Early Outpatient Treatment for Covid-19 with Convalescent Plasma.

BACKGROUND: Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain. METHODS: In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion. RESULTS: Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized. CONCLUSIONS: In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.).

Emergency Physicians' Ethical Issues with Hospital Business Models.

BACKGROUND: The changing hospital business model has raised ethical issues for emergency physicians (EPs) in a healthcare system that often prioritizes profits over patient welfare. For-profit hospitals, driven by profit motives, may prioritize treating patients with lucrative insurance plans and those who can afford expensive treatments. Private equity investors, who now own many for-profit hospitals, focus on short-term financial gains, leading to cost-cutting measures and pressure on EPs to prioritize financial goals over patient welfare. Nonprofit hospitals, mandated to provide charity care to the underserved, may fail to meet their community service obligations, resulting in disparities in healthcare access. OBJECTIVE: This review examines the ethical challenges faced by emergency physicians (EPs) in response to the evolving hospital business model, which increasingly prioritizes profits over patient welfare. DISCUSSION: Emergency physicians face ethical dilemmas in this changing environment, including conflicts between patient care and financial interests. Upholding professional ethics and the principle of beneficence is essential. Another challenge is equitable access to healthcare, with some nonprofit hospitals reducing charity care, thus exacerbating disparities. EPs must uphold the ethical principle of justice, ensuring quality care for all patients, regardless of financial means. Conflicts of interest may arise when EPs work in hospitals owned by private equity firms or with affiliations with pharmaceutical companies or medical device manufacturers, potentially compromising patient care. CONCLUSION: Emergency physicians must navigate these ethical issues while upholding professional ethics and advocating for patients' best interests. Collaboration with hospital administrators, policymakers, and stakeholders is vital to address these concerns and prioritize patient welfare in healthcare delivery.

Coronavirus Disease 2019 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-Analysis of Individual Participant Data From 5 Randomized Trials.

BACKGROUND: Outpatient monoclonal antibodies are no longer effective and antiviral treatments for coronavirus disease 2019 (COVID-19) disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma (CCP) is promising, clinical trials among outpatients have shown mixed results. METHODS: We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching Medline, Embase, medRxiv, World Health Organization COVID-19 Research Database, Cochrane Library, and Web of Science from January 2020 to September 2022. RESULTS: Five included studies from 4 countries enrolled and transfused 2620 adult patients. Comorbidities were present in 1795 (69%). The virus neutralizing antibody dilutional titer levels ranged from 8 to 14 580 in diverse assays. One hundred sixty of 1315 (12.2%) control patients were hospitalized, versus 111 of 1305 (8.5%) CCP-treated patients, yielding a 3.7% (95% confidence interval [CI], 1.3%-6.0%; P = .001) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titer with a 7.6% absolute risk reduction (95% CI, 4.0%-11.1%; P = .0001) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment >5 days after symptom onset or in those receiving CCP with antibody titers below the median titer. CONCLUSIONS: Among outpatients with COVID-19, treatment with CCP reduced the rate of all-cause hospitalization and may be most effective when given within 5 days of symptom onset and when antibody titer is higher.

Transfusing Convalescent Plasma as Post-Exposure Prophylaxis Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Double-Blinded, Phase 2 Randomized, Controlled Trial.

BACKGROUND: The efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection. METHODS: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed coronavirus disease 2019 (COVID-19) in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection. RESULTS: In total, 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) positivity. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs 25.2 days; P = .49) and COVID-19 (26.3 vs 25.9 days; P = .35) was similar for both groups. CONCLUSIONS: Administration of high-titer CCP as post-exposure prophylaxis, although appearing safe, did not prevent SARS-CoV-2 infection. CLINICAL TRIALS REGISTRATION: NCT04323800.

Transfusion reactions associated with COVID-19 convalescent plasma in outpatient clinical trials.

