Understanding the treatment experiences of adults diagnosed with early-onset colorectal cancer: A qualitative study.

OBJECTIVE: Early-onset colorectal cancer (CRC) incidence in adults aged under 50 is increasing. There is a critical lack of knowledge regarding the challenges faced by early-onset CRC patients and their experiences of treatment. The aim of this study was to explore the lived experiences of individuals receiving treatment for early-onset CRC, and the resulting impact on their lives. METHODS: Semi-structured interviews of patients with early-onset CRC in the UK (n = 21) were conducted from August 2021 to March 2022. Interviews were recorded and transcribed verbatim. Data were analysed using thematic analysis. RESULTS: Results identified four key themes: (1) early-onset CRC treatment results in sudden physical, psychological and social impacts in all aspects of life; (2) early-onset CRC patients have unique supportive care needs which are not recognised in current practice; (3) there is a need for tailored information; (4) a lack of support was identified in the areas of mental health, sexual health and fertility. CONCLUSIONS: Our study highlights numerous unique issues experienced by the early-onset CRC patient group during treatment. There is a need for change in clinical practice, along with the development of international guidelines and tailored resources for both patients and healthcare professionals, in order to improve care.

Reluctant heroes: New doctors negotiating their identities dialogically on social media.

BACKGROUND: Ensuring that students transition smoothly into the identity of a doctor is a perpetual challenge for medical curricula. Developing professional identity, according to cultural-historical activity theory, requires negotiation of dialectic tensions between individual agency and the structuring influence of institutions. We posed the research question: How do medical interns, other clinicians and institutions dialogically construct their interacting identities? METHODS: Our qualitative methodology was rooted in dialogism, Bakhtin's cultural-historical theory that accounts for how language mediates learning and identity. Reasoning that the COVID pandemic would accentuate and expose pre-existing tensions, we monitored feeds into the Twitter microblogging platform during medical students' accelerated entry to practice; identified relevant posts from graduating students, other clinicians and institutional representatives; and kept an audit trail of chains of dialogue. Sullivan's dialogic methodology and Gee's heuristics guided a reflexive, linguistic analysis. RESULTS: There was a gradient of power and affect. Institutional representatives used metaphors of heroism to celebrate 'their graduates', implicitly according a heroic identity to themselves as well. Interns, meanwhile, identified themselves as incapable, vulnerable and fearful because the institutions from which they had graduated had not taught them to practise. Senior doctors' posts were ambivalent: Some identified with institutions, maintaining hierarchical distance between themselves and interns; others, along with residents, acknowledged interns' distress, expressing empathy, support and encouragement, which constructed an identity of collegial solidarity. CONCLUSIONS: The dialogue exposed hierarchical distance between institutions and the graduates they educated, which constructed mutually contradictory identities. Powerful institutions strengthened their identities by projecting positive affects onto interns who, by contrast, had fragile identities and sometimes strongly negative affects. We speculate that this polarisation may be contributing to the poor morale of doctors in training and propose that, to maintain the vitality of medical education, institutions should seek to reconcile their projected identities with the lived identities of graduates.

Essential workers? An institutional ethnographic lens on pandemic GP placements.

BACKGROUND: Clinical placements for medical students in the United Kingdom (UK) came to an abrupt halt in March 2020. The rapidly evolving Covid19 pandemic created specific challenges for educators, balancing safety concerns for patients, students and healthcare staff alongside the imperative to continue to train future clinicians. Organisations such as the Medical Schools Council (MSC) published guidance to help plan return of students to clinical placements. This study aimed to examine how GP education leads made decisions around students returning to clinical placements for the 20/21 academic year. METHOD: Data collection and analysis was informed by an Institutional Ethnographic approach. Five GP education leads from medical schools throughout the UK were interviewed (over MS TEAMS™). Interviews focused on the work the participants did to plan students' return to clinical placements and how they used texts to inform this work. Analysis focused on the interplay between the interview and textual data. RESULTS AND DISCUSSION: GP education leads actively used MSC guidance which confirmed students to be 'essential workers', an unquestioned and unquestionable phrase at the time. This permitted students to return to clinical placements by affording the GP education leads authority to ask or persuade GP tutors to accept them. Furthermore, by describing teaching as 'essential work' in its own right in the guidance, this extended what the GP tutors came to expect to do as 'essential workers' themselves. CONCLUSION: GP education leads activated authoritarian phrases such as 'essential workers' and 'essential work' contained within MSC guidance to direct students' return to clinical placements in GP settings.

