Early Convalescent Plasma for High-Risk Outpatients with Covid-19.

BACKGROUND: Early administration of convalescent plasma obtained from blood donors who have recovered from coronavirus disease 2019 (Covid-19) may prevent disease progression in acutely ill, high-risk patients with Covid-19. METHODS: In this randomized, multicenter, single-blind trial, we assigned patients who were being treated in an emergency department for Covid-19 symptoms to receive either one unit of convalescent plasma with a high titer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression. In addition, all the patients presented to the emergency department within 7 days after symptom onset and were in stable condition for outpatient management. The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included the worst severity of illness on an 8-category ordinal scale, hospital-free days within 30 days after randomization, and death from any cause. RESULTS: A total of 511 patients were enrolled in the trial (257 in the convalescent-plasma group and 254 in the placebo group). The median age of the patients was 54 years; the median symptom duration was 4 days. In the donor plasma samples, the median titer of SARS-CoV-2 neutralizing antibodies was 1:641. Disease progression occurred in 77 patients (30.0%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group (risk difference, 1.9 percentage points; 95% credible interval, -6.0 to 9.8; posterior probability of superiority of convalescent plasma, 0.68). Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups. CONCLUSIONS: The administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression. (SIREN-C3PO ClinicalTrials.gov number, NCT04355767.).

Stroke Prophylaxis for Atrial Fibrillation? To Prescribe or Not to Prescribe-A Qualitative Study on the Decisionmaking Process of Emergency Department Providers.

STUDY OBJECTIVE: Although clinical guidelines recommend oral anticoagulation for atrial fibrillation patients at high risk of stroke, emergency physicians inconsistently prescribe it to patients with newly diagnosed atrial fibrillation. We interview emergency physicians to gain insight into themes influencing prescribing of oral anticoagulation for patients discharged from the ED with new-onset atrial fibrillation. METHODS: From September 2015 to January 2017, we conducted semistructured qualitative interviews with a purposeful sampling of 18 ED attending physicians who had evaluated a patient with new-onset atrial fibrillation within the past 30 days. Interview prompts examined physicians' attitudes toward prescription of oral anticoagulation therapy and current clinical guidelines. We used a constructivist grounded theory approach to analyze data and develop a theory on prescribing practices among emergency physicians. RESULTS: Three broad domains emerged from our analyses. (1) Oral anticoagulation prescribing practice: underlying themes affecting oral anticoagulation prescribing from the ED included physician practice patterns, beliefs, and barriers (including experience, comfort, and insurance coverage), and patient factors (including comorbidities, bleeding risk, and social concerns). Ultimately, these themes indicated physician discomfort and a sense of futility in prescribing oral anticoagulation for atrial fibrillation. (2) Guideline usage for oral anticoagulation prescribing: regardless of experience, most emergency physicians did not report using clinical guidelines when treating patients. (3) Recommendations for improved prescribing: physicians recommended the development of a validated, reliable, simple, accessible, and population-specific guideline that considers patient social factors. CONCLUSION: The decision to prescribe oral anticoagulation in the ED is complex. Improving guideline adherence will require a multifaceted approach inclusive of system-level improvements, physician education, and the development of ED-specific tools and guidelines.

Recognising Bias in Studies of Diagnostic Tests Part 1: Patient Selection.

In this two-part series on sources of bias in studies of diagnostic test performance, we outline common errors and optimal conditions during three study phases: patient selection, interpretation of the index test and disease verification by a gold standard. Here in part 1, biases associated with suboptimal participant selection are discussed through the lens of partial verification bias and spectrum bias, both of which increase the proportion of participants who are the 'sickest of the sick' or the 'wellest of the well.' Especially through retrospective methodology, partial verification introduces bias by including patients who are test positive by a gold standard, since patients with a positive index test are more likely to go on to further gold standard testing. Spectrum bias is frequently introduced through case-control design, dropping of indeterminate results or convenience sampling. After reading part 1, the informed clinician should be better able to judge the quality of a diagnostic test study, its inherent limitations and whether its results could be generalisable to their practice. Part 2 will describe how interpretation of the index test and disease verification by a gold standard can contribute to diagnostic test bias.

