[Electroencephalography and connectivity in delirium]. / Eeg en innovatieve behandeling van verminderde hersenconnectiviteit bij delirium.

BACKGROUND: Delirium is associated with neurophysiological changes that can be identified with quantitative EEG analysis techniques (qEEG). AIM: To provide an overview of studies on neurophysiological changes in delirium using various qEEG analysis techniques. METHOD: Literature review. RESULTS: In delirium, there is an increase in delta and theta activity but a decrease in activity in the alpha frequency band. Additionally, there is a decrease in functional connectivity and efficiency of the brain network in the alpha frequency band. CONCLUSION: Delirium is characterized by diffuse slowing of the EEG, reduced functional connectivity, and decreased efficiency of the brain network. Improved functional connectivity could be a new approach to treat delirium.

Population Pharmacokinetics of Remdesivir and GS-441524 in Hospitalized COVID-19 Patients.

The objective of this study was to describe the population pharmacokinetics of remdesivir and GS-441524 in hospitalized coronavirus disease 2019 (COVID-19) patients. A prospective observational pharmacokinetic study was performed in non-critically ill hospitalized COVID-19 patients with hypoxemia. For evaluation of the plasma concentrations of remdesivir and its metabolite GS-441524, samples were collected on the first day of therapy. A nonlinear mixed-effects model was developed to describe the pharmacokinetics and identify potential covariates that explain variability. Alternative dosing regimens were evaluated using Monte Carlo simulations. Seventeen patients were included. Remdesivir and GS-441524 pharmacokinetics were best described by a one-compartment model. The estimated glomerular filtration rate (eGFR) on GS-441524 clearance was identified as a clinically relevant covariate. The interindividual variability in clearance and volume of distribution for both remdesivir and GS-441524 was high (remdesivir, 38.9% and 47.9%, respectively; GS-441525, 47.4% and 42.9%, respectively). The estimated elimination half-life for remdesivir was 0.48 h, and that for GS-441524 was 26.6 h. The probability of target attainment (PTA) of the in vitro 50% effective concentration (EC50) for GS-441524 in plasma can be improved by shortening the dose interval of remdesivir and thereby increasing the total daily dose (PTA, 51.4% versus 94.7%). In patients with reduced renal function, the metabolite GS-441524 accumulates. A population pharmacokinetic model for remdesivir and GS-441524 in COVID-19 patients was developed. Remdesivir showed highly variable pharmacokinetics. The elimination half-life of remdesivir in COVID-19 patients is short, and the clearance of GS-441524 is dependent on the eGFR. Alternative dosing regimens aimed at optimizing the remdesivir and GS-441524 concentrations may improve the effectiveness of remdesivir treatment in COVID-19 patients.

Association between delirium and cognitive change after cardiac surgery.

BACKGROUND: Previous studies provide inconsistent data on whether postoperative delirium (POD) is a risk factor for postoperative cognitive decline (POCD). We thus investigated the relationship between POD and cognitive change after cardiac surgery and assessed the relationship between preoperative cognitive domain scores and POD. METHODS: Postoperative delirium was assessed with the Confusion Assessment Method (CAM) adapted for the intensive care unit and the conventional CAM accompanied by chart review. Cognitive function was assessed with a neuropsychological test battery before elective cardiac surgery and 1 month and 1 yr afterwards. Cognitive change was calculated using the Reliable Change Index (RCI). Multiple linear regression was used to adjust for confounding. RESULTS: Of the 184 patients who completed baseline assessment, 23 (12.5%) developed POD. At 1 month, the decline in cognitive performance was worse in patients with POD [median composite RCI -1.00, interquartile range (IQR) -1.67 to 0.28] than in patients without POD (RCI -0.04, IQR -0.70 to 0.63, P =0.02). At 1 yr, both groups showed cognitive improvement on average compared with baseline (POD patients median composite RCI 0.25, IQR -0.42 to 1.31, vs non-POD patients RCI 0.92, IQR 0.18-1.53; P =0.08). Correction for differences in age and level of education did not change the results. Patients with POD performed less well than patients without POD on the preoperative Trailmaking test part A ( P =0.03). CONCLUSIONS: Postoperative delirium is independently associated with cognitive decline 1 month after surgery, but cognitive performance generally recovers in 1 yr. Patients with a predisposition to POD can be identified before surgery by worse performance in an attention task. CLINICAL TRIAL REGISTRATION: NCT00293592.