Operationalising generalism in medical education: a narrative review of international policy and mission documents.

INTRODUCTION: Despite moves across medical education to increase learning of generalist principles, a lack of clarity about what generalism means and how we should train doctors as 'generalists', has remained. This study explores how international, undergraduate and postgraduate, policy and educational mission documents characterise the practice and learning of generalism and how this can inform physician training. METHODS: A narrative literature review was conducted based on policy and mission documents identified through grey literature searches and a wider systematic review looking at empirical texts. Texts published between 1999 and present and related to 'generalism' were eligible for inclusion. Texts were coded and codes were reviewed and grouped into key themes. RESULTS: Thirty-four documents were included. Definitions vary: some described generalism as a basic skill, whilst others emphasised expertise. Factors which support learning generalism include: favourable financial outcomes; ageing populations; coordination of multidisciplinary care; demand for doctors with transferable skills; and patient expectations. Barriers to learning about generalism include: preference for specialisation; structure of undergraduate teaching and assessment; and the hidden curriculum. Solutions may include re-imagining generalists and specialists as being on a continuum as well as increasing exposure throughout medical education. DISCUSSION: Whilst generalism is consistently positioned as valuable, less clarity exists about how best to operationalise this in medical education. Fundamental ideological and structural changes within teaching curricula and assessment, are necessary to improve generalist learning and to promote sustainable practice. Medical education needs careful, considered planning to ensure workforce expertise is meeting population needs.

Digital undergraduate medical education and patient and carer involvement: a rapid systematic review of current practice.

BACKGROUND: Involving patients and carers in medical students' learning aims to centralise the perspective of healthcare users and supports our future medical workforce in the development of key skills. Medical schools are increasingly using digital technology for teaching and it is timely to understand how to maintain patient and carer involvement in this context. METHODS: Ovid MEDLINE, Ovid EMBASE and medRxiv were searched in October 2020 and reference lists of key articles were hand searched. Eligible studies reported authentic patient or carer involvement in undergraduate medical education where technology was also used. Study quality was assessed by the Mixed Methods Appraisal Tool (MMAT). Levels of patient or carer involvement were assessed using Towle et al.'s (2010) taxonomy, from Level 1 (lowest level) to Level 6 (highest level). RESULTS: Twenty studies were included in this systematic review. In 70% of studies, patients and carers featured in video or web-based case scenarios with no interaction between healthcare users and students. The remaining 30% of studies reported real-time interactions between students and patients via remote clinical encounters. Digital teaching sessions involving patients or carers were perceived to be valuable by students and educators, and increased student engagement, patient-centred attitudes, clinical knowledge, and communication skills. No studies reported the perspective of patients or carers. DISCUSSION: Digital technology has not yet driven higher levels of patient and carer involvement in medical training. "Live" interactions between students and patients are becoming more common but challenges need addressing to ensure positive experiences for all involved. Future teaching should enhance the role of patients and carers in medical education and support them to overcome any potential barriers to doing so remotely.

Pivot to online learning for adapting or continuing workplace-based clinical learning in medical education following the COVID-19 pandemic: A BEME systematic review: BEME Guide No. 70.

BACKGROUND: The novel coronavirus disease was declared a pandemic in March 2020, which necessitated adaptations to medical education. This systematic review synthesises published reports of medical educational developments and innovations that pivot to online learning from workplace-based clinical learning in response to the pandemic. The objectives were to synthesise what adaptations/innovation were implemented (description), their impact (justification), and 'how' and 'why' these were selected (explanation and rationale). METHODS: The authors systematically searched four online databases up to December 21, 2020. Two authors independently screened titles, abstracts and full-texts, performed data extraction, and assessed the risk of bias. Our findings are reported in alignment with the STORIES (STructured apprOach to the Reporting in healthcare education of Evidence Synthesis) statement and BEME guidance. RESULTS: Fifty-five articles were included. Most were from North America (n = 40), and nearly 70% focused on undergraduate medical education (UGME). Key developments were rapid shifts from workplace-based learning to virtual spaces, including online electives, telesimulation, telehealth, radiology, and pathology image repositories, live-streaming or pre-recorded videos of surgical procedures, stepping up of medical students to support clinical services, remote adaptations for clinical visits, multidisciplinary team meetings and ward rounds. Challenges included lack of personal interactions, lack of standardised telemedicine curricula and need for faculty time, technical resources, and devices. Assessment of risk of bias revealed poor reporting of underpinning theory, resources, setting, educational methods, and content. CONCLUSIONS: This review highlights the response of medical educators in deploying adaptations and innovations. Whilst few are new, the complexity, concomitant use of multiple methods and the specific pragmatic choices of educators offers useful insight to clinical teachers who wish to deploy such methods within their own practice. Future works that offer more specific details to allow replication and understanding of conceptual underpinnings are likely to justify an update to this review.

