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• Various unexpected events may occur at any time during Intrahospital transport. • An appropriate scoring tool should be used to assess the patient's basic condition. • The Worthing Physiological Scoring System is a simple and suitable tool. The aim of this study was to assess the value of the National Early Warning Score and Worthing Physiological Scoring System for predicting changes in the condition of critical cases during transfer from the emergency department to the intensive care unit. This prospective single-centre study was conducted at a 1759-bed hospital in Beijing. We recorded the vital signs in the cases before leaving the emergency department and their changes in condition during transit. A total of 258 critically ill cases were included. Forty-four cases (17.05%) exhibited changes in their condition during transit. Compared with cases with NEWS ≤ 5, cases with NEWS > 5 were more likely to experience changes with an OR of 5.744 (95% CI 2.888–11.426). Compared with cases with WPS ≤ 2, cases with WPS > 2 were more likely to experience changes with an OR of 7.217 (95% CI 3.575–14.569). The difference between the areas under the curve of the NEWS (0.751 ± 0.045) and the WPS (0.736 ± 0.045) was not statistically significant (P = 0.4518). In our study, the Worthing Physiological Scoring System and National Early Warning Score both exhibited good discriminatory power, but the Worthing Physiological Scoring System is simpler to use and more suitable for use in a busy emergency department. [ABSTRACT FROM AUTHOR]

Remdesivir, an intravenous nucleotide prodrug, has been approved for treating COVID-19 in hospitalized adults and pediatric patients. Upon administration, remdesivir can be readily hydrolyzed to form its active form GS-441524, while the cleavage of the carboxylic ester into GS-704277 is the first step for remdesivir activation. This study aims to assign the key enzymes responsible for remdesivir hydrolysis in humans, as well as to investigate the kinetics of remdesivir hydrolysis in various enzyme sources. The results showed that remdesivir could be hydrolyzed to form GS-704277 in human plasma and the microsomes from human liver (HLMs), lung (HLuMs) and kidney (HKMs), while the hydrolytic rate of remdesivir in HLMs was the fastest. Chemical inhibition and reaction phenotyping assays suggested that human carboxylesterase 1 (hCES1A) played a predominant role in remdesivir hydrolysis, while cathepsin A (CTSA), acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) contributed to a lesser extent. Enzymatic kinetic analyses demonstrated that remdesivir hydrolysis in hCES1A (SHUTCM) and HLMs showed similar kinetic plots and much closed K m values to each other. Meanwhile, GS-704277 formation rates were strongly correlated with the CES1A activities in HLM samples from different individual donors. Further investigation revealed that simvastatin (a therapeutic agent for adjuvant treating COVID-19) strongly inhibited remdesivir hydrolysis in both recombinant hCES1A and HLMs. Collectively, our findings reveal that hCES1A plays a predominant role in remdesivir hydrolysis in humans, which are very helpful for predicting inter-individual variability in response to remdesivir and for guiding the rational use of this anti-COVID-19 agent in clinical settings. • The liver is the major organ for hydrolyzing remdesivir to form GS-704277 in humans. • Human CES1A is the key enzyme responsible for remdesivir hydrolysis in human liver. • The kinetic parameters (K m and V max) of remdesivir hydrolysis in various enzyme sources are assayed. • Simvastatin strongly inhibited remdesivir hydrolysis in both recombinant hCES1A and HLM. [ABSTRACT FROM AUTHOR]