The cardiovascular benefits of GLP1-RA are directly related to their positive effect on glycaemic control: A meta-regression analysis

Review question / Objective: P (patient population) = Type 2 diabetes patients with high CV risk or established atherosclerotic cardiovascular disease; I (intervention) = Received drugs: GLP1-RA; C (control group) = Compared to a control group that received a placebo; O (outcome) = Outcomes of interest included primary CV outcomes (MACE, CV death, MI, and Stroke). Condition being studied: To explore whether the heterogeneity associated with the primary outcomes benefits can be attributed to the metabolic improvements associated with GLP1-RA. The plan is to use HBA1c, weight, and SBP reduction as moderators attempting to explain any variance between the true and observed effect size.

Value of variation of end-tidal carbon dioxide for predicting fluid responsiveness during the passive leg raising test in patients with mechanical ventilation: a systematic review and meta-analysis

Background The ability of end-tidal carbon dioxide (ΔEtCO2) for predicting fluid responsiveness has been extensively studied with conflicting results. This meta-analysis aimed to explore the value of ΔEtCO2 for predicting fluid responsiveness during the passive leg raising (PLR) test in patients with mechanical ventilation. Methods PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched up to November 2021. The diagnostic odds ratio (DOR), sensitivity, and specificity were calculated. The summary receiver operating characteristic curve was estimated, and the area under the curve (AUROC) was calculated. Q test and I2 statistics were used for study heterogeneity and publication bias was assessed by Deeks’ funnel plot asymmetry test. We performed meta-regression analysis for heterogeneity exploration and sensitivity analysis for the publication bias. Results Overall, six studies including 298 patients were included in this review, of whom 149 (50%) were fluid responsive. The cutoff values of ΔEtCO2 in four studies was 5%, one was 5.8% and the other one was an absolute increase 2 mmHg. Heterogeneity between studies was assessed with an overall Q = 4.098, I2 = 51%, and P = 0.064. The pooled sensitivity and specificity for the overall population were 0.79 (95% CI 0.72–0.85) and 0.90 (95% CI 0.77–0.96), respectively. The DOR was 35 (95% CI 12–107). The pooled AUROC was 0.81 (95% CI 0.77–0.84). On meta-regression analysis, the number of patients was sources of heterogeneity. The sensitivity analysis showed that the pooled DOR ranged from 21 to 140 and the pooled AUC ranged from 0.92 to 0.96 when one study was omitted. Conclusions Though the limited number of studies included and study heterogeneity, our meta-analysis confirmed that the ΔEtCO2 performed moderately in predicting fluid responsiveness during the PLR test in patients with mechanical ventilation.

Color Change of Resin-based Composites After In Vitro Bleaching Protocols: A Systematic Review and Meta-analysis

SUMMARY Objectives: To systematically review the literature on color stability of resin-based composites (RBC) after in vitro bleaching protocols and to assess the influence of bleaching protocols by meta-regression analysis on RBC color stability, and the association with clinical and experimental characteristics. Methods: The electronic search was conducted in MEDLINE/PubMed, Scopus, and Web of Science databases and included English language studies that evaluated and reported color differences (CIELAB values) of RBC after in vitro bleaching procedures using hydrogen peroxide and/or carbamide peroxide. Results: Database search for color change of RBC after bleaching retrieved 1335 eligible papers after removing duplicates. After initial screening, 66 articles were assessed for full-text reading with final inclusion of 23 published papers. A meta-regression analysis showed that storage time (p≤0.01), color measuring device (p≤0.01), and background color (p≤0.01) had influenced on color changes of RBC. The bleaching protocol (bleaching agent and time of application) did not influence on color changes of RBC (p>0.01). Conclusions: There is evidence that RBC change color after bleaching, but the change is not clinically significant.

Molecular Investigation of miRNA Biomarkers as Chemoresistance Regulators in Melanoma: A Protocol for Systematic Review and Meta-Analysis