BACKGROUND: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials. STUDY DESIGN AND METHODS: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.S. that evaluated the efficacy of CCP versus control plasma in various ambulatory settings. Multivariable logistic regression was used to assess whether CCP was associated with transfusion reactions, after adjusting for potential confounders. RESULTS: The combined study reported 79/1351 (5.9%) adverse events during the transfusion visit, with the majority 62/1351 (4.6%) characterized by mild, allergic-type findings of urticaria, and/or pruritus consistent with minor allergic transfusion reactions; the other reported events were attributed to the patients' underlying disease, COVID-19, or vasovagal in nature. We found no difference in the likelihood of allergic transfusion reactions between those receiving CCP versus control plasma (adjusted odds ratio [AOR], 0.75; 95% CI, 0.43-1.31). Risk of urticaria and/or pruritus increased with a pre-existing diagnosis of asthma (AOR, 2.33; 95% CI, 1.16-4.67). We did not observe any CCP-attributed antibody disease enhancement in participants with COVID-19 or increased risk of infection. There were no life-threatening severe transfusion reactions and no patients required hospitalization related to transfusion-associated complications. DISCUSSION: Outpatient plasma administration was safely performed for nearly 1400 participants. CCP is a safe therapeutic option for outpatients at risk of hospitalization from COVID-19.

The Effect of Missing Data on the Measurement of Cardiac Arrest Outcomes According to Race.

INTRODUCTION: High-quality data are important to understanding racial differences in outcome following out of hospital cardiac arrest (OHCA). Previous studies have shown differences in OHCA outcomes according to both race and socioeconomic status. EMS reporting of data on race is often incomplete. We aim to determine the effect of missing data on the determination of racial differences in outcomes for OHCA patients. METHODS: We performed a secondary analysis of a data set developed by probabilistically linking the Michigan Cardiac Arrest Registry to Enhance Survival (CARES) and the Michigan Inpatient Database (MIDB). Adult OHCA patients (age >18) who survived to hospital admission between 2014 and 2017 were included. Both datasets recorded patient race and ethnicity with CARES using a single race/ethnicity variable. Patients were categorized as White, Black, other, or missing and only a single choice was allowed. Due to the small number of Hispanic patients and the combined race/ethnicity variable, these patients were excluded. The outcomes of interest were survival to hospital discharge and survival to discharge with Cerebral Performance Category 1 or 2 (good outcome). Outcomes were stratified according to EMS- or hospital-documented race. RESULTS: We included 3,756 matched patients, after excluding 34 Hispanic patients from analysis. Documentation of patient race was missing in 892 (22.1%) of CARES and 212 (5.6%) of MIDB patients. When both datasets documented Black or White race, agreement in race documentation was excellent (κ=0.83). White patients were more likely to have good outcomes than Black in both the CARES (27.3% vs 14.8%) and MIDB (26.9% vs 16.1%) databases (both p < 0.001), but were not more likely to survive (30.8% vs 27.3% p = 0.22; 30.3% vs 28.1%, p = 0.07). Moreover, we found no significant difference in outcome measures based on race documentation for White vs Black patients (good outcome [27.3 vs 26.9% (MIDB)] and [16.1% vs 14.8% (CARES)] respectively and survival [30.8% vs 30.3% (MIDB)] and [27.3 vs 28.1% (CARES)] respectively). CONCLUSION: Despite higher rates of missing EMS documentation, we identified statistically similar rates in OHCA outcome measures between databases. Further work is needed to determine the true effect of missing documentation of race on OHCA outcome measures.

How do I implement an outpatient program for the administration of convalescent plasma for COVID-19?

Convalescent plasma, collected from donors who have recovered from a pathogen of interest, has been used to treat infectious diseases, particularly in times of outbreak, when alternative therapies were unavailable. The COVID-19 pandemic revived interest in the use of convalescent plasma. Large observational studies and clinical trials that were executed during the pandemic provided insight into how to use convalescent plasma, whereby high levels of antibodies against the pathogen of interest and administration early within the time course of the disease are critical for optimal therapeutic effect. Several studies have shown outpatient administration of COVID-19 convalescent plasma (CCP) to be both safe and effective, preventing clinical progression in patients when administered within the first week of COVID-19. The United States Food and Drug Administration expanded its emergency use authorization (EUA) to allow for the administration of CCP in an outpatient setting in December 2021, at least for immunocompromised patients or those on immunosuppressive therapy. Outpatient transfusion of CCP and infusion of monoclonal antibody therapies for a highly transmissible infectious disease introduces nuanced challenges related to infection prevention. Drawing on our experiences with the clinical and research use of CCP, we describe the logistical considerations and workflow spanning procurement of qualified products, infrastructure, staffing, transfusion, and associated management of adverse events. The purpose of this description is to facilitate the efforts of others intent on establishing outpatient transfusion programs for CCP and other antibody-based therapies.

