Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Morphological Features and Sorption Performance of Materials Based on Birnessite Exposed to Various Reductive Conditions

The article is devoted to the evolution of structural, morphological, and sorption characteristics of layered manganese oxide (birnessite) under various conditions close to the real operating regime of the sorbents for radioactive waste processing. To identify the phase composition in the birnessites, we implemented XRD analysis, while SEM and temperature-programmed reduction (TPR) were used to study morphological and redox features of the materials, respectively. Structural changes after various kinds of treatment of birnessites were tracked using low temperature nitrogen sorption. Sorption characteristics were assessed under static and in dynamic conditions on the efficiency of Sr2+ removal from simulated seawater. TPR combined with kinetic analysis revealed the decrease of particle sizes in the birnessites after repeated use in sorption-regeneration cycle and reduction with hydrazine. Despite the fact that the porous structure of the materials remains preserved, the surface morphology of birnessite changes drastically depending on the reducing agent. Hydrazine treatment increases the sorption performance of the birnessite followed by degradation of mechanical properties, thus, preventing such sorbent from repeated use. Kinetic analysis of TPR allows quantifying differences in morphology and porous structure of manganese oxide materials. The specific surface area, amorphous surface structure, and accessibility of Mn+3 sites are the most important factors for birnessite sorption performance

Outcomes of Cryoballoon Ablation in High-and Low-Volume Atrial Fibrillation Ablation Centres: A Russian Pilot Survey

properly cited. Purpose. The results of cryoballoon ablation (CBA) procedure have been mainly derived from studies conducted in experienced atrial fibrillation (AF) ablation centres. Here, we report on CBA efficacy and complications resulting from real practice of this procedure at both high-and low-volume centres. Methods. Among 62 Russian centres performing AF ablation, 15 (24%) used CBA technology for pulmonary vein isolation. The centres were asked to provide a detailed description of all CBA procedures performed and complications, if encountered. Results. Thirteen sites completed interviews on all CBAs in their centres (>95% of CBAs in Russia). Six sites were high-volume AF ablation (>100 AF cases/year) centres, and 7 were low-volume AF ablation. There was no statistical difference in arrhythmia-free rates between high-and low-volume centres (64.6 versus 60.8% at 6 months). Major complications developed in 1.5% of patients and were equally distributed between high-and low-volume centres. Minor procedurerelated events were encountered in 8% of patients and were more prevalent in high-volume centres. Total event and vascular access site event rates were higher in women than in men. Conclusions. CBA has an acceptable efficacy profile in real practice. In less experienced AF ablation centres, the major complication rate is equal to that in high-volume centres

Outcomes of Cryoballoon Ablation in High- and Low-Volume Atrial Fibrillation Ablation Centres: A Russian Pilot Survey

Purpose. The results of cryoballoon ablation (CBA) procedure have been mainly derived from studies conducted in experienced atrial fibrillation (AF) ablation centres. Here, we report on CBA efficacy and complications resulting from real practice of this procedure at both high- and low-volume centres. Methods. Among 62 Russian centres performing AF ablation, 15 (24%) used CBA technology for pulmonary vein isolation. The centres were asked to provide a detailed description of all CBA procedures performed and complications, if encountered. Results. Thirteen sites completed interviews on all CBAs in their centres (>95% of CBAs in Russia). Six sites were high-volume AF ablation (>100 AF cases/year) centres, and 7 were low-volume AF ablation. There was no statistical difference in arrhythmia-free rates between high- and low-volume centres (64.6 versus 60.8% at 6 months). Major complications developed in 1.5% of patients and were equally distributed between high- and low-volume centres. Minor procedure-related events were encountered in 8% of patients and were more prevalent in high-volume centres. Total event and vascular access site event rates were higher in women than in men. Conclusions. CBA has an acceptable efficacy profile in real practice. In less experienced AF ablation centres, the major complication rate is equal to that in high-volume centres