High-Alert Medication Stratification Tool-Revised Phase II: A Multisite Study Examining the Validity, Interrater Reliability, and Ease of Use of the High-Alert Medication Stratification Tool-Revised.

OBJECTIVES: The primary objective of this multisite study, High-Alert Medication Stratification Tool-Revised (HAMST-R) phase II, was to assess the content validity of HAMST-R. Secondary outcomes included interrater reliability and ease of use. METHODS: HAMST-R was designed as an objective tool to evaluate high-alert medications (HAMs) at a single site during HAMST-R Phase I. Medication safety experts from 7 health systems across the United States volunteered to participate in this phase II study. Participants completed a demographic survey, oversaw evaluation of 47 HAMs and 35 non-HAMs using HAMST-R, and submitted scores for each medication evaluated. In addition, participants rated each question of HAMST-R on its relevance to assess a medication's safety risk, measured as scale-content validity index. Positive and negative predictive values were evaluated in a post hoc analysis. Interrater reliability was evaluated using the Kendall coefficient of concordance (K), and ease of use was assessed using a mixed-methods approach. RESULTS: Scale-content validity index was 0.80, indicating that the tool was valid. Positive predictive value was 90.5% (95% confidence interval, 87.2%-93.0%), and negative predictive value was 98.2% (95% confidence interval, 95.4%-99.3%). A score of 4 or more differentiated between HAMs and non-HAMs, confirming phase I findings. K was 0.56, indicating moderate agreement. Participants confirmed that the tool was easy to use and plan to incorporate the tool into HAM policies and procedures, formulary review, and safety strategy implementation. CONCLUSIONS: HAMST-R is a valid, objective, and easy to use method that institutions may implement to evaluate a medication's potential safety risk.

TGFß1 induces resistance of human lung myofibroblasts to cell death via down-regulation of TRPA1 channels.

BACKGROUND AND PURPOSE: TGFß1-mediated myofibroblast activation contributes to pathological fibrosis in many diseases including idiopathic pulmonary fibrosis (IPF), where myofibroblast resistance to oxidant-mediated apoptosis is also evident. We therefore investigated the involvement of redox-sensitive TRPA1 ion channels on human lung myofibroblasts (HLMFs) cell death and TGFß1-mediated pro-fibrotic responses. EXPERIMENTAL APPROACH: The effects of TGFß1 stimulation on TRPA1 expression and cell viability was studied in HLMFs derived from IPF patients and non-fibrotic patients. We also examined a model of TGFß1-dependent fibrogenesis in human lung. We used qRT-PCR, immunofluorescent assays, overexpression with lentiviral vectors and electrophysiological methods. KEY RESULTS: TRPA1 mRNA, protein and ion currents were expressed in HLMFs derived from both non-fibrotic patient controls and IPF patients, and expression was reduced by TGFß1. TRPA1 mRNA was also down-regulated by TGFß1 in a model of lung fibrogenesis in human lung. TRPA1 over-expression or activation induced HLMF apoptosis, and activation of TRPA1 channel activation by H2 O2 induced necrosis. TRPA1 inhibition following TGFß1 down-regulation or pharmacological inhibition, protected HLMFs from both apoptosis and necrosis. Lentiviral vector mediated TRPA1 expression was also found to induce sensitivity to H2 O2 induced cell death in a TRPA1-negative HEK293T cell line. CONCLUSION AND IMPLICATIONS: TGFß1 induces resistance of HLMFs to TRPA1 agonist- and H2 O2 -mediated cell death via down-regulation of TRPA1 channels. Our data suggest that therapeutic strategies which prevent TGFß1-dependent down-regulation of TRPA1 may reduce myofibroblast survival in IPF and therefore improve clinical outcomes.

A sentinel COVID-19 case in Houston, Texas: Informing frontline emergency department screening and preparedness.

In December 2019, a cluster of severe pneumonia cases of unknown cause was reported in Wuhan, Hubei province, China. A novel strain of coronavirus belonging to the same family of viruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) was identified. In February 2020, cases began being identified in the United States. We describe a sentinel COVID-19 patient in Houston, Texas, who first presented on March 1, 2020. The patient did not meet criteria for a Person Under Investigation (PUI) as recommended by the Centers for Disease Control and Prevention (CDC) at the time. This case has broad implications for emergency department screening and preparedness for COVID-19 and other future infectious diseases.