An update on developments in medical education in response to the COVID-19 pandemic: A BEME scoping review: BEME Guide No. 64.

BACKGROUND: COVID-19 has fundamentally altered how education is delivered. Gordon et al. previously conducted a review of medical education developments in response to COVID-19; however, the field has rapidly evolved in the ensuing months. This scoping review aims to map the extent, range and nature of subsequent developments, summarizing the expanding evidence base and identifying areas for future research. METHODS: The authors followed the five stages of a scoping review outlined by Arskey and O'Malley. Four online databases and MedEdPublish were searched. Two authors independently screened titles, abstracts and full texts. Included articles described developments in medical education deployed in response to COVID-19 and reported outcomes. Data extraction was completed by two authors and synthesized into a variety of maps and charts. RESULTS: One hundred twenty-seven articles were included: 104 were from North America, Asia and Europe; 51 were undergraduate, 41 graduate, 22 continuing medical education, and 13 mixed; 35 were implemented by universities, 75 by academic hospitals, and 17 by organizations or collaborations. The focus of developments included pivoting to online learning (n = 58), simulation (n = 24), assessment (n = 11), well-being (n = 8), telehealth (n = 5), clinical service reconfigurations (n = 4), interviews (n = 4), service provision (n = 2), faculty development (n = 2) and other (n = 9). The most common Kirkpatrick outcome reported was Level 1, however, a number of studies reported 2a or 2b. A few described Levels 3, 4a, 4b or other outcomes (e.g. quality improvement). CONCLUSIONS: This scoping review mapped the available literature on developments in medical education in response to COVID-19, summarizing developments and outcomes to serve as a guide for future work. The review highlighted areas of relative strength, as well as several gaps. Numerous articles have been written about remote learning and simulation and these areas are ripe for full systematic reviews. Telehealth, interviews and faculty development were lacking and need urgent attention.

Organ Transplant Recipients' Experiences of Physical Activity: Health, Self-Care, and Transliminality.

Physical activity (PA) is an important lifestyle component of long-term health management for organ transplant recipients, yet little is known about recipients' experiences of PA. The purpose of this study was to shed light on this experience and to investigate the possible implications of PA in the context of what is a complex patient journey. Phenomenological analysis was used to examine interviews with 13 organ transplant recipients who had taken part in sporting opportunities posttransplantation. Findings illuminate how participants' experiences of PA were commonly shaped by the transliminal nature of being an organ transplant recipient as well as a sense of duty to enact health, self-care, and donor-directed gratitude. This analysis underlines the potential role of PA in supporting organ transplant recipients' attempts to live well following transplantation and makes novel connections between PA and our existing knowledge about challenges related to identity, survivorship, obligation, and patient empowerment.

Angiotensin II induced proteolytic cleavage of myocardial ACE2 is mediated by TACE/ADAM-17: a positive feedback mechanism in the RAS.

Angiotensin converting enzyme (ACE) 2 is a key negative regulator of the renin-angiotensin system where it metabolizes angiotensin (Ang) II into Ang 1-7. We hypothesize that Ang II suppresses ACE2 by increasing TNF-α converting enzyme (TACE) activity and ACE2 cleavage. Ang II infusion (1.5 mg/kg/day) in wild-type mice for 2 weeks resulted in substantial decrease in myocardial ACE2 protein levels and activity with corresponding increase in plasma ACE2 activity, prevented by AT1R blockade. Ang II resulted in AT1R-mediated increase in myocardial TACE expression and activity, and membrane translocation of TACE. Ang II treatment in Huh7 cells exhibited AT1R-dependent metalloproteinase mediated shedding of ACE2 while transfection with siTACE prevented shedding of ACE2; cardiomyocyte-specific deletion of TACE also prevented shedding of ACE2. Reactive oxygen species played a key role since p47(phox)KO mice were resistant to Ang II-induced TACE phosphorylation and activation with preservation of myocardial ACE2 which dampened Ang II-induced cardiac dysfunction and hypertrophy. In conclusion, Ang II induces ACE2 shedding by promoting TACE activity as a positive feedback mechanism whereby Ang II facilitates the loss of its negative regulator, ACE2. In HF, elevated plasma ACE2 activity likely represents loss of the protective effects of ACE2 in the heart.

Epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress.

ACE2 (angiotensin-converting enzyme 2) counterbalances the actions of ACE (angiotensin-converting enzyme) by metabolizing its catalytic product, the vasoactive and fibrogenic peptide AngII (angiotensin II), into Ang-(1-7) [angiotensin-(1-7)]. Enhanced ACE2 expression may be protective in diabetes, cardiovascular disease and cancer. However, relatively little is known about the specific physiological factors regulating ACE2 expression. In the present paper, we show, by Western blotting and qPCR (quantitative real-time PCR), that ACE2 expression is increased under conditions of cell stress, including hypoxic conditions, IL (interleukin)-1ß treatment and treatment with the AMP mimic AICAR (5-amino-4-imidazolecarboxamide riboside). The NAD+-dependent deacetylase SIRT1 (silent information regulator T1) was found to be up-regulated after AICAR treatment but, conversely, was down-regulated after IL-1ß treatment. ChIP analysis demonstrated that SIRT1 bound to the ACE2 promoter and that binding was increased after AICAR treatment, but decreased after IL-1ß treatment. Inhibition of SIRT1 activity ablated the AICAR-induced increase in ACE2. In conclusion, we have established that the expression of the ACE2 transcript is controlled by the activity of SIRT1 under conditions of energy stress.

Angiotensin-converting enzyme 2 is subject to post-transcriptional regulation by miR-421.

ACE2 (angiotensin converting enzyme 2) plays a critical role in the local tissue RAS (renin-angiotensin system) by hydrolysing the potent hypertensive and mitogenic peptide AngII (angiotensin II). Changes in the levels of ACE2 have been observed in a number of pathologies, including cardiovascular disease, but little is known of the mechanisms regulating its expression. In the present study, therefore, the potential role of miRNAs in the regulation of ACE2 expression in primary human cardiac myofibroblasts was examined. Putative miRNA-binding sites were identified in the 3'-UTR of the ACE2 transcript using online prediction algorithms. Two of these, miR-200b and miR-421, were selected for further analysis. A reporter system using the 3'-UTR of ACE2 fused to the coding region of firefly luciferase was used to determine the functionality of the identified binding sites in vitro. This identified miR-421, but not miR-200b, as a potential regulator of ACE2. The ability of miR-421, an miRNA implicated in the development of thrombosis, to down-regulate ACE2 expression was subsequently confirmed by Western blot analysis of both primary cardiac myofibroblasts and transformed cells transfected with a synthetic miR-421 precursor. Real-time PCR analysis of miR-421 revealed widespread expression in human tissues. miR-421 levels in cardiac myofibroblasts showed significant inter-patient variability, in keeping with the variability of ACE2 expression we have observed previously. In conclusion, the present study is the first to demonstrate that ACE2 may be subject to post-transcriptional regulation and reveals a novel potential therapeutic target, miR-421, which could be exploited to modulate ACE2 expression in disease.

Clinical, humanistic and economic outcomes, including experiencing of patient safety events, associated with admitting patients to single rooms compared with shared accommodation for acute hospital admissions: a systematic review and narrative synthesis.

OBJECTIVES: Assess the impact of single rooms versus multioccupancy accommodation on inpatient healthcare outcomes and processes. DESIGN: Systematic review and narrative synthesis. DATA SOURCES: Medline, Embase, Google Scholar and the National Institute for Health and Care Excellence website up to 17 February 2022. ELIGIBILITY CRITERIA: Eligible papers assessed the effect on inpatients staying in hospital of being assigned to a either a single room or shared accommodation, except where that assignment was for a direct clinical reason like preventing infection spread. DATA EXTRACTION AND SYNTHESIS: Data were extracted and synthesised narratively, according to the methods of Campbell et al. RESULTS: Of 4861 citations initially identified, 145 were judged to be relevant to this review. Five main method types were reported. All studies had methodological issues that potentially biased the results by not adjusting for confounding factors that are likely to have contributed to the outcomes. Ninety-two papers compared clinical outcomes for patients in single rooms versus shared accommodation. No clearly consistent conclusions could be drawn about overall benefits of single rooms. Single rooms were most likely to be associated with a small overall clinical benefit for the most severely ill patients, especially neonates in intensive care. Patients who preferred single rooms tended to do so for privacy and for reduced disturbances. By contrast, some groups were more likely to prefer shared accommodation to avoid loneliness. Greater costs associated with building single rooms were small and likely to be recouped over time by other efficiencies. CONCLUSIONS: The lack of difference between inpatient accommodation types in a large number of studies suggests that there would be little effect on clinical outcomes, particularly in routine care. Patients in intensive care areas are most likely to benefit from single rooms. Most patients preferred single rooms for privacy and some preferred shared accommodation for avoiding loneliness. PROSPERO REGISTRATION NUMBER: CRD42022311689.

A Quality Improvement Project to Minimize COVID-19 Infections in Patients Receiving Haemodialysis and the Role of Routine Surveillance Using Nose and Throat Swabs for SARS-CoV-2 rRT-PCR and Serum Antibody Testing.

BACKGROUND: Patients receiving in-centre haemodialysis (ICHD) are highly vulnerable to COVID-19. OBJECTIVE: We created a quality improvement (QI) project aimed to eliminate outbreaks of COVID-19 in haemodialysis units and evaluated the utility of surveillance rRT-PCR test and SARS-CoV-2 serum antibodies for prompt identification of patients infected with COVID-19. METHODS: A multifaceted QI programme including a bundle of infection prevention control (IPC) measures was implemented across 5 ICHD units following the first wave of the pandemic in June 2020. Primary outcomes evaluated before and after QI implementation were incidence of outbreaks and severe COVID-19 illness defined as COVID-19-related death or hospitalization. Secondary outcomes included the proportion of patients identified in the pre-symptomatic/asymptomatic phase on surveillance rRT-PCR screening and the incidence and longevity of SARS-CoV-2 antibody response. RESULTS: Following the implementation of the QI project, there were no further outbreaks. Pre- and post-implementation comparison showed a significant reduction in COVID-19-related mortality and hospitalization (26 vs. 13 events, respectively, p < 0.001). Surveillance rRT-PCR screening identified 39 asymptomatic or pre-symptomatic cases out of a total of 59 rRT-PCR-positive patients (39/59, 66%). SARS-CoV-2 antibody levels were detected in 72/74 (97%) rRT-PCR-positive patients. Amongst rRT-PCR-positive patients diagnosed before August 2020, 96% had detectable antibodies until January 2021 (days from the rRT-PCR test to last antibody testing, 245-280). CONCLUSIONS: Systematic implementation of a bundle of IPC measures using QI methodology and surveillance rRT-PCR eliminated outbreaks in HD facilities. Most HD patients mount and sustain antibody response to COVID-19 for over 8 months.

Not just angiotensinases: new roles for the angiotensin-converting enzymes.

The renin-angiotensin system (RAS) is a critical regulator of blood pressure and fluid homeostasis. Angiotensin II, the primary bioactive peptide of the RAS, is generated from angiotensin I by angiotensin-converting enzyme (ACE). A homologue of ACE, ACE2, is able to convert angiotensin II to a peptide with opposing effects, angiotensin-(1-7). It is proposed that disturbance of the balance of ACE and ACE2 expression and/or function is important in pathologies in which angiotensin II plays a role. These include cardiovascular and renal disease, lung injury and liver fibrosis. The critical roles of ACE and ACE2 in regulating angiotensin II levels have traditionally focussed attention on their activities as angiotensinases. Recent discoveries, however, have illuminated the roles of these enzymes and of the ACE2 homologue, collectrin, in intracellular trafficking and signalling. This paper reviews the key literature regarding both the catalytic and non-catalytic roles of the angiotensin-converting enzyme gene family.

Calmodulin interacts with angiotensin-converting enzyme-2 (ACE2) and inhibits shedding of its ectodomain.

Angiotensin-converting enzyme-2 (ACE2) is a regulatory protein of the renin-angiotensin system (RAS) and a receptor for the causative agent of severe-acute respiratory syndrome (SARS), the SARS-coronavirus. We have previously shown that ACE2 can be shed from the cell surface in response to phorbol esters by a process involving TNF-alpha converting enzyme (TACE; ADAM17). In this study, we demonstrate that inhibitors of calmodulin also stimulate shedding of the ACE2 ectodomain, a process at least partially mediated by a metalloproteinase. We also show that calmodulin associates with ACE2 and that this interaction is decreased by calmodulin inhibitors.

A person-centred enquiry into the teaching and learning experiences of reflection and reflective practice--part one.

Reflection and reflective practice has become a key issue for curriculum development within nurse education, particularly mental health nursing. The Nursing and Midwifery Council has linked the demonstration of reflective skills to clinical competence to gain entrance onto the professional register. However, despite a significant volume of literature on reflection there is a paucity of research evidence regarding how nurse educators teach mental health nursing students to reflect and become effective reflective practitioners and, little research exploring experiences of staff and students engaged in reflection for teaching and learning purposes. A person-centred enquiry was undertaken to explore staff and student perceptions and understanding of reflection in the context of the undergraduate pre- and post-registration mental health nursing diploma programme, utilising a framework involving four focus groups and conducted in a university setting. The findings from the discussions that took place within the focus group setting produced a new model and an extended description of reflection together with non-prescriptive recommendations aimed at enhancing teaching practice.

Angiotensin-converting enzyme 2: the first decade.

The renin-angiotensin system (RAS) is a critical regulator of hypertension, primarily through the actions of the vasoactive peptide Ang II, which is generated by the action of angiotensin-converting enzyme (ACE) mediating an increase in blood pressure. The discovery of ACE2, which primarily metabolises Ang II into the vasodilatory Ang-(1-7), has added a new dimension to the traditional RAS. As a result there has been huge interest in ACE2 over the past decade as a potential therapeutic for lowering blood pressure, especially elevation resulting from excess Ang II. Studies focusing on ACE2 have helped to reveal other actions of Ang-(1-7), outside vasodilation, such as antifibrotic and antiproliferative effects. Moreover, investigations focusing on ACE2 have revealed a variety of roles not just catalytic but also as a viral receptor and amino acid transporter. This paper focuses on what is known about ACE2 and its biological roles, paying particular attention to the regulation of ACE2 expression. In light of the entrance of human recombinant ACE2 into clinical trials, we discuss the potential use of ACE2 as a therapeutic and highlight some pertinent questions that still remain unanswered about ACE2.

Angiotensin converting enzyme (ACE) and ACE2 bind integrins and ACE2 regulates integrin signalling.

The angiotensin converting enzymes (ACEs) are the key catalytic components of the renin-angiotensin system, mediating precise regulation of blood pressure by counterbalancing the effects of each other. Inhibition of ACE has been shown to improve pathology in cardiovascular disease, whilst ACE2 is cardioprotective in the failing heart. However, the mechanisms by which ACE2 mediates its cardioprotective functions have yet to be fully elucidated. Here we demonstrate that both ACE and ACE2 bind integrin subunits, in an RGD-independent manner, and that they can act as cell adhesion substrates. We show that cellular expression of ACE2 enhanced cell adhesion. Furthermore, we present evidence that soluble ACE2 (sACE2) is capable of suppressing integrin signalling mediated by FAK. In addition, sACE2 increases the expression of Akt, thereby lowering the proportion of the signalling molecule phosphorylated Akt. These results suggest that ACE2 plays a role in cell-cell interactions, possibly acting to fine-tune integrin signalling. Hence the expression and cleavage of ACE2 at the plasma membrane may influence cell-extracellular matrix interactions and the signalling that mediates cell survival and proliferation. As such, ectodomain shedding of ACE2 may play a role in the process of pathological cardiac remodelling.

Rat Ace allele variation determines susceptibility to AngII-induced renal damage.

INTRODUCTION: Ace b/l polymorphism in rats is associated with differential tissue angiotensin-converting enzyme (ACE) expression and activity, and susceptibility to renal damage. Same polymorphism was recently found in outbred Wistar rat strain with b allele accounting for higher renal ACE, and provided a model for studying renin-angiotensin-aldosterone system (RAAS) response behind the innate high or low ACE conditions. METHODS: We investigated the reaction of these alleles on chronic angiotensin II (AngII) infusion. Wistar rats were selected to breed male homozygotes for the b (WU-B) or l allele (WU-L) (n = 12). For each allele, one group (n = 6) received AngII infusion via an osmotic minipump (435 ng/kg/min) for 3 weeks. The other group (n = 6) served as a control. RESULTS: WU-B had higher ACE activity at baseline then WU-L. Interestingly, baseline renal ACE2 expression and activity were higher in WU-L. AngII infusion induced the same increase in blood pressure in both genotypes, no proteinuria, but caused tubulo-interstitial renal damage with increased α-SMA and monocyte/macrophage influx only in WU-B (p < 0.05). Low ACE WU-L rats did not develop renal damage. CONCLUSION: AngII infusion causes proteinuria-independent renal damage only in rats with genetically predetermined high ACE while rats with low ACE seemed to be protected against the detrimental effect of AngII. Differences in renal ACE2, mirroring those in ACE, might be involved.