Purpose: Describe the differences in characteristics and outcomes between COVID-19 and other viral pneumonia patients admitted to Dutch ICUs. Materials and methods: Data from the National-Intensive... Show morePurpose: Describe the differences in characteristics and outcomes between COVID-19 and other viral pneumonia patients admitted to Dutch ICUs. Materials and methods: Data from the National-Intensive-Care-Evaluation-registry of COVID-19 patients admitted between February 15th and January 1th 2021 and other viral pneumonia patients admitted between January 1st 2017 and January 1st 2020 were used. Patients' characteristics, the unadjusted, and adjusted in-hospital mortality were compared. Results: 6343 COVID-19 and 2256 other viral pneumonia patients from 79 ICUs were included. The COVID-19 patients included more male (71.3 vs 49.8%), had a higher Body-Mass-Index (28.1 vs 25.5), less comorbidities (42.2 vs 72.7%), and a prolonged hospital length of stay (19 vs 9 days). The COVID-19 patients had a significantly higher crude in-hospital mortality rate (Odds ratio (OR) = 1.80), after adjustment for patient characteristics and ICU occupancy rate the OR was respectively 3.62 and 3.58. Conclusion: Higher mortality among COVID-19 patients could not be explained by patient characteristics and higher ICU occupancy rates, indicating that COVID-19 is more severe compared to other viral pneumonia. Our findings confirm earlier warnings of a high need of ICU capacity and high mortality rates among relatively healthy COVID-19 patients as this may lead to a higher mental workload for the staff. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
Purpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all... Show morePurpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. Materials & methods: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. Results: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when con -sidering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. Conclusions: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients. ? 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
Vorst, E. van der; Theodorou, K.; Wu, Y.; Hoeksema, M.; Goossens, P.; Bursill, C.; ... ; Donners, M. 2016
Objectives: Membrane cholesterol is known to modulate a variety of cell signaling pathways and functions. While cholesterol depletion by High-Density-Lipoproteins (HDL) has potent anti-inflammatory... Show moreObjectives: Membrane cholesterol is known to modulate a variety of cell signaling pathways and functions. While cholesterol depletion by High-Density-Lipoproteins (HDL) has potent anti-inflammatory effects in various cell types, its effects on inflammatory responses in macrophages remain ill defined.Methods: Human and murine macrophages were pre-incubated with human reconstituted (apolipoproteinA-I/phosphatidylcholine) or native HDL.Results: HDL pre-incubation significantly decreased LPS-induced anti-inflammatory IL-10 production, while the opposite was observed for the pro-inflammatory mediators IL-12 and TNF. We show that these effects are mediated by passive cholesterol depletion and lipid raft disruption, without involvement of ABCA1, ABCG1, SR-BI or CD36. These pro-inflammatory effects are confirmed in vivoin peritoneal macrophages from ApoA-I transgenic mice, which have high circulating HDL levels. Native and reconstituted HDL enhances Toll-Like-Receptor-induced signaling by activating protein kinase C (PKC), since inhibition of PKC ablated the observed HDL effects. Using macrophages from NF-κB luciferase mice, we observed that HDL induces NF-κB activation. Western blot analyses showed that in particular the p65 subunit was activated. Using specific knock-out mice, we show that the observed HDL effects are independent of IKK, NIK and CKII. Furthermore, we observed that STAT1 is involved in the pro-inflammatory HDL effects on IL-10 and IL-12. On the other hand, we show that HDL enhances ADAM protease activity, thereby mediating TNF-α release.Conclusions: HDL exerts pro-inflammatory effects on macrophages via passive cholesterol depletion by activation of PKC-NF-kB/STAT1. These pro-inflammatory activities on macrophages could at least partly underlie the disappointing therapeutic potential of HDL raising therapy in current cardiovascular clinical trials. Show less
