Tracking genomic cancer evolution for precision medicine: the lung TRACERx study.

The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types.

Incorporating patient partner scores into high stakes assessment: an observational study into opinions and attitudes.

BACKGROUND: Volunteer patients (also known as patient partners (PPs)) play a vital role in undergraduate healthcare curricula. They frequently take part in objective structured clinical examinations (OSCE) and rate aspects of students' performance. However, the inclusion and weighting of PP marks varies, while attitudes and opinions regarding how (and if) they should contribute towards the pass/fail outcome are uncertain. METHODS: A prospective observational study was conducted to explore beliefs of PPs regarding inclusion of their scores in a high stakes undergraduate OSCE in a single UK medical school. All PPs delivering components of the local MBChB curriculum were asked to participate in the questionnaire study. Quantitative and qualitative data were analysed using descriptive statistics and framework analysis respectively. RESULTS: Fifty out of 160 (31% response rate) PPs completed the questionnaire; 70% had participated in a final year OSCE. Thirty (60%) felt their marks should be incorporated into a student's overall score, while 28% were uncertain. The main reasons for inclusion were recognition of the patient perspective (31%) and their ability to assess attitudes and professionalism (27%), while reasons against inclusion included lack of PP qualification/training (18%) and concerns relating to consistency (14%). The majority of PPs were uncertain what proportion of the total mark they should contribute, although many felt that 5-10% of the total score was reasonable. Most respondents (70%) felt that globally low PP scores should not result in an automatic fail and many (62%) acknowledged that prior to mark inclusion, further training was required. CONCLUSION: These data show that most respondents considered it reasonable to "formalise their expertise" by contributing marks in the overall assessment of students in a high stakes OSCE, although what proportion they believe this should represent was variable. Some expressed concerns that using marks towards progress decisions may alter PP response patterns. It would therefore seem reasonable to compare outcomes (i.e. pass/fail status) using historical data both incorporating and not incorporating PP marks to evaluate the effects of doing so. Further attention to existing PP training programmes is also required in order to provide clear instruction on how to globally rate students to ensure validity and consistency.

Twelve tips for enhancing anatomy teaching and learning using radiology.

Anatomy is a keystone of many healthcare curricula and its understanding fundamental to patient care. The close relationship between clinical radiology and anatomy is well recognised and expanding. Imaging resources can be effectively integrated alongside traditional methods for learning anatomy in a resource efficient manner in order to enhance anatomy teaching. The following 12 tips have been divided into imaging tips, clinical tips and educational tips and offer practical advice and suggestions for designing and integrating radiological resources across the curriculum.

Cardiac sarcoid or arrhythmogenic right ventricular cardiomyopathy: a role for positron emission tomography (PET)?

We present a case of cardiac sarcoidosis of insidious onset mimicking arrhythmogenic right ventricular cardiomyopathy. Our patient initially presented with systemic sarcoidosis but later developed palpitations. The similarity in clinical presentation and cardiac magnetic resonance findings in both conditions posed a challenge in differentiating between the two in the absence of histological diagnosis. We highlighted the role of positron emission tomography in aiding a diagnosis.

Tablet versus paper marking in assessment: feedback matters.

BACKGROUND: The Objective Structured Clinical Examination (OSCE) is a cornerstone in healthcare assessment. As a potential tool for providing learner-centred feedback on a large scale, the use of tablet devices has been proposed for the recording of OSCE marks, moving away from the traditional, paper-based checklist. METHODS: Examiner-recorded comments were collated from successive first year formative and summative OSCE examinations, with paper-based checklists used in 2012 and iPad-based checklists used in 2013. A total of 558 and 498 examiner-candidate interactions took place in the January OSCE examinations, and 1402 and 1344 for the May OSCE examination for 2012 and 2013 respectively. Examiner comments were analyzed for quantity and quality. A tool was developed and validated to assess the quality of the comments left by examiners for use as feedback (Kappa = 0.625). RESULTS: A direct comparison of paper-based checklists and iPad-recorded examinations showed an increase in the quantity of comments left from 41 to 51 % (+ 10 %). Furthermore, there was an increase in the number of comments left for students deemed 'borderline': + 22 %. In terms of the quality of the comments for feedback, there was a significant improvement (p < 0.001) between comments left in written-recorded and iPad-recorded examinations. CONCLUSIONS: iPad-marked examinations resulted in a greater quantity and quality of examiner comment for use as feedback, particularly for students performing less well, enabling tutors to direct further learning for these students.

