05), and there were no significant differences in the incidence of headache (OR = 1.14, 95%CI 0.79–1.65) and insomnia (OR = 1.06, 95%CI 0.72–1.55) were found between 2 groups (all P > .05).Conclusions:Ropinirole can help improve the ability of daily living and exercise function of PD patients, but it will increase the incidence of related adverse reactions, which needs to be further confirmed by subsequent large-scale, high-quality RCTs.