Non-technical skills learning in healthcare through simulation education: Integrating the SECTORS learning model and Complexity theory

Background: Recent works have reported the SECTORS model for non-technical skills learning in healthcare. The TINSELS programme applied this model, together with complexity theory, to guide the design and piloting of a non-technical skills based simulation training programme in the context of medicines safety. Methods: The SECTORS model defined learning outcomes. Complexity Theory led to a simulation intervention that employed authentic multi-professional learner teams, included planned and unplanned disturbances from the norm and used a staged debrief to encourage peer observation and learning. Assessment videos of non-technical skills in each learning outcome were produced and viewed as part of a Non-Technical Skills Observation Test (NOTSOT) both pre and post intervention. Learner observations were assessed by two researchers and statistical difference investigated using a student’s t-test Results: The resultant intervention is described and available from the authors. 18 participants were recruited from a range of inter-professional groups and were split into two cohorts. There was a statistically significant improvement (P=0.0314) between the Mean (SD) scores for the NOTSOT pre course 13.9 (2.32) and post course 16.42 (3.45). Conclusions: An original, theoretically underpinned, multi-professional, simulation based training programme has been produced by the integration of the SECTORS model for non-technical skills learning the complexity theory. This pilot work suggests the resultant intervention can enhance nontechnical skills

Enhancing health care non-technical skills: the TINSELS programme

Background and Context: Training in ‘non-technical skills’, social (communication and team work) and cognitive (analytical and personal behaviour) skills, in healthcare have been of great interest over the last decade. Whilst the majority of publications focus on ‘whether’ such education can be successful, they overlook the question of ‘how’ they enhance skills. We designed and piloted an original, theoretically robust and replicable teaching package that addresses non-technical skills in the context of medicines safety through simulation-based inter professional learning: the TINSELS (Training In Non-technical Skills to Enhance Levels of Medicines Safety) Programme. Innovation: A modified Delphi process was completed to identify learning outcomes, and recruitment of multi-professional teams was through local publicity. The faculty developed a three-session simulation based intervention: session one was a simulated ward encounter with multiple medicine related activities; session two was an extended debrief and facilitated discussion; and session three a ‘chamber of horrors’ where inter professional teams identified potential sources of error. Each session was completed in the simulation suite with 6 – 9 participants, lasted approximately 90m minutes, and took place over 2 weeks. Full details of the course will be presented to facilitate dissemination. Implications: Likert scale feedback was collected after the course (1 strongly disagree-5 strongly agree). Mean scores were all greater than 4, with qualitative feedback noting the fidelity of the authentic inter professional learner groups. A previously validated safety attitudes questionnaire found changes in attitudes towards handover of care and perceptions of safety levels in the workplace post intervention. An original, simulation based, multi-professional training programme has been developed with learning and assessment materials available for widespread replication

Development and governance of FAIR thresholds for a data federation

The FAIR (findable, accessible, interoperable, and re-usable) principles and practice recommendations provide high level guidance and recommendations that are not research-domain specific in nature. There remains a gap in practice at the data provider and domain scientist level demonstrating how the FAIR principles can be applied beyond a set of generalist guidelines to meet the needs of a specific domain community. We present our insights developing FAIR thresholds in a domain specific context for self-governance by a community (agricultural research). ‘Minimum thresholds’ for FAIR data are required to align expectations for data delivered from providers’ distributed data stores through a community-governed federation (the Agricultural Research Federation, AgReFed). Data providers were supported to make data holdings more FAIR. There was a range of different FAIR starting points, organisational goals, and end user needs, solutions, and capabilities. This informed the distilling of a set of FAIR criteria ranging from ‘Minimum thresholds’ to ‘Stretch targets’. These were operationalised through consensus into a framework for governance and implementation by the agricultural research domain community. Improving the FAIR maturity of data took resourcing and incentive to do so, highlighting the challenge for data federations to generate value whilst reducing costs of participation. Our experience showed a role for supporting collective advocacy, relationship brokering, tailored support, and low-bar tooling access particularly across the areas of data structure, access and semantics that were challenging to domain researchers. Active democratic participation supported by a governance framework like AgReFed’s will ensure participants have a say in how federations can deliver individual and collective benefits for members. © 2022 The Author(s)

Unexpected medical undergraduate simulation training (UMUST): can unexpected medical simulation scenarios help prepare medical students for the transition to foundation year doctor?

BACKGROUND: Preparing medical students with the skills necessary to deal with emergency situations as junior doctors can be challenging due to the complexities of creating authentic ‘real life’ experiences in artificial environments. The following paper is an evaluation of the UMUST (Unexpected Medical Undergraduate Simulation Training) project; a high-fidelity simulation based training programme designed to emulate the experience of dealing with medical emergencies for final year medical students preparing for practice as Foundation Year trainees. METHODS: Final year medical students from Liverpool University who undertake their clinical placements at Blackpool Teaching Hospitals NHS Foundation Trust and St. Helens & Knowsley Teaching Hospitals NHS Trust were randomly allocated into groups and took part in a series of four unexpected simulation based scenarios. At the beginning of the week in which the scenarios ran, participants were issued with a hospital bleep which they carried with them during their placement. At an unknown time to them, the participants were bleeped to attend a simulated emergency scenario, and on arrival to the Clinical Skills and Simulation facility, members of the education team undertook a standardised simulation scenario. Each session was recorded on video which the participants subsequently watched as part of a debriefing process. An assessment tool was developed to gauge whether the participants made progress in their learning over the course of the four sessions. Focus groups were held with the participants in order to evaluate their experience of the programme, and questionnaires were later distributed to all participants once they had begun working as a Foundation Year trainee. The questionnaires asked them how relevant UMUST was in preparing them for dealing with medical emergencies. RESULTS: The questionnaires and the focus groups clearly showed that the doctors felt like UMUST was very valuable in preparing them to work as junior doctors. They had enjoyed taking part in UMUST and thought was a realistic and useful part of their undergraduate training. CONCLUSIONS: The feedback from the focus groups and the subsequent questionnaires clearly demonstrate that participants felt the UMUST programme helped to prepare them as junior doctors in terms of dealing with emergency situations

Ronapreve (REGN-CoV; casirivimab and imdevimab) reduces the viral burden and alters the pulmonary response to the SARS-CoV 2 Delta variant (B.1.617.2) in K18-hACE2 mice using an experimental design reflective of a treatment use case

Background: Ronapreve demonstrated clinical application in post-exposure prophylaxis, mild/moderate disease and in the treatment of seronegative patients with severe COVID19 prior to the emergence of the Omicron variant in late 2021. Numerous reports have described loss of in vitro neutralisation activity of Ronapreve and other monoclonal antibodies for BA.1 Omicron and subsequent sub-lineages of the Omicron variant. With some exceptions, global policy makers have recommended against the use of existing monoclonal antibodies in COVID19. Gaps in knowledge regarding the mechanism of action of monoclonal antibodies are noted, and further preclinical study will help understand positioning of new monoclonal antibodies under development. Objectives: The purpose of this study was to investigate the impact of Ronapreve on compartmental viral replication as a paradigm for a monoclonal antibody combination. The study also sought to confirm absence of in vivo activity against BA.1 Omicron (B.1.1.529) relative to the Delta (B.1.617.2) variant. Methods: Virological efficacy of Ronapreve was assessed in K18-hACE2 mice inoculated with either the SARS-CoV-2 Delta or Omicron variants. Viral replication in tissues was quantified using qRT-PCR to measure sub-genomic viral RNA to the E gene (sgE) as a proxy. A histological examination in combination with staining for viral antigen served to determine viral spread and associated damage. Results: Ronapreve reduced sub-genomic viral RNA levels in lung and nasal turbinate, 4 and 6 days post infection, for the Delta variant but not the Omicron variant of SARS-CoV-2 at doses 2-fold higher than those shown to be active against previous variants of the virus. It also appeared to block brain infection which is seen with high frequency in K18-hACE2 mice after Delta variant infection. At day 6, the inflammatory response to lung infection with the Delta variant was altered to a mild multifocal granulomatous inflammation in which the virus appeared to be confined. A similar tendency was also observed in Omicron infected, Ronapreve-treated animals. Conclusions: The current study provides evidence of an altered tissue response to the SARS-CoV-2 after treatment with a monoclonal antibody combination that retains neutralization activity. These data also demonstrate that experimental designs that reflect the treatment use case are achievable in animal models for monoclonal antibodies deployed against susceptible variants. Extreme caution should be taken when interpreting prophylactic experimental designs when assessing plausibility of monoclonal antibodies for treatment use cases

