Characteristics of Cocaine Users Presenting to an Emergency Department Chest Pain Observation Unit

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73770/1/j.aem.2004.11.021.pd

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

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

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

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

Evaluation and Treatment of Depression (Part I): Benefits for Patients, Providers, and Payors

Depression is one of the leading causes of disability worldwide, contributing to high medical expenditures, poor clinical outcomes, low productivity, and compromised quality of life. Efficacious treatments are available for the treatment of depression across a broad age range (children/adolescents to elderly). Care management initiatives that include these promising interventions ameliorate the impact of the disorder among patients receiving mental health services in primary care and behavioral healthcare settings. Part I of this two-part article series provides the reader with an overview of issues related to improving the treatment of depression. The approaches used to treat depression and strategies employed to evaluate treatment success are critical. Disease management is one strategy used for improving depression treatment that benefits the consumer and yields positive results for providers and payors. The most effective strategies are those with multiple components, including patient education, coordination of care between primary care and mental health specialists, and ongoing evaluation and feedback. Although the benefits of such interventions are profound in producing improvements in depressive symptoms, social and emotional functioning, and overall satisfaction, there have been few healthcare systems that have successfully integrated such programs into routine care. Despite indirect advantages to providers and payors, the costs of implementing such programs may present a larger barrier to system-wide adoption of disease management for depression. Certainly, the potential for healthcare cost reductions needs to be systematically examined, particularly the extent to which certain patient groups (the most interesting being those with the highest healthcare costs or catastrophic outcomes of their depression) will benefit from disease management programs. Subpopulations (e.g. children, adolescent and older adults) have associated extant barriers that impede progress with implementing disease management support services and programs. Part II provides an overview of quality improvement strategies demonstrated to be effective in improving depression treatment and discusses examples of programs implemented in various care settings.Depression, Disease-management-programmes

Simulation-based training in urology residency programmes in the USA: Results of a nationwide survey

Objective: To evaluate the current usage of simulation in urological education in the USA and the barriers to incorporating a simulation-based educational curriculum, as the shift towards competency-based medical education has necessitated the introduction of simulation for training and assessing both non-technical and technical skills. Materials and methods: Residency programme directors at Accreditation Council for Graduate Medical Education (ACGME)-accredited urology training programmes in the USA were invited to respond to an anonymous electronic survey. The study evaluated the programme directors’ experiences and opinions for the current usage of existing urology simulators. The survey also elicited receptiveness and the barriers for incorporating simulation-based training curricula within urology training programmes. Results: In all, 43 completed surveys were received (35% response rate). Amongst responders, 97% (42/43) reported having access to a simulation education centre, and 60% (25/42) have incorporated simulation into their curriculum. A total of 87% (37/43) agreed that there is a role for a standardised simulator training curriculum, and 75% (30/40) agreed that simulators would improve operating room performance. A total of 64% (27/42) agreed that cost was a limiting factor, 12% (5/42) agreed on the cost-effectiveness of simulators, 35% (17/41) agreed there was an increased need for simulator education within work-hour limitations, and 38% (16/42) agreed a simulation programme would reduce patient risks and complications. Conclusions: The majority of urology programme directors consider that there is a role for incorporating a simulation-based curriculum into urology training. Barriers to implementation include cost burden, need for constant technology updates, need for advanced planning, and willingness of faculty to participate in administration. Keywords: Computer simulation, Education, Residency, Curriculu

Crystal clear or tin ear: how do medical students interpret derogatory comments about patients and other professionals?

Purpose: To assess the learning environment at our medical school, third-year medical students complete an 11-item survey called the Learning Environment for Professionalism (LEP) at the end of each clerkship. The LEP survey asks about the frequency of faculty and resident professional and unprofessional behaviors that students observed; two of the items specifically address derogatory comments. This study used focus group methodology to explore how medical students interpret the derogatory comments they reported on the LEP survey. Methods: Seven focus groups were conducted with 82 medical students after they completed the LEP survey. Analysis of focus group transcripts was performed to better understand the nature and meaning that students ascribe to derogatory comments. Results: The study results provide insights into the types of derogatory comments that medical students heard during their clerkship rotations, why the comments were made and how they were interpreted. Emergent themes, labeled by the authors as 1) ‘onstage-offstage’, 2) ‘one bad apple’, and 3) ‘pressure cooker environment’, highlight the contextual aspects and understandings ascribed by students to the derogatory comments. Incidentally, students felt that the comments were not associated with fatigue, but were associated with cumulative stress and burn-out. Conclusions: The results suggest students have a clear understanding of the nature of unprofessional comments made by role models during clerkships and point to important systems-related issues that could be leveraged to improve clinical learning environments

Use of Electronic Medical Record Data for Quality Improvement in Schizophrenia Treatment

An understanding of the strengths and limitations of automated data is valuable when using administrative or clinical databases to monitor and improve the quality of health care. This study discusses the feasibility and validity of using data electronically extracted from the Veterans Health Administration (VHA) computer database (VistA) to monitor guideline performance for inpatient and outpatient treatment of schizophrenia. The authors also discuss preliminary results and their experience in applying these methods to monitor antipsychotic prescribing using the South Central VA Healthcare Network (SCVAHCN) Data Warehouse as a tool for quality improvement