LIC in the time of COVID: experiences of LIC tutors during the COVID-19 pandemic in Scotland.

In March 2020, due to the escalating global coronavirus (COVID-19) pandemic, clinical placements for most medical students in the UK were suspended. A phased resumption of clinical placements started at the beginning of academic year 2020/2021. For the Scottish Graduate Entry Medicine programme (ScotGEM), 2020/21 was the first year that Dundee School of Medicine's comprehensive LIC was extended to all 54 students in the penultimate year of the ScotGEM programme. This cross-sectional qualitative study explored aspects of tutors' experiences of supporting LIC students in their practices. Thematic analysis of the data identified significant themes relating to the effects of the coronavirus pandemic on the organisation of the LIC placements and the experiences of the tutors, and the ways in which they adapted placements to the rapidly changing clinical and social landscapes. The changes necessitated by the pandemic posed significant challenges for practice-based tutors in ensuring that students had valuable educational experiences despite the constraints of social distancing requirements and the reduction in face-to-face consultations. However, tutors also identified several positive aspects of the changes which will be of interest to those involved in the organisation and delivery of both LIC and shorter General Practice based clinical attachments. Positive relationships between LIC students and practices enhanced the success of LIC placements. We will discuss how lessons learned from the experience of tutors in the pandemic could be used in the longer term to enrich the LIC experience and General Practice placements more generally.

Consensus statement on the content of clinical reasoning curricula in undergraduate medical education.

INTRODUCTION: Effective clinical reasoning is required for safe patient care. Students and postgraduate trainees largely learn the knowledge, skills and behaviours required for effective clinical reasoning implicitly, through experience and apprenticeship. There is a growing consensus that medical schools should teach clinical reasoning in a way that is explicitly integrated into courses throughout each year, adopting a systematic approach consistent with current evidence. However, the clinical reasoning literature is 'fragmented' and can be difficult for medical educators to access. The purpose of this paper is to provide practical recommendations that will be of use to all medical schools. METHODS: Members of the UK Clinical Reasoning in Medical Education group (CReME) met to discuss what clinical reasoning-specific teaching should be delivered by medical schools (what to teach). A literature review was conducted to identify what teaching strategies are successful in improving clinical reasoning ability among medical students (how to teach). A consensus statement was then produced based on the agreed ideas and the literature review, discussed by members of the consensus statement group, then edited and agreed by the authors. RESULTS: The group identified 30 consensus ideas that were grouped into five domains: (1) clinical reasoning concepts, (2) history and physical examination, (3) choosing and interpreting diagnostic tests, (4) problem identification and management, and (5) shared decision making. The literature review demonstrated a lack of effectiveness for teaching the general thinking processes involved in clinical reasoning, whereas specific teaching strategies aimed at building knowledge and understanding led to improvements. These strategies are synthesised and described. CONCLUSION: What is taught, how it is taught, and when it is taught can facilitate clinical reasoning development more effectively through purposeful curriculum design and medical schools should consider implementing a formal clinical reasoning curriculum that is horizontally and vertically integrated throughout the programme.

Disrupting the consultation: students empowering patients in a longitudinal clerkship.

Although well-established worldwide as a method of clinical medical education, Longitudinal Integrated Clerkships (LICs) are green shoots in the UK medical education landscape. The first comprehensive LIC in the UK was introduced in Dundee, Scotland in 2016. Substantial work has been carried out to evaluate the experiences of students and primary care tutors involved in the Dundee LIC, but the experiences of the patients LIC students cared for had not been evaluated. The purpose of this study was to explore the experiences of these patients, particularly the impact the involvement of a LIC student might have on their experience of healthcare. The study is a cross-sectional qualitative study involving semi-structured interviews with five patients who had experienced several contacts with LIC students. An interpretive phenomenological approach was taken. We describe the presence of the student as a disruptive force leading to the empowerment of patients. Students disrupted the status quo in the consultation by altering both the structure of the interaction and the doctor-patient relationship. The student-patient relationship was a powerful enabler of patient empowerment through the provision of education and information to the patient and through increasing patient centredness in the consultation. The positive social interaction provided by the student-patient relationship led to a reframing of patients' perceptions of the medical profession, challenging their perceptions of occupational hierarchy and power of the medical profession.

