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

The Characterization of the Microbiome for the Northern Two-lined Salamander (Eurycea bislineata) and its Ecological Interactions with the Pathogen Batrachochytrium dendrobatidis

Undergraduate Basi

Seroprevalence of SARS-CoV-2 Antibodies in a University Student Population

Undergraduate Applie

Amphibian Skin Pathogen Batrachochytrium dendrobatidis Surveillance in Ecuador

Undergraduate Theoretical Proposa

Temporal and Spatial Patterns of Inflammation and Tissue Injury in Patients with Postoperative Respiratory Failure after Lung Resection Surgery: A Nested Case–Control Study

Thoracic surgeries involving resection of lung tissue pose a risk of severe postoperative pulmonary complications, including acute respiratory distress syndrome (ARDS) and respiratory failure. Lung resections require one-lung ventilation (OLV) and, thus, are at higher risk of ventilator-induced lung injury (VILI) attributable to barotrauma and volutrauma in the one ventilated lung, as well as hypoxemia and reperfusion injury on the operated lung. Further, we also aimed to assess the differences in localized and systemic markers of tissue injury/inflammation in those who developed respiratory failure after lung surgery versus matched controls who did not develop respiratory failure. We aimed to assess the different inflammatory/injury marker patterns induced in the operated and ventilated lung and how this compared to the systemic circulating inflammatory/injury marker pattern. A case–control study nested within a prospective cohort study was performed. Patients with postoperative respiratory failure after lung surgery (n = 5) were matched with control patients (n = 6) who did not develop postoperative respiratory failure. Biospecimens (arterial plasma, bronchoalveolar lavage separately from ventilated and operated lungs) were obtained from patients undergoing lung surgery at two timepoints: (1) just prior to initiation of OLV and (2) after lung resection was completed and OLV stopped. Multiplex electrochemiluminescent immunoassays were performed for these biospecimen. We quantified 50 protein biomarkers of inflammation and tissue injury and identified significant differences between those who did and did not develop postoperative respiratory failure. The three biospecimen types also display unique biomarker patterns

Water quality, weather and environmental factors associated with fecal indicator organism density in beach sand at two recreational marine beaches

Recent studies showing an association between fecal indicator organisms (FIOs) in sand and gastrointestinal (GI) illness among beachgoers with sand contact have important public health implications because of the large numbers of people who recreate at beaches and engage in sand contact activities. Yet, factors that influence fecal pollution in beach sand remain unclear. During the 2007 National Epidemiological and Environmental Assessment of Recreational (NEEAR) Water Study, sand samples were collected at three locations (60 m apart) on weekend days (Sat, Sun) and holidays between June and September at two marine beaches — Fairhope Beach, AL and Goddard Beach, RI — with nearby publicly-owned treatment works (POTWs) outfalls. F(+) coliphage, enterococci, Bacteroidales, fecal Bacteroides spp., and Clostridium spp. were measured in sand using culture and qPCR-based calibrator-cell equivalent methods. Water samples were also collected on the same days, times and transects as the 144 sand samples and were assayed using the same FIO measurements. Weather and environmental data were collected at the time of sample collection. Mean FIO concentrations in sand varied over time, but not space. Enterococci CFU and CCE densities in sand were not correlated, although other FIOs in sand were. The strongest correlation between FIO density in sand and water was fecal Bacteroides CCE, followed by enterococci CFU, Clostridium spp. CCE, and Bacteroidales CCE. Overall, the factors associated with FIO concentrations in sand were related to the sand–water interface (i.e., sand-wetting) and included daily average densities of FIOs in water, rainfall, and wave height. Targeted monitoring that focuses on daily trends of sand FIO variability, combined with information about specific water quality, weather, and environmental factors may inform beach monitoring and management decisions to reduce microbial burdens in beach sand. The views expressed in this paper are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency