Effectiveness of using high-fidelity simulation to teach the management of general anesthesia for Cesarean delivery.

PURPOSE: The objective of this study was to assess the influence of a teaching plan consisting of didactic teaching and repeated simulations on the performance of anesthesia residents in the management of general anesthesia (GA) for emergency Cesarean delivery (CD). METHODS: Twenty-one postgraduate year 2 (PGY2) and 3 (PGY3) anesthesia residents from the University of Toronto were recruited in this prospective cohort study. All participants received didactic teaching in the management of GA for emergency CD, which was followed one week later by assessment of performance in the same scenario using a high-fidelity simulator. Another simulation assessment was repeated two months later in the same scenario. All simulation video recordings were assessed by two blinded experts using a validated checklist and an Anaesthetists' Non-Technical Skills (ANTS) scale in order to rate their technical and non-technical skills, respectively. The participants' performance (based on the above scales) in the two simulation sessions were then compared. RESULTS: Nineteen residents completed both simulation sessions. There was an improvement in the mean (SD) weighted checklist score from 64.5% (7.1%) in session 1 to 76.7% (6.7%) in session 2 (P < 0.001). The mean (SD) ANTS scores also increased from 2.8 (0.5) in session 1 to 3.3 (0.4) in session 2 (P = 0.001). No difference in the checklist or ANTS scores was seen between PGY2 and PGY3 residents in any of the simulation sessions. Several common performance errors were identified, but these improved in the second session. The correlation between checklist and ANTS scores was moderately high (correlation coefficient [r] = 0.7; P < 0.001). The inter-rater reliability among the experts was also high (intraclass correlation coefficient [ICC] for the checklist = 0.72; 95% confidence interval [CI] 0.62 to 0.81; ICC for the ANTS = 0.74; 95% CI 0.49 to 0.89). CONCLUSION: Didactic teaching followed by simulation sessions enhances not only the technical skills but also the non-technical skills of residents, most likely due to the feedback received after the first simulation session. Repeated simulation sessions may help prepare residents to deal more effectively with similar critical situations in clinical practice with minimum errors.

Identification of isothiazole-4-carboxamidines derivatives as a novel class of allosteric MEK1 inhibitors.

The development of potent, orally bioavailable, and selective series of 5-amino-3-hydroxy-N(1-hydroxypropane-2-yl)isothiazole-4-carboxamidine inhibitors of MEK1 and MEK-2 kinase is described. Optimization of the carboxamidine and the phenoxyaniline group led to the identification of 55 which gave good potency as in vitro MEK1 inhibitors, and good oral exposure in rat.

Discovery of 3-hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles as potent MEK1 inhibitors.

3-Hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles were discovered as potent in vitro MEK1 inhibitors.

Design, synthesis and structure-activity relationships of novel taxane-based multidrug resistance reversal agents.

A series of novel taxane-based multidrug resistance (MDR) reversal agents (TRAs) has been designed and synthesized. Structure-activity relationship (SAR) study clearly indicates that modification of the C-7 position with hydrophobic arenecarbonylcinnamoyl groups brings about high potency against drug efflux mediated by P-glycoprotein (P-gp). Six TRAs exhibit ability to modulate a wide range of ATP-binding cassette (ABC) transporters, such as P-gp, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which may serve as novel broad-spectrum modulators of ABC transporters.