Pre-prescribing: Creating a zone of proximal development where medical students can safely fail.

PURPOSE: Prescribing is a common task, often performed by junior clinicians, with potential for significant harm. Despite this, it is common for medical students to qualify having only prescribed in simulated scenarios or assessments. We implemented an alternative: students were given pens with purple ink, which permitted them to write prescriptions for real patients. We set out to understand how this intervention, pre-prescribing, created a zone of proximal development (ZPD) for learners. METHODS: An anonymous, mixed methods, evaluation questionnaire was distributed to all final-year medical students at one university in the United Kingdom. Analysis was guided by Experience Based Learning theory. RESULTS: Two hundred and eighteen students made 386 free-text comments. Most participants reported that pre- helped them become capable doctors (Strongly Agree n = 96, 45%; Agree: n = 110, 50%). Pre-prescribing created a ZPD in which participants could use the tools of practice in authentic contexts under conditions that made it safe to fail. CONCLUSIONS: This research shows how a theoretically informed intervention can create conditions to enhance learning. It encourages educators to identify aspects of routine practice that could be delegated, or co-performed, by learners. With appropriate support, educators can create 'safe-fails' which allow learners to participate safely in authentic, risky, and indeterminate situations they will be expected to navigate as newly qualified clinicians.

Analysis of the interactions between small pulmonary nodules, clinical factors and the risk of malignancy in the chest following diagnosis of head and neck cancer.

BACKGROUND: This study aims to investigate radiological and clinical factors which predict malignancy in indeterminate pulmonary nodules in patients with head and neck cancer (HNC). METHODS: Prospective data were collected in 424 patients who were reviewed in the NHS Lothian HNC multidisciplinary meeting from May 2016 to May 2018. Staging and follow-up CT chest imaging were reviewed to identify and assess pulmonary nodules in all patients. RESULTS: About 61.8% of patients had at least one pulmonary nodule at staging CT. In total, 25 patients developed malignancy in the chest. Metastatic disease in the chest was significantly associated with unknown or negative p16 status (p < .0005). Pleural indentation and spiculation were associated with indeterminate nodules, subsequently being shown to represent metastatic disease (p > .0005 and p = .046, respectively). CONCLUSION: Negative or unknown p16 status was associated with an increased propensity to develop metastatic disease in the chest in patients with HNC.

The pen is mightier than the sword. Reinstating patient care as the object of prescribing education.

Prescribing (writing medication orders) is one of residents' commonest tasks. Superficially, all they have to do is complete a form. Below this apparent simplicity, though, lies the complex task of framing patients' needs and navigating relationships with them and other clinicians. Mistakes, which compromise patient safety, commonly result. There is no evidence that competence-based education is preventing harm. We found a profound contradiction between medical students becoming competent, as defined by passing competence assessments, and becoming capable of safely caring for patients. We reinstated patients as the object of learning by allowing students to 'pre-prescribe' (complete, but not authorise prescriptions). This turned a disabling tension into a driver of curriculum improvement. Students 'knotworked' within interprofessional teams to the benefit of patients as well as themselves. Refocusing undergraduate medical education on patient care showed promise as a way of improving patient safety.

Harnessing insights from an activity system - OSCEs past and present expanding future assessments.