Dundee's Longitudinal Integrated Clerkship: drivers, implementation and early evaluation.

Dundee University School of Medicine established a pilot for a 40 week long comprehensive Longitudinal Integrated Clerkship (LIC) in 2016. Ten places for year 4 students are available which are shared between two regions of Scotland which are largely rural areas by UK definitions. This paper describes the drivers for the pilot, its implementation and early evaluation. For the evaluation, data were collected using focus groups and semi-structured interviews from the first cohort of seven students, four health service employed staff (two with leadership roles and two with regional student facing roles), 21 General Practitioner tutors, and from reflective audio-diaries kept by all students. Analysis was thematic, the themes being identified from the data. Summative assessment data were collated. Students reported positive learning experiences though access to secondary care learning linked to their patients was sometimes problematic. GP tutors were positive and enthusiastic about the programme and could see the potential benefits on recruitment to GP careers. Pre-existing workload pressures were a challenge. Summative assessment results were encouraging. The Dundee LIC is successful in delivering Dundee's year 4 curriculum. Ongoing development has been focused on improving awareness of the programme in secondary care services.

'Knowledge leech' to 'part of the team': students' learning in rural communities of practice.

BACKGROUND: Keele Medical School has a small accommodation hub for students placed within ten associated general practices in a predominantly rural area of England. Groups of up to eleven final year students spend fifteen weeks learning generic and transferable clinical skills in these practices. AIM: To explore the evolving perceptions on students on their experiences throughout their placements. METHOD: All ten students placed at the hub between August and December 2013 were invited to participate in focus groups in weeks zero, seven, and fifteen. Analysis was qualitative and thematic. RESULTS: Ten, five and eight students chose to participate in successive focus groups. Five themes were identified from the data; acceptance, learning opportunities, relationships, development, and injustice with a subtheme of isolation. CONCLUSION: The placements had a powerful impact on students' learning and development. Their perceptions changed from seeing themselves as 'knowledge leeches' to legitimate contributors to health care over the course of fifteen weeks. They did not recognise that managing perceived adversity led to personal development. This illustrates the need to both identify perceived adversity and explicitly signpost and scaffold life learning. The students described experiences which challenged them intellectually and offered them opportunities to recognise the breadth and complexity of general practice.

Improving the quality of written feedback using written feedback.

BACKGROUND: Educational feedback is amongst the most powerful of all learning interventions. RESEARCH QUESTIONS: (1) Can we measure the quality of written educational feedback with acceptable metrics? (2) Based on such a measure, does a quality improvement (QI) intervention improve the quality of feedback? STUDY DESIGN: We developed a QI instrument to measure the quality of written feedback and applied it to written feedback provided to medical students following workplace assessments. We evaluated the measurement characteristics of the QI score using generalisability theory. In an uncontrolled intervention, QI profiles were fed back to GP tutors and pre and post intervention scores compared. STUDY RESULTS: A single assessor scoring 6 feedback summaries can discriminate between practices with a reliability of 0.82.The quality of feedback rose for two years after the introduction of the QI instrument and stabilised in the third year. The estimated annual cost to provide this feedback is £12 per practice. Interpretation and recommendations: It is relatively straightforward and inexpensive to measure the quality of written feedback with good reliability. The QI process appears to improve the quality of written feedback. We recommend routine use of a QI process to improve the quality of educational feedback.

MALDI-MSI for the analysis of a 3D tissue-engineered psoriatic skin model.

MALDI-MS Imaging is a novel label-free technique that can be used to visualize the changes in multiple mass responses following treatment. Following treatment with proinflammatory cytokine interleukin-22 (IL-22), the epidermal differentiation of Labskin, a living skin equivalent (LSE), successfully modeled psoriasis in vitro. Masson's trichrome staining enabled visualization and quantification of epidermal differentiation between the untreated and IL-22 treated psoriatic LSEs. Matrix-assisted laser desorption ionization mass spectrometry imaging was used to observe the spatial location of the psoriatic therapy drug acetretin following 48 h treatments within both psoriatic and normal LSEs. After 24 h, the drug was primarily located in the epidermal regions of both the psoriatic and nonpsoriatic LSE models whereas after 48 h it was detectible in the dermis.

Cosmologies of selection: lessons from the faculty biscuit tin.

We conducted an ethnography of the faculty biscuit tin as we were interested in the lived experience of the biscuits contained within it. We used a constructivist epistemology, a social constructionist interpretive framework and a phenomenological methodology that included analysis from the perspectives of deixis and cosmology. The biscuits perceived that they were important to a selecting force and that the characteristics of one particular group had a specific value to the selector. Some enduring benefits may derive from the selection of this group, although its attractions were less immediately obvious than those of others. What is immediately attractive may not be the most fit for purpose; lessons for the selection of medical students may arise from this exploration of the selection experiences of biscuits in a faculty biscuit tin.

Do quality indicators for general practice teaching practices predict good outcomes for students?

Keele medical students spend 113 days in general practices over our five-year programme. We collect practice data thought to indicate good quality teaching. We explored the relationships between these data and two outcomes for students; Objective Structured Clinical Examination (OSCE) scores and feedback regarding the placements. Though both are surrogate markers of good teaching, they are widely used. We collated practice and outcome data for one academic year. Two separate statistical analyses were carried out: (1) to determine how much of the variation seen in the OSCE scores was due to the effect of the practice and how much to the individual student. (2) to identify practice characteristics with a relationship to student feedback scores. (1) OSCE performance: 268 students in 90 practices: six quality indicators independently influenced the OSCE score, though without linear relationships and not to statistical significance. (2) Student satisfaction: 144 students in 69 practices: student feedback scores are not influenced by practice characteristics. The relationships between the quality indicators we collect for practices and outcomes for students are not clear. It may be that neither the quality indicators nor the outcome measures are reliable enough to inform decisions about practices' suitability for teaching.

Teaching undergraduate students in rural general practice: an evaluation of a new rural campus in England.

INTRODUCTION: One approach to facilitating student interactions with patient pathways at Keele University School of Medicine, England, is the placement of medical students for 25% of their clinical placement time in general practices. The largest component is a 15-week 'student attachment' in primary care during the final year, which required the development of a new network of teaching practices in a rural district of England about 90 km (60 mi) from the main campus in North Staffordshire. The new accommodation and education hub was established in 2011-2012 to enable students to become immersed in those communities and learn about medical practice within a rural and remote context. Objectives were to evaluate the rural teaching from the perspectives of four groups: patients, general practice tutors, community hospital staff and students. Learning outcomes (as measured by objective structured clinical examinations) of students learning in rural practices in the final year were compared with those in other practices. METHODS: Data were gathered from a variety of sources. Students' scores in cohort-wide clinical assessment were compared with those in other locations. Semi-structured interviews were conducted with general practice tutors and community hospital staff. Serial focus groups explored the perceptions of the students, and questionnaires were used to gather the views of patients. RESULTS: Patients reported positive experiences of students in their consultations, with 97% expressing willingness to see students. The majority of patients considered that teaching in general practice was a good thing. They also expressed altruistic ideas about facilitating learning. The tutors were enthusiastic and perceived that teaching had positive impacts on their practices despite negative effects on their workload. The community hospital staff welcomed students and expressed altruistic ideas about helping them learn. There was no significant difference between the rurally placed students' objective structured clinical examination performance and that of their peers in other locations. Some students had difficulty with the isolation from peers and academic activities, and travel was a problem despite their accommodation close to the practices. CONCLUSIONS: Students valued the learning opportunities offered by the rural practice placements. The general practice tutors, patients and community hospital staff found teaching to be a positive experience overall and perceived a value to the health system and broader community in students learning locally for substantial periods of time. The evaluation has identified some student concerns about transport times and costs, social isolation, and access to resources and administrative tasks, and these are being addressed.

Hereditary Connective Tissue Diseases and Risk of Post-Acute SARS-CoV-2.

