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The present study is an overview of systematic reviews focusing on adverse events of antimyeloma treatments. It provides a systematic description of adverse events as they are reported in the systematic reviews as well as a critical appraisal of included reviews. We conducted a comprehensive literature search in the most widely used electronic databases looking for systematic reviews that had an adverse event of an antimyeloma treatment intervention as primary outcome. Two independent reviewers conducted selection of included studies and data extraction on predesigned online forms and assessed study quality using AMSTAR 2. Overall corrected covered area (CCA) was calculated to examine the overlap of primary studies across systematic reviews. After screening eligible studies, 23 systematic reviews were included in this overview. Seven reviews with overall CCA of 14.7% examined cardiovascular adverse events of different drugs, including immunomodulatory drugs and proteasome inhibitors (mainly carfilzomib). Nine focused on infections, presenting with overall CCA of 5.8%, each one focused on a different drug or drug class. Three studied thromboembolism in patients treated either with lenalidomide, any immunomodulatory drug, or with daratumumab and had an overall CCA equal to 1.5%. Four more reviews focused on bortezomib-associated neurotoxicity, carfilzomib-associated renal toxicity, or second primary malignancies as an adverse event of lenalidomide or anti-CD38 monoclonal antibody treatment. The quality of included studies as judged by AMSTAR 2 was mostly critically low. Absence of a priori registered protocol and formal assessment of risk of bias of included primary studies were the most common shortcomings. Reporting of antimyeloma drug-associated toxicity is supported by multiple systematic reviews; nevertheless, methodological quality of existing reviews is mostly low. [ABSTRACT FROM AUTHOR]

Context The cardiovascular benefits of semaglutide are established; however, its effects on surrogate vascular markers and liver function are not known. Objective To investigate the effects of semaglutide on vascular, endothelial, and liver function in patients with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD). Methods Overall, 75 consecutive subjects with T2DM and NAFLD were enrolled: 50 patients received semaglutide 1 mg (treatment group) and 25 patients received dipeptidyl peptidase 4 inhibitors (control group). All patients underwent a clinical, vascular, and hepatic examination with Fibroscan elastography at 4 and 12 months after inclusion in the study. Results Treatment with semaglutide resulted in a reduction of Controlled Attenuation Parameter (CAP) score, E fibrosis score, NAFLD fibrosis score, Fibrosis-4 (FIB-4) score and perfused boundary region (PBR) at 4 and at 12 months (P <.05), contrary to controls. Patients treated with semaglutide showed a greater decrease of central systolic blood pressure (SBP) (−6% vs −4%, P =.048 and −11% vs −9%, P =.039), augmentation index (AIx) (−59% vs −52%, P =.041 and −70% vs −57%, P =.022), and pulse wave velocity (PWV) (−6% vs −3.5%, P =.019 and −12% vs −10%, P =.036) at 4 and at 12 months, respectively. In all patients, ΔPWV and ΔPBR were correlated with a corresponding reduction of CAP, E fibrosis, NAFLD fibrosis, and FIB-4 scores. Conclusion Twelve-month treatment with semaglutide simultaneously improves arterial stiffness, endothelial function, and liver steatosis and fibrosis in patients with T2DM and NAFLD. [ABSTRACT FROM AUTHOR]

We conducted a systematic review and meta‐analysis of randomized controlled trials to assess the effect of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) on microvascular endpoints in adult patients with type 2 diabetes. We included 60 studies with 60 077 patients. GLP‐1 RAs marginally reduced urinary albumin‐to‐creatinine ratio compared with placebo or other antidiabetic agents (weighted mean difference − 2.55 mg/g; 95% confidence interval [CI] −4.37 to −0.73 and −5.52; −10.89 to −0.16, respectively) and had no clinically relevant effect on change in estimated glomerular filtration rate. Treatment with GLP‐1 RAs did not increase incidence of diabetic retinopathy, macular oedema, retinal detachment and retinal haemorrhage, irrespective of comparator. Nevertheless, incidence of vitreous haemorrhage was higher in subjects treated with GLP‐1 RAs compared with placebo (odds ratios 1.93; 95% CI 1.09 to 3.42). In conclusion, GLP‐1 RAs are safe regarding nephropathy‐ and retinopathy‐related outcomes. Caution may be warranted for incidence of vitreous haemorrhage. The low overall quality of evidence highlights the need for consistent assessment and reporting of microvascular endpoints in future trials. [ABSTRACT FROM AUTHOR]

PROBLEM IDENTIFICATION: Secondary lymphedema is a chronic condition that may result from cancer-related treatments. Evidence is emerging on prospective surveillance and risk reduction. LITERATURE SEARCH: Databases were systematically searched through April 1, 2019, for comparative studies evaluating interventions aiming to prevent lymphedema in patients with cancer. DATA EVALUATION: A random-effects model was used to perform meta-analysis, when appropriate. SYNTHESIS: A total of 26 studies (4,095 patients) were included, with 23 providing data sufficient for meta-analysis. Surveillance programs increased the likelihood of detecting lymphedema. Physiotherapy, exercise programs, and delayed exercise reduced the incidence of lymphedema. IMPLICATIONS FOR RESEARCH: Future research should standardize (a) evidence-based interventions to reduce the development of lymphedema and increase the likelihood of early detection and (b) outcome measures to build a body of evidence that leads to practice change. [ABSTRACT FROM AUTHOR]

