Nosocomial or not? A combined epidemiological and genomic investigation to understand hospital-acquired COVID-19 infection on an elderly care ward.

BACKGROUND: COVID-19 has the potential to cause outbreaks in hospitals. Given the comorbid and elderly cohort of patients hospitalized, hospital-acquired COVID-19 infection is often fatal. Pathogen genome sequencing is becoming increasingly important in infection prevention and control (IPC). AIM: To inform the understanding of in-hospital SARS-CoV-2 transmission in order to improve IPC practices and to inform the future development of virological testing for IPC. METHODS: Patients detected COVID-19 positive by polymerase chain reaction on Ward A in April and May 2020 were included with contact tracing to identify other potential cases. Genome sequencing was undertaken for a subgroup of cases. Epidemiological, genomic, and cluster analyses were performed to describe the epidemiology and to identify factors contributing to the outbreak. FINDINGS: Fourteen cases were identified on Ward A. Contact tracing identified 16 further patient cases; in addition, eight healthcare workers (HCWs) were identified as being COVID-19 positive through a round of asymptomatic testing. Genome sequencing of 16 of these cases identified viral genomes differing by two single nucleotide polymorphisms or fewer, with further cluster analysis identifying two groups of infection (a five-person group and a six-person group). CONCLUSION: Despite the temporal relationship of cases, genome sequencing identified that not all cases shared transmission events. However, 11 samples were found to be closely related and these likely represented in-hospital transmission. This included three HCWs, thereby confirming transmission between patients and HCWs.S.R. and A.B. are part-funded from Research England’s Expanding Excellence in England (E3) Fund. The sequencing costs were funded by the COVID-19 Genomics UK (COG-UK) Consortium which is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute for Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The global variation of medical student engagement in teaching: Implications for medical electives

Introduction: International medical electives, whereby undergraduates visit an institution in a country other than their own, are a common part of medical training. Visiting students are often asked to provide local teaching, which may be acceptable where the visitor is acting within the bounds of their own competency and the normal practices of both their home and host institutions. However, the extent to which teaching is an accepted student activity globally has not previously been described. This study aims to address this using an international survey approach. Methods: A voluntary electronic survey, created using the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) framework, was distributed across established international medical student networks. This assessed the involvement of medical students in teaching and the educator training they receive, with the intention of comparing experiences between high-income countries (HICs) and low/middle-income countries (LMICs) to gauge the engagement of both "host" and "visiting" students. Results: 443 students from 61 countries completed the survey, with an equal proportion of respondents from LMICs (49.4%, 219/443) and HICs (50.6%, 224/443). Around two thirds of students reported providing teaching whilst at medical school, with most reporting teaching numerous times a year, mainly to more junior medical students. There was with no significant difference between LMICs and HICs. Around 30 per cent of all medical students reported having received no teacher training, including 40 per cent of those already providing teaching. Conclusion: This study suggests that students are engaged in teaching globally, with no difference between HIC and LMIC contexts. However, students are underprepared to act as educators in both settings. Providing teaching as part of an elective experience may be ethically acceptable to both host and home institutions, but needs to be supported by formal training in delivering teaching

Global health education in medical schools (GHEMS): a national, collaborative study of medical curricula

Background: Global health is the study, research, and practice of medicine focused on improving health and achieving health equity for all persons worldwide. International and national bodies stipulate that global health be integrated into medical school curricula. However, there is a global paucity of data evaluating the state of global health teaching in medical schools. This study aimed to evaluate the extent of global health teaching activities at United Kingdom (UK) medical schools. Methods: A national, cross-sectional study assessing all timetabled teachings sessions within UK medical courses for global health content during the academic year 2018/19. Global health content was evaluated against a comprehensive list of global health learning outcomes for medical students. Results: Data from 39 medical courses representing 86% (30/36) of eligible medical schools was collected. Typically, medical courses reported timetabled teaching covering over three-quarters of all global health learning outcomes. However, a wide degree of variation existed among granular global health learning objectives covered within the different medical courses. On average, each learning outcome had a 79% [95% CI: 73, 83%] probability of being included in course curricula. There were a number of learning outcomes that had a lower probability, such as ‘access to surgeons with the necessary skills and equipment in different countries’ (36%) [95% CI: 21, 53%], ‘future impact of climate change on health and healthcare systems’ (67%) [95% CI: 50, 81%], and ‘role of the WHO’ (54%) [95% CI: 28, 60%]. Conclusions: This study served as the first national assessment of global health education and curricula within UK medical schools. Through a formalised assessment of teaching events produced by medical schools around the country, we were able to capture a national picture of global health education, including the strengths of global health prioritisation in the UK, as well as areas for improvement. Overall, it appears broad-level global health themes are widely discussed; however, the granularities of key, emerging areas of concern are omitted by curricula. In particular, gaps persist relating to international healthcare systems, multilateral global health agencies such as the WHO, global surgery, climate change and more

P2X receptor antagonists for pain management: examination of binding and physicochemical properties

Enhanced sensitivity to noxious stimuli and the perception of non-noxious stimuli as painful are hallmark sensory perturbations associated with chronic pain. It is now appreciated that ATP, through its actions as an excitatory neurotransmitter, plays a prominent role in the initiation and maintenance of chronic pain states. Mechanistically, the ability of ATP to drive nociceptive sensitivity is mediated through direct interactions at neuronal P2X3 and P2X2/3 receptors. Extracellular ATP also activates P2X4, P2X7, and several P2Y receptors on glial cells within the spinal cord, which leads to a heightened state of neural-glial cell interaction in ongoing pain states. Following the molecular identification of the P2 receptor superfamilies, selective small molecule antagonists for several P2 receptor subtypes were identified, which have been useful for investigating the role of specific P2X receptors in preclinical chronic pain models. More recently, several P2X receptor antagonists have advanced into clinical trials for inflammation and pain. The development of orally bioavailable blockers for ion channels, including the P2X receptors, has been traditionally difficult due to the necessity of combining requirements for target potency and selectivity with suitable absorption distribution, metabolism, and elimination properties. Recent studies on the physicochemical properties of marketed orally bioavailable drugs, have identified several parameters that appear critical for increasing the probability of achieving suitable bioavailability, central nervous system exposure, and acceptable safety necessary for clinical efficacy. This review provides an overview of the antinociceptive pharmacology of P2X receptor antagonists and the chemical diversity and drug-like properties for emerging antagonists of P2X3, P2X2/3, P2X4, and P2X7 receptors