We completed a retrospective review of data collected by the JH-CROWN consortium based on ICD10 codes for a hospitalized cohort. The severity and prevalence of COVID-19 and development of PASC within heritable connective tissue diseases were unknown; however, clinical observation suggested a thorough examination was necessary. We compared rates of disease severity, death, and PASC in connective tissue diseases versus the entire cohort as well as in diabetes and hypertension to determine if connective tissue disease was a risk factor. Of the 15,676 patients in the database, 63 (0.40%) had a connective tissue disease, which is elevated relative to the distribution in the population, suggesting a higher risk of severe disease. Within these 63 patients, 9.52% developed PASC compared to 2.54% in the entire cohort (p < 0.005). Elucidation of populations at high risk for severe disease and development of PASC is integral to improving treatment approaches. Further, no other study to date has examined the risk in those with connective tissue diseases and these data support a need for enhanced awareness among physicians, patients, and the community.

Development of automated microfluidic immunoassays for the detection of SARS-CoV-2 antibodies and antigen.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) global pandemic. Rapid and sensitive detection of the virus soon after infection is important for the treatment and prevention of transmission of COVID-19, and detection of antibodies is important for epidemiology, assessment of vaccine immunogenicity, and identification of the natural reservoir and intermediate host(s). Patient nasal or oropharyngeal swabs or saliva used in conjunction with polymerase chain reaction (PCR) detect SARS-CoV-2 RNA, whereas lateral flow immunoassays (LFI) detect SARS-CoV-2 proteins. Enzyme-linked immunosorbent assays (ELISA) detect anti-SARS-CoV-2 antibodies in blood. Although effective, these assays have poor sensitivity (e.g., LFI) or are labor intensive and time consuming (PCR and ELISA). Here we describe the development of rapid, automated ELISA-based immunoassays to detect SARS-CoV-2 antigens and antibodies against the virus. The Simple Plex™ platform uses rapid microfluidic reaction kinetics for sensitive analyte detection with small sample volumes. We developed three sensitive <90-min Simple Plex immunoassays that measure either the SARS-CoV-2 antigens or the immune response to SARS-CoV-2, including neutralizing antibodies, in serum from COVID-19 patients.

Phenotypic and transcriptional changes in peripheral blood mononuclear cells during alphavirus encephalitis in mice.

Sindbis virus (SINV) infection of mice provides a model system for studying the pathogenesis of alphaviruses that infect the central nervous system (CNS) to cause encephalomyelitis. While studies of human viral infections typically focus on accessible cells from the blood, this compartment is rarely evaluated in mice. To bridge this gap, single-cell RNA sequencing (scRNAseq) was combined with flow cytometry to characterize the transcriptional and phenotypic changes of peripheral blood mononuclear cells (PBMCs) from SINV-infected mice. Twenty-one clusters were identified by scRNAseq at 7 days after infection, with a unique cluster and overall increase in naive B cells for infected mice. Uninfected mice had fewer immature T cells and CCR9+ CD4 T cells and a unique immature T cell cluster. Gene expression was most altered in the Ki67+ CD8 T cell cluster, with chemotaxis and proliferation-related genes upregulated. Global analysis indicated metabolic changes in myeloid cells and increased expression of Ccl5 by NK cells. Phenotypes of PBMCs and cells infiltrating the CNS were analyzed by flow cytometry over 14 days after infection. In PBMCs, CD8 and Th1 CD4 T cells increased in representation, while B cells showed a transient decrease at day 5 in total, Ly6a+, and naive cells, and an increase in activated B cells. In the brain, CD8 T cells increased for the first 7 days, while Th1 CD4 T cells and naive and Ly6a+ B cells continued to accumulate for 14 days. Therefore, dynamic immune cell changes can be identified in the blood as well as the CNS during viral encephalomyelitis. IMPORTANCE: The outcome of viral encephalomyelitis is dependent on the host immune response, with clearance and resolution of infection mediated by the adaptive immune response. These processes are frequently studied in mouse models of infection, where infected tissues are examined to understand the mechanisms of clearance and recovery. However, studies of human infection typically focus on the analysis of cells from the blood, a compartment rarely examined in mice, rather than inaccessible tissue. To close this gap, we used single-cell RNA sequencing and flow cytometry to profile the transcriptomic and phenotypic changes of peripheral blood mononuclear cells (PBMCs) before and after central nervous system (CNS) infection in mice. Changes to T and B cell gene expression and cell composition occurred in PBMC and during entry into the CNS, with CCL5 being a differentially expressed chemokine. Therefore, dynamic changes occur in the blood as well as the CNS during the response of mice to virus infection, which will inform the analysis of human studies.

