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• Second-line (2L) treatment for metastatic clear-cell renal cell carcinoma (ccRCC) remains challenging due to limited information comparing the available options and the influence of newly expanding first-line (1L) choices. • Based on overall survival (OS) and progression-free survival (PFS), the combination Lenvatinib+everolimus yielded superior, followed by cabozantinib and lenvatinib monotherapies • Nivolumab and pazopanib had the lowest odds of severe adverse events (SAEs). • The availability of newer front-line combinations of immune-checkpoint inhibitors and tyrosine-kinase inhibitors will influence 2L decision-making. Deciding on the optimal second-line (2L) treatment for metastatic clear-cell renal cell carcinoma (ccRCC) remains challenging due to the limited information comparing each of the available options and the influence of the newly expanding first-line (1L) agents. We identified phase II/III randomized controlled trials (RCTs) evaluating 2L treatments in metastatic ccRCC. This Network Meta-analysis (NMA) evaluates the overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and severe adverse events (SAE). We used normal likelihood model to incorporate log hazard ratios (HRs), odds ratios (OR), and 95%-confidence-intervals (CI). Treatment p-scores were used for ranking. Data was analyzed in a fixed-effects model using the netmeta package in R v.1.5-0. All therapies demonstrated some benefits over placebo. Lenvatinib + everolimus ranked first for OS (HR = 0.44; 95%CI = 0.24–0.82; p-score = 0.92), PFS (HR = 0.13; 95%CI = 0.07–0.24, p-score = 0.98), and ORR (OR = 35.95; 95%CI = 11.55–111.87; p-score = 0.93) compared to placebo, though with a higher SAE (OR = 5.27; p-score = 0.23). Cabozantinib ranked second for OS (HR = 0.57, p-score = 0.80), PFS (HR = 0.19; p-score = 0.86), and ORR (OR = 27.24, p-score = 0.84). Nivolumab was third for ORR (p-score = 0.79), fourth for OS (p-score = 0.69), fifth for PFS (p-score = 0.61), and last for SAE (p-score = 0.83). Lenvatinib monotherapy ranked worst SAE (OR = 5.89, p-score = 0.17) and third for OS and PFS. The latest drug, tivozanib, was sixth for PFS, OS, and ORR. The NMA matrix revealed no differential OS benefit between cabozantinib, lenvatinib + everolimus, and nivolumab. Other regimens had no significant OS benefit when compared to placebo. Based on OS and PFS, the lenvtatinib + everolimus combination yielded superior, followed by cabozantinib and Lenvatinib monotherapies; all were limited by a worse SAE profile. Nivolumab and pazopanib had the lowest odds of SAEs. [ABSTRACT FROM AUTHOR]

Abstract Objective This study aimed to assess and compare the clinical efficacy and safety of acupuncture and related therapies (ARTs) add-on to conventional treatment (CT) for heart failure (HF) through pairwise and network meta-analyses. Methods Six electronic databases, including PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI) and Wanfang Database were searched from inceptions to December 2017. Randomized controlled trials (RCTs) regarding ARTs combining with CT for HF were eligible. The primary outcomes were changes in heart function classification (HFC) according to New York Heart Association class and left ventricular ejection fraction (LVEF). Risk of bias assessment was conducted by two independent authors. Pairwise and network meta-analyses were performed using STATA 13.0 and WinBUGS 1.4.3 software. Results A total of 26 RCTs were enrolled for analyses, with 5 kinds of ARTs and 2116 patients in all. Pairwise meta-analyses showed that acupoint application (OR: 3.28, 95%CI[2.26, 4.76]), acupuncture (OR: 2.78, 95%CI[1.21, 6.41]), acupoint injection (OR: 3.33, 95%CI[1.85, 6.00]) and moxibustion (OR: 2.51, 95%CI[1.02, 6.21]) could significantly improve HFC when they were used as add-on to CT. Acupoint application (MD: 3.57, 95%CI[1.45, 5.70]), acupuncture (MD: 7.75, 95%CI[2.33, 13.17]), acupoint injection (MD: 4.81, 95%CI[2.99, 6.63]) and moxibustion (MD: 6.99, 95%CI[3.62, 10.36]) were significantly beneficial in improving LVEF. Network meta-analyses showed that acupoint injection (SUCRA = 70.0%) and acupuncture (SUCRA = 90.4%) respectively had the greatest probability in improving HFC and LVEF. Conclusion Most of the included ARTs add-on to CT was effective in improving HFC and LVEF. Acupoint injection and acupuncture may respectively have better effect than others for HFC and LVEF. However, due to the small sample size and poor quality of the included studies, hence well-designed RCTs are needed to confirm our findings. This study was registered in PROSPERO, CRD42018087700. [ABSTRACT FROM AUTHOR]

Objective: Network meta-analyses (NMAs) aim to rank the benefits (or harms) of interventions, based on all available randomized controlled trials. Thus, the identification of relevant data is critical. We assessed the conduct of the literature searches in NMAs. Study Design: Published NMAs were retrieved by searching electronic bibliographic databases and other sources. Two independent reviewers selected studies and five trained reviewers abstracted data regarding literature searches, in duplicate. Search method details were examined using descriptive statistics. Results: Two hundred forty-nine NMAs were included. Eight used previous systematic reviews to identify primary studies without further searching, and five did not report any literature searches. In the 236 studies that used electronic databases to identify primary studies, the median number of databases was 3 (interquartile range: 3-5). MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were the most commonly used databases. The most common supplemental search methods included reference lists of included studies (48%), reference lists of previous systematic reviews (40%), and clinical trial registries (32%). None of these supplemental methods was conducted in more than 50% of the NMAs. Conclusion: Literature searches in NMAs could be improved by searching more sources, and by involving a librarian or information specialist. [ABSTRACT FROM AUTHOR]