A previous efficacy trial found benefit from inhaled budesonide for COVID-19 in patients not admitted to hospital, but effectiveness in high-risk individuals is unknown. We aimed to establish whether ...inhaled budesonide reduces time to recovery and COVID-19-related hospital admissions or deaths among people at high risk of complications in the community.
PRINCIPLE is a multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial done remotely from a central trial site and at primary care centres in the UK. Eligible participants were aged 65 years or older or 50 years or older with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to hospital. Participants were randomly assigned to usual care, usual care plus inhaled budesonide (800 μg twice daily for 14 days), or usual care plus other interventions, and followed up for 28 days. Participants were aware of group assignment. The coprimary endpoints are time to first self-reported recovery and hospital admission or death related to COVID-19, within 28 days, analysed using Bayesian models. The primary analysis population included all eligible SARS-CoV-2-positive participants randomly assigned to budesonide, usual care, and other interventions, from the start of the platform trial until the budesonide group was closed. This trial is registered at the ISRCTN registry (ISRCTN86534580) and is ongoing.
The trial began enrolment on April 2, 2020, with randomisation to budesonide from Nov 27, 2020, until March 31, 2021, when the prespecified time to recovery superiority criterion was met. 4700 participants were randomly assigned to budesonide (n=1073), usual care alone (n=1988), or other treatments (n=1639). The primary analysis model includes 2530 SARS-CoV-2-positive participants, with 787 in the budesonide group, 1069 in the usual care group, and 974 receiving other treatments. There was a benefit in time to first self-reported recovery of an estimated 2·94 days (95% Bayesian credible interval BCI 1·19 to 5·12) in the budesonide group versus the usual care group (11·8 days 95% BCI 10·0 to 14·1 vs 14·7 days 12·3 to 18·0; hazard ratio 1·21 95% BCI 1·08 to 1·36), with a probability of superiority greater than 0·999, meeting the prespecified superiority threshold of 0·99. For the hospital admission or death outcome, the estimated rate was 6·8% (95% BCI 4·1 to 10·2) in the budesonide group versus 8·8% (5·5 to 12·7) in the usual care group (estimated absolute difference 2·0% 95% BCI –0·2 to 4·5; odds ratio 0·75 95% BCI 0·55 to 1·03), with a probability of superiority 0·963, below the prespecified superiority threshold of 0·975. Two participants in the budesonide group and four in the usual care group had serious adverse events (hospital admissions unrelated to COVID-19).
Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications.
National Institute of Health Research and United Kingdom Research Innovation.
The pathogenesis of asthma is complex and multi-faceted. Asthma patients have a diverse range of underlying dominant disease processes and pathways despite apparent similarities in clinical ...expression. Here, we present the current understanding of asthma pathogenesis. We discuss airway inflammation (both T2
and T2
), airway hyperresponsiveness (AHR) and airways remodelling as four key factors in asthma pathogenesis, and also outline other contributory factors such as genetics and co-morbidities. Response to current asthma therapies also varies greatly, which is probably related to the inter-patient differences in pathogenesis. Here, we also summarize how our developing understanding of detailed pathological processes potentially translates into the targeted treatment options we require for optimal asthma management in the future.
Eosinophils are innate immune cells that, under certain conditions, can be recruited to the lungs, where they have an incompletely understood role in health and disease. Eosinophils have been found ...in the airways, tissues, and circulation of patients with COPD, during both stable disease and exacerbations. Epidemiological studies and post-hoc analyses of clinical trials of corticosteroid treatment for COPD have shown that the blood eosinophil count is associated with the risk of COPD exacerbations, mortality, decline in FEV
, and response to both inhaled and systemic corticosteroids. Further studies are urgently needed to explore the contribution of eosinophils to the mechanism of disease in COPD and to identify their association with levels of clinical risk. In this review, we explore the role of the eosinophil as a biomarker and mediator of disease in COPD.
This title is part of UC Press's Voices Revived program, which commemorates University of California Press's mission to seek out and cultivate the brightest minds and give them voice, reach, and ...impact. Drawing on a backlist dating to 1893, Voices Revived makes high-quality, peer-reviewed scholarship accessible once again using print-on-demand technology. This title was originally published in 1967.
This study demonstrates the existence of a sex difference in facial contrast. By measuring carefully controlled photographic images, female faces were shown to have greater luminance contrast between ...the eyes, lips, and the surrounding skin than did male faces. This sex difference in facial contrast was found to influence the perception of facial gender. An androgynous face can be made to appear female by increasing the facial contrast, or to appear male by decreasing the facial contrast. Application of cosmetics was found to consistently increase facial contrast. Female faces wearing cosmetics had greater facial contrast than the same faces not wearing cosmetics. Female facial beauty is known to be closely linked to sex differences, with femininity considered attractive. These results suggest that cosmetics may function in part by exaggerating a sexually dimorphic attribute—facial contrast—to make the face appear more feminine and hence attractive.
This study will enable readers to gain clearer understanding of the life and major works of Seamus Heaney. It considers literary influences on Heaney, ranging from English poets such as Wordsworth, ...Hughes, and Auden to Irish poets such as Kavanagh and Yeats to world poets such as Virgil and Dante.
COPD and asthma exacerbations result in many emergency department admissions. Not all treatments are successful, often leading to hospital readmissions. We sought to develop predictive models for ...exacerbation treatment outcome in a cohort of exacerbating asthma and COPD patients presenting to the emergency department. Treatment failure was defined as the need for additional systemic corticosteroids (SCS) and/or antibiotics, hospital readmissison or death within 30 days of initial emergency department visit. We performed univariate analysis comparing characteristics of patients either given or not given SCS at exacerbation and of patients who succeeded versus failed treatment. Patient demographics, medications and exacerbation symptoms, physiology and biology were available. We developed multivariate random forest models to identify predictors of SCS prescription and for predicting treatment failure. Data were available for 81 patients, 43 (53%) of whom failed treatment. 64 (79%) of patients were given SCS. A random forest model using presence of wheeze at exacerbation and blood eosinophil percentage predicted SCS prescription with area under receiver operating characteristic curve (AUC) 0.69. An 11 variable random forest model (which included medication, previous exacerbations, symptoms and quality of life scores) could predict treatment failure with AUC 0.81. A random forest model using just the two best predictors of treatment failure, namely, visual analogue scale for breathlessness and sputum purulence, predicted treatment failure with AUC 0.68. Prediction of exacerbation treatment outcome can be achieved via supervised machine learning combining different predictors at exacerbation. Validation of our predictive models in separate, larger patient cohorts is required.
LINKED CONTENT
This article is linked to Vuijk et al papers. To view these articles, visit https://doi.org/10.1111/apt.18000 and https://doi.org/10.1111/apt.18053
James Joyce and Samaritan Hospitality reads Dubliners and Ulysses through studies of hospitality, particularly that articulated in the Lukan parable of the Good Samaritan. It traces the origins of ...the novel in part to the physical attacks on Joyce in 1904 Dublin and 1907 Rome, showing how these incidents and the parable were incorporated into his short story ‘Grace’ and throughout Ulysses, especially its last four episodes. Richard Rankin Russell discusses the rich theory of hospitality developed by Joyce and demonstrates that he sought to make us more charitable readers through his explorations and depictions of Samaritan hospitality.
PDF