Treatment of Sindbis Virus-Infected Neurons with Antibody to E2 Alters Synthesis of Complete and nsP1-Expressing Defective Viral RNAs.

Alphaviruses are positive-sense RNA viruses that are important causes of viral encephalomyelitis. Sindbis virus (SINV), the prototype alphavirus, preferentially infects neurons in mice and is a model system for studying mechanisms of viral clearance from the nervous system. Antibody specific to the SINV E2 glycoprotein plays an important role in SINV clearance, and this effect is reproduced in cultures of infected mature neurons. To determine how anti-E2 antibody affects SINV RNA synthesis, Oxford Nanopore Technologies direct long-read RNA sequencing was used to sequence viral RNAs following antibody treatment of infected neurons. Differentiated AP-7 rat olfactory neuronal cells, an in vitro model for mature neurons, were infected with SINV and treated with anti-E2 antibody. Whole-cell RNA lysates were collected for sequencing of poly(A)-selected RNA 24, 48, and 72 h after infection. Three primary species of viral RNA were produced: genomic, subgenomic, and defective viral genomes (DVGs) encoding the RNA capping protein nsP1. Antibody treatment resulted in overall lower production of SINV RNA, decreased synthesis of subgenomic RNA relative to genomic RNA, and suppressed production of the nsP1 DVG. The nsP1 DVG was packaged into virus particles and could be translated. Because antibody-treated cells released a higher proportion of virions with noncapped genomes and transient transfection to express the nsP1 DVG improved viral RNA capping in antibody-treated cells, we postulate that one mechanism by which antibody inhibits SINV replication in neurons is to suppress DVG synthesis and thus decrease production of infectious virions containing capped genomes. IMPORTANCE Alphaviruses are important causes of viral encephalomyelitis without approved treatments or vaccines. Antibody to the Sindbis virus (SINV) E2 glycoprotein is required for immune-mediated noncytolytic virus clearance from neurons. We used direct RNA nanopore sequencing to evaluate how anti-E2 antibody affects SINV replication at the RNA level. Antibody altered the viral RNAs produced by decreasing the proportion of subgenomic relative to genomic RNA and suppressing production of a previously unrecognized defective viral genome (DVG) encoding nsP1, the viral RNA capping enzyme. Antibody-treated neurons released a lower proportion of SINV particles with capped genomes necessary for translation and infection. Decreased nsP1 DVG production in antibody-treated neurons led to lower expression of nsP1 protein, decreased genome capping efficiency, and release of fewer infectious virus particles. Capping was increased with exogenous expression of the nsP1 DVG. These studies identify a novel alphavirus DVG function and new mechanism for antibody-mediated control of virus replication.

Continued Virus-Specific Antibody-Secreting Cell Production, Avidity Maturation and B Cell Evolution in Patients Hospitalized with COVID-19.

Understanding the development and sustainability of the virus-specific protective immune response to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains incomplete with respect to the appearance and disappearance of virus-specific antibody-secreting cells (ASCs) in circulation. Therefore, we performed cross-sectional and longitudinal analyses of peripheral blood mononuclear cells and plasma collected from 55 hospitalized patients up to 4 months after onset of COVID-19 symptoms. Spike (S)- and nucleocapsid (N)-specific IgM and IgG ASCs appeared within 2 weeks accompanied by flow cytometry increases in double negative plasmablasts consistent with a rapid extrafollicular B cell response. Total and virus-specific IgM and IgG ASCs peaked at 3-4 weeks and were still being produced at 3-4 months accompanied by increasing antibody avidity consistent with a slower germinal center B cell response. N-specific ASCs were produced for longer than S-specific ASCs and avidity maturation was greater for antibody to N than S. Patients with more severe disease produced more S-specific IgM and IgG ASCs than those with mild disease and had higher levels of N- and S-specific antibody. Women had more B cells in circulation than men and produced more S-specific IgA and IgG and N-specific IgG ASCs. Flow cytometry analysis of B cell phenotypes showed an increase in circulating B cells at 4-6 weeks with decreased percentages of switched and unswitched memory B cells. These data indicate ongoing antigen-specific stimulation, maturation, and production of ASCs for several months after onset of symptoms in patients hospitalized with COVID-19.