PROBLEM IDENTIFICATION: Preventing and managing skin toxicities can minimize treatment disruptions and improve well-being. This systematic review aimed to evaluate the effectiveness of interventions for the prevention and management of cancer treatment-related skin toxicities. LITERATURE SEARCH: The authors systematically searched for comparative studies published before April 1, 2019. Study selection and appraisal were conducted by pairs of independent reviewers. DATA EVALUATION: The random-effects model was used to conduct meta-analysis when appropriate. SYNTHESIS: 39 studies (6,006 patients) were included; 16 of those provided data for metaanalysis. Prophylactic minocycline reduced the development of all-grade and grade 1 acneform rash in patients who received erlotinib. Prophylaxis with pyridoxine 400 mg in capecitabine-treated patients lowered the risk of grade 2 or 3 hand-foot syndrome. Several treatments for hand-foot skin reaction suggested benefit in heterogeneous studies. Scalp cooling significantly reduced the risk for severe hair loss or total alopecia associated with chemotherapy. IMPLICATIONS FOR RESEARCH: Certainty in the available evidence was limited for several interventions, suggesting the need for future research. [ABSTRACT FROM AUTHOR]

Background: The controlled attenuation parameter (CAP) enables the noninvasive assessment of liver steatosis. We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of CAP for identifying liver steatosis in patients at risk for metabolic dysfunction-associated steatotic liver disease (MASLD), using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard., Methods: We searched Medline, Embase, Cochrane Library and gray literature sources up to March 2024. We defined MASLD as MRI-PDFF ≥5%. We also assessed the accuracy of CAP for identifying patients with MRI-PDFF ≥10%. We calculated pooled sensitivity and specificity estimates using hierarchical random-effects models. We assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool, and the certainty in meta-analysis estimates using the Grading of Recommendations Assessment, Development and Evaluation framework., Results: We included 8 studies with 1116 participants. The prevalence of MASLD ranged from 65.2-93.9%. Pooled sensitivity and specificity of CAP for MRI-PDFF ≥5% were 0.84 (95% confidence interval [CI] 0.79-0.88) and 0.77 (95%CI 0.68-0.84), respectively, with an area under the receiver operating characteristic curve (AUROC) of 0.88. The pooled sensitivity and specificity for MRI-PDFF ≥10% were 0.83 (95%CI 0.80-0.87) and 0.72 (95%CI 0.59-0.82), with an AUROC of 0.85. The certainty in our estimates was low to very low because of the high risk of bias, inconsistency and imprecision., Conclusions: CAP has acceptable diagnostic accuracy for both MRI-PDFF ≥5% and MRI-PDFF ≥10%. Adequately powered and rigorously conducted diagnostic accuracy studies are warranted to establish the optimal CAP thresholds., Competing Interests: Conflict of Interest: AT has received research support from Boehringer Ingelheim. EB and ES have received research support from Novo Nordisk. All other authors declare no conflicts of interest, (Copyright: © 2024 Hellenic Society of Gastroenterology.)

Background and Aims: Portal hypertension is a serious complication of cirrhosis, which leads to life-threatening complications. HVPG, a surrogate of portal pressure, is the reference standard test to assess the severity of portal hypertension. However, since HVPG is limited by its invasiveness and availability, noninvasive liver disease assessments to assess portal pressure, especially clinically significant portal hypertension (CSPH), are needed., Approach and Results: We conducted a systematic review of Ovid MEDLINE(R) Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from each database's inception to April 22, 2022. We included only studies in English that examined ≥50 patients in single liver disease etiologies, which compared noninvasive tests (blood and/or imaging) to HVPG for predicting clinically significant portal hypertension (CSPH; defined as HVPG ≥ 10 mm Hg) in patients with chronic liver disease. Outcomes included measures of diagnostic test accuracy. Additionally, a narrative review of studies not eligible for the systematic review is also provided. Nine studies with 2492 patients met the inclusion criteria. There was substantial heterogeneity with regard to liver disease studied and cutoff values used to detect CSPH. Blood-based tests, including aspartate-to-platelet ratio index (APRI) (56% sensitivity and 68% specificity) and FIB-4 (54% sensitivity and 73% specificity) had low accuracy measures. Imaging-based tests (transient elastography and shear wave elastography detection of liver stiffness measurement [LSM]) had better accuracy but also had substantial variation; at 15 kPa, TE sensitivity was 90%-96% and specificity was 48%-50%, while at 25 kPa, its sensitivity and specificity were 57%-85% and 82%-93%, respectively. The narrative review suggested that imaging-based tests are the best available noninvasive liver disease assessment to detect CSPH; CSPH is highly unlikely to be present at an LSM ≤15 kPa and likely to be present at an LSM ≥25 kPa., Conclusions: While imaging-based noninvasive liver disease assessment appeared to have higher accuracy than blood-based tests to detect CSPH, only 9 studies fit the a priori established inclusion criteria for the systematic review. In addition, there was substantial study heterogeneity and variation in cutoffs for LSM to detect CSPH, limiting the ability to establish definitive cutoffs to detect CSPH., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Randomized controlled trials represent the cornerstone for the regulatory approval of drugs and evidence-based medicine and policy. Compared with observational studies random assignment of participants to each study arm guarantees an equal distribution of potential confounders thus achieving impartiality in the evaluation of between group differences and allowing for causal inferences to be drawn. These complex and costly medical experiments are tightly regulated and require substantial planning with great attention to several methodological aspects ranging from allocation concealment and blinding to sample size estimation, statistical analysis, and handling of protocol deviations. This brief guide offers useful insights into the design, conduct, and interpretation of clinical trial findings for beginners., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.