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

Teaching Medical Students About Communicating with Patients Who Have Sensory or Physical Disabilities

No abstract availabl

An Intensive Continuity Clinic Immersion Experience for Interns: A Springboard to Confidence and Satisfaction With Continuity Clinic

BackgroundProviding a robust continuity clinic experience is difficult due to uneven distribution of resident time. Immersion experiences early in training may improve residents' learning experiences.ObjectiveWe designed and implemented a continuity immersion experience to improve internal medicine interns' satisfaction and confidence with their outpatient skills, and we evaluated the timing of the experience and its benefits for learners.MethodsTwo cohorts of interns at 1 academic institution participated in a 3-week immersion block (during the first or second quarter of the intern year). Interns were surveyed twice about satisfaction and confidence. Analysis included independent and paired sample t tests to compare interns' responses pre- and postimmersion, and to evaluate effects over time.ResultsA total of 124 interns completed the immersion, with a survey response rate of 61%. Interns' self-rated confidence on a 5-point Likert scale improved significantly compared with preimmersion in the areas of medical knowledge and confidence with their electronic health record and communication skills (P ≤ .010 for all assessments). Interns reported high satisfaction with continuity clinic following immersion (cohort 1: 4.5 ± 0.54; cohort 2: 4.3 ± 0.68; on a 5-point scale with 5 = very satisfied). Improvements in knowledge, skills, and satisfaction in cohort 1 were sustained over 3 months.ConclusionsA 3-week immersion experience in the first 6 months of residency improved interns' confidence in ambulatory content areas and satisfaction with clinic

Decision Making and Counseling around Mammography Screening for Women Aged 80 or Older

BACKGROUND: Despite uncertain benefit, many women over age 80 (oldest-old) receive screening mammography. OBJECTIVE: To explore decision-making and physician counseling of oldest-old women around mammography screening. DESIGN: Qualitative research using in-depth semi-structured interviews. PARTICIPANTS: Twenty-three women aged 80 or older who received care at a large academic primary care practice (13 had undergone mammography screening in the past 2 years) and 16 physicians at the same center. APPROACH: We asked patients and physicians to describe factors influencing mammography screening decisions of oldest-old women. We asked physicians to describe their counseling about screening to the oldest-old. RESULTS: Patients and/or physicians identified the importance of physician influence, patient preferences, system factors, and social influences on screening decisions. Although physicians felt that patient's health affected screening decisions, few patients felt that health mattered. Three types of elderly patients were identified: (1) women enthusiastic about screening mammography; (2) women opposed to screening mammography; and (3) women without a preference who followed their physician's recommendation. However, physician counseling about mammography screening to elderly women varies; some individualize discussions; others encourage screening; few discourage screening. Physicians report that discussions about stopping screening can be uncomfortable and time consuming. Physicians suggest that more data could facilitate these discussions. CONCLUSIONS: Some oldest-old women have strong opinions about screening mammography while others are influenced by physicians. Discussions about stopping screening are challenging for physicians. More data about the benefits and risks of mammography screening for women aged 80 or older could inform patients and improve provider counseling to lead to more rational use of mammography

Teaching Medical Students about Communicating with Patients with Major Mental Illness

Persons with major mental illness often have chronic diseases and poor physical health. Therefore, all practicing physicians should learn about communicating effectively with these patients. Few efforts to teach medical students communication skills have specifically targeted patients with major mental illness. Indeed, most of the limited literature on this topic is decades old, predating significant scientific advances in cognitive neuroscience and psychiatric therapeutics and changes in social policies regarding major mental illness. To gather preliminary insight into training needs, we interviewed 13 final-year students from 2 Boston medical schools. Students' observations coalesced around 4 themes: fears and anxieties about interacting with persons with major mental illness; residents “protecting” students from patients with major mental illness; lack of clinical maturity; and barriers to learning during psychiatry rotations. Educational researchers must explore ways to better prepare young physicians to communicate effectively with patients with major mental illness

Implementation of genomic medicine for rare disease in a tertiary healthcare system: Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD)

Abstract Background In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education. Methods Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers. Results Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results. Conclusion Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities