Search

Ioannis Avgerinos,1 Aris Liakos,1,2 Apostolos Tsapas,1–3 Eleni Bekiari1,2 1Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Diabetes Centre, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Harris Manchester College, University of Oxford, Oxford, UKCorrespondence: Ioannis AvgerinosClinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Konstantinoupoleos 49, Thessaloniki 54642, GreeceEmail iavgerik@auth.grAbstract: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are currently used as second-line therapy for treatment of patients with type 2 diabetes mellitus (T2DM). Based on the results from dedicated cardiovascular outcome trials (CVOTs), current guidelines suggest the use of SGLT-2 inhibitors for patients with T2DM and established atherosclerotic cardiovascular disease (ASCVD) or heart failure. The cardiovascular safety profile of dapagliflozin, a novel SGLT-2 inhibitor, has been recently explored in large CVOTs. Treatment with dapagliflozin reduced the risk of the composite outcome of cardiovascular mortality or hospitalization for heart failure compared with placebo, both among patients with T2DM who had or were at risk of ASCVD, as well as among patients with heart failure and a reduced ejection fraction. The observed cardiovascular benefit was mainly attributed to the lower rate of hospitalization for heart failure. Additionally, treatment with dapagliflozin was associated with a lower rate of renal adverse events. The safety and efficacy of dapagliflozin on glycemic and non-glycemic endpoints has been also well established in a series of other clinical trials and real-word studies. The aim of the present review is to summarize the available evidence regarding the cardiovascular profile of dapagliflozin in patients with T2DM. Overall, by reducing the rate of hospitalization for heart failure and ameliorating renal adverse events, dapagliflozin is a valuable option for the management of patients with T2DM and multiple cardiovascular risk factors.Keywords: dapagliflozin, sodium-glucose co-transporter 2 inhibitors, SGLT-2 inhibitors, type 2 diabetes, cardiovascular risk

Zhen Wang,1–3 Juan P Brito,4 Apostolos Tsapas,5 Marcio L Griebeler,4 Fares Alahdab,1,3 Mohammad Hassan Murad,1,3,61Robert D and Patricia E Kern Center for the Science of Health Care Delivery, 2Division of Health Care Policy and Research, Department of Health Sciences Research, 3Knowledge and Evaluation Research Unit, 4Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA; 5Aristotle University of Thessaloniki, Thessaloniki, Greece; 6Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, MN, USABackground: High-quality systematic reviews (SRs) require rigorous approaches to identify, appraise, select, and synthesize research evidence relevant to a specific question. In this study, we evaluated the association between two steps in the conduct of an SR – restricting the search to English, and author contact for missing data – and the overall credibility of a SR.Methods: All SRs cited by the Endocrine Society's Clinical Practice Guidelines published from October 2006 through January 2012 were included. The main outcome was the overall A Measurement Tool to Assess Systematic Reviews (AMSTAR) score, as a surrogate of SR credibility. Nonparametric Kruskal–Wallis tests and multivariable linear regression models were used to investigate the association between language restriction, author contact for missing data, and the overall AMSTAR score.Results: In all, 69 SRs were included in the analysis. Only 31 SRs (45%) reported searching non-English literature, with an average AMSTAR score of 7.90 (standard deviation [SD] =1.64). SRs that reported language restriction received significantly lower AMSTAR scores (mean =5.25, SD =2.32) (P

Abstract Background Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. Methods All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. Discussion With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. Systematic review registration PROSPERO CRD42021272686.

Abstract Background Neuropathic pain can reduce the quality of life and independence of 30% to 50% of patients with diabetes. The comparative effectiveness of analgesics for patients with diabetic neuropathy remains unclear. The aim of the current work, therefore, was to summarize the evidence about the analgesic effectiveness of the most common oral and topical agents used for the treatment of peripheral diabetic neuropathy. Methods We will use an umbrella approach (systematic review of systematic reviews) to identify eligible randomized controlled trials (RCTs) for the most common oral or topical analgesics for painful diabetic neuropathy. Two reviewers will independently determine RCT eligibility. Disagreement will be solved by consensus and arbitrated by a third reviewer. We will extract descriptive, methodological and efficacy data in duplicate. Results will be pooled and analyzed using classic random-effects meta-analyses and network meta-analyses to compute the absolute and relative efficacy of therapeutic options. We will use the I2 statistic and Cochran’s Q test to assess heterogeneity. Risk of bias and publication bias, if appropriate, will be evaluated, as well as overall strength of the evidence. Discussion This network meta-analysis aims to synthesize available direct and indirect evidence of effectiveness of analgesics in the treatment of painful diabetic neuropathy. The network approach will offer the opportunity to generate a ranking based on efficacy and along with known side effects, costs, and administration burdens will enable patients and clinicians to make choices that best reflect their preferences for treatment of painful diabetic neuropathy.