Imaging Utilization Patterns and Injury Characteristics Associated with Electric Standing Scooters in a Major Urban Area.

BACKGROUND: The recent proliferation of electric standing scooters in major urban areas of the United States has been accompanied by injuries of varying severity and nature, representing a growing public health concern. OBJECTIVE: Our aim was to characterize imaging utilization patterns for injuries associated with electric scooter (e-scooter) use, including their initial emergency department (ED) management. METHODS: We conducted a retrospective review of the electronic medical record for all patients presenting to affiliated EDs for e-scooter-related injuries between July 2018 and April 2020. Demographics, date and time of presentation, imaging study type, resultant injury, and procedural details were recorded. RESULTS: Ninety-seven patients were included; mean age was 27.6 years. Of these, 55 patients (57%) had injuries identified on imaging and 40% of all imaging studies were positive. Most identified injuries (61%) were musculoskeletal, with a small number of neurological (2%) and genitourinary (1%) injuries. The highest prevalence of presentations occurred in August; most patients (72%) presented between 3 pm and 1 am and granular peaks were between 12 am and 1 am and 5 pm and 6 pm. CONCLUSIONS: Patients presenting with e-scooter injuries have a high likelihood of injury to the radial head, nasal bone, and malleoli. Emergency physicians should be especially vigilant for injuries in these areas at presentation. Visceral injuries are uncommon but may be severe enough to warrant surgery.

Blood pressure variability as an indicator of sepsis severity in adult emergency department patients.

STUDY OBJECTIVE: Quantify the correlation between blood pressure variability (BPV) and markers of illness severity: serum lactate (LAC) or Sequential Organ Failure Assessment (SOFA) scores. METHODS: We performed a secondary analysis of data from a prospective, observational study evaluating fluid resuscitation on adult, septic, ED patients. Vital signs and fluid infusion volumes were recorded every 15min during the 3h following ED arrival. BPV was assessed via average real variability (ARV): the average of the absolute differences between consecutive BP measurements. ARV was calculated for the time periods before and after 3 fluid infusion milestones: 10-, 20-, and 30-mL/kg total body weight (TBW). Spearman's rho correlation coefficient analysis was utilized. A p-value<0.05 was considered statistically significant. RESULTS: Forty patients were included. Mean fluid infusion was 33.7mL/kg TBW (SD 22.1). All patients received fluid infusion≥10mL/kg TBW, 25 patients received fluid infusion>20mL/kg TBW, and 16 patients received fluid infusion>30mL/kg TBW. Mean initial LAC was 4.0mmol/L (SD 3.2). Mean repeat LAC was 3.1mmol/L (SD 3.2), obtained an average of 6.6h (SD 5.3) later. Mean SOFA score was 7.0 (SD 4.4). BPV correlated with both follow-up LAC (r=0.564; p=0.023) and SOFA score (r=0.544; p=0.024) among the cohort that received a fluid infusion>20-mL/kg TBW. CONCLUSION: With the finding of a positive correlation between BPV and markers of illness severity (LAC and SOFA scores), this pilot study introduces BPV analysis as a real-time, non-invasive tool for continuous sepsis monitoring in the ED.

Headpulse measurement can reliably identify large-vessel occlusion stroke in prehospital suspected stroke patients: Results from the EPISODE-PS-COVID study.

BACKGROUND: Large-vessel occlusion (LVO) stroke represents one-third of acute ischemic stroke (AIS) in the United States but causes two-thirds of poststroke dependence and >90% of poststroke mortality. Prehospital LVO stroke detection permits efficient emergency medical systems (EMS) transport to an endovascular thrombectomy (EVT)-capable center. Our primary objective was to determine the feasibility of using a cranial accelerometry (CA) headset device for prehospital LVO stroke detection. Our secondary objective was development of an algorithm capable of distinguishing LVO stroke from other conditions. METHODS: We prospectively enrolled consecutive adult patients suspected of acute stroke from 11 study hospitals in four different U.S. geographical regions over a 21-month period. Patients received device placement by prehospital EMS personnel. Headset data were matched with clinical data following informed consent. LVO stroke diagnosis was determined by medical chart review. The device was trained using device data and Los Angeles Motor Scale (LAMS) examination components. A binary threshold was selected for comparison of device performance to LAMS scores. RESULTS: A total of 594 subjects were enrolled, including 183 subjects who received the second-generation device. Usable data were captured in 158 patients (86.3%). Study subjects were 53% female and 56% Black/African American, with median age 69 years. Twenty-six (16.4%) patients had LVO and 132 (83.6%) were not LVO (not-LVO AIS, 33; intracerebral hemorrhage, nine; stroke mimics, 90). COVID-19 testing and positivity rates (10.6%) were not different between groups. We found a sensitivity of 38.5% and specificity of 82.7% for LAMS ≥ 4 in detecting LVO stroke versus a sensitivity of 84.6% (p < 0.0015 for superiority) and specificity of 82.6% (p = 0.81 for superiority) for the device algorithm (CA + LAMS). CONCLUSIONS: Obtaining adequate recordings with a CA headset is highly feasible in the prehospital environment. Use of the device algorithm incorporating both CA and LAMS data for LVO detection resulted in significantly higher sensitivity without reduced specificity when compared to the use of LAMS alone.

Mind the GAHP: A novel protocol for improved vascular access in the hypotensive patient.

Background: Obtaining intravenous access in hypotensive patients is challenging and may critically delay resuscitation. The Graduated Vascular Access for Hypotensive Patient (GAHP) protocol leverages intraosseous fluid boluses to specifically dilate proximal veins. This study aims to evaluate the efficacy of GAHP in maximizing venous targets through early distal intraosseous access and a small fluid bolus. Methods: This was a prospective randomized cadaveric pilot study to evaluate extremity venous engorgement during intraosseous infusion. Cadavers (n = 23) had an intraosseous needle inserted into four sites: distal radius, proximal humerus, distal femur, and distal tibia. Intraosseous saline was rapidly infused, venous optimization was measured using real-time ultrasound. Primary outcome was maximum vessel circumference increase with intraosseous infusion. Secondary outcomes were: time to maximum circumference, and infusion volume required. Statistical analyses included Levene's test for equality of variances, Wilcoxon signed-rank test, and generalized estimating equation. Results: There was a significant mean increase of 1.03 cm (95% CI 0.86, 1.20), representing a difference of 102%. We found no significant difference in time to optimize vessel circumference across sites, but volume required significantly differed. Conclusion: GAHP quickly and effectively increased the circumference of anatomically adjacent veins. Anatomical sites did not differ on time to reach maximum enlargement of vessels following intraosseous infusion but did differ in terms of volume required to maximize vessel circumference. Further research is needed using live, hypotensive patients.

COVID-19 convalescent plasma therapy decreases inflammatory cytokines: a randomized controlled trial.

IMPORTANCE: This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.RESULTSSARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).CONCLUSIONIn unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

A novel simulation model for tube thoracostomy.

Objective: Tube thoracostomy is a life-saving procedure that must be performed competently and expeditiously by emergency care providers. The primary objective of this project was to develop a simple, easily-reproducible, and realistic simulation model for tube thoracostomy placement by learners of emergency medicine. Methods: This chest tube simulator utilizes two slabs of pork ribs with associated intercostal muscle and fascial planes to aid learners in identifying anatomic landmarks, palpating intercostal spaces, and performing blunt dissection in a manner that approximates human anatomy. Holes are cut on both sides of a 1.8-bushel capacity rectangular plastic clothing hamper, and rib slabs are secured to the hamper with zip ties or metal wire. A bed pillow with plastic cover is then placed inside of the plastic hamper to simulate lung tissue. The rib-hamper complex is then wrapped with cellophane or elastic compression bandages to further anchor the rib slabs and simulate skin and subcutaneous tissues. Results: The initial cost of our thoracostomy model is approximately $50, much less than the $1,000-$3,000 cost for a commercial model. Although the hamper and pillow can be reused an indefinite number of times, the other components of our model must be replaced occasionally. Assuming a lifespan of 1,000 uses, our model costs approximately $1.78 per attempt, compared to $4.00 per attempt with the cheapest commercial mannequin system. In fact, assuming a longer useful lifespan for the mannequin does not substantially improve this comparison (e.g. $3.10 versus $1.77 per attempt for a 10,000 attempt lifespan for the commercial mannequin), largely due to the higher cost of commercial replacement skin pads when compared to the components consumed in our model with each attempt. Conclusions: We describe a porcine thoracostomy model that simulates the look and feel of human ribs for purposes of tube thoracostomy training, although it could also be used for thoracentesis and thoracotomy simulation. This model is relatively cheap (costing around $50) and easy to produce within a few minutes utilizing commonly-available materials. Further study is needed to determine whether an inexpensive model like ours provides the same educational value as more expensive commercial mannequin models.

The Effect of a Flipped Classroom Learning Model Versus Traditional Lecture Model on Resident's Knowledge Acquisition for Atraumatic Back Pain in the Emergency Department.

Objective: The effectiveness of lecture-based (LB) formats for residency education has recently been challenged as the gold standard. Studies suggest a flipped classroom (FC) lecture improves resident satisfaction, but evidence that showing improved knowledge acquisition is lacking. To determine whether the flipped classroom model improves knowledge acquisition compared to traditional LB model. Methods: Emergency medicine resident physicians at 2 academic programs were included in December 2019; at Sinai-Grace Hospital, a traditional lecture was the teaching method and at Detroit Receiving Hospital, FC was utilized. Residents completed prelecture and postlecture content tests. The primary outcome was change in test results (pretest to post-test). A noninferiority design comparing the changes between intervention and control groups was utilized (1-sided t-test, noninferiority margin of -0.5; 1-sided alpha = 0.05). Results: Results were available for 31 residents (17 controls and 14 interventions) out of 83 enrolled. There were 14 postgraduate year 1 (PGY-1), 9 PGY-2, and 8 PGY-3 residents. The mean difference in score was +0.71 (SD 1.38) and +0.77 (SD 1.48) for the FC and LB groups, respectively. This resulted in a mean difference between groups of -0.05 (lower bound of the upper 95% confidence interval -0.93 and therefore crossing the noninferiority margin of -0.05; P = .20). Conclusions: This study of resident education at 2 training programs was unable to demonstrate noninferiority of an FC format compared to standard lecture. Surprisingly, there was little improvement in test results after both teaching formats. Larger studies are needed to power results.

A comparison of the effect of patient-specific versus weight-based protocols to treat vaso-occlusive episodes in the emergency department.

BACKGROUND: Vaso-occlusive crises (VOCs) cause debilitating pain and are a common cause of emergency department (ED) visits, for people with sickle cell disease (SCD). Strategies for achieving optimal pain control vary widely despite evidence-based guidelines. We tested existing guidelines and hypothesized that a patient-specific pain protocol (PSP) written by their SCD provider may be more effective than weight-based (WB) dosing of parenteral opiate medication, in relieving pain. METHODS: This study was a prospective, randomized controlled trial comparing a PSP versus WB protocol for patients presenting with VOCs to six EDs. Patients were randomized to a PSP or WB protocol prior to an ED visit. The SCD provider wrote their protocol and placed it in the electronic health record for future ED visits with VOC exclusion criteria that included preexisting PSP excluding parenteral opioid analgesia or outpatient use of buprenorphine or methadone or highly suspected for COVID-19. Pain intensity scores, side effects, and safety were obtained every 30 min for up to 6 h post-ED bed placement. The primary outcome was change in pain intensity score from placement in an ED space to disposition or 6 h. RESULTS: A total of 328 subjects were randomized; 104 participants enrolled (ED visit, target n = 230) with complete data for 96 visits. The study was unable to reach the target sample size and stopped early due to the impact of COVID-19. We found no significant differences between groups in the primary outcome; patients randomized to a PSP had a shorter ED length of stay (p = 0.008), and the prevalence of side effects was low in both groups. Subjects in both groups experienced both a clinically meaningful and a statistically significant decrease in pain (27 mm on a 0- to 100-mm scale). CONCLUSIONS: We found a shorter ED length of stay for patients assigned to a PSP. Patients in both groups experienced good pain relief without significant side effects.

Early Treatment, Inflammation and Post-COVID Conditions.