Recognising bias in studies of diagnostic tests part 2: interpreting and verifying the index test.

Multiple pitfalls can occur with the conduct and analysis of a study of diagnostic tests, resulting in biased accuracy. Our conceptual model includes three stages: patient selection, interpretation of the index test and disease verification. In part 2, we focus on (1) Interpretation bias (or workup bias): where the classification of an indeterminate index test result can bias the accuracy of a test or how lack of blinding can bias a subjective test result, and (2) Disease verification bias: where the index test result is incorporated into the gold standard or when the gold standard is applied only to a select population as the gold standard is an invasive test. In an example with age-adjusted D-dimer for pulmonary embolism, differential verification bias was a limitation due to the use of two gold standards-CT for a high-risk population and follow-up for symptoms in a low-risk population. However, there are circumstances when certain choices in study design are unavoidable, and result in biased test characteristics. In this case, the informed reader will better judge the quality of a study by recognising the potential biases and limitations by being methodical in their approach to understanding the methods, and in turn, better apply studies of diagnostic tests into their clinical practice.

Association of Overall Opioid Prescriptions on Adolescent Opioid Abuse.

BACKGROUND: Opioid abuse is a public health epidemic in the United States. Much literature has focused on the prescribing practices of physicians and opioid misuse by adults. However, there are limited data on the effect of opioid prescriptions on adolescent recreational ingestion of these medications. OBJECTIVES: The objective of this study was to assess for a relationship between opioid prescribing practices across the United States and adolescent opioid ingestion calls to poison centers. METHODS: This was an observational study using the National Poison Data System. The study population consisted of poison center calls regarding adolescents between 2005 and 2010 in the database with a coding of "intentional abuse" and an opioid ingestion. National opioid prescription estimates were generated using nationally representative outpatient and inpatient databases. RESULTS: There were 4186 adolescent opioid ingestion calls during the study period. There was a general increase between 2005 and 2010 in both teen opioid abuse calls (617 in 2005 to 782 in 2010) and national opioid prescriptions (approximately 78 million in 2005 to 108 million in 2010). For each opioid prescription increase per 100 persons per year, the annual teen opioid abuse calls increased by 1.8% (95% confidence interval 0.9-2.8%), equivalent to an absolute increase of about 0.04 to 0.05 calls per 100,000 teens annually. CONCLUSIONS: There appears to be an association between opioid prescriptions nationally and poison center calls for adolescent opioid ingestions. This is particularly important in this patient population because of impulsivity and early exposure to substance abuse. Providers should be aware of the nonmedical use of opioids by adolescents and educate patients accordingly.

What is the clinical significance of chest CT when the chest x-ray result is normal in patients with blunt trauma?

BACKGROUND: Computed tomography (CT) has been shown to detect more injuries than plain radiography in patients with blunt trauma, but it is unclear whether these injuries are clinically significant. STUDY OBJECTIVES: This study aimed to determine the proportion of patients with normal chest x-ray (CXR) result and injury seen on CT and abnormal initial CXR result and no injury on CT and to characterize the clinical significance of injuries seen on CT as determined by a trauma expert panel. METHODS: Patients with blunt trauma older than 14 years who received emergency department chest imaging as part of their evaluation at 2 urban level I trauma centers were enrolled. An expert trauma panel a priori classified thoracic injuries and subsequent interventions as major, minor, or no clinical significance. RESULTS: Of 3639 participants, 2848 (78.3%) had CXR alone and 791 (21.7%) had CXR and chest CT. Of 589 patients who had chest CT after a normal CXR result, 483 (82.0% [95% confidence interval [CI], 78.7-84.9%]) had normal CT results, and 106 (18.0% [95% CI, 15.1%-21.3%]) had CTs diagnosing injuries-primarily rib fractures, pulmonary contusion, and incidental pneumothorax. Twelve patients had injuries classified as clinically major (2.0% [95% CI, 1.2%-3.5%]), 78 were clinically minor (13.2% [95% CI, 10.7%-16.2%]), and 16 were clinically insignificant (2.7% (95% CI, 1.7%-4.4%]). Of 202 patients with CXRs suggesting injury, 177 (87.6% [95% CI, 82.4%-91.5%]) had chest CTs confirming injury and 25 (12.4% [95% CI, 8.5%-17.6%]) had no injury on CT. CONCLUSION: Chest CT after a normal CXR result in patients with blunt trauma detects injuries, but most do not lead to changes in patient management.