The new SARS-CoV-2 outbreak has rapidly spread to many countries and has pushed health systems to radical changes in healthcare provision. This study aims to investigate the impact of the COVID-19 pandemic on the management of chronic patients in Primary Health Care (PHC). A narrative review of the literature was carried out in the PubMed and Google Scholar databases. It was found that since the pandemic’s onset, many regular medical visits have led to delays, postponements, and even cancellations. The reasons for this discontinuity of chronic care were individual (fear and reluctance, home isolation), but also collective (shortages of medical staff, weakening of PHC, and suspension of outpatient care). Therefore, postponements of scheduled medical visits, delayed seeking of help and lack of medication adherence could lead to deregulation of chronic diseases, posing a risk for catastrophic health consequences. In order to ensure the continuity of chronic care provision, health systems have adopted new practices such as telemedicine and self-monitoring. The inclusion of chronic care in national pandemic response plans, the strengthening of PHC and the improvement of communication between patients and public health officials are essential preconditions to mitigate the indirect effects of the pandemic on chronic care.

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 dysfunctionassociated steatotic liver disease (MASLD), using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. Method 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. [ABSTRACT FROM AUTHOR]

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]

The assessment of health-related quality of life (HRQoL) in thalassemia offers a holistic approach to the disease and facilitates better communication between physicians and patients. This study aimed to evaluate the HRQoL of transfusion-dependent thalassemia (TDT) patients in Greece. This was a multicentric, cross-sectional study conducted in 2017 involving 283 adult TDT patients. All participants completed a set of two QoL questionnaires, the generic SF-36v2 and the disease-specific TranQol. Demographic and clinical characteristics were used to predefine patient subgroups. Significant factors identified in the univariate analysis were entered into a multivariate analysis to assess their effect on HRQoL. The SF-36 scores of TDT patients were consistently lower compared to the general population in Greece. The mean summary score of TranQol was relatively high (71 ± 14%), exceeding levels observed in national surveys in other countries. Employment emerged as the most significant independent factor associated with better HRQoL, whereas age had the most significant negative effect. This study represents the first comprehensive QoL assessment of a representative sample of the TDT population in Greece. The implementation of TranQol allowed for the quantification of HRQoL in Greece, establishing a baseline for future follow-up, and identifying more vulnerable patient subgroups. [ABSTRACT FROM AUTHOR]

We present a methodological framework for conducting and interpreting subgroup meta-analyses. Methodological steps comprised evaluation of clinical heterogeneity regarding the definition of subpopulations, credibility assessment of subgroup meta-analysis, and translation of relative into absolute treatment effects. We used subgroup data from type 2 diabetes cardiovascular outcomes trials (CVOTs) with glucagon-like peptide 1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors for patients with established cardiovascular disease and those at high cardiovascular risk without manifest cardiovascular disease. First, we evaluated the variability in definitions of the subpopulations across CVOTs using major adverse cardiovascular events (MACE) incidence in the placebo arm as a proxy for baseline cardiovascular risk. As baseline risk did not differ considerably across CVOTs, we conducted subgroup meta-analyses of hazard ratios (HRs) for MACE and assessed the credibility of a potential effect modification. Results suggested using the same overall relative effect for each of the two subpopulations (HR 0.85, 95% CI 0.80–0.90, for GLP-1 receptor agonists and HR 0.91, 95% CI 0.85–0.97, for SGLT2 inhibitors). Finally, we calculated 5-year absolute treatment effects (number of fewer patients with event per 1,000 patients). Treatment with GLP-1 receptor agonists resulted in 30 fewer patients with event in the subpopulation with established cardiovascular disease and 14 fewer patients with event in patients without manifest cardiovascular disease. For SGLT2 inhibitors, the respective absolute effects were 18 and 8 fewer patients with event per 1,000 patients. This framework can be applied to subgroup meta-analyses regardless of outcomes or modification variables. [ABSTRACT FROM AUTHOR]