Introduction: Melanoma is a global disease that is predominant in Western countries. However, reliable data resources and comprehensive studies on the theragnostic efficiency of miRNAs in melanoma are scarce. Hence, a decisive study or comprehensive review is required to collate the evidence for profiling miRNAs as a theragnostic marker. This protocol details a comprehensive systematic review and meta-analysis on the impact of miRNAs on chemoresistance and their association with theragnosis in melanoma. Methods and analysis: The articles will be retrieved from online bibliographic databases, including Cochrane Review, EMBASE, MEDLINE, PubMed, Scopus, Science Direct, and Web of Science, with different permutations of ‘keywords’. To obtain full-text papers of relevant research, a stated search method will be used, along with selection criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Protocols 2015 (PRISMA-P) standards were used to create this study protocol. The hazard ratio (HR) with a 95% confidence interval will be analyzed using Comprehensive Meta-Analysis (CMA) software 3.0. (CI). The pooled effect size will be calculated using a random or fixed-effects meta-analysis model. Cochran’s Q test and the I2 statistic will be used to determine heterogeneity. Egger’s bias indicator test, Orwin’s and the classic fail-safe N tests, the Begg and Mazumdar rank collection test, and Duval and Tweedie’s trim and fill calculation will all be used to determine publication bias. The overall standard deviation will be evaluated using Z-statistics. Subgroup analyses will be performed according to the melanoma participants’ clinicopathological and biological characteristics and methodological factors if sufficient studies and retrieved data are identified and available. The source of heterogeneity will be assessed using a meta-regression analysis. A pairwise matrix could be developed using either a pairwise correlation or expression associations of miRNA with patients’ survival for the same studies.

Meta-analysis of the diagnostic performance of serum carbohydrate antigen 19-9 for the detection of gallbladder cancer

Introduction Carbohydrate antigen 19-9 (CA19-9) is a well-studied tumor marker, yet its diagnostic value for gallbladder cancer remains unclear. The present meta-analysis was conducted to validate the role of serum CA19-9 for the detection of gallbladder cancer. Methods A systematic search of digital databases was conducted, complemented by additional hand-searching. Studies that reported serum CA19-9 for the differentiation of gallbladder cancer cases from non-gallbladder cancer controls were considered eligible. Results A total of 27 studies involving 4300 subjects were included. The pooled sensitivity, specificity, and area under the curve in diagnosing gallbladder cancer were 0.70 (95% confidence interval (CI): 0.63–0.76), 0.92 (95% CI: 0.88–0.94), and 0.89 (95% CI: 0.86–0.92), respectively. The pooled positive likelihood rate, negative likelihood rate, and diagnostic odds rate were 8.30 (95% CI: 5.84–11.69), 0.33 (95% CI: 0.27–0.41), and 25.13 (95% CI: 5.83–39.89), respectively. Meta-regression analysis revealed that there was significantly lower sensitivity (0.69, 95% CI: 0.61–0.77) and specificity (0.91, 95% CI: 0.87–0.95) when CA19-9 was used for the differentiation of gallbladder cancer cases from benign biliary diseases. A better specificity of 0.93 (95% CI: 0.90–0.96) was reached in the setting of a sample size ≥100. Conclusions Serum CA19-9 can be a potential candidate marker for the detection of gallbladder cancer, which maintains moderate sensitivity and good specificity. Attention should be paid to the control type and sample size, which may affect its diagnostic accuracy. Also, results should be interpreted with caution due to significant heterogeneity primarily caused by different thresholds between included studies.

Effects of statin therapy on coronary plaque volume by decreasing CRP/hsCRP levels: A meta-regression of randomized controlled trials

Background and aims: Several clinical trials have indicated that statins stabilize and reverse atherosclerotic plaque. However, different studies have provided inconsistent findings regarding mechanisms and influencing factors of plaque regression under statin therapy. In this study, meta-analysis and meta-regression were used to determine the effect of statin medication on coronary plaque volume as determined by intravenous ultrasound. Meanwhile, the impact of statins on CRP/hsCRP reduction on plaque regression was discussed. Methods: Up to May 28, 2021, a systematic PubMed, EMBASE, and Cochrane search was performed for randomized controlled trials that assessed treatment effect using total atheroma volume (TAV), percent atheroma volume (PAV), or plaque volume (PV). Only CRP/hsCRP and LDL-C values reported before and after treatment were considered. Results: 12 studies fulfilled the inclusion criteria and were included in the systematic review. Compared with control groups, meta-analysis of 15 statin-treated arms reported change of TAV/PV showed standardized mean difference (SMD) at -0.27 (95% confidence intervals [CI]: -0.42, -0.12). Meta-analysis of 7 studies reported change of PAV revealed SMD at -0.16 (95% CI: -0.29, -0.03). Meta-regression analysis revealed percent change of CRP/hsCRP statistically influences SMD in change of TAV/PVafter adjusting for percent change of LDL-C, age and gender. Meta-regression analysis showed that percent change of CRP/hsCRP statistically influences SMD in change of PAV. Conclusion: In conclusion, statin therapy is beneficial for plaque regression. Statins promote plaque regression through their anti-inflammatory ability while lowering LDL-C is unaffected. Keywords: Statins; Reduction of atherosclerosis; C-reactive protein; Randomized controlled trial; Meta-analysis