Optimization and Reproducibility of Aortic Valve 18F-Fluoride Positron Emission Tomography in Patients With Aortic Stenosis.

BACKGROUND: 18F-Fluoride positron emission tomography (PET) and computed tomography (CT) can measure disease activity and progression in aortic stenosis. Our objectives were to optimize the methodology, analysis, and scan-rescan reproducibility of aortic valve 18F-fluoride PET-CT imaging. METHODS AND RESULTS: Fifteen patients with aortic stenosis underwent repeated 18F-fluoride PET-CT. We compared nongated PET and noncontrast CT, with a modified approach that incorporated contrast CT and ECG-gated PET. We explored a range of image analysis techniques, including estimation of blood-pool activity at differing vascular sites and a most diseased segment approach. Contrast-enhanced ECG-gated PET-CT permitted localization of 18F-fluoride uptake to individual valve leaflets. Uptake was most commonly observed at sites of maximal mechanical stress: the leaflet tips and the commissures. Scan-rescan reproducibility was markedly improved using enhanced analysis techniques leading to a reduction in percentage error from ±63% to ±10% (tissue to background ratio MDS mean of 1.55, bias -0.05, limits of agreement -0·20 to +0·11). CONCLUSIONS: Optimized 18F-fluoride PET-CT allows reproducible localization of calcification activity to different regions of the aortic valve leaflet and commonly to areas of increased mechanical stress. This technique holds major promise in improving our understanding of the pathophysiology of aortic stenosis and as a biomarker end point in clinical trials of novel therapies. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02132026.

Reduced interleukin-18 levels in BAL specimens from patients with asthma compared to patients with sarcoidosis and healthy control subjects.

STUDY OBJECTIVES: To investigate whether differing airway interleukin (IL)-18 levels may be implicated in the pathogenesis of asthma and sarcoidosis. SETTING: University teaching hospital. PATIENTS AND METHODS: IL-18 levels were measured in BAL fluid and in the supernatant of lipopolysaccharide (LPS)-stimulated alveolar macrophages obtained by BAL from 15 patients with sarcoidosis, 11 patients with asthma, and 13 healthy subjects. We also examined the relationship between IL-18 levels and macrophage and lymphocyte concentrations in BAL fluid. IL-18 was measured using an in-house enzyme-linked immunosorbent assay. RESULTS: IL-18 levels were significantly lower in BAL fluid from patients with asthma (median, 0.0 pg/mL; interquartile range, 0.0 to 0.0 pg/mL) compared to patients with sarcoidosis (median, 222.0 pg/10(6); interquartile range, 110 to 340 pg/mL; p = 0.009, Mann Whitney rank-sum test) and healthy control subjects (median, 162 pg/mL; interquartile range, 38 to 203 pg/mL; p = 0.025, Mann Whitney rank-sum test). Individual analyses comparing IL-18 levels with BAL macrophage counts, and IL-18 with lymphocyte counts in the three groups showed no correlation between these indexes. The mean levels of IL-18 in unstimulated macrophage supernatants were 410 pg/10(6) cells for patients with asthma, 723.4 pg/10(6) cells for patients with sarcoidosis, and 734.8 pg/10(6) cells for healthy control subjects (p > 0.05). Stimulated macrophages from patients with sarcoidosis responded with increasing amounts of IL-18 at lower doses of LPS than macrophages from healthy control subjects or patients with asthma. CONCLUSION: Our findings suggest that inherently low levels of IL-18 may be associated with the pathogenesis of asthmatic airway inflammation.

A novel 3D stereoscopic anatomy tutorial.

BACKGROUND: Advancement in technology is an important driver for the evolution of the medical curriculum. With continued criticism of medical students' knowledge of anatomy, further investigation into adjuncts for anatomy teaching seems appropriate. This project sought to create an interactive 3D stereoscopic tutorial to bridge the teaching of anatomy and pathology. METHODS: Anonymised computed tomography (CT) scans were collected of a normal aorta and a ruptured abdominal aortic aneurysm. These scans were rendered into 3D stereoscopic images using open-source software. These images were then annotated with interactive labels and buttons to access information on normal aortic anatomy and the clinical details of abdominal aortic aneurysms. A total of 183 first-year medical students viewed the tutorial, and 160 gave feedback (87%). RESULTS: The students found the 3D system aided their understanding of anatomy and pathology (93 versus 3%), and provided an advantage when compared with current anatomy classes (93 versus 1%). The students highlighted the musculoskeletal system and cerebral vasculature as areas for future 3D visualisation. Of the responders, 96 per cent felt that the curriculum would benefit from further 3D stereoscopic anatomy/pathology tutorials. DISCUSSION: This technology has the exciting potential to use the radiographic libraries in hospitals for medical education. The computer software, however, has some limitations at present. It is not able to effectively distinguish between tissues of similar densities. Furthermore, not all tissues are amenable to CT scanning of a high enough resolution for presentation. Despite these limitations, the software continues to advance and is capable of producing very high quality anatomy images.

