Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral antidiabetic agents that hold the potential of slowing the progress of type 2 diabetes mellitus. Their long-term safety is still a subject of debate. A systematic review of randomized, controlled trials was undertaken to comprehensively profile the safety of chronic treatment of type 2 diabetes mellitus with DPP-4 inhibitors. We searched data sources including MEDLINE, CENTRAL, publishers' and manufacturers' databases. Eligible trials were double-blind, randomized, placebo or active-controlled trials with ≥18 weeks duration in patients with type 2 diabetes reporting safety outcomes. Meta-analysis was performed separately for trials in which the control group received placebo (44 studies), another gliptin (3 studies) and any other antidiabetic drug (20 studies). Risk ratios with 95% confidence intervals were computed using a Mantel-Haenszel fixed-effect model for general safety outcomes, hypoglycaemia and adverse events by system organ class. Of 307 publications retrieved, 67 randomized, controlled trials met the eligibility criteria and were included in this review (4 alogliptin, 8 linagliptin, 8 saxagliptin, 20 sitagliptin, and 27 vildagliptin trials). Adverse events with gliptin treatment were at placebo level (relative risk (RR) 1.02 [0.99, 1.04]). No increased risk of infections was detectable (RR 0.98 [0.93, 1.05] compared to placebo and 1.02 [0.97, 1.07] compared to other antidiabetic drugs). Asthenia (RR 1.57 [1.09, 2.27]) as well as cardiac (RR 1.37 [1.00, 1.89]) and vascular disorders (RR 1.74 [1.05, 2.86] for linagliptin) emerged as adverse events associated with DPP-4 inhibitor treatment. The risk of hypoglycaemia was low with DPP-4 inhibitor treatment (RR 0.92 [0.74, 1.15] compared to placebo, RR 0.20 [0.17, 0.24] compared to sulphonylureas) in the absence of sulphonylurea or insulin co-therapy, but significantly elevated for combination therapy of sulphonylurea or insulin with sitagliptin or linagliptin (RR 1.86 [1.46, 2.37] compared to placebo). A large body of data supports the long-term safety of gliptin treatment and refutes an increased risk of infections. Further research is needed to clarify a possible link to asthenia, cardiac and vascular events. For combination therapy with insulin or insulin secretagogues, a careful choice of the agent used may limit the risk of hypoglycaemia.

For surgical systematic reviews, the optimal literature search for RCT employs MEDLINE and CENTRAL. For surgical systematic reviews of NRS, Web of Science instead of CENTRAL should be searched. EMBASE does not contribute substantially to reviews with a surgical intervention.

The efficacy and safety of icodextrin versus glucose-only peritoneal dialysis (PD) regimens is unclear. The aim of this study was to compare once-daily long-dwell icodextrin versus glucose among patients with kidney failure undergoing PD. Study Design: Systematic review of randomized controlled trials (RCTs), enriched with unpublished data from investigator-initiated and industry-sponsored studies. Setting & Study Populations: Individuals with kidney failure receiving regular PD treatment enrolled in clinical trials of dialysate composition. Selection Criteria for Studies: Medline, Embase, CENTRAL, Ichushi Web, 10 Chinese databases, clinical trials registries, conference proceedings, and citation lists from inception to November 2018. Further data were obtained from principal investigators and industry clinical study reports. Data Extraction: 2 independent reviewers selected studies and extracted data using a prespecified extraction instrument. Analytic Approach: Qualitative synthesis of demographics, measurement scales, and outcomes. Quantitative synthesis with Mantel-Haenszel risk ratios (RRs), Peto odds ratios (ORs), or (standardized) mean differences (MDs). Risk of bias of included studies at the outcome level was assessed using the Cochrane risk-of-bias tool for RCTs. Results: 19 RCTs that enrolled 1,693 participants were meta-analyzed. Ultrafiltration was improved with icodextrin (medium-term MD, 208.92 [95% CI, 99.69-318.14] mL/24 h; high certainty of evidence), reflected also by fewer episodes of fluid overload (RR, 0.43 [95% CI, 0.24-0.78]; high certainty). Icodextrin-containing PD probably decreased mortality risk compared to glucose-only PD (Peto OR, 0.49 [95% CI, 0.24-1.00]; moderate certainty). Despite evidence of lower peritoneal glucose absorption with icodextrin-containing PD (medium-term MD, −40.84 [95% CI, −48.09 to −33.59] g/ long dwell; high certainty), this did not directly translate to changes in fasting plasma glucose (−0.50 [95% CI, −1.19 to 0.18] mmol/L; low certainty) and hemoglobin A 1c levels (−0.14% [95% CI, −0.34% to 0.05%]; high certainty). Safety outcomes and residual kidney function were similar in both groups; health-related quality-of-life and pain scores were inconclusive. Limitations: Trial quality was variable. The followup period was heterogeneous, with a paucity of assessments over the long term. Mortality results are based on just 32 events and were not corroborated using time-to-event analysis of individual patient data. Conclusions: Icodextrin for once-daily long-dwell PD has clinical benefit for some patients, including those not meeting ultrafiltration targets and at risk for fluid overload. Future research into patient-centered outcomes and costeffectiveness associated with icodextrin is needed. T he prevalence of kidney replacement therapy is expected to increase steeply. 1 Approximately 15% of dialysis patients globally use peritoneal dialysis (PD), and this proportion is increasing. 2 PD is probably associated with the same survival as hemodialysis (HD) 3-6 but pre...

Background: When conducting an Overviews of Reviews on health-related topics, it is unclear which combination of bibliographic databases authors should use for searching for SRs. Our goal was to determine which databases included the most systematic reviews and identify an optimal database combination for searching systematic reviews. Methods: A set of 86 Overviews of Reviews with 1219 included systematic reviews was extracted from a previous study. Inclusion of the systematic reviews was assessed in MEDLINE, CINAHL, Embase, Epistemonikos, PsycINFO, and TRIP. The mean inclusion rate (% of included systematic reviews) and corresponding 95% confidence interval were calculated for each database individually, as well as for combinations of MEDLINE with each other database and reference checking. Results: Inclusion of systematic reviews was higher in MEDLINE than in any other single database (mean inclusion rate 89.7%; 95% confidence interval [89.0-90.3%]). Combined with reference checking, this value increased to 93.7% [93.2-94.2%]. The best combination of two databases plus reference checking consisted of MEDLINE and Epistemonikos (99.2% [99.0-99.3%]). Stratification by Health Technology Assessment reports (97.7% [96.5-98.9%]) vs. Cochrane Overviews (100.0%) vs. non-Cochrane Overviews (99.3% [99.1-99.4%]) showed that inclusion was only slightly lower for Health Technology Assessment reports. However, MEDLINE, Epistemonikos, and reference checking remained the best combination. Among the 10/1219 systematic reviews not identified by this combination, five were published as websites rather than journals, two were included in CINAHL and Embase, and one was included in the database ERIC. Conclusions: MEDLINE and Epistemonikos, complemented by reference checking of included studies, is the best database combination to identify systematic reviews on health-related topics.

E-CEA increases the risk for post-CEA hypertension, whereas C-CEA is more often associated with hypotension, Careful BP monitoring at least in the early postoperative period after CEA is mandatory, especially when the eversion technique is used.