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

Medical emergency team response for the non-hospitalized patient

OBJECTIVES: Rapid response systems (RRS) evolved to care for deteriorating hospitalized patients outside of the ICU. However, emergent critical care needs occur suddenly and unexpectedly throughout the hospital campus, including areas with non-hospitalized persons. The efficacy of RRS in this population has not yet been described or tested. We hypothesize that non-hospitalized patients accrue minimal benefit from ICU physician participation in the RRS. DESIGN: A retrospective review of all RRS events in non-hospitalized patients for a 28 month period was performed in a large, urban university medical center. Location, patient type and age, activation trigger, interventions performed, duration of event and disposition were recorded. Admission diagnosis and length of stay were also recorded for patients admitted to the hospital. SETTING: Academic medical center. PATIENTS: Non-hospitalized persons requiring evaluation by the medical emergency team. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were a total of 1778 RRS activations during the study period. 232 (13%) of activations were for non-hospitalized patients. The patient cohort consisted of outpatients, visitors, and staff. Triggers for RRS activation were neurologic change (42%), cardiac (27%), respiratory (16%), and staff concerns (16%). The mean duration of the response was 38 min. The most common interventions performed included administration of oxygen (46%), intravenous fluids (13%) and dextrose (6%). 82% of patients were taken to the emergency department and 32% of the ED cohort were admitted to the hospital. CONCLUSIONS: Perceived emergencies in non-hospitalized patients occur commonly but require minimal emergent intervention. Restriction of critical care physician involvement to inpatient deteriorations should be considered when designing a RRS. Future studies are needed to evaluate the utility of nonphysician provider led rapid response teams with protocol-driven interventions for similar populations

The Eastern Association for the Surgery of Trauma\u27s Injury Control and Violence Prevention Committee\u27s annual distracted driving outreach event: Evaluating attitude and behavior change in high school students.

BACKGROUND: The National Center for Statistics and Analysis reports at least eight deaths and 1,160 daily injuries due to distracted driving (DD) in the United States. Drivers younger than 20 years are most likely to incur a distraction-related fatal crash. We aimed to determine short- and long-term impact of a multimodal educational program including student-developed interventions, simulated driving experiences, and presentations by law enforcement and medical personnel. METHODS: A single-day program aimed at teen DD prevention was conducted at a high school targeting students aged 15 years to 19 years old. Students were surveyed before, after, and at 6 weeks. We surveyed age, gender, knowledge, and experience regarding DD. Summary statistics were obtained at each survey time point. Bivariate and multivariable analysis were conducted to assess whether change in responses varied over time points. Multivariable models were adjusted for sex and urban and rural driving. RESULTS: Preintervention, postintervention, and 6-week follow-up surveys were completed by 359, 272 (76%), and 331 (92%) students, respectively. At baseline and 6-week follow-up, the most frequent passenger-reported DD behaviors were cell phone (63% [63% at follow-up) and radio use (61% [63%]). Similarly, the most frequent driver-reported DD behaviors were cell phone (68% [72%]) and radio use (79% [80%]). When students were asked, How likely are you to use your cell phone while driving? they answered never 35%, 70%, and 46% on the preintervention, postintervention, and 6-week surveys. They were less likely to report consequences to be worse or change in attitude to a great extent at 6 weeks (p \u3c 0.01). Gender and urban or rural driving were not significantly associated with responses. CONCLUSIONS: While DD education may facilitate short-term knowledge and attitude changes, there appears to be no lasting effect. Research should be focused toward strategies for longer-term impact. LEVEL OF EVIDENCE: Therapeutic study, level II

American Association for the Surgery of Trauma Prevention Committee review: Family Justice Centers—a not-so-novel, but unknown gem

The American College of Surgeons Committee on Trauma requires that trauma centers demonstrate adequate financial support for an injury prevention program as part of the verification process. With the ongoing challenges that arise with important social determinants of health, trauma centers have the important task of navigating a patient through the complex process of obtaining services and tools for success. This summary from the American Association for the Surgery of Trauma Prevention Committee focuses on a model that has been present for several years, but has not been brought to full awareness in the trauma world. It highlights the importance of the Family Justice Center concept that brings a multitude of organizations under one roof, thus eliminating the hurdles encompassed by trauma patients, seeking life-changing resources necessary to mitigate the impact of both community violence exposure and intimate partner/domestic violence. It discusses the potential benefits of a partnership between trauma centers and Family Justice Centers and similar models. Finally, it also raises awareness of important programmatic evaluation research required in the arena of injury prevention targeting a population whose outcomes are difficult to measure

Socially Responsible Surgery: Building Recognition and Coalition.

ImportanceSocially responsible surgery (SRS) integrates surgery and public health, providing a framework for research, advocacy, education, and clinical practice to address the social barriers of health that decrease surgical access and worsen surgical outcomes in underserved patient populations. These patients face disparities in both health and in health care, which can be effectively addressed by surgeons in collaboration with allied health professionals.ObjectiveWe reviewed the current state of surgical access and outcomes of underserved populations in American rural communities, American urban communities, and in low- and middle-income countries.Evidence reviewWe searched PubMed using standardized search terms and reviewed the reference lists of highly relevant articles. We reviewed the reports of two recent global surgery commissions.ConclusionThere is an opportunity for scholarship in rural surgery, urban surgery, and global surgery to be unified under the concept of SRS. The burden of surgical disease and the challenges to management demonstrate that achieving optimal health outcomes requires more than excellent perioperative care. Surgeons can and should regularly address the social determinants of health experienced by their patients. Formalized research and training opportunities are needed to meet the growing enthusiasm among surgeons and trainees to develop their practice as socially responsible surgeons

Socially Responsible Surgery: Building Recognition and Coalition.

ImportanceSocially responsible surgery (SRS) integrates surgery and public health, providing a framework for research, advocacy, education, and clinical practice to address the social barriers of health that decrease surgical access and worsen surgical outcomes in underserved patient populations. These patients face disparities in both health and in health care, which can be effectively addressed by surgeons in collaboration with allied health professionals.ObjectiveWe reviewed the current state of surgical access and outcomes of underserved populations in American rural communities, American urban communities, and in low- and middle-income countries.Evidence reviewWe searched PubMed using standardized search terms and reviewed the reference lists of highly relevant articles. We reviewed the reports of two recent global surgery commissions.ConclusionThere is an opportunity for scholarship in rural surgery, urban surgery, and global surgery to be unified under the concept of SRS. The burden of surgical disease and the challenges to management demonstrate that achieving optimal health outcomes requires more than excellent perioperative care. Surgeons can and should regularly address the social determinants of health experienced by their patients. Formalized research and training opportunities are needed to meet the growing enthusiasm among surgeons and trainees to develop their practice as socially responsible surgeons