Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

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

A ten-year survey of onychomycosis in the Central Region of the Rio Grande do Sul, Brazil Um estudo de 10 anos sobre onicomicoses na região central do Rio Grande do Sul, Brasil

Onychomycosis is a common infection of the nail plate caused by fungal microrganisms, and represents approximately 50% of nails disorders and 30% of all superficial mycotic infections. We present a study of the frequency, epidemiology and clinical aspects of onychomycosis in the central region of Rio Grande do Sul during the period 1988-1997.<br>Onicomicoses são infecções comuns da lâmina ungueal causadas por fungos filamentosos e leveduras, que representam aproximadamente 50% das alterações das unhas e 30% de todas as infecções fúngicas superficiais. Apresentamos um estudo sobre a freqüência, epidemiologia e aspectos clínicos das onicomicoses na região central do Rio Grande do Sul durante o período 1988-1997

Middle Eastern Appearances: “Ethnic Gangs”, Moral Panic and Media Framing

This article details a moral panic in 1998-2000 about |ethnic gangs| in Sydney's south-western suburbs and analyses its ideological construction of the links between ethnicity, youth and crime. It documents the racisms of labelling and targeting of immigrant young people which misread, oversimplify and misrepresent complex and class related social realities as racial, and the common-sense¹ sharing of these understandings, representations and practices by |mainstream| media, police and vocal representatives in state, local and |ethnic| politics. The data used in this analysis are largely comprised of English-language media extracts, press, radio, television - both commercial and government funded; and national, state and local in circulation, supplemented by interview material, from an ethnographic pilot study, with Lebanese-Australian youth, Lebanese immigrant parents, ethnic community workers, community leaders and police

The Economy of Live Music in the Digital Age

Popular music culture has changed significantly with the diffusion of networked digital media in the late 1990s. The present article theorizes the concept of live music in light of those changes and develops the idea of a new economy of live music. The perception of concerts as live music is central, so this is explored conceptually and historically before outlining the main elements of the new economy. Two immediate elements are the new economic centrality of live music and the categorical change in concert ticket prices. Two other elements are the rise of new and renewed event genres and the broader dynamics of the digital information society. The article integrates perspectives of cultural and performance studies. Keywords concerts, cultural economy, live music, live performance, media and performing arts, popular culture The promoter called me around noon [on 11 September 2001] and said, ‘Look, a lot of people have been calling and saying they’re coming to the show. Do you wanna do it? ’ I said … [long pause] I really like being with people. I trust people. I like being in a group of people. I like that kind of energy. This is one of the reasons I bothered to go out on tour and not just concoct these things in my studio and ship them out and sell them. I actually like the energy of seeing real people and seeing what will happen … So, yes, that evening was very, very intense. (Laurie Anderson on Sound Opinions, Chicago Public Radio, 5 May 2008) Live Nation owes its window of opportunity to the rise of the live show as a profi

IntCal13 radiocarbon calibration databases

Tree-ring, coral, speleothem, varve sediment and foraminifera 14C and calendar age determinations used to build the IntCal13 and Marine13 calibration curves. Data relates to paper - 'IntCal13 and Marine13 Radiocarbon Age Calibration Curves 0-50,000 Years Cal BP', Radiocarbon. 55, 4, p. 1869-1887 19 p

High pathogenicity avian influenza (H5N1) in northern gannets: global spread, clinical signs, and demographic consequences

During 2021 and 2022 High Pathogenicity Avian Influenza (HPAI) killed thousands of wild birds across Europe and North America, suggesting a change in infection dynamics and a shift to new hosts, including seabirds. Northern Gannets (Morus bassanus) appeared especially severely impacted, but a detailed account of the data available is required to help understand how the virus spread across the metapopulation, and the ensuing demographic consequences. Accordingly, we analyse information on confirmed and suspected HPAIV outbreaks across most North Atlantic Gannet colonies and for the largest colony (Bass Rock, UK), provide impacts on population size, breeding success, and preliminary results on apparent adult survival and serology. Unusually high numbers of dead Gannets were first noted at colonies in Iceland during April 2022. Outbreaks in May occurred in many Scottish colonies, followed by colonies in Canada, Germany and Norway. By the end of June, outbreaks had occurred in colonies in Canada and the English Channel. Outbreaks in 12 UK and Ireland colonies appeared to follow a clockwise pattern with the last infected colonies recorded in late August/September. Unusually high mortality was recorded at 40 colonies (75% of global total colonies). Dead birds testing positive for HPAIV H5N1 were associated with 58% of these colonies. At Bass Rock, the number of occupied nest sites decreased by at least 71%, breeding success declined by ~66% compared to the long-term UK mean and the resighting of marked individuals suggested that apparent adult survival between 2021 and 2022 could have been substantially lower than the preceding 10-year average. Serological investigation detected antibodies specific to H5 in apparently healthy birds indicating that some Gannets recover from HPAIV infection. Further, most of these recovered birds had black irises, suggestive of a phenotypic indicator of previous infection. Untangling the impacts of HPAIV infection from other challenges faced by seabirds is key to establishing effective conservation strategies for threatened seabird populations as the likelihood of further epizootics increases, due to increasing habitat loss and the industrialization of poultry production