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 Nemadji Review, Volume 5

Editor-in-Chief: Rebekah Kromm; Assistant Editor: Kourtney Sande; Design Editor: David Tromblay; Editorial Staff: Kelci Greenwood, Jami Taft, David Tromblay; Faculty Advisor: Jayson IwenVolume 5 of The Nemadji Review. Includes poetry, short fiction, creative non-fiction, and drama

Randomized clinical trial of first‐line genome sequencing in pediatric white matter disorders

Genome sequencing (GS) is promising for unsolved leukodystrophies, but its efficacy has not been prospectively studied.A prospective time-delayed cross-over design trial of GS to assess the efficacy of GS as a first-line diagnostic tool for genetic white matter disorders took place between 12/01/2015 - 09/27/2017. Patients were randomized to receive GS immediately with concurrent standard of care (SoC) testing, or to receive SoC testing for four months followed by GS.34 individuals were assessed at interim review. The genetic origin of two patient's leukoencephalopathy was resolved before randomization. Nine patients stratified to the immediate intervention group and 23 patients to the delayed-GS arm. The efficacy of GS was significant relative to SoC in the Immediate (5 of 9 [56%] vs. 0 of 9 [0%]; Wild-Seber

National Prison Rape Elimination Commission (NPREC) Report

Commissioner Brenda V. Smith Commissioner Brenda V. Smith is a Professor at American University’s Washington College of Law, where she teaches community and economic development law, legal ethics and women, and crime and law. Her research interests center on women in conflict with the law and on sexual abuse of individuals in custody. Professor Smith is also Project Director and Principal Investigator for the U.S. Department of Justice’s National Institute of Corrections Cooperative Agreement on Addressing Staff Sexual Misconduct with Offenders. She is an expert on issues affecting women in prison, a topic about which she has widely published and spoken. Before her appointment to the faculty of the Washington College of Law, Professor Smith was Senior Counsel for Economic Security at the National Women’s Law Center. She has also served as the Director of the Center’s Women in Prison Project and its Child and Family Support Project. Professor Smith earned her Bachelor of Arts from Spelman College and her Juris Doctor from Georgetown University Law Center

National Prison Rape Elimination Commission (NPREC) Report

Commissioner Brenda V. Smith Commissioner Brenda V. Smith is a Professor at American University’s Washington College of Law, where she teaches community and economic development law, legal ethics and women, and crime and law. Her research interests center on women in conflict with the law and on sexual abuse of individuals in custody. Professor Smith is also Project Director and Principal Investigator for the U.S. Department of Justice’s National Institute of Corrections Cooperative Agreement on Addressing Staff Sexual Misconduct with Offenders. She is an expert on issues affecting women in prison, a topic about which she has widely published and spoken. Before her appointment to the faculty of the Washington College of Law, Professor Smith was Senior Counsel for Economic Security at the National Women’s Law Center. She has also served as the Director of the Center’s Women in Prison Project and its Child and Family Support Project. Professor Smith earned her Bachelor of Arts from Spelman College and her Juris Doctor from Georgetown University Law Center

Growth Rates of Infants Randomized to Continuous Positive Airway Pressure or Intubation After Extremely Preterm Birth.

Objective To evaluate the effects of early treatment with continuous positive airway pressure (CPAP) on nutritional intake and in-hospital growth rates of extremely preterm (EPT) infants. Study design EPT infants (240/7-276/7 weeks of gestation) enrolled in the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) were included. EPT infants who died before 36 weeks of postmenstrual age (PMA) were excluded. The growth rates from birth to 36 weeks of PMA and follow-up outcomes at 18-22 months corrected age of EPT infants randomized at birth to either early CPAP (intervention group) or early intubation for surfactant administration (control group) were analyzed. Results Growth data were analyzed for 810 of 1316 infants enrolled in SUPPORT (414 in the intervention group, 396 in the control group). The median gestational age was 26 weeks, and the mean birth weight was 839 g. Baseline characteristics, total nutritional intake, and in-hospital comorbidities were not significantly different between the 2 groups. In a regression model, growth rates between birth and 36 weeks of PMA, as well as growth rates during multiple intervals from birth to day 7, days 7-14, days 14-21, days 21-28, day 28 to 32 weeks PMA, and 32-36 weeks PMA did not differ between treatment groups. Independent of treatment group, higher growth rates from day 21 to day 28 were associated with a lower risk of having a Bayley-III cognitive score Conclusions EPT infants randomized to early CPAP did not have higher in-hospital growth rates than infants randomized to early intubation