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Abstracts from the Research Symposium for Medical Students and Foundation Doctors 20 November 2019 Abstracts from the Research Symposium for Medical Students and Foundation Doctors 20 November 2019 November 2019 This abstract book has been produced using author-supplied copy and no editing has been undertaken. No responsibility is assumed for any claims, instructions, methods or drug dosages included in the abstracts: it is recommended that these are verified independently. Undergraduate Prizes Best undergraduate oral presentation Socioeconomic differences in cardiovascular disease risk factor prevalence in people with type 2 diabetes in Scotland: a cross-sectional study Edward Whittaker (Supervisor: Prof. Sarah Wild) University of Edinburgh INTRODUCTION: Health inequalities exist in outcomes of diabetes in different socioeconomic groups and these are particularly marked for cardiovascular disease and its risk factors1. The aim of this study was to describe the association between socioeconomic status and prevalence of cardiovascular risk factors (smoking, body mass index, HbA1C, blood pressure and cholesterol) in people with type 2 diabetes in contemporary Scottish data. PATIENTS AND METHODS: A cross-sectional study was performed of 264,011 people with type 2 diabetes in Scotland who were alive on 30/06/16, identified from the population-based diabetes register. Socioeconomic status was defined using quintiles of the area-based SIMD with Q1 and Q5 used to identify the most and least deprived fifths of the population respectively. Logistic regression models adjusted for age, sex, health board, history of cardiovascular disease and duration of diabetes were used to estimate odds ratios (OR) (and 95% confidence intervals) for Q1 compared to Q5 for each risk factor. RESULTS: The mean (SD) age of the study population was 66.7 (12.8) years, 56.1% were men, 23.6% were in Q1 and 15.1% in Q5. Crude prevalence in Q1/Q5 was 24.4/8.8% for smoking, 61.9/49.4% for BMI ≥30kg/m2, 43.7/39.7% for HbA1C ≥58mmol/mol, 30.5/31.3% for systolic blood pressure (SBP) ≥140mmHg and 24.4/24.5% for total cholesterol ≥5mmol/l respectively. Adjusted prevalence of current smoking (OR 3.08 (95% CI 2.95-3.21)), ≥30kg/m2 (OR 1.48 (1.44-1.52)) and HbA1C ≥58mmol/mol (OR 1.11 (1.08-1.15)) were higher in Q1 compared to Q5. The prevalence of SBP ≥140mmHg was similar (OR 1.03 (1.00-1.06)), and the prevalence of total cholesterol ≥5mmol/l was lower in Q1 compared to Q5 (OR 0.87 (0.84-0.90)). CONCLUSIONS: Socioeconomic deprivation is associated with higher prevalence of smoking, obesity, and HbA1C ≥58mmol/mol among people with type 2 diabetes in Scotland. Effective approaches to reducing inequalities at both population and individual levels are required as well as reducing risk factor prevalence across the whole population. REFERENCES: 1. Read, S., Fischbacher, C., Colhoun, H., Gasevic, D., Kerssens, J., McAllister, D., Sattar, N., Wild, S. (2019). Trends in incidence and case fatality of acute myocardial infarction, angina and coronary revascularisation in people with and without type 2 diabetes in Scotland between 2006 and 2015. Diabetologia, 62(3), 418-425. Best Undergraduate Poster Establishing the effect of multi-ErbB inhibitors on TRIB2 mediated signalling in acute myeloid leukaemia Rachel Porter (MBChB4), Dr Karen Keeshan University of Glasgow INTRODUCTION: TRIB2 is a pseudokinase which functions as a scaffold in cellular signalling and promotes proteasomal degradation. TRIB2 is an oncogene in Acute Myeloid Leukaemia (AML). AML is classified by genetic subtypes, many having no pharmacological targets putting paediatric mortality at 30-40%. The structure of the ATP binding site in TRIB2 provides a potential drug target. In the Ras-MAPK pathway, TRIB2 facilitates uncontrolled proliferation in AML through proposed interaction with MEK1 and ERK1/2. This pathway begins with ligand binding to multi-ErbB receptor tyrosine kinases (RTKs). Drugs which target these RTKs may be repurposed for AML therapy due to “on-target” binding to and destabilising TRIB2 which kills AML cells. Afatinib, Neratinib and Osimertinib are multi-ErbB inhibitors licenced for biological treatment. Erlotinib binds only to ErbB1 (EGFR) and has not been shown to destabilise TRIB2. PATIENTS AND METHODS: Aims: This study aims to be the first stage in investigating if TRIB2 facilitates ErbB signalling in AML cells and has a role in response of leukaemia to multi-ErbB inhibitors. This research seeks to establish if multi-ErbB inhibitors induce AML cytotoxicity by performing dose response curves of Afatinib, Neratinib, Osimertinib and Erlotinib in TRIB2 positive human U937 AML cells in vitro using flow cytometry based apoptotic assay. RESULTS: This study found micromolar cell toxicity for the multi-ErbB inhibitors, Afatinib, Neratinib, Osimertinib but not the single-ErbB1 inhibitor Erlotinib .The multi-ErbB inhibitors IC50 doses were determined to be below 20μM. Erlotinib did not show any AML cytotoxicity no statistical significance was seen between this drug and the control. CONCLUSIONS: These findings support targeting ErbB1 alone is not enough to cause cell death in AML. These results provide a baseline for research into the association between cell kill and expression of active kinases in the Ras-Raf-MEK-ERK pathway and its regulation by TRIB2. This may have potential pharmacological implications in paediatric AML treatment. REFERENCES: 1. Eyers PA, Keeshan K, Kannan N. Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease. Trends Cell Biol. 2017;27(4):284-98 2. Salomè M, Campos J, Keeshan K. TRIB2 and the ubiquitin proteasome system in cancer. Biochem Soc Trans. 2015;43(5):1089-94. 3. Foulkes DM et al. Covalent inhibitors of EGFR family protein kinases induce degradation of human Tribbles 2 (TRIB2) pseudokinase in cancer cells. Sci Signal. 2018;11(549). Commended Undergraduate Poster Junior Doctor’s Perceptions and Experiences of the Emergency Department Departmental Handover Miss Emily Park, Dr Susie Roy, Dr Janet Skinner Edinburgh Medical School INTRODUCTION: It is known there is a high prevalence of stress and burnout in both junior doctors and doctors working in Emergency Medicine. Although research has examined which aspects of working life doctors find stressful, no literature was identified exploring if departmental handover itself is a source of stress for junior doctors. Therefore, the aim of this project is to investigate if junior doctors find the Emergency Department (ED) departmental handover stressful. PATIENTS AND METHODS: Non-probabilistic sampling methods were used to recruit junior doctors (FY2-CT1) working in Royal Infirmary of Edinburgh’s (RIE) Emergency Department (ED). Qualitative semi-structured interviews were undertaken between March and April 2019 until data saturation was reached. Perceptions and experiences of the ED departmental handover were explored. Interviews were audio-recorded and transcribed verbatim. Data were analysed thematically using NVivo software to identify emerging themes. RESULTS: 10 participants were interviewed between the grades of FY2 and CT1. Interviews lasted between 16 and 61 minutes with an average duration of 30 minutes. Following thematic analysis of the data four themes were identified: stress decreases as familiarity increases, time pressure is an ongoing stressor, the handover as a solace and it’s nice to be nice. Participants noted the fear of humiliation and appearing incompetent in front of seniors and colleagues as the main stressor when beginning work in the department. It was noted that with time; as relationships form and clinical experience improves that those stressors are ameliorated. Conversely, time pressure is an ongoing stressor due to the ED’s focus on efficient handovers, busyness of the department and pressure from colleagues who are ending their shift to handover succinctly. It was found that the handover can also help to alleviate stress by facilitating the opportunity for peer socialisation, education and morale boosting. The final theme explores how the attitudes and behaviours of others in the department can affect the experiences of people working there. This encompasses support from seniors; attitudes, approaches and personalities of those running the handover; language and tone used in handovers, and team morale - with focus on fostering a civil and pleasant working environment. CONCLUSIONS: Junior doctors find certain aspects of ED handover stressful. These include: wanting to make a good impression to seniors, workload (busyness of department), unfamiliarity and uncertainty, time pressures and the negative effects of hierarchy. However, it was also found that the ED departmental handover can help to ameliorate stress felt by junior doctors in the ED by facilitating the opportunity for socialisation, education and team morale boosting. REFERENCES: BeyondBlue (2013). National mental health survey of doctors and medical students. Executive Summary; Braun V & Clarke V (2006). Using thematic analysis in psychology. Qualitative Research in Psychology. 3, 77–101; Facey AD, Tallentire V, Selzer RM, Rotstein L (2015). Understanding and reducing work- related psychological distress in interns: a systematic review. Internal Medicine Journal. Royal Austrailasian College of Physicians. Machaczek K K (2014). Barriers to effective communication between doctors at shift handover. Sheffield Hallam University, UK; NHS Scotland (2016). Practicing Realistic Medicine. Chief Medical Officer’s Annual Report 2016-17; Porath C & Pearson C (2013). The price of incivility. Harvard Business
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