Community pharmacists' perceptions of barriers to communication with migrants.

OBJECTIVES: Effective communication by pharmacists is essential to ensure patient safety in terms of provision and use of medications by patients. Global migration trends mean community pharmacists increasingly encounter patients with a variety of first languages. The aim of this study was to explore community pharmacists' perceptions of communication barriers during the provision of care to A8 (nationals from central/Eastern European states) migrants. METHODS: A qualitative face-to-face interview study of purposively sampled community pharmacists, North East Scotland. KEY FINDINGS: Participants (n = 14) identified a number of barriers to providing optimal care to A8 migrants including: communication (information gathering and giving); confidentiality when using family/friends as translators; the impact of patient healthcare expectations on communication and the length of the consultation; and frustration with the process of the consultation. CONCLUSIONS: Several barriers were specific to A8 migrants but most seemed pertinent to any group with limited English proficiency and reflect those found in studies of healthcare professionals caring for more traditional UK migrant populations. Further research is needed using objective outcome measures, such as consultation recordings, to measure the impact of these perceived barriers on pharmacist-patient consultations. Language and cultural barriers impact on the quality of pharmacist-patient communication and thus may have patient safety and pharmacist training implications.

Massive spontaneous hemothorax during the immediate postpartum period.

Nontraumatic hemothorax is a rare cause of postpartum respiratory distress. We present a case of massive spontaneous hemothorax, which presented during the immediate postpartum period and was initially treated as pulmonary embolism. Further investigation revealed a tiny lung nodule: although pulmonary arteriovenous malformation was considered, the imaging appearances tended to counter this interpretation. Eventually, in the absence of another cause for spontaneous hemothorax, on either clinical or imaging grounds, we diagnosed spontaneous arteriovenous malformation. Its management is discussed herein.

A survey of clinical teaching fellowships in UK medical schools.

CONTEXT: Undergraduate medical education in the UK has changed considerably over the last decade. One development has involved the creation of teaching-specific posts for junior doctors by medical schools. These posts are generally termed 'clinical teaching fellowships', but it is not known how many of them exist, or whether they are similar in terms of educational activities, professional development, and research and clinical experience opportunities. METHODS: Teaching deans in all UK medical schools were sent a questionnaire relating to clinical teaching fellowships, and were asked to distribute a second set of different questionnaires to their clinical teaching fellows, which were to be returned to the authors separately. RESULTS: A total of 28 deans and 46 fellows responded. Fifteen medical schools had clinical teaching fellows and there appeared to be a total of 77 such posts in the UK. There was little uniformity in the activities undertaken within the posts. Deans who employed clinical teaching fellows were unanimously positive regarding the posts. Fellows were generally positive but expressed reservations relating to approval for postgraduate training, career development, deterioration in clinical skills, financial disincentives, credibility within one's own specialty, and provision of training and support. CONCLUSIONS: Clinical teaching fellow posts are generally enjoyed by fellows and valued by deans. Fellows carry out differing duties and their training in medical education is variable. The posts can be unstructured and may lack credibility to doctors outside medical education. Providing specific structured training in medical education, recognised at a national level, would help deal with these concerns.

Good for them or good for us? The role of academic guidance interviews.

CONTEXT: Weak students may pass unnoticed through their undergraduate programme until they fail a summative assessment. Early recognition and support of struggling students is crucial if they are to avoid subsequent failure at high stakes assessments. METHODS: We introduced a whole-class formative assessment 5 months before a summative assessment. Subsequently, we supported poorly performing students with academic guidance interviews and remedial support. RESULTS: The programme was evaluated by questionnaires issued to staff and students involved in the guidance interviews, and by recording the performance of students who had failed the formative assessment in the subsequent summative assessment. CONCLUSIONS: We conclude that the rescue of failing students requires early recognition and tailored intervention, with support for all participants.