Genomic features of humoral immunity support tolerance model in Egyptian rousette bats.

Bats asymptomatically harbor many viruses that can cause severe human diseases. The Egyptian rousette bat (ERB) is the only known reservoir for Marburgviruses and Sosuga virus, making it an exceptional animal model to study antiviral mechanisms in an asymptomatic host. With this goal in mind, we constructed and annotated the immunoglobulin heavy chain locus, finding an expansion on immunoglobulin variable genes associated with protective human antibodies to different viruses. We also annotated two functional and distinct immunoglobulin epsilon genes and four distinctive functional immunoglobulin gamma genes. We described the Fc receptor repertoire in ERBs, including features that may affect activation potential, and discovered the lack of evolutionary conserved short pentraxins. These findings reinforce the hypothesis that a differential threshold of regulation and/or absence of key immune mediators may promote tolerance and decrease inflammation in ERBs.

The do's, don'ts and don't knows of establishing a sustainable longitudinal integrated clerkship.

INTRODUCTION: The longitudinal integrated clerkship is a model of clinical medical education that is increasingly employed by medical schools around the world. These guidelines are a result of a narrative review of the literature which considered the question of how to maximize the sustainability of a new longitudinal integrated clerkship program. METHOD: All four authors have practical experience of establishing longitudinal integrated clerkship programs. Each author individually constructed their Do's, Don'ts and Don't Knows and the literature that underpinned them. The lists were compiled and revised in discussion and a final set of guidelines was agreed. A statement of the strength of the evidence is included for each guideline. RESULTS: The final set of 18 Do's, Don'ts and Don't Knows is presented with an appraisal of the evidence for each one. CONCLUSION: Implementing a longitudinal integrated clerkship is a complex process requiring the involvement of a wide group of stakeholders in both hospitals and communities. The complexity of the change management processes requires careful and sustained attention, with a particular focus on the outcomes of the programs for students and the communities in which they learn. Effective and consistent leadership and adequate resourcing are important. There is a need to select teaching sites carefully, involve students and faculty in allocation of students to sites and support students and faculty though the implementation phase and beyond. Work is needed to address the Don't Knows, in particular the question of how cost-effectiveness is best measured.

Correction to: The do's, don'ts and don't knows of establishing a sustainable longitudinal integrated clerkship.

Unfortunately information regarding the disclaimer of Paul Worley's affiliation is missing from the original article. Please find the information here:Paul Worley is affiliated to the Prideaux Centre for Research in Health Professions Education, Flinders University, Adelaide, Australia. He is the ….

Acute RNA Viral Encephalomyelitis and the Role of Antibodies in the Central Nervous System.

Acute RNA viral encephalomyelitis is a serious complication of numerous virus infections. Antibodies in the cerebral spinal fluid (CSF) are correlated to better outcomes, and there is substantive evidence of antibody secreting cells (ASCs) entering the central nervous system (CNS) and contributing to resolution of infection. Here, we review the RNA viruses known to cause acute viral encephalomyelitis with mechanisms of control that require antibody or ASCs. We compile the cytokines, chemokines, and surface receptors associated with ASC recruitment to the CNS after infection and compare known antibody-mediated mechanisms as well as potential noncytolytic mechanisms for virus control. These non-canonical functions of antibodies may be employed in the CNS to protect precious non-renewable neurons. Understanding the immune-specialized zone of the CNS is essential for the development of effective treatments for acute encephalomyelitis caused by RNA viruses.