Objective Structured Clinical Examinations (OSCEs) are a dominant, yet problematic, assessment tool across health professions education (HPE). OSCEs' standardised approach aligns with regulatory accountability, allowing learners to exchange exam success for the right to practice. We offer a sociohistorical account of OSCEs' development to support an interpretation of present assessment practices. OSCEs create tensions. Preparing for OSCE success diverts students away from the complexity of authentic clinical environments. Students will not qualify and will, therefore, be of no use to patients without getting marks providing evidence of competence. Performing in a formulaic and often non patient-centred way is the price to pay for a qualification. Acknowledging the stultifying effect of standardising human behaviour for OSCEs opens up possibilities to release latent energy for change in medical education. In this imagined future, the overall object of education is refocused on patient care.

Becoming a clinician: Trainee identity formation within the general practice supervisory relationship.

OBJECTIVES: Becoming a clinician is a trajectory of identity formation in the context of supervised practice. This is a social process where the supervisory relationship is key. Therefore, to know how to support identity formation of clinical trainees, it is necessary to understand how this happens within the supervisory relationship. Our aim was to develop a conceptualisation of trainee identity formation within the general practice supervisory relationship to aid its support. METHODS: We took a critical realist approach using case study design and 'cultural worlds' theory as a conceptual frame. Each case comprised a general practice trainee and supervisor pair. Our data were weekly audiorecordings of interactions between trainee, supervisor and a patient over 12 weeks augmented by post-interaction reflections and sequential interviews. We undertook interpretive analysis using dialogic methods focusing on the doing of language and the cultural discourses expressed. RESULTS: We identified three social discourses centring on: clinical responsibility; ownership of clinical knowledge, and measures of trainee competency. Versions of these discourses defined four trainee-supervisor relational arrangements within which trainee and supervisor assumed reciprocal identities. We labelled these: junior learner and expert clinician; apprentice assistant and master coach, and lead clinician and advisor. We found a trajectory across these identity arrangements. Behind this trajectory was an invitation by the supervisor to the trainee into the social space of clinician and a readiness of the trainee to accept this invitation. Congruence in supervisor and trainee positioning was important. CONCLUSIONS: In the supervisory relationship, trainee and supervisor adopted reciprocal identities. For trainees to progress to identity of 'lead clinician,' supervisors needed to invite their trainee into this space and vacate it themselves. Congruence between supervisor positioning of their trainee and trainee authorship of themselves was important and was aided by explicit dialogue and common purpose. We offer a model and language for trainees, supervisors and departments or schools to facilitate this.

NTP42, a novel antagonist of the thromboxane receptor, attenuates experimentally induced pulmonary arterial hypertension.

BACKGROUND: NTP42 is a novel antagonist of the thromboxane prostanoid receptor (TP), currently in development for the treatment of pulmonary arterial hypertension (PAH). PAH is a devastating disease with multiple pathophysiological hallmarks including excessive pulmonary vasoconstriction, vascular remodelling, inflammation, fibrosis, in situ thrombosis and right ventricular hypertrophy. Signalling through the TP, thromboxane (TX) A2 is a potent vasoconstrictor and mediator of platelet aggregation. It is also a pro-mitogenic, pro-inflammatory and pro-fibrotic agent. Moreover, the TP also mediates the adverse actions of the isoprostane 8-iso-prostaglandin F2α, a free-radical-derived product of arachidonic acid produced in abundance during oxidative injury. Mechanistically, TP antagonists should treat most of the hallmarks of PAH, including inhibiting the excessive vasoconstriction and pulmonary artery remodelling, in situ thrombosis, inflammation and fibrosis. This study aimed to investigate the efficacy of NTP42 in the monocrotaline (MCT)-induced PAH rat model, alongside current standard-of-care drugs. METHODS: PAH was induced by subcutaneous injection of 60 mg/kg MCT in male Wistar-Kyoto rats. Animals were assigned into groups: 1. 'No MCT'; 2. 'MCT Only'; 3. MCT + NTP42 (0.25 mg/kg BID); 4. MCT + Sildenafil (50 mg/kg BID), and 5. MCT + Selexipag (1 mg/kg BID), where 28-day drug treatment was initiated within 24 h post-MCT. RESULTS: From haemodynamic assessments, NTP42 reduced the MCT-induced PAH, including mean pulmonary arterial pressure (mPAP) and right systolic ventricular pressure (RSVP), being at least comparable to the standard-of-care drugs Sildenafil or Selexipag in bringing about these effects. Moreover, NTP42 was superior to Sildenafil and Selexipag in significantly reducing pulmonary vascular remodelling, inflammatory mast cell infiltration and fibrosis in MCT-treated animals. CONCLUSIONS: These findings suggest that NTP42 and antagonism of the TP signalling pathway have a relevant role in alleviating the pathophysiology of PAH, representing a novel therapeutic target with marked benefits over existing standard-of-care therapies.