Reduction in oxidatively generated DNA damage following smoking cessation

<p>Abstract</p> <p>Background</p> <p>Cigarette smoking is a known cause of cancer, and cancer may be in part due to effects of oxidative stress. However, whether smoking cessation reverses oxidatively induced DNA damage unclear. The current study sought to examine the extent to which three DNA lesions showed significant reductions after participants quit smoking.</p> <p>Methods</p> <p>Participants (n = 19) in this study were recruited from an ongoing 16-week smoking cessation clinical trial and provided blood samples from which leukocyte DNA was extracted and assessed for 3 DNA lesions (thymine glycol modification [d(T^gpA)]; formamide breakdown of pyrimidine bases [d(T^gpA)]; 8-oxo-7,8-dihydroguanine [d(G^h)]) via liquid chromatography tandem mass spectrometry (LC-MS/MS). Change in lesions over time was assessed using generalized estimating equations, controlling for gender, age, and treatment condition.</p> <p>Results</p> <p>Overall time effects for the d(T^gpA) (χ²(3) = 8.068, p < 0.045), d(P^fpA) (χ²(3) = 8.477, p < 0.037), and d(G^h) (χ²(3) = 37.599, p < 0.001) lesions were seen, indicating levels of each decreased significantly after CO-confirmed smoking cessation. The d(T^gpA) and d(P^fpA) lesions show relatively greater rebound at Week 16 compared to the d(G^h) lesion (88% of baseline for d(T^gpA), 64% of baseline for d(P^fpA), vs 46% of baseline for d(G^h)).</p> <p>Conclusions</p> <p>Overall, results from this analysis suggest that cigarette smoking contributes to oxidatively induced DNA damage, and that smoking cessation appears to reduce levels of specific damage markers between 30-50 percent in the short term. Future research may shed light on the broader array of oxidative damage influenced by smoking and over longer durations of abstinence, to provide further insights into mechanisms underlying carcinogenesis.</p

Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters

The successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention that is implementable alongside vaccination programmes. Nafamostat is a serine protease inhibitor that inhibits SARS-CoV-2 entry in vitro, but it has not been characterised for chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and has an extremely short plasma half-life. This study sought to determine whether intranasal dosing of nafamostat at 5 mg/kg twice daily was able to prevent the airborne transmission of SARS-CoV-2 from infected to uninfected Syrian Golden hamsters. SARS-CoV-2 RNA was detectable in the throat swabs of the water-treated control group 4 days after cohabitation with a SARS-CoV-2 inoculated hamster. However, throat swabs from the intranasal nafamostat-treated hamsters remained SARS-CoV-2 RNA negative for the full 4 days of cohabitation. Significantly lower SARS-CoV-2 RNA concentrations were seen in the nasal turbinates of the nafamostat-treated group compared to the control (p = 0.001). A plaque assay quantified a significantly lower concentration of infectious SARS-CoV-2 in the lungs of the nafamostat-treated group compared to the control (p = 0.035). When taken collectively with the pathological changes observed in the lungs and nasal mucosa, these data are strongly supportive of the utility of intranasally delivered nafamostat for the prevention of SARS-CoV-2 infection

Learning health ‘safety’ within non-technical skills interprofessional simulation education: a qualitative study

