Bekiari, Eleni

Abstract Background and Aim Following the approval of the first agent for the management of metabolic dysfunction‐associated steatohepatitis (MASH), identification of patients with fibrotic MASH (MASH with NAS ≥ 4 and fibrosis stage ≥ 2) is crucial. We assessed the performance of FibroScan‐aspartate aminotransferase (AST) score (FAST) for ruling in/out fibrotic MASH. Methods We searched Medline, Cochrane Library, Web of Science, Scopus, and gray literature sources up to January 11, 2024. Studies were eligible if they assessed the accuracy of FAST score for the detection of fibrotic MASH using biopsy as the reference standard at previously reported thresholds (FAST ≥ 0.67 for ruling‐in and ≤ 0.35 for ruling‐out fibrotic MASH). We calculated pooled sensitivity and specificity estimates for FAST thresholds alongside 95% confidence intervals following bivariate random‐ effects models. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Results We included 16 studies with 8838 participants. A FAST score ≥ 0.67 yielded a pooled specificity of 0.87 (0.82–0.90) while a FAST score ≤ 0.35 yielded a summary sensitivity of 0.88 (0.83–0.91). At a prevalence of 30%, the positive predictive value for ruling‐in fibrotic MASH was 60% while the negative predictive value for ruling‐out the target condition was 91%. AST levels, cirrhosis prevalence, and number of pathologists reviewing biopsies were sources of heterogeneity among studies. The certainty of evidence was low to very low. Conclusions FAST score can be used as a triage test for ruling out fibrotic MASH. Nevertheless, its low positive predictive value necessitates sequential testing for ruling‐in fibrotic MASH.

AbstractObjectivesWe performed a systematic review and meta‐regression analysis of randomized control trials to investigate the association between response to initial treatment and survival outcomes in patients with newly diagnosed multiple myeloma (MM).MethodsResponse outcomes included complete response (CR) and the combined outcome of CR or very good partial response (VGPR), while survival outcomes were overall survival (OS) and progression‐free survival (PFS). We used random‐effect meta‐regression models and conducted sensitivity analyses based on definition of CR and study quality.ResultsSeventy‐two trials were included in the systematic review, 63 of which contributed data in meta‐regression analyses. There was no association between OS and CR in patients without autologous stem cell transplant (ASCT) (regression coefficient: .02, 95% confidence interval [CI] −0.06, 0.10), in patients undergoing ASCT (−.11, 95% CI −0.44, 0.22) and in trials comparing ASCT with non‐ASCT patients (.04, 95% CI −0.29, 0.38). Similarly, OS did not correlate with the combined metric of CR or VGPR, and no association was evident between response outcomes and PFS. Sensitivity analyses yielded similar results.ConclusionsThis meta‐regression analysis suggests that there is no association between conventional response outcomes and survival in patients with newly diagnosed MM.

Aim To assess the efficacy and safety of recently approved once‐weekly glucagon‐like peptide 1 receptor agonists ( GLP ‐1 RAs ) in patients with type 2 diabetes. Methods We conducted a systematic review and meta‐analysis of randomized controlled trials comparing any GLP ‐1 RA licensed for once‐weekly dosing (albiglutide, dulaglutide or exenatide extended release) with placebo or other antidiabetic agents. We searched M edline, E mbase, the C ochrane L ibrary and grey literature for articles published up to D ecember 2014 and extracted data in duplicate. Results In our systematic review we included 33 trials with a total of 16 003 participants. Compared with placebo the change in glycated haemoglobin ( HbA1c ) concentration was −0.66% [six studies; 95% confidence interval ( CI ) −1.14 to −0.19; I 2 = 88%] with albiglutide, and −1.18% (seven studies; 95% CI −1.34 to −1.02; I 2 = 65%) with dulaglutide. Based on data from placebo‐controlled trials, we did not detect statistically significant weight‐sparing benefits for albiglutide or dulaglutide. Compared with other antidiabetic agents, once‐weekly GLP ‐1 RAs outperformed sitagliptin, daily exenatide and insulin glargine in terms of HbA1c ‐lowering (mean differences −0.40%; 95% CI −0.66 to −0.14; I 2 = 85%, −0.44%; 95% CI −0.58 to −0.29; I 2 = 40% and −0.28; 95% CI −0.45 to −0.10; I 2 = 81%, respectively). The main adverse effects of treatment included gastrointestinal and injection site reactions. Conclusions Given their dosing scheme and overall efficacy and safety profile, once‐weekly GLP ‐1 RAs are a convenient therapeutic option for use as add‐on to metformin.