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

Rate of Change of Rapid Shallow Breathing Index and Extubation Outcome in Mechanically Ventilated Patients

Background. Rapid shallow breathing index (RSBI) has been widely used as a predictor of extubation outcome in mechanically ventilated patients. We hypothesize that the rate of change of RSBI between the beginning and end of a 120-minute spontaneous breathing trial (SBT) could be a better predictor of extubation outcome than a single RSBI measured at the end of SBT in mechanically ventilated patients. Methodology. In this prospective observational study, we enrolled 193 patients who met the inclusion criteria, of whom 33 patients were unable to tolerate a 120-minute SBT and were excluded from the study. The study population consisted of 160 patients, categorized into three subgroups: patients with normal lung (no reported history of respiratory diseases), patients with airway disease, and patients with parenchymal disease who completed 120 minutes of SBT on low levels of pressure support ventilation. RSBI was obtained from the ventilator display at the 5th and the 120th minutes of SBT. The rate of change of RSBI (RSBI 5–120) was calculated as (RSBI 2-RSBI 1)/RSBI 1 × 100. Receiver-operating characteristic (ROC) curves were plotted for RSBI 5–120 and RSBI 120 in all patients and among the three subgroups (normal group, airway group, and parenchymal group) to compare the superiority of their best thresholds in predicting extubation failure. Results. The RSBI 5–120 threshold for extubation failure in the entire patient group was 23% with an overall accuracy of 88% (AUC = 0.933, sensitivity = 91%, and specificity = 86%) and the threshold of RSBI 120 for extubation failure in the entire patient group was 70 breaths/min/L with an overall accuracy of 82% (AUC = 0.899, sensitivity = 85%, and specificity = 81%). In patients in the normal lung group, the threshold of RSBI 5–120 was 22%, with an overall accuracy of 89% (AUC = 0.892, sensitivity = 87.5%, and specificity = 90%), and the RSBI 120 threshold was 70 breaths/min/L, with an overall accuracy of 89% (AUC = 0.956, sensitivity = 88%, and specificity = 90%). The RSBI 5–120 threshold in patients with airway disease was 25% with an accuracy of 86% (AUC = 0.892, sensitivity = 85%, and specificity = 86%) and the threshold of RSBI 120 was 73 breaths/min/L with an accuracy of 83% (AUC = 0.874, sensitivity = 85%, and specificity = 82%). In patients in the parenchymal disease group, the threshold of RSBI 5–120 was 24%, with an accuracy of 90% (AUC = 0.966, sensitivity = 92%, and specificity = 89%) and RSBI 120 threshold was 71 breaths/min/L, which was 88% accurate (AUC = 0.893, sensitivity = 85%, and specificity = 89%). Conclusion. The rate of change of RSBI between the 5th and 120th minutes was moderately more accurate than the single value of RSBI measured at the 120th minute in predicting extubation outcome

Rapid shallow breathing index

Predicting successful liberation of patients from mechanical ventilation has been a focus of interest to clinicians practicing in intensive care. Various weaning indices have been investigated to identify an optimal weaning window. Among them, the rapid shallow breathing index (RSBI) has gained wide use due to its simple technique and avoidance of calculation of complex pulmonary mechanics. Since its first description, several modifications have been suggested, such as the serial measurements and the rate of change of RSBI, to further improve its predictive value. The objective of this paper is to review the utility of RSBI in predicting weaning success. In addition, the use of RSBI in specific patient populations and the reported modifications of RSBI technique that attempt to improve the utility of RSBI are also reviewed

Hypericum perforatum L.

原著和名: セイヨウオトギリソウ科名: オトギリソウ科 = Guttiferae採集地:採集日: 1969/7/1採集者: 萩庭丈壽整理番号: JH038300国立科学博物館整理番号: TNS-VS-98830

Feasibility of a randomized controlled trial to assess treatment of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Saudi Arabia: a survey of physicians

Abstract Background The Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging respiratory pathogen with a high mortality rate and no specific treatments available to date. The purpose of this study was to determine the feasibility of conducting a randomized controlled trial (RCT) of convalescent plasma therapy for MERS-CoV-infected patients by using MERS-CoV-specific convalescent plasma obtained from previously recovered patients. Methods A survey was adapted from validated questionnaire originally aimed to measure network capacities and capabilities within the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC). The questionnaire was modified for this study to include 26 items that were divided into three main domains of interest: (1) the ability to care for critically ill MERS-CoV patients; (2) laboratory capacity to diagnose MERS-CoV and blood bank ability to prepare convalescent plasma; and (3), research capacity to conduct randomized controlled trials. The questionnaire was emailed to physicians. Results Of 582 physicians who were invited to the survey, 327 responded (56.2 %). The professional focus of the majority of respondents was critical care (106/249 (43 %)), pediatrics (59/249, (24 %)) or internal medicine (52/249 (21 %)) but none was blood banking. Nearly all respondents (251/263 (95 %)) reported to have access to ICU facilities within their institutions. Most respondents (219/270 (81 %)) reported that intensivists were the most physician group responsible for treatment decisions about critically ill SARI patients. While 125/165 respondents (76 %) reported that they conduct research in ICUs, and 80/161 (49.7 %) had been involved in the conduct of RCTs, including using a placebo comparison (60/161 (37 %)), only 49/226 (21 %) of respondents regularly participated in research networks. Conclusions Our survey indicated that in the Kingdom of Saudi Arabia (KSA), ICUs are the most likely clinical locations for conducting a clinical trial of convalescent plasma therapy for MERS-CoV, and that most ICUs have experience with such research designs

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

International audienc