Background: Healthcare increasingly recognises and focusses on the phenomena of ‘safe practice’ and ‘patient safety.’ Success with non-technical skills (NTS) training in other industries has led to widespread transposition to healthcare education, with communication and teamwork skills central to NTS frameworks. Objective: This study set out to identify how the context of interprofessional simulation learning influences NTS acquisition and development of ‘safety’ amongst learners. Methods: Participants receiving a non-technical skills (NTS) safety focussed training package were invited to take part in a focus group interview which set out to explore communication, teamwork, and the phenomenon of safety in the context of the learning experiences they had within the training programme. The analysis was aligned with a constructivist paradigm and took an interactive methodological approach. The analysis proceeded through three stages, consisting of open, axial, and selective coding, with constant comparisons taking place throughout each phase. Each stage provided categories that could be used to explore the themes of the data. Additionally, to ensure thematic saturation, transcripts of observed simulated learning encounters were then analysed. Results: Six themes were established at the axial coding level, i.e., analytical skills, personal behaviours, communication, teamwork, context, and pedagogy. Underlying these themes, two principal concepts emerged, namely: intergroup contact anxiety – as both a result of and determinant of communication – and teamwork, both of which must be considered in relation to context. These concepts have subsequently been used to propose a framework for NTS learning. Conclusions: This study highlights the role of intergroup contact anxiety and teamwork as factors in NTS behaviour and its dissipation through interprofessional simulation learning. Therefore, this should be a key consideration in NTS education. Future research is needed to consider the role of the affective non-technical attributes of intergroup contact anxiety and teamwork as focuses for education and determinants of safe behaviour

Anticipation of regulatory needs for nanotechnology-enabled health products

Development of nanotechnology-based applications in health sector offer innovative therapeutic and diagnostic opportunities to address medical needs. At the moment, no specific regulatory framework exists for nano-enabled health products and the current regulatory practise might require additional guidance in order to fully cover the particularities of such products. This white paper summarizes the major challenges associated with the regulation of the nano-enabled health products. Depending on their mode of action nano-enabled health products are regulated either as medicinal products or medical devices. However, due to the increased complexity of such products and their size-related properties the selection of the regulatory path can become challenging since the primary mode of action might be difficult to determine. Due to the fast progress in the field and the lack of robust datasets, only initial guidance on regulatory information needs is currently available and the question remains whether these identified requirements are sufficient for a reliable characterisation of nano-enabled products. In relation to the need for additional information on the quality, safety and efficacy standardised methods have to be available. However, many conventional methods might not be suitable or reliable for nanomaterial testing due to the interference of nanomaterial with assays components. New state-of-art methods, instruments, approaches or tools have not yet sufficiently proven their reliability and relevance for the given purpose. As patents are expiring generic versions of the innovator products will require access to the market. Since the physicochemical characteristics can be very complex and depend on the manufacturing process, pharmacokinetic assessment might not be sufficient and more guidance is needed on how the bioequivalence can be demonstrated. For the nano-enabled health products classified as medical devices, the European Definition on nanomaterials will apply, determining its further classification and regulatory requirements. Yet, the implementation of the definition and the necessity to determine the exposure to nanomaterials may pose additional challenges. The regulatory challenges highlighted in this white paper should guide the research projects and the involved communities willing to advance the regulatory science in the area of nanomedicine.JRC.F.2-Consumer Products Safet

Quantitation of tizoxanide in multiple matrices to support cell culture, animal and human research

Currently nitazoxanide is being assessed as a candidate therapeutic for SARS-CoV-2. Nitazoxanide is rapidly broken down to its active metabolite tizoxanide upon administration. Unlike many other candidates being investigated, tizoxanide plasma concentrations achieve antiviral levels after administration of the approved dose, although higher doses are expected to be needed to maintain these concentrations across the dosing interval in the majority of patients. Here an LC-MS/MS assay is described that has been validated in accordance with Food and Drug Administration (FDA) guidelines. Fundamental parameters have been evaluated, and these included accuracy, precision and sensitivity. The assay was validated for human plasma, mouse plasma and Dulbecco's Modified Eagles Medium (DMEM) containing varying concentrations of Foetal Bovine Serum (FBS). Matrix effects are a well-documented source of concern for chromatographic analysis, with the potential to impact various stages of the analytical process, including suppression or enhancement of ionisation. Herein a validated LC-MS/MS analytical method is presented capable of quantifying tizoxanide in multiple matrices with minimal impact of matrix effects. The validated assay presented here was linear from 15.6 ng/mL to 1000 ng/mL. The presented assay here has applications in both pre-clinical and clinical research and may be used to facilitate further investigations into the application of nitazoxanide against SARS-CoV-2