The ability to generate patient-specific human induced pluripotent stem cells (iPSCs) offers a new paradigm for modelling human disease and for individualizing drug testing. Congenital long QT syndrome (LQTS) is a familial arrhythmogenic syndrome characterized by abnormal ion channel function and sudden cardiac death. Here we report the development of a patient/disease-specific human iPSC line from a patient with type-2 LQTS (which is due to the A614V missense mutation in the KCNH2 gene). The generated iPSCs were coaxed to differentiate into the cardiac lineage. Detailed whole-cell patch-clamp and extracellular multielectrode recordings revealed significant prolongation of the action-potential duration in LQTS human iPSC-derived cardiomyocytes (the characteristic LQTS phenotype) when compared to healthy control cells. Voltage-clamp studies confirmed that this action-potential-duration prolongation stems from a significant reduction of the cardiac potassium current I(Kr). Importantly, LQTS-derived cells also showed marked arrhythmogenicity, characterized by early-after depolarizations and triggered arrhythmias. We then used the LQTS human iPSC-derived cardiac-tissue model to evaluate the potency of existing and novel pharmacological agents that may either aggravate (potassium-channel blockers) or ameliorate (calcium-channel blockers, K(ATP)-channel openers and late sodium-channel blockers) the disease phenotype. Our study illustrates the ability of human iPSC technology to model the abnormal functional phenotype of an inherited cardiac disorder and to identify potential new therapeutic agents. As such, it represents a promising paradigm to study disease mechanisms, optimize patient care (personalized medicine), and aid in the development of new therapies.

the manuscript. None of these individuals received compensation for their contributions. 1. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA.

In many countries, procedural sedation outside of the operating room is performed by pediatricians. We examined if in situ sedation simulation training (SST) of pediatricians improves the performance of tasks related to patient safety during sedation in the Emergency Department (ED). We performed a single-center, quasi-experimental, study evaluating the performance of sedation, before-and-after SST. Sixteen pediatricians were evaluated during sedation as part of their usual practice, using the previously validated Sedation-Performance-Score (SPS). This tool evaluates physician behaviors during sedation that are conducive to safe patient outcomes. Following the sedation, providers completed SST, followed by a structured debriefing. They were then re-evaluated with the SPS during a subsequent patient sedation in the ED. Using multivariate regression, odds ratios were calculated for each SPS component, and were compared before and after the SST. Thirty-two sedations were performed, 16 before and 16 after SST. SPS scores improved from a median of 4 (IQR 2-5) to 6 (IQR 4-7) following SST (p < 0.0009, median difference 2, 95% CI 1-3). SST was associated with improved performance in four SPS components. The findings of this pilot study suggest that sedation simulation training of pediatricians improves several tasks related to patient safety during sedation.

Triage level was predictive of hospitalization, admission to the ICU, and proportions of LWBS and LOS in the ED. The findings suggest validity of the PedCTAS in this cohort. This is the first report of the performance of a triage tool in an Israeli ED.