Instagram for peer teaching: opportunity and challenge.

Medical education is increasingly being delivered beyond the boundaries of the classroom. Online learning and peer teaching are particularly popular among educators to complement traditional, didactic teaching methods. In light of the COVID-19 pandemic, students at the Queen's University Belfast's (QUB) General Practice Society started creating daily multiple-choice questions (MCQs) on Instagram to help continue learning while placements were suspended. There were high levels of engagement with the MCQs, with students reporting the content to be both relevant and useful for their learning. The project also allowed us to gain early experience of teaching, furthered our own learning and helped develop key skills (e.g. providing constructive feedback, creativity, self-directed learning) important for both our professional and personal development. Nonetheless, there are few published examples of the use of Instagram within medical education. Further work needs to be carried out to summarise projects delivered on the platform, train educators in using Instagram, and encourage students to get involved in finding further, novel methods of delivering medical education.

Differential expression of the TPα and TPß isoforms of the human T Prostanoid receptor during chronic inflammation of the prostate: Role for FOXP1 in the transcriptional regulation of TPß during monocyte-macrophage differentiation.

Inflammation is linked to prostate cancer (PCa) and to other diseases of the prostate. The prostanoid thromboxane (TX)A2 is a pro-inflammatory mediator implicated in several prostatic diseases, including PCa. TXA2 signals through the TPα and TPß isoforms of the T Prostanoid receptor (TP) which exhibit several functional differences and transcriptionally regulated by distinct promoters Prm1 and Prm3, respectively, within the TBXA2R gene. This study examined the expression of TPα and TPß in inflammatory infiltrates within human prostate tissue. Strikingly, TPß expression was detected in 94% of infiltrates, including in B- and T-lymphocytes and macrophages. In contrast, TPα was more variably expressed and, where present, expression was mainly confined to macrophages. To gain molecular insight into these findings, expression of TPα and TPß was evaluated as a function of monocyte-to-macrophage differentiation in THP-1 cells. Expression of both TPα and TPß was upregulated following phorbol-12-myristate-13-acetate (PMA)-induced differentiation of monocytic THP-1 to their macrophage lineage. Furthermore, FOXP1, an essential transcriptional regulator down-regulated during monocyte-to-macrophage differentiation, was identified as a key trans-acting factor regulating TPß expression through Prm3 in THP-1 cells. Knockdown of FOXP1 increased TPß, but not TPα, expression in THP-1 cells, while genetic reporter and chromatin immunoprecipitation (ChIP) analyses established that FOXP1 exerts its repressive effect on TPß through binding to four cis-elements within Prm3. Collectively, FOXP1 functions as a transcriptional repressor of TPß in monocytes. This repression is lifted in differentiated macrophages, allowing for upregulation of TPß expression and possibly accounting for the prominent expression of TPß in prostate tissue-resident macrophages.

Considering axiological integrity: a methodological analysis of qualitative evidence syntheses, and its implications for health professions education.

