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

Jonathan Swift, the Earl of Rosse, Duke of Wharton, and Sir Charles Wogan

Drawing on unpublished documents in the Diocesan Archive in Galway, Ireland, this essay investigates the correspondence of Sir Charles Wogan, with Jonathan Swift, Dean of St. Patrick’s Cathedral, in Dublin. They reveal Wogan’s collaboration with Phillip, Duke of Wharton, Grand Master of Écossais Freemasonry, in Spain in 1729-31. By examining Swift’s Masonic publications and relation with the Earl of Rosse, friend of Wharton and Grand Master of Ireland; and with other Jacobites in Spain; and admirers of Wogan, probable Mason and devotee of Don Quixote, we gain a new perspective on Swift’s Jacobite sympathies and Irish-Spanish Masonic connections.  Basado en documentos inéditos del Archivo Diocesano de Galway, Irlanda, este trabajo investiga la correspondencia de sir Charles Wogan con Jonathan Swift, el decano de la Catedral de San Patricio en Dublín. Wogan colaboró con Phillip, el duque de Wharton, y el gran maestro de la masonería escocesa en España desde1729 hasta 1731. Examinando las publicaciones masónicas de Swift y su relación con otros jacobitas en España, obtenemos una nueva perspectiva de las simpatías jacobitas de Swift y de las conexiones masónicas irlandesas-españolas de los admiradores de Wogan, probable masón

News from the Thames (Blake! There’s something in the water)

Investigating the Thames, this chapter explores late eighteenth-century newspaper articles that narrate stories of animals, such as: a gigantic eel trapped in a coffin, eroticised swan-men, and blindfolded tigers arriving on the docks after Tipu Sultan’s defeat in Mysore. These articles provoke new ways of reading motifs of sexuality, empire and hell in works by Blake, including The Marriage of Heaven and Hell, Urizen, the Large and Small Books of Designs, and illustrations to John Gabriel Stedman, Dante and the Bible. The chapter draws on writing by Walter Benjamin and J. Hillis Miller, developing the idea of the literary caption as an alternative form of academic writing. By using sensationalist animal stories as captions for Blake, we can discover new magical and ethical aspects of his work, within a circulation of fantastical narratives around the Thames. Human–animal relationships become a model for understanding the relationship between texts and images—intimate and visionary, infecting each other without directly touching