Provider perceptions concerning use of chest x-ray studies in adult blunt trauma assessments.

BACKGROUND: Although they infrequently lead to management changing diagnoses, chest x-rays (CXRs) are the most commonly ordered imaging study in blunt trauma evaluation. OBJECTIVES: To determine: 1) the reasons physicians order chest X-ray studies (CXRs) in blunt trauma assessments; 2) what injuries they expect CXRs to reveal; and 3) whether physicians can accurately predict low likelihood of injury on CXR. METHODS: At a Level I Trauma Center, we asked resident and attending physicians treating adult blunt trauma patients: 1) the primary reason(s) for getting CXRs; 2) what, if any, significant intrathoracic injuries (SITI) they expected CXRs to reveal; and 3) the likelihood of these injuries. An expert panel defined SITI as two or more rib fractures, sternal fracture, pulmonary contusion, pneumothorax, hemothorax, or aortic injury on official CXR readings. RESULTS: There were 484 patient encounters analyzed--65% of participating physicians were residents and 35% were attendings; 16 (3.3%) patients had SITI. The most common reasons for ordering CXRs were: "enough concern for significant injury" (62.9%) and belief that CXR is a "standard part of trauma work-up" (24.8%). Residents were more likely than attendings to cite "standard trauma work-up" (mean difference = 13.5%, p = 0.003). When physicians estimated a < 10% likelihood of SITI on CXR, 2.1% (95% confidence interval [CI] 1.0-4.1%) of patients had SITI; when they predicted a 10-25% likelihood, 5.7% (95% CI 1.2-15.7%) had SITI; and when they predicted a > 25% likelihood, 9.1% (95% CI 3.0-20.0%) had SITI. CONCLUSIONS: Physicians order CXRs in blunt trauma patients because they expect to find injuries and believe that CXRs are part of a "standard" work-up. Providers commonly do not expect CXRs to reveal SITI. When providers estimated low likelihood of SITI, the rate of SITI was very low.

Intermittent complete heart block with ventricular standstill after Pfizer COVID-19 booster vaccination: A case report.

As the COVID-19 pandemic continues around the globe, vaccines are undoubtedly central to the fight to control the spread of the virus. However, as with any therapy, these vaccines are not without side effects. Documented cardiac complications of COVID-19 vaccination include myocarditis, pericarditis, and cardiac conduction abnormalities. Here, we report a novel case of intermittent complete heart block with ventricular standstill occurring within 24 hours of administration of a Pfizer-BioNTech COVID-19 booster vaccine. The patient presented to the emergency department (ED) via ambulance for evaluation of syncope. On arrival, the patient lost pulses as a result of intermittent complete heart block with ventricular standstill. He required cardiopulmonary resuscitation (CPR) with intubation, transcutaneous pacing, and subsequent transvenous pacing in the ED. After stabilization and extensive workup, the patient was diagnosed with lymphocytic myocarditis and complete heart block that is suspected to be secondary to COVID-19 booster vaccination. Ultimately, the patient's complete heart block resolved spontaneously, and he was discharged home with ambulatory rhythm monitoring.

Evaluating fomite risk of brown paper bags storing personal protective equipment exposed to SARS-CoV-2: A quasi-experimental study.

INTRODUCTION: Literature is lacking on the safety of storing contaminated PPE in paper bags for reuse, potentially increasing exposure to frontline healthcare workers (HCW) and patients. The aim of this study is to evaluate the effectiveness of paper bags as a barrier for fomite transmission of SARS-CoV-2 by storing face masks, respirators, and face shields. METHODS: This quasi-experimental study evaluated the presence of SARS-CoV-2 on the interior and exterior surfaces of paper bags containing PPE that had aerosolized exposures in clinical and simulated settings. Between May and October 2020, 30 unique PPE items were collected from COVID-19 units at two urban hospitals. Exposed PPE, worn by either an infected patient or HCW during a SARS-CoV-2 aerosolizing event, were placed into an unused paper bag. Samples were tested at 30-minute and 12-hour intervals. RESULTS: A total of 177 swabs were processed from 30 PPE samples. We found a 6.8% positivity rate among all samples across both collection sites. Highest positivity rates were associated with ventilator disconnection and exposure to respiratory droplets from coughing. Positivity rates differed between hospital units. Total positivity rates were similar between 30-minute (6.7%) and 12-hour (6.9%) sample testing time intervals. Control samples exposed to inactivated SARS-CoV-2 droplets had higher total viral counts than samples exposed to nebulized aerosols. CONCLUSIONS: Data suggests paper bags are not a significant fomite risk for SARS-CoV-2 transmission. However, controls demonstrated a risk with droplet exposure. Data can inform guidelines for storing and re-using PPE in situations of limited supplies during future pandemics.

Global Oral Anticoagulation Use Varies by Region in Patients With Recent Diagnosis of Atrial Fibrillation: The GLORIA-AF Phase III Registry.

Background Effective stroke prevention with oral anticoagulants (OAC) is recommended for some patients with atrial fibrillation (AF). We aimed to describe OAC use by geographical region and type of site in patients with recent-onset AF enrolled in a large global registry. Methods and Results Eligible participants were recruited into GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation), a prospective observational cohort study from 2014 to 2016 in 4 international regions: North America, Europe, Asia, and Latin America. Cumulative incidence functions were generated for direct OACs (DOAC), vitamin K antagonists, and antiplatelet drugs considering competing risks, stratified by region and type of site. Time-to-treatment initiation after AF diagnosis was analyzed with Fine-Gray subdistribution hazard models. A total of 21 237 patients eligible for analysis were identified. By 30 days after AF diagnosis, 40%, 16%, and 8.6% of patients had DOAC, vitamin K antagonists, and antiplatelet drugs initiated, respectively. Earlier initiation of DOACs was observed in Europe, with Asia and Latin America having lower hazard rates of DOAC time-to-treatment initiation than Europe (hazard ratio [HR], 0.66; 95% CI, 0.62-0.70 and HR, 0.79; 95% CI, 0.73-0.85, respectively). DOAC initiation was highest in community hospitals, vitamin K antagonists in outpatient health care centers/anticoagulation clinics, and antiplatelet drugs in primary care clinics. Conclusions Important geographic variability exists with the use of OACs for patients with AF. Differences in the time-to-treatment initiation of OAC by type of site suggests suboptimal implementation of guideline recommendations and could result in less benefit and more harm. Optimizing OAC use for patients with AF may improve outcomes and reduce health care costs. Registration URL: http://www.clinicaltrials.gov; Unique identifiers: NCT01468701, NCT01671007.

Utility of COVID-19 antigen testing in the emergency department.