Qualitative evidence synthesis (QES) is a suite of methodologies that combine qualitative techniques with the synthesis of qualitative knowledge. They are particularly suited to medical education as these approaches pool findings from original qualitative studies, whilst paying attention to context and theoretical development. Although increasingly sophisticated use is being made of qualitative primary research methodologies in health professions education (HPE) the use of secondary qualitative reviews in HPE remains underdeveloped. This study examined QES methods applied to clinical humanism in healthcare as a way of advancing thinking around the use of QES in HPE in general. A systematic search strategy identified 49 reviews that fulfilled the inclusion criteria. Meta-study was used to develop an analytic summary of methodological characteristics, the role of theory, and the synthetic processes used in QES reviews. Fifteen reviews used a defined methodology, and 17 clearly explained the processes that led from data extraction to synthesis. Eight reviews adopted a specific theoretical perspective. Authors rarely described their reflexive relationship with their data. Epistemological positions tended to be implied rather than explicit. Twenty-five reviews included some form of quality appraisal, although it was often unclear how authors acted on its results. Reviewers under-reported qualitative approaches in their review methodologies, and tended to focus on elements such as systematicity and checklist quality appraisal that were more germane to quantitative evidence synthesis. A core concern was that the axiological (value) dimensions of the source materials were rarely considered let alone accommodated in the synthesis techniques used. QES can be used in HPE research but only with careful attention to maintaining axiological integrity.

Management of pulmonary nodules in head and neck cancer patients - Our experience and interpretation of the British Thoracic Society Guidelines.

BACKGROUND: and purpose of the study: The frequency of lung nodules in the head and neck cancer population is unknown, currently the only guidance available recommends following local policy. The aim of this study was to determine the incidence of pulmonary nodules in our head and neck cancer group and interpret the recently updated British Thoracic Society (BTS) Lung Nodule Guidelines in a head and neck cancer setting. METHODS: 100 patients were diagnosed with head and neck cancer between July 2013-March 2014, clinico-pathological, demographic and radiological data was extracted from the electronic records. Images with lung findings were re-reviewed by a single consultant radiologist for patients with lung pathology on the initial staging CT report. RESULTS: Twenty patients (20%) had discreet pulmonary findings on CT. Eleven (11%) had lung nodules, 6 (6%) had lesions suspicious for metastasis and 3 (3%) had co-incidental bronchogenic primary cancers. These patients were re-imaged between 6 and 18 months and in 1 patient the previously identified 7 mm nodule had progressed to 16 mm at 1 year. There was no set follow up imaging protocol used. CONCLUSION: The MDT in NHS Lothian has reviewed the BTS guidance and now has a local policy for the management of lung nodules in head and neck cancer patients. Lung Nodules in the head and neck cancer population are common >10%. Higher risk patients with larger nodules should be risk assessed with validated assessment tools. PET-CT has a place in the assessment of lung nodules when risk of malignancy is high.

Texas Team: Academic Progression and IOM Toolkit.

BACKGROUND: The Institute of Medicine (IOM) Future of Nursing report, identified eight recommendations for nursing to improve health care for all Americans. AIM: The Texas Team for Advancing Health Through Nursing embraced the challenge of implementing the recommendations through two diverse projects. METHOD: One group conducted a broad, online survey of leadership, practice, and academia, focusing on the IOM recommendations. The other focused specifically on academic progression through the use of CABNET (Consortium for Advancing Baccalaureate Nursing Education in Texas) articulation agreements. RESULTS: The survey revealed a lack of knowledge and understanding of the IOM recommendations, prompting development of an online IOM toolkit. The articulation agreements provide a clear pathway for students to the RN-to-BSN degree students. CONCLUSION: The toolkit and articulation agreements provide rich resources for implementation of the IOM recommendations.

Laser ablation-inductively coupled plasma mass spectrometry: an emerging technology for detecting rare cells in tissue sections.