Background: Post-COVID conditions (PCC) are common and have significant morbidity. Risk factors for PCC include advancing age, female sex, obesity, and diabetes mellitus. Little is known about early treatment, inflammation, and PCC. Methods: Among 883 individuals with confirmed SARS-CoV-2 infection participating in a randomized trial of CCP vs. control plasma with available biospecimens and symptom data, the association between early COVID treatment, cytokine levels and PCC was evaluated. Cytokine and chemokine levels were assessed at baseline, day 14 and day 90 using a multiplexed sandwich immuosassay (Mesoscale Discovery). Presence of any self-reported PCC symptoms was assessed at day 90. Associations between COVID treatment, cytokine levels and PCC were examined using multivariate logistic regression models. Results: One-third of the 882 participants had day 90 PCC symptoms, with fatigue (14.5%) and loss of smell (14.5%) being most common. Cytokine levels decreased from baseline to day 90. In a multivariable analysis including diabetes, body mass index, race, and vaccine status, female sex (adjusted odds ratio[AOR]=2.70[1.93-3.81]), older age (AOR=1.32[1.17-1.50]), and elevated baseline levels of IL-6 (AOR=1.59[1.02-2.47]) were associated with development of PCC.There was a trend for decreased PCC in those with early CCP treatment (≤5 days after symptom onset) compared to late CCP treatment. Conclusion: Increased IL-6 levels were associated with the development of PCC and there was a trend for decreased PCC with early CCP treatment in this predominately unvaccinated population. Future treatment studies should evaluate the effect of early treatment and anti-IL-6 therapies on PCC development.

Dynamics of inflammatory responses after SARS-CoV-2 infection by vaccination status in the USA: a prospective cohort study.

BACKGROUND: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection. METHODS: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples and symptom data collected at screening (pre-transfusion), day 14, and day 90 visits. Associations between COVID-19 vaccination status and concentrations of 21 cytokines and chemokines (measured using multiplexed sandwich immunoassays) were examined using multivariate linear mixed-effects regression models, adjusted for age, sex, BMI, hypertension, diabetes, trial group, and COVID-19 waves (pre-alpha or alpha and delta). FINDINGS: Between June 29, 2020, and Sept 30, 2021, 882 participants recently infected with SARS-CoV-2 were enrolled, of whom 506 (57%) were female and 376 (43%) were male. 688 (78%) of 882 participants were unvaccinated, 55 (6%) were partly vaccinated, and 139 (16%) were fully vaccinated at baseline. After adjusting for confounders, geometric mean concentrations of interleukin (IL)-2RA, IL-7, IL-8, IL-15, IL-29 (interferon-λ), inducible protein-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α were significantly lower among the fully vaccinated group than in the unvaccinated group at screening. On day 90, fully vaccinated participants had approximately 20% lower geometric mean concentrations of IL-7, IL-8, and vascular endothelial growth factor-A than unvaccinated participants. Cytokine and chemokine concentrations decreased over time in the fully and partly vaccinated groups and unvaccinated group. Log10 cytokine and chemokine concentrations decreased faster among participants in the unvaccinated group than in other groups, but their geometric mean concentrations were generally higher than fully vaccinated participants at 90 days. Days since full vaccination and type of vaccine received were not correlated with cytokine and chemokine concentrations. INTERPRETATION: Initially and during recovery from symptomatic COVID-19, fully vaccinated participants had lower concentrations of inflammatory markers than unvaccinated participants suggesting vaccination is associated with short-term and long-term reduction in inflammation, which could in part explain the reduced disease severity and mortality in vaccinated individuals. FUNDING: US Department of Defense, National Institutes of Health, Bloomberg Philanthropies, State of Maryland, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation, and the Shear Family Foundation.

Early antibody treatment, inflammation, and risk of post-COVID conditions.

IMPORTANCE: Approximately 20% of individuals infected with SARS-CoV-2 experienced long-term health effects, as defined PCC. However, it is unknown if there are any early biomarkers associated with PCC or whether early intervention treatments may decrease the risk of PCC. In a secondary analysis of a randomized clinical trial, this study demonstrates that among outpatients with SARS-CoV-2, increased IL-6 at time of infection is associated with increased odds of PCC. In addition, among individuals treated early, within 5 days of symptom onset, with COVID-19 convalescent plasma, there was a trend for decreased odds of PCC after adjusting for other demographic and clinical characteristics. Future treatment studies should be considered to evaluate the effect of early treatment and anti-IL-6 therapies on PCC development.