BACKGROUND: The BinaxNOW coronavirus disease 2019 (COVID-19) Ag Card test (Abbott Diagnostics Scarborough, Inc.) is a lateral flow immunochromatographic point-of-care test for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein antigen. It provides results from nasal swabs in 15 minutes. Our purpose was to determine its sensitivity and specificity for a COVID-19 diagnosis. METHODS: Eligible patients had symptoms of COVID-19 or suspected exposure. After consent, 2 nasal swabs were collected; 1 was tested using the Abbott RealTime SARS-CoV-2 (ie, the gold standard polymerase chain reaction test) and the second run on the BinaxNOW point of care platform by emergency department staff. RESULTS: From July 20 to October 28, 2020, 767 patients were enrolled, of which 735 had evaluable samples. Their mean (SD) age was 46.8 (16.6) years, and 422 (57.4%) were women. A total of 623 (84.8%) patients had COVID-19 symptoms, most commonly shortness of breath (n = 404; 55.0%), cough (n = 314; 42.7%), and fever (n = 253; 34.4%). Although 460 (62.6%) had symptoms ≤7 days, the mean (SD) time since symptom onset was 8.1 (14.0) days. Positive tests occurred in 173 (23.5%) and 141 (19.2%) with the gold standard versus BinaxNOW test, respectively. Those with symptoms >2 weeks had a positive test rate roughly half of those with earlier presentations. In patients with symptoms ≤7 days, the sensitivity, specificity, and negative and positive predictive values for the BinaxNOW test were 84.6%, 98.5%, 94.9%, and 95.2%, respectively. CONCLUSIONS: The BinaxNOW point-of-care test has good sensitivity and excellent specificity for the detection of COVID-19. We recommend using the BinasNOW for patients with symptoms up to 2 weeks.

Derivation of a decision instrument for selective chest radiography in blunt trauma.

BACKGROUND: To derive a decision instrument (DI) that identifies patients who have virtually no risk of significant intrathoracic injury (SITI) visible on chest radiography and, therefore, no need for chest imaging. METHODS: This is a prospective observational study. At three Level 1 trauma centers, physicians caring for blunt trauma patients aged >14 years were asked to record the presence or absence of 12 clinical criteria before viewing chest imaging results. SITI was defined as pneumothorax, hemothorax, aortic/great vessel injury, two or more rib fractures, ruptured diaphragm, sternal fracture, and pulmonary contusion on official radiograph readings. The κ (interrater reliability) and screening performance of individual criteria were determined. By using recursive partitioning, the most highly sensitive combination of criteria for SITI was derived. RESULTS: Of the 2,628 subjects enrolled, 271 (10.3%) were diagnosed with a total of 462 SITIs, with rib fractures (73%), pneumothorax (38%), and pulmonary contusion (29%) as the most common injuries. Chest pain and chest wall tenderness had the highest sensitivity for SITI (65%). The DI of chest pain, distracting injury, chest wall tenderness, intoxication, age >60 years, rapid deceleration, and altered alertness/mental status had the following screening performance: sensitivity 99.3% (95% confidence interval [CI], 97.4-99.8), specificity 14.0% (95% CI, 12.6-15.4), negative predictive value 99.4% (95% CI, 97.8-99.8), and positive predictive value 11.7% (95% CI, 10.5-13.1). All seven criteria in the DI met the predetermined cut off for acceptable κ (range, 0.51-0.81). CONCLUSIONS: We derived a DI consisting of seven clinical criteria that can identify SITI in blunt trauma patients with extremely high sensitivity. If validated, this instrument will allow for safe, selective chest imaging with potential resource savings.

A pilot study to develop a prediction instrument for endocarditis in injection drug users admitted with fever.

OBJECTIVE: Seeking to evaluate the feasibility of a prediction instrument for endocarditis in febrile injection drug users (IDUs), we determined (1) the frequency percentage of IDUs admitted with fever diagnosed with endocarditis and (2) whether individual or combinations of emergency department (ED) clinical criteria (patient history, physical examination findings, and laboratory tests) are associated with endocarditis in IDUs admitted to rule out endocarditis. METHODS: The ED and inpatient charts of all IDUs with a diagnosis of rule out endocarditis admitted at 3 urban hospitals in 2006 were reviewed. Screening performance of individual criteria was determined, and the most sensitive combination of criteria was derived by classification tree analysis. RESULTS: Of 236 IDUs admitted with fever, 20 (8.5%) were diagnosed with endocarditis. Lack of skin infection, tachycardia, hyponatremia, pneumonia on chest radiograph, history of endocarditis, thrombocytopenia, and heart murmur had the best screening performance. The classification tree-derived best criteria combination of tachycardia, lack of skin infection, and cardiac murmur had a sensitivity of 100% (95% confidence interval, 84%-100%) and negative predictive value of 100% (95% confidence interval, 88%-100%). CONCLUSIONS: Using ED clinical criteria, a multicenter prospective study to develop an instrument for endocarditis prediction in febrile IDUs is feasible, with an estimated target enrollment of 588 patients.

An international survey of healthcare workers use of personal protective equipment during the early stages of the COVID-19 pandemic.

OBJECTIVE: Little is known regarding the specific ways personal protective equipment (PPE) has been used and reused during the coronavirus disease 2019 (COVID-19) pandemic. The objective of this study was to evaluate the patterns of PPE use and the impact of PPE availability on the attitudes and well-being of an international population of healthcare workers. METHODS: This was an online, cross-sectional survey of healthcare workers. The survey was disseminated internationally using social media, specialty society list-serves, and email augmented by snowball sampling to healthcare workers who provided direct care to patients with suspected or confirmed COVID-19. The survey was conducted between April 13 and May 1, 2020. The primary outcome was self-reported PPE use during aerosol-generating medical procedures. Other outcomes included PPE use during care for respiratory patients in general, PPE reuse, PPE decontamination, and healthcare worker impressions related to their work and the pandemic. RESULTS: A total of 2227 healthcare workers from 23 countries completed the survey. The N95 was the most common respirator among the 1451 respondents who performed aerosol-generating procedures (n = 1050, 72.3%). Overall, 1783 (80.1%) of providers reported general reuse of PPE, which was similar across US regions but less common in Canada, Italy, and Spain. The most commonly reused item of PPE was the N95 respirator, with the majority of respondents who reused PPE reporting N95 reuse (n = 1157, 64.9%). Of the 1050 individuals who wore an N95 mask while performing an aerosol-generating medical procedure, 756 (72%) reported re-using an N95, and 344 (45.5%) reported reuse for >3 days. Qualitative results identified several common themes, including (1) lack of availability of PPE, (2) fear and anxiety as a result of inadequate PPE, (3) potential exposure to family members, and (4) concerns regarding workload and pay. CONCLUSIONS: This international survey of healthcare workers found that N95 respirators were commonly used to care for patients with respiratory symptoms with and without aerosol-generating medical procedures. Healthcare workers reported an unprecedented need to reuse PPE that was designed for single-use, specifically the N95 respirator. The reuse of PPE increased the perceived risk for COVID-19 infection and harmed mental health.

Predictors of Acute Atrial Fibrillation and Flutter Hospitalization across 7 U.S. Emergency Departments: A Prospective Study.

INTRODUCTION: International rates of hospitalization for atrial fibrillation and flutter (AFF) from the emergency department (ED) vary widely without clear evidence to guide the identification of high-risk patients requiring inpatient management. We sought to determine (1) variation in hospital admission and (2) modifiable factors associated with hospitalization of AFF patients within a U.S. integrated health system. METHODS: This multicenter prospective observational study of health plan members with symptomatic AFF was conducted using convenience sampling in 7 urban community EDs from 05/2011 to 08/2012. Prospective data collection included presenting symptoms, characteristics of atrial dysrhythmia, ED physician impression of hemodynamic instability, comorbid diagnoses, ED management, and ED discharge rhythm. All centers had full-time on-call cardiology consultation available. Additional variables were extracted from the electronic health record. We identified factors associated with hospitalization and included predictors in a multivariate Poisson Generalized Estimating Equations regression model to estimate adjusted relative risks while accounting for clustering by physician. RESULTS: Among 1,942 eligible AFF patients, 1,074 (55.3%) were discharged home and 868 (44.7%) were hospitalized. Hospitalization rates ranged from 37.4% to 60.4% across medical centers. After adjustment, modifiable factors associated with increased hospital admission from the ED included non-sinus rhythm at ED discharge, no attempted cardioversion, and heart rate reduction. DISCUSSION: Within an integrated health system, we found significant variation in AFF hospitalization rates and identified several modifiable factors associated with hospital admission. Standardizing treatment goals that specifically address best practices for ED rate reduction and rhythm control may reduce hospitalizations.