Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3): a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery

Background For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes. Methods The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. Discussion Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. Trial registration ClinicalTrials.gov NCT03505723. Registered on 23 April 2018

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

LandEscapes, 2006

Evangeline by Lesa Lauders, Guest contributor p. 11 - Shaking the Shadow by Ingrid Rachinski p. 21 - Sign me up, Sister by Kate Patterson p. 31 - Snakes and Certainties by Megan Carper, Editor’s Choice p. 45 - Inspiration by Katie Tembley p. 53 - Lapwai by Zachary A. Mazur p. 54 - Milwaukee Road by Michelle White p. 55 - Waterfall by Jeremiah Thomas Gray p. 56 - Composition by Sarah Rollinger p. 57 - Shut Down by Love by Kelsey Parpart, Editor’s Choice p. 61 - The Roof by Isaac Barton p. 73 - Flamingo by Laura West p. 83 - Cold Shoulder by Shannon Bartlett p. 89 - Licentious Phoenix by Jane Copland p. 93 - Yakima Morning by Heather Ireton p. 97 - Infrared Sepia by Michelle White p. 98 - Hair, Hats ‘n Cracks by Heather Ireton p. 99 - Green Dublin River by Sarah Rollinger p. 100 - Glacial Park by Zachary A. Mazur, Editor’s choice p. 101 - Untitled by Amber Birkhimer p. 102 - Umbrellas by Sarah Rollinger p. 103 - We are Many by Pablo Neruda p. 107 - Red Skeletons by Jeff Zundel, Editor’s choice p. 108 - Industrialism Illuminates the Room by Boyd Benson’s fall 2005 English 251 Class p. 110 - Days since the day by Tim Hetland p. 111 - Auditions by Tim Hetland p. 112 - Untitled by Jeff Zundel p. 114 - Angola by Bethany Lee p. 115 - America by Katie Trembley p. 116 - Insomniac Stew by Nancy Schaefer p. 117 - Harvest by Gail Ritchie p. 118 - X by Kevin Lewis p. 119 - Young Men by Jonathan Mark Ehlinger p. 120 - Mudrassling by Heather Ireton p. 12

Telmisartan, ramipril, or both in patients at high risk for vascular events

BACKGROUND: In patients who have vascular disease or high-risk diabetes without heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and morbidity from cardiovascular causes, but the role of angiotensin-receptor blockers (ARBs) in such patients is unknown. We compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes. METHODS: After a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. RESULTS: Mean blood pressure was lower in both the telmisartan group (a 0.9/0.6 mm Hg greater reduction) and the combination-therapy group (a 2.4/1.4 mm Hg greater reduction) than in the ramipril group. At a median follow-up of 56 months, the primary outcome had occurred in 1412 patients in the ramipril group (16.5%), as compared with 1423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94 to 1.09). As compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P<0.001) and angioedema (0.1% vs. 0.3%, P=0.01) and a higher rate of hypotensive symptoms (2.6% vs. 1.7%, P<0.001); the rate of syncope was the same in the two groups (0.2%). In the combination-therapy group, the primary outcome occurred in 1386 patients (16.3%; relative risk, 0.99; 95% CI, 0.92 to 1.07); as compared with the ramipril group, there was an increased risk of hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P=0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001). CONCLUSIONS: Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit. (ClinicalTrials.gov number, NCT00153101 [ClinicalTrials.gov].)

Struggle Music: South African Politics in Song

Music, and especially singing, plays a central role in African cultures. Songs and rhythm have been described as 'a truly African way of communication' and it is therefore not surprising that music has played, and continues to play, an important role in African politics. This article will consider the important role that struggle music - also known as freedom songs – played in South Africa during the apartheid years and the struggle for liberation, and how it continues to play an important role in contemporary South African politics. First, the genre of struggle music will be circumscribed and differentiated from other politically motivated music. Then the discussion will turn to the struggle music of South Africa during the apartheid years, and how it is still being utilised in politics today. With regard to the contemporary use of struggle music in South African politics, the discussion will focus on the controversial struggle song Dubulu' iBhunu and the decision of the South African Equality Court in Afriforum & another v Malema and another (Vereniging van Regslui vir Afrikaans as Amicus Curiae) 2011 (12) BCLR 1289 (EQC) prohibiting the singing of the song in public and declaring its lyrics to be hate speech