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1.
Diabet Med ; : e15116, 2023 Apr 13.
Article in English | MEDLINE | ID: covidwho-2325911

ABSTRACT

AIMS: To compare the time required for perioperative glucose management using fully automated closed-loop versus standard insulin therapy. METHODS: We performed a time-motion study to quantify the time requirements for perioperative glucose management with fully closed-loop (FCL) and standard insulin therapy applied to theoretical scenarios. Following an analysis of workflows in different periods of perioperative care in elective surgery patients receiving FCL or standard insulin therapy upon hospital admission (pre- and intra-operatively, at the intermediate care unit and general wards), the time of process-specific tasks was measured by shadowing hospital staff. Each task was measured 20 times and its average duration in combination with its frequency according to guidelines was used to calculate the cumulative staff time required for blood glucose management. Cumulative time was calculated for theoretical scenarios consisting of elective minor and major abdominal surgeries (pancreatic surgery and sleeve gastrectomy, respectively) to account for the different care settings and lengths of stay. RESULTS: The FCL insulin therapy reduced the time required for perioperative glucose management compared to standard insulin therapy, across all assessed care periods and for both perioperative pathways (range 2.1-4.5). For a major abdominal surgery, total time required was 248.5 min using FCL versus 753.9 min using standard insulin therapy. For a minor abdominal surgery, total time required was 68.6 min and 133.2 min for FCL and standard insulin therapy, respectively. CONCLUSIONS: The use of fully automated closed-loop insulin delivery for inpatient glucose management has the potential to alleviate the workload of diabetes management in an environment with adequately trained staff.

2.
Mol Syst Biol ; 17(8): e10239, 2021 08.
Article in English | MEDLINE | ID: covidwho-1335457

ABSTRACT

Understanding the mechanism of SARS-CoV-2 infection and identifying potential therapeutics are global imperatives. Using a quantitative systems pharmacology approach, we identified a set of repurposable and investigational drugs as potential therapeutics against COVID-19. These were deduced from the gene expression signature of SARS-CoV-2-infected A549 cells screened against Connectivity Map and prioritized by network proximity analysis with respect to disease modules in the viral-host interactome. We also identified immuno-modulating compounds aiming at suppressing hyperinflammatory responses in severe COVID-19 patients, based on the transcriptome of ACE2-overexpressing A549 cells. Experiments with Vero-E6 cells infected by SARS-CoV-2, as well as independent syncytia formation assays for probing ACE2/SARS-CoV-2 spike protein-mediated cell fusion using HEK293T and Calu-3 cells, showed that several predicted compounds had inhibitory activities. Among them, salmeterol, rottlerin, and mTOR inhibitors exhibited antiviral activities in Vero-E6 cells; imipramine, linsitinib, hexylresorcinol, ezetimibe, and brompheniramine impaired viral entry. These novel findings provide new paths for broadening the repertoire of compounds pursued as therapeutics against COVID-19.


Subject(s)
Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Drug Evaluation, Preclinical/methods , Virus Internalization/drug effects , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , COVID-19/genetics , COVID-19/virology , Chlorocebus aethiops , Drug Repositioning , HEK293 Cells , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/physiology , Humans , Imidazoles/pharmacology , Pyrazines/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Salmeterol Xinafoate/pharmacology , Vero Cells
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