Should COVID-19 symptoms be used to cohort patients in the emergency department? A retrospective analysis.

OBJECTIVE: To determine how cohorting patients based on presenting complaints affects risk of nosocomial infection in crowded Emergency Departments (EDs) under conditions of high and low prevalence of COVID-19. METHODS: This was a retrospective analysis of presenting complaints and PCR tests collected during the COVID-19 epidemic from 4 EDs from a large hospital system in Bronx County, NY, from May 1, 2020 to April 30, 2021. Sensitivity, specificity, positive and negative predictive value (PPV, NPV) were calculated for a symptom screen based on the CDC list of COVID-19 symptoms: fever/chills, shortness of breath/dyspnea, cough, muscle or body ache, fatigue, headache, loss of taste or smell, sore throat, nasal congestion/runny nose, nausea, vomiting, and diarrhea. PPV was calculated for varying values of prevalence. RESULTS: There were 80,078 visits with PCR tests. The sensitivity of the symptom screen was 64.7% (95% CI: 63.6, 65.8), specificity 65.4% (65.1, 65.8). PPV was 16.8% (16.5, 17.0) and NPV was 94.5% (94.4, 94.7) when the observed prevalence of COVID-19 in the ED over the year was 9.7%. The PPV of fever/chills, cough, body and muscle aches and nasal congestion/runny nose were each approximately 25% across the year, while diarrhea, nausea, vomiting and headache were less predictive, (PPV 4.7%-9.6%) The combinations of fever/chills, cough, muscle/body aches, and shortness of breath had PPVs of 40-50%. The PPV of the screen varied from 3.7% (3.6, 3.8) at 2% prevalence of COVID-19 to 44.3% (44.0, 44.7) at 30% prevalence. CONCLUSION: The proportion of patients with a chief complaint of COVID-19 symptoms and confirmed COVID-19 infection was exceeded by the proportion without actual infection. This was true when prevalence in the ED was as high as 30%. Cohorting of patients based on the CDC's list of COVID-19 symptoms will expose many patients who do not have COVID-19 to risk of nosocomially acquired COVID-19. EDs should not use the CDC list of COVID-19 symptoms as the only strategy to minimize exposure.

A Randomized, Placebo-Controlled Study of Intranasal Fentanyl as an Analgesic Adjunct For Incision and Drainage of Abscess.

BACKGROUND: Incision and drainage (I&D) of abscesses is one of the most painful procedures performed in emergency departments (EDs). OBJECTIVE: We tested the following hypothesis: The addition of intranasal fentanyl to the standard practice of local infiltration with lidocaine would provide better pain control than lidocaine alone for adult ED patients undergoing I&D. METHODS: This was a randomized, double-blind study. Participants received 2 µg/kg of intranasal fentanyl or a comparable amount of intranasal water in addition to local lidocaine infiltration. The primary outcome, which we assessed immediately after the I&D was completed, was a summary 0-10 pain score for which we asked study subjects to provide a number depicting their entire experience with the procedure. RESULTS: During a 19-month enrollment period, we screened 176 patients for eligibility and enrolled 49; 25 received placebo and 24 received fentanyl. Baseline characteristics were comparable. Mean (standard deviation) summary pain scores were as follows: fentanyl 6.2 (3.3) and placebo 7.0 (3.2). The 95% confidence interval for a rounded between-group difference of 0.9 was -1.1 to 2.6. CONCLUSIONS: In this small study, the addition of intranasal fentanyl did not substantially impact the pain scores of ED patients undergoing I&D.

Development and application of fully functional epitope-tagged forms of transforming growth factor-beta.

Administration of transforming growth factor-beta (TGF-beta) has been found to be of therapeutic benefit in various mouse disease models and has potential clinical usefulness. However, the ability to track the distribution of exogenously administered, recombinant forms of these proteins has been restricted by cross-reactivity with endogenous TGF-beta and related TGF-beta isoforms. We describe novel FLAG- and hemagglutinin (HA)-tagged versions of mature TGF-beta1 that retain full biological activity as demonstrated by their ability to inhibit the growth of Mv1Lu epithelial cells, and to induce phosphorylation of the TGF-beta signaling intermediate, smad 2. Intracellular FLAG- and HA-TGF-beta1 can be detected in transfected cells by confocal immunofluorescence microscopy. We also describe sandwich ELISAs designed to specifically detect epitope-tagged TGF-beta and demonstrate the utility of these tagged ligands as probes for TGF-beta receptor expression by flow cytometry. The design of these fully functional epitope-tagged TGF-beta proteins should facilitate studies such as the evaluation of in vivo peptide pharmacodynamics and trafficking of TGF-beta ligand-receptor complexes.

Disruption of transforming growth factor beta signaling by a novel ligand-dependent mechanism.

Transforming growth factor (TGF)-beta is the prototype in a family of secreted proteins that act in autocrine and paracrine pathways to regulate cell development and function. Normal cells typically coexpress TGF-beta receptors and one or more isoforms of TGF-beta, thus the synthesis and secretion of TGF-beta as an inactive latent complex is considered an essential step in regula-ting the activity of this pathway. To determine whether intracellular activation of TGF-beta results in TGF-beta ligand-receptor interactions within the cell, we studied pristane-induced plasma cell tumors (PCTs). We now demonstrate that active TGF-beta1 in the PCT binds to intracellular TGF-beta type II receptor (TbetaRII). Disruption of the expression of TGF-beta1 by antisense TGF-beta1 mRNA restores localization of TbetaRII at the PCT cell surface, indicating a ligand-induced impediment in receptor trafficking. We also show that retroviral expression of a truncated, dominant-negative TbetaRII (dnTbetaRII) effectively competes for intracellular binding of active ligand in the PCT and restores cell surface expression of the endogenous TbetaRII. Analysis of TGF-beta receptor-activated Smad2 suggests the intracellular ligand-receptor complex is not capable of signaling. These data are the first to demonstrate the formation of an intracellular TGF-beta-receptor complex, and define a novel mechanism for modulating the TGF-beta signaling pathway.