How we make choices and sacrifices in medical education during the COVID-19 pandemic

Abstract

In this commentary, we highlight some of the pressing choices and sacrifices we must make in medical education during the COVID-19 pandemic.     

Value of non-clinical cardiac repolarization assays in supporting the discovery and development of safer medicines

Non-clinical QT-related assays aligned to the pharmaceutical drug discovery and development phases are used in several ways. During the early discovery phases, assays are used for hazard identification and wherever possible for hazard elimination. The data generated enable us to: (i) establish structure–activity relationships and thereby; (ii) influence the medicinal chemistry design and provide tools for effective decision making; and provide structure–activity data for in silico predictive databases; (iii) solve problems earlier; (iv) provide reassurance for compound or project to progress; and (v) refine strategies as scientific and technical knowledge grows. For compounds progressing into pre-clinical development, the ‘core battery’ QT-related data enable an integrated risk assessment to: (i) fulfil regulatory requirements; (ii) assess the safety and risk–benefit for compound progression to man; (iii) contribute to defining the starting dose during the phase I clinical trials; (iv) influence the design of the phase I clinical trials; (v) identify clinically relevant safety biomarkers; and (vi) contribute to the patient risk management plan. Once a compound progresses into clinical development, QT-related data can be applied in the context of risk management and risk mitigation. The data from ‘follow-up’ studies can be used to: (i) support regulatory approval; (ii) investigate discrepancies that may have emerged within and/or between non-clinical and clinical data; (iii) understand the mechanism of an undesirable pharmacodynamic effect; (iv) provide reassurance for progression into multiple dosing in humans and/or large-scale clinical trials; and (v) assess drug–drug interactions. Based on emerging data, the integrated risk assessment is then reviewed in this article, and the benefit–risk for compound progression was re-assessed. Project examples are provided to illustrate the impact of non-clinical data to support compound progression throughout the drug discovery and development phases, and regulatory approval.This article is part of a themed section on QT safety. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010     

Copper thiocyanato complexes and cocaine – a case of ‘black cocaine’

The chemical composition of a black powder confiscated by German customs was elucidated. Black powders are occasionally used as a ‘transporter’ for cocaine and are obviously especially designed to cloak the presence of the drug. The material consisting of cocaine, copper, iron, thiocyanate, and graphite was approached by analytical tools and chemical modelling. Graphite is added to the material probably with the intention of masking the typical infrared (IR) fingerprints of cocaine and can be clearly detected by powder X‐ray diffraction (XRD) and Raman spectroscopy. Cu²⁺ and NCS^? ions, when carefully reacted with cocaine hydrochloride, form the novel compound (CocH)₂[Cu(NCS)₄] (CocH⁺ = protonated cocaine), which has been characterised by single crystal XRD, IR, NMR, UV/Vis absorption and EPR spectroscopy. Based on some further experiments the assumed composition of the original black powder is discussed. Copyright © 2014 John Wiley & Sons, Ltd.     

Effect of one-rescuer compression/ventilation ratios on cardiopulmonary resuscitation in infant, pediatric, and adult manikins.

OBJECTIVE: Optimal chest compression to ventilation ratio (C:V) for one-rescuer cardiopulmonary resuscitation (CPR) is not known, with current American Heart Association recommendations 3:1 for newborns, 5:1 for children, and 15:2 for adults. C:V ratios influence effectiveness of CPR, but memorizing different ratios is educationally cumbersome. We hypothesized that a 10:2 ratio might provide adequate universal application for all age arrest victims. DESIGN: Clinical study. SETTING: Tertiary care children's hospital. SUBJECTS: Thirty-five health care providers. INTERVENTIONS: Thirty-five health care providers performed 5-min epochs of one-rescuer CPR at C:V ratios of 3:1, 5:1, 10:2, and 15:2 in random order on infant, pediatric, and adult manikins. Compressions were paced at 100/min by metronome. The number of effective compressions and ventilations delivered per minute was recorded by a trained basic life support instructor. Subjective assessments of fatigue (self-report) and exertion (change in rescuer pulse rate compared with baseline) were assessed. Analysis was by repeated measures analysis of variance and paired Student's t-test. MEASUREMENTS AND MAIN RESULTS: Effective infant compressions per minute did not differ by C:V ratio, but ventilations per minute were greater at 3:1 vs. 5:1, 10:2, and 15:2 (p < .05). Effective pediatric compressions per minute were less at 3:1 vs. 5:1, 10:2, and 15:2 (p < .05) and not different between 5:1, 10:2, and 15:2 ratios. Effective pediatric ventilations per minute were greater at 3:1 than all other ratios and both 5:1 and 10:2 were >15:2 (p < .05). Effective adult compressions per minute were progressively greater with 3:1 vs. 5:1 vs. 10:2 vs. 15:2 (p < .05). Self-efficacy was assessed, and rescuers always subjectively rated 10:2 and 15:2 ratios as easier than 5:1 or 3:1 ratios for all manikins. Rescuer pulse change (exertion) was greater after pediatric and adult vs. infant CPR (p < .05), with no significant difference by C:V ratio. CONCLUSIONS: C:V ratio and manikin size have a significant influence on the number of effective compressions and ventilations delivered during ideal, metronome-paced, one-rescuer CPR. Low ratios of 3:1, 5:1, and 10:2 favor ventilation, and high ratios of 15:2 favor compression, especially in adult manikins. Rescuers subjectively preferred C:V ratios of 10:2 and 15:2 over 3:1 or 5:1. Infant CPR caused less exertion and subjective fatigue than pediatric or adult CPR technique, without significant difference by C:V ratio. We speculate that a universal 10:2 C:V ratio for one-rescuer layperson CPR is physiologically reasonable but warrants further study with particular attention to educational value and technique retention.     

Spheciosterol sulfates, PKCzeta inhibitors from a philippine sponge Spheciospongia sp

Three new sterol sulfates, spheciosterol sulfates A-C (1-3), and the known sterol sulfate topsentiasterol sulfate E (4) have been isolated from the sponge Spheciospongia sp., collected in the Philippines. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1-4 inhibited PKCzeta with IC50 values of 1.59, 0.53, 0.11, and 1.21 microM, respectively. In a cell-based assay, 1-4 also inhibited NF-kappaB activation with EC50 values of 12-64 microM.