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 four month prospective descriptive exploratory study of patients receiving antibiotics in one Emergency Department

Background: Any infection can potentially develop into sepsis. Many patients present to the Emergency Department (ED) with infection and go on to require antibiotics. However, the timeliness of antibiotics can make a difference to patient survival and reduce the risk of infection developing into sepsis and or septic shock. Methods: Our study was a 4 month prospective descriptive exploratory pilot study. Results: Of all adult (n = 18,807) presentations 3339 (18%) patients had a primary diagnosis related to infection. The study collected data on 104 (3%) patients who were administered antibiotics. One hundred (95%) patients who received antibiotics were admitted to hospital. Triage code did not influence time to antibiotic (p = .352). Eighty-five (81%) patients waited longer than 1 h for their first antibiotic with the shortest administration time 19 min (mean 233 min, SD 247) and the maximum wait for antibiotics was 1481 min. For sepsis or septic shock patients (n = 8) the average time to antibiotics was 411 min (SD = 455 min). Conclusion: The study provides a detailed analysis of ED patients receiving antibiotics. Further research is needed to identify strategies to improve the timely delivery of antibiotics for patients with infections

The prevalence and triage characteristics of patients presenting with infection to one tertiary referral hospital

Background: Globally, severe infection and or sepsis is a problem that is costing billions of dollars, using hundreds of hospital beds, and often results in patient death. Any infection can potentially develop a sepsis health trajectory if left unrecognised and unmanaged. Methods: We conducted a 12 month retrospective descriptive exploratory study. Our research explored the prevalence and triage characteristics of patients presenting with infection to one tertiary referral hospital. Electronic medical records were reviewed to identify patients that had a primary diagnosis related to infection. Results: The study identified that 16% (n = 7756) of adult presentations had a discharge diagnosis related to infection. A significant difference (X2 = 297.83, df = 4, p ≤ .001) in Triage Code allocation for the infection group was identified compared with the non-infection patient group. Thirty-nine percent (n = 3027) of patients with infections were admitted to hospital. Of the patients (n = 1930; 4%) admitted to a critical care area, 6% (n = 122) had a primary diagnosis related to infection. Of the ED deaths (n = 81), 12% (n = 10) had a primary diagnosis related to infection. Conclusion: The study provides a detailed analysis of the prevalence and triage characteristics of patients with infection presenting to one ED. Further research is needed to identify strategies to improve the triage nurse's recognition of severe infection and consistency of urgency code allocation to prevent patient deterioration

Opportunities for Regulatory Changes to Promote Pediatric Device Innovation in the United States: Joint Recommendations From Pediatric Innovator Roundtables.

ObjectiveThe purpose of this report is to provide insight from pediatric stakeholders with a shared desire to facilitate a revision of the current United States regulatory pathways for the development of pediatric healthcare devices.MethodsOn August 5, 2020, a group of innovators, engineers, professors and clinicians met to discuss challenges and opportunities for the development of new medical devices for pediatric health and the importance of creating a regulatory environment that encourages and accelerates the research and development of such devices. On January 6, 2021, this group joined regulatory experts at a follow-up meeting.ResultsOne of the primary issues identified was the need to present decision-makers with opportunities that change the return-on-investment balance between adult and pediatric devices to promote investment in pediatric devices.Discussion/conclusionSeveral proposed strategies were discussed, and these strategies can be divided into two broad categories: 1. Removal of real and perceived barriers to pediatric device innovation; 2. Increasing incentives for pediatric device innovation

Does one workshop on respecting cultural differences increase health professionals' confidence to improve the care of Australian Aboriginal patients with cancer? An evaluation

© 2017 The Author(s). Background: Aboriginal Australians have worse cancer survival rates than other Australians. Reasons include fear of a cancer diagnosis, reluctance to attend mainstream health services and discrimination from health professionals. Offering health professionals education in care focusing on Aboriginal patients' needs is important. The aim of this paper was to evaluate whether participating in a workshop improved the confidence of radiation oncology health professionals in their knowledge, communication and ability to offer culturally safe healthcare to Aboriginal Australians with cancer. Methods: Mixed methods using pre and post workshop online surveys, and one delivered 2 months later, were evaluated. Statistical analysis determined the relative proportion of participants who changed from not at all/a little confident at baseline to fairly/extremely confident immediately and 2 months after the workshop. Factor analysis identified underlying dimensions in the items and nonparametric tests recorded changes in mean dimension scores over and between times. Qualitative data was analysed for emerging themes. Results: Fifty-nine participants attended the workshops, 39 (66% response rate) completed pre-workshop surveys, 32 (82% of study participants) completed post-workshop surveys and 25 (64% of study participants) completed surveys 2 months later. A significant increase in the proportion of attendees who reported fair/extreme confidence within 2 days of the workshop was found in nine of 14 items, which was sustained for all but one item 2 months later. Two additional items had a significant increase in the proportion of fair/extremely confident attendees 2 months post workshop compared to baseline. An exploratory factor analysis identified three dimensions: communication; relationships; and awareness. All dimensions' mean scores significantly improved within 2 days (p < 0.005) and persisted to 2 months. The workshop raised awareness about barriers and enablers to delivering services respectful of cultural differences, led to a willingness to reflect on pre-existing beliefs and assumptions about Aboriginal Australians that in some cases resulted in improved care. Conclusion: Single workshops co-delivered by an Aboriginal and non-Aboriginal presenter can be effective in building health professionals' confidence and translating into practice knowledge of respectful care of Aboriginal patients with cancer. Sustaining improvements may require integrating this approach into ongoing professional development

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc