Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Pharmaceutical compounding and dispensing, 2nd ed./ John Marriot (et al)

xiii, 288 hal.: ill, tab.; 24 cm

Pharmaceutical compounding and dispensing, 2nd ed./ John Marriot (et al)

xiii, 288 hal.: ill, tab.; 24 cm

Gendered Horizons:Boys’ and girls’ perceptions of job and career choices

At what age and how do children in Wales form ideas about work and gender? The research study report in Gendered Horizons draws on evidence from stakeholder interviews, a survey of parents, interviews with children in primary school and young people in secondary school and a literature review. It finds that children and young people’s awareness of gendered roles in the workplace is not well developed for example they do not recognise the pay and progression implications of their expressed choices or a range of work roles. Whilst the younger children were still expressing their career ambitions in terms of fantasy roles that were clearly stereotypical in most cases, the older age group were also predominantly talking about job roles that they saw around them and roles that conformed to stereotypical gender roles, such as psychology for girls, working outdoors for boys, and teaching for both genders. In their mid-teens these young people did however have a better understanding of the world of work and of associated gender expectations. Furthermore, some of them expressed ideas about consciously challenging those stereotypes. There was consensus that young people need good guidance on was what their options were. While there is always debate on when career-related learning should start, there was agreement that it had to be before Year 9 when subject choices needed to be made. There was some evidence from the stakeholders that suggested that if young people are given opportunities to see workplaces, to talk to people who work in those places (whether introduced through family or school or other networks), then they are more likely to consider these as possibilities. Further, if they are supported with a programme of career learning they will know where to find information about pay, employment conditions, job opportunities, qualification requirements and career progression –they will understand why knowledge of these matters is important and will begin to challenge stereotypical thinking that underpins career choices.Chwarae Te

The art and science of walking: mobility, gender and footwear in the long eighteenth century

In the early eighteenth century mobility within the urban or rural environments was confined to restricted areas. In the town, the bad state of streets did not allow “walking for pleasure” outside the private parks or pleasure gardens. This situation underwent a sudden change in the mid-eighteenth century. The provision of public spaces in which to walk was part of the urban improvement measures of many British towns. This paper examines how these changes were mirrored in material artefacts such as footwear. Patterns, clogs and other devices designed to keep feet above ground level quickly disappeared, allowing easier mobility. However, these changes were negotiated in different ways in the public sphere by men and women. While men's footwear embraced functional notions, women's shoes became expressive of a female environment increasingly considered to be a domestic and private space. Men's boots contrasted with light and flimsy neoclassical women's shoes. By the end of the century boots became symbolic of democracy and participation in public affairs. The product's image was reshaped by military values - the famous Wellington boots are a good example of this phenomenon. Women, on the other hand, wore stylish but impractical shoes that were unsuitable for outdoor activities. The reason for these changes were political and social and were supplemented by a vast medical literature - mainly for women - on health and posture. The physical barriers that prevented free mobility gave way to more socially, culturally and psychologically constructed barriers