Administering immunoregulatory cells to patients as medicinal agents is a potentially revolutionary approach to the treatment of immunologically mediated diseases. Presently, there are no satisfactory, clinically applicable methods of tracking human cells in patients with adequate spatial resolution and target cell specificity over a sufficient period of time. Laser ablation-inductively coupled plasma mass spectrometry (LA-ICP-MS) represents a potential solution to the problem of detecting very rare cells in tissues. In this article, this exquisitely sensitive technique is applied to the tracking of gold-labeled human regulatory macrophages (Mregs) in immunodeficient mice. Optimal conditions for labeling Mregs with 50-nm gold particles were investigated by exposing Mregs in culture to variable concentrations of label: Mregs incubated with 3.5 × 10(9) particles/ml for 1 h incorporated an average of 3.39 × 10(8) Au atoms/cell without loss of cell viability. Analysis of single, gold-labeled Mregs by LA-ICP-MS registered an average of 1.9 × 10(5) counts/cell. Under these conditions, 100% labeling efficiency was achieved, and label was retained by Mregs for ≥36 h. Gold-labeled Mregs adhered to glass surfaces; after 24 h of culture, it was possible to colabel these cells with human-specific (154)Sm-tagged anti-HLA-DR or (174)Yb-tagged anti-CD45 mAbs. Following injection into immunodeficient mice, signals from gold-labeled human Mregs could be detected in mouse lung, liver, and spleen for at least 7 d by solution-based inductively coupled plasma mass spectrometry and LA-ICP-MS. These promising results indicate that LA-ICP-MS tissue imaging has great potential as an analytical technique in immunology.

Content and discontent: a qualitative exploration of obstacles to elearning engagement in medical students.

BACKGROUND: Elearning is ubiquitous in healthcare professions education. Its equivalence to 'traditional' educational delivery methods is well established. There is a research imperative to clarify when and how to use elearning most effectively to mitigate the potential of it becoming merely a 'disruptive technology.' Research has begun to broadly identify challenges encountered by elearning users. In this study, we explore in depth the perceived obstacles to elearning engagement amongst medical students. Sensitising concepts of achievement emotions and the cognitive demands of multi-tasking highlight why students' deeply emotional responses to elearning may be so important in their learning. METHODS: This study used focus groups as a data collection tool. A purposeful sample of 31 participated. Iterative data gathering and analysis phases employed a constant comparative approach to generate themes firmly grounded in participant experience. RESULTS: Key themes that emerged from the data included a sense of injustice, passivity and a feeling of being 'lost at sea'. The actual content of the elearning resource provided important context. CONCLUSIONS: The identified themes have strong emotional foundations. These responses, interpreted through the lens of achievement emotions, have not previously been described. Appreciation of their importance is of benefit to educators involved in curriculum development or delivery.

Transcriptional regulation of the human thromboxane A2 receptor gene by Wilms' tumor (WT)1 and hypermethylated in cancer (HIC) 1 in prostate and breast cancers.

The prostanoid thromboxane (TX) A(2) plays a central role in hemostasis and is increasingly implicated in neoplastic disease, including prostate and breast cancers. In humans, TXA(2) signals through the TPα and TPß isoforms of the T prostanoid receptor, two structurally related receptors transcriptionally regulated by distinct promoters, Prm1 and Prm3, respectively, within the TP gene. Focusing on TPα, the current study investigated its expression and transcriptional regulation through Prm1 in prostate and breast cancers. Expression of TPα correlated with increasing prostate and breast tissue tumor grade while the TXA(2) mimetic U46619 promoted both proliferation and migration of the respective prostate (PC3) and breast (MCF-7 and MDA-MD-231) derived-carcinoma cell lines. Through 5' deletional and genetic reporter analyses, several functional upstream repressor regions (URRs) were identified within Prm1 in PC3, MCF-7 and MDA-MB-231 cells while site-directed mutagenesis identified the tumor suppressors Wilms' tumor (WT)1 and hypermethylated in cancer (HIC) 1 as the trans-acting factors regulating those repressor regions. Chromatin immunoprecipitation (ChIP) studies confirmed that WT1 binds in vivo to multiple GC-enriched WT1 cis-elements within the URRs of Prm1 in PC3, MCF-7 and MDA-MB-231 cells. Furthermore, ChIP analyses established that HIC1 binds in vivo to the HIC1((b))cis-element within Prm1 in PC3 and MCF-7 cells but not in the MDA-MB-231 carcinoma line. Collectively, these data establish that WT1 and HIC1, both tumor suppressors implicated in prostate and breast cancers, transcriptionally repress TPα expression and thereby provide a strong genetic basis for understanding the role of TXA2 in the progression of certain human cancers.