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

Methicillin-resistant staphylococcus aureus as a uropathogen in an irish setting

Urinary tract infections are one of the most common infectious diseases diagnosed in the community and in the hospital setting. Their treatment is complicated by drug-resistant pathogens and the colonization by microbes of indwelling urinary catheters. This study assessed the occurrence and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) uropathogens isolated for 5 consecutive years at University Hospital Waterford between 2010 and 2014. We created 4 clinically relevant subdivisions, based on urine source: hospital inpatients, patients from the Emergency Department, patients referred from their General Practitioner, and Nursing Home patients. We performed a retrospective review from the hospital\u27s electronic microbiological system and calculated resistance rates for each of the standard antimicrobial agents. During the 5-year study period, we studied 151 urine isolates obtained from 128 patients who had an MRSA cultured in their urine sample. There was 100% resistance of all MRSA isolates to Flucloxacillin and Coamoxiclav. Ninety-eight percent of isolates were resistant to Ciprofloxacin. The resistance rate for Trimethoprim was 7.4% and there was only 2.7% resistance for Nitrofurantoin. For a clinical subset of patients, we also demonstrated 100% sensitivity for samples tested against Teicoplanin and Vancomycin. Urinary MRSA is an infrequently studied phenomenon, but with the rising trend of hospital superbugs nationally, its management is of critical importance. Suitable agents to address this within our population include Nitrofurantoin in the well patient requiring urinary MRSA eradication or Vancomycin/Teicoplanin in the unwell patient requiring intravenous therapy. In all groups, fluoroquinolones should be avoided due to significant resistance rates

Methicillin-resistant staphylococcus aureus as a uropathogen in an irish setting

Urinary tract infections are one of the most common infectious diseases diagnosed in the community and in the hospital setting. Their treatment is complicated by drug-resistant pathogens and the colonization by microbes of indwelling urinary catheters. This study assessed the occurrence and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) uropathogens isolated for 5 consecutive years at University Hospital Waterford between 2010 and 2014. We created 4 clinically relevant subdivisions, based on urine source: hospital inpatients, patients from the Emergency Department, patients referred from their General Practitioner, and Nursing Home patients. We performed a retrospective review from the hospital's electronic microbiological system and calculated resistance rates for each of the standard antimicrobial agents. During the 5-year study period, we studied 151 urine isolates obtained from 128 patients who had an MRSA cultured in their urine sample. There was 100% resistance of all MRSA isolates to Flucloxacillin and Coamoxiclav. Ninety-eight percent of isolates were resistant to Ciprofloxacin. The resistance rate for Trimethoprim was 7.4% and there was only 2.7% resistance for Nitrofurantoin. For a clinical subset of patients, we also demonstrated 100% sensitivity for samples tested against Teicoplanin and Vancomycin. Urinary MRSA is an infrequently studied phenomenon, but with the rising trend of hospital superbugs nationally, its management is of critical importance. Suitable agents to address this within our population include Nitrofurantoin in the well patient requiring urinary MRSA eradication or Vancomycin/Teicoplanin in the unwell patient requiring intravenous therapy. In all groups, fluoroquinolones should be avoided due to significant resistance rates

Clinical unity and community empowerment: the use of smartphone technology to empower community management of chronic venous ulcers through the support of a tertiary unit

Background: Chronic ulcers affect roughly 60,000 Irish people, at a total cost of J600,000,000, or J10,000 per patient annually. By virtue of their chronicity, these ulcers also contribute a significant burden to tertiary outpatient vascular clinics. Objective: We propose utilizing mobile phone technology to decentralise care from tertiary centres to the community, improving efficiency and patient satisfaction, while maintaining patient safety. Methods: Bespoke mobile software was developed for Apples iPhone 4 platform. This allowed for the remote collection of patient images prospectively and their transmission with clinical queries, from the primary healthcare team to the tertiary centre. Training and iPhones were provided to five public health nurses in geographically remote areas of the region. Data were uploaded securely and user end software was developed allowing the review and manipulation of images, along with two way communication between the teams. Establishing reliability, patients were reviewed clinically as well as remotely, and concordance analysed. Qualitative data were collected through focus group discussion. Results: From October to December 2011 eight patients (61–83 yrs, mean 75.3 yrs) with chronic venous ulceration and their five public health nurses were recruited. Data were transmitted using 3 G, Edge, GPRS and WiFi, at a mean speed of 69.03 kps. Concordance was 100% for wound bed assessment, 80% for skin integrity/colour and 60% for exudate assessment. Focus group analysis explored the concept, practicalities and future applications of the system. Conclusions: With an evolving national data network, the secure transmission of clinical images is a safe alternative to regular clinic appointments for patients with chronic venous ulceration. With further development, and package