DeltaScan for the Assessment of Acute Encephalopathy and Delirium in ICU and non-ICU Patients, a Prospective Cross-Sectional Multicenter Validation Study

Objectives: To measure the diagnostic accuracy of DeltaScan: a portable real-time brain state monitor for identifying delirium, a manifestation of acute encephalopathy (AE) detectable by polymorphic delta activity (PDA) in single-channel electroencephalograms (EEGs). Design: Prospective cross-sectional study. Setting: Six Intensive Care Units (ICU's) and 17 non-ICU departments, including a psychiatric department across 10 Dutch hospitals. Participants: 494 patients, median age 75 (IQR:64-87), 53% male, 46% in ICUs, 29% delirious. Measurements: DeltaScan recorded 4-minute EEGs, using an algorithm to select the first 96 seconds of artifact-free data for PDA detection. This algorithm was trained and calibrated on two independent datasets. Methods: Initial validation of the algorithm for AE involved comparing its output with an expert EEG panel's visual inspection. The primary objective was to assess DeltaScan's accuracy in identifying delirium against a delirium expert panel's consensus. Results: DeltaScan had a 99% success rate, rejecting 6 of the 494 EEG's due to artifacts. Performance showed and an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.86 (95% CI: 0.83-0.90) for AE (sensitivity: 0.75, 95%CI=0.68-0.81, specificity: 0.87 95%CI=0.83-0.91. The AUC was 0.71 for delirium (95%CI=0.66-0.75, sensitivity: 0.61 95%CI=0.52-0.69, specificity: 72, 95%CI=0.67-0.77). Our validation aim was an NPV for delirium above 0.80 which proved to be 0.82 (95%CI: 0.77-0.86). Among 84 non-delirious psychiatric patients, DeltaScan differentiated delirium from other disorders with a 94% (95%CI: 87-98%) specificity. Conclusions: DeltaScan can diagnose AE at bedside and shows a clear relationship with clinical delirium. Further research is required to explore its role in predicting delirium-related outcomes.</p

Highly Functionalized β-Enamino Esters via C-C Coupling Reactions of Lithium Enolates of Protected Glycine Esters and Isothiocyanates

Lithium enolates of N, N-diprotected glycine esters were reacted with isothiocyanates, affording Et{2}O coordinated lithium thiolates R}1{N(H)-C(SLi)@?C(NR{2})-COOEt (2a: R{2} = -Si(CH{3}){2}-CH{2}CH{2}-Si(CH{3}){2}-; R}1{ = Ph; 2b: R{2} = -Si(CH{3}){2}-CH{2}CH{2}-Si(CH{3}){2}-; R}1{ = -CH{2}Ph; 2c: R = Et; R}1{ = Ph), in which the carboxyl oxygen atom is coordinated to lithium. Thiolate 2a was shown to be dimeric in the solid state by X-ray crystal structure determination.Hydrolysis of N-protected lithium thiolates 2a and 2b afforded 2-aminothiomalonamic esters 3a and 3b, resulting from C-protonation. N,N-diethyl substituted lithium thiolate 2c afforded mainly [2-(N,N-diethyl)amino-3-mercapto]-@b-enamino ester 3c', the S-protonated product, which is in slow equilibrium with the C-protonated tautomer. Ring closure to 4-thioxo-@b-lactams was unsuccessful. Highly functionalized 3-methylthio-@b-enamino esters were obtained via S-alkylation of the lithium thiolates 2 with iodomethane

(3R,4S)-3-Phenyl[(R)-1-phenylethyl]-4-[(R0-1-phenylethyliminomethyl]azetidin-2-one

The configuration of the chiral ring atoms of the title compound, C26H26N2O, obtained in an enantioselective synthesis, has been established relative to the known R configuration of the ?-methylbenzyl moieties. The crystal packing involves a two-dimensional network of C-H...? interactions between the aromatic rings