Ibuprofen, Flurbiprofen, Etoricoxib or Paracetamol Do Not Influence ACE2 Expression and Activity In Vitro or in Mice and Do Not Exacerbate In-Vitro SARS-CoV-2 Infection.

SARS-CoV-2 uses the human cell surface protein angiotensin converting enzyme 2 (ACE2) as the receptor by which it gains access into lung and other tissue. Early in the pandemic, there was speculation that a number of commonly used medications-including ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs)-have the potential to upregulate ACE2, thereby possibly facilitating viral entry and increasing the severity of COVID-19. We investigated the influence of the NSAIDS with a range of cyclooxygenase (COX)1 and COX2 selectivity (ibuprofen, flurbiprofen, etoricoxib) and paracetamol on the level of ACE2 mRNA/protein expression and activity as well as their influence on SARS-CoV-2 infection levels in a Caco-2 cell model. We also analysed the ACE2 mRNA/protein levels and activity in lung, heart and aorta in ibuprofen treated mice. The drugs had no effect on ACE2 mRNA/protein expression and activity in the Caco-2 cell model. There was no up-regulation of ACE2 mRNA/protein expression and activity in lung, heart and aorta tissue in ibuprofen-treated mice in comparison to untreated mice. Viral load was significantly reduced by both flurbiprofen and ibuprofen at high concentrations. Ibuprofen, flurbiprofen, etoricoxib and paracetamol demonstrated no effects on ACE2 expression or activity in vitro or in vivo. Higher concentrations of ibuprofen and flurbiprofen reduced SARS-CoV-2 replication in vitro.

Love and breakup letter methodology: A new research technique for medical education.

In everyday life, feelings are important to us, influencing our decision-making and motivating our actions. This is equally true within medicine and medical education, where feelings influence key aspects such as clinical decision-making, empathy, resilience, professional identity, reflection, team dynamics, career choices and questions of prejudice and bias. Feelings are therefore legitimate targets in medical education research, but asking research participants to talk openly about feelings can be challenging for participants and researchers alike. Within the disciple of User Experience (UX)-a relatively new research discipline used in the world of technology-researchers also seek to understand their customer's feelings, which are central to aspects of brand loyalty and choice of software platforms. UX researchers have developed innovative ways to explore feelings, in particular through the use of Love and Breakup Methodology (LBM)-participants are asked to write love and breakup letters to the product or app under study, and the letters are then used to guide the focus group discussion that follows. Methods: In this article, we describe the theoretical underpinnings of LBM, including ontological considerations. We also consider how LBM can be successfully used in medical education research and outline how we have adapted it in our own research studies and programme evaluations. Conclusions: Love and breakup letters are creative ways of understanding participants' positive and negative emotions about the matter under study. LBM has been utilised extensively by UX researchers in technology, but has been little used in medical education. It has rich potential to enhance research approaches to aspects of medicine that are influenced by feelings, including empathy and resilience, team working and many other aspects of professional practice. Although principally a focus group research tool, it can be adapted to other approaches, including questionnaire surveys and individual interviews.

How medical school alters empathy: Student love and break up letters to empathy for patients.

INTRODUCTION: Medical education is committed to promoting empathic communication. Despite this, much research indicates that empathy actually decreases as students progress through medical school. In qualitative terms, relatively little is known about this changing student relationship with the concept of empathy for patients and how teaching affects it. This study explores that knowledge gap. METHODS: Adopting a constructivist paradigm, we utilised a research approach new to medical education: Love and Breakup Letter Methodology. A purposive sample of 20 medical students were asked to write love and break up letters to 'empathy for patients'. The letters were prompts for the focus group discussions that followed. Forty letters and three focus group discussions were thematically analysed. RESULTS: The three major themes were: art and artifice; empathic burden; and empathy as a virtue. Students were uncomfortable with the common practice of faking empathic statements, a problem exacerbated by the need to 'tick the empathy box' during examinations. Students evolved their own empathic style, progressing from rote empathic statements towards phrases which suited their individual communication practice. They also learned non-verbal empathy from positive clinician role-modelling. Students reported considerable empathic burden. Significant barriers to empathy were reported within the hidden curriculum, including negative role-modelling that socialises students into having less compassion for difficult patients. Students strongly associated empathy with virtue. CONCLUSIONS: Medical education should address the problem of inauthentic empathy, including faking empathic s in assessments. Educators should remember the value of non-verbal compassionate communication. The problems of empathic burden, negative role modelling and of finding empathy difficult for challenging patients may account for some of the empathy decline reported in quantitative research. Framing empathy as a virtue may help students utilise empathy more readily when faced with patients they perceive as challenging and may promote a more authentic empathic practice.

Empathy in Medical Education: Its Nature and Nurture - a Qualitative Study of the Views of Students and Tutors.

Context: Medical education is committed to teaching patient centred communication and empathy. However, quantitative research suggests empathy scores tend to decline as students progress through medical school. In qualitative terms, there is a need to better understand how students and tutors view the practice and teaching of clinical empathy and the phenomenon of empathic erosion. Methods: Working within a constructivist paradigm, researchers thematically analysed the individual interview data from a purposive sample of 13 senior students and 9 tutors. Results: The four major themes were as follows: (1) 'the nature of empathy', including the concept of the innate empathy that students already possess at the beginning of medical school; (2) 'beyond the formal curriculum' and the central importance of role modelling; (3) 'the formal curriculum and the tick-box influence of assessments'; and (4) the 'durability of empathy', including ethical erosion and resilience. A garden model of empathy development is proposed - beginning with the innate seeds of empathy that students bring to medical school, the flowering of empathy is a fragile process, subject to both enablers and barriers in the formal, informal, and hidden curricula. Conclusion: This study provides insights into empathic erosion in medical school, including the problems of negative role modelling and the limitations of an assessment system that rewards 'tick-box' representations of empathy, rather than true acts of compassion. It also identifies factors that should enable the flowering of empathy, such as new pedagogical approaches to resilience and a role for the arts and humanities.

'I'm sorry to hear that'-Empathy and Empathic Dissonance: the Perspectives of PA Students.

CONTEXT: Our understanding of clinical empathy could be enhanced through qualitative research-research currently under-represented in the field. Physician associates within the UK undergo an intensive 2-year postgraduate medical education. As a new group of health professionals, they represent a fresh pair of eyes through which to examine clinical empathy, its nature and teaching. METHODS: Working with a constructivist paradigm, utilising grounded theory methodology, researchers studied 19 purposively sampled physician associate students in two UK medical schools. One-to-one semi-structured interviews were transcribed verbatim. Data were analysed using a grounded theory approach. RESULTS: The global themes were the pathways to empathy, empathy modifiers and empathic dissonance a novel term to describe the discomfort students experience when pressurised into making empathic statements they don't sincerely feel. Students preferred using non-verbal over verbal expressions of empathy. A conceptual model is proposed. The more substantial empathic pathway, affective empathy, involves input from the heart. An alternative empathy, more constrained, comes from the head: cognitive empathy was considered a solution to time pressure and emotional burden. Formal teaching establishes empathic dissonance, a problem which stems from over-reliance on the empathic statement as the means to deliver clinical empathy. CONCLUSIONS: This study furthers our understanding of the construct and teaching of empathy. It identifies empathic barriers, especially time pressure. It proposes a novel concept-empathic dissonance-a concept that challenges medical educationalists to reframe future empathy teaching.