Cardiogenic shock trajectories: is the Society for Cardiovascular Angiography and Interventions definition the right one?

PURPOSE OF REVIEW: We review the current Society for Cardiovascular Angiography and Interventions (SCAI) cardiogenic shock classification system and consider alternatives or iterations that may enhance our current descriptions of cardiogenic shock trajectory. RECENT FINDINGS: Several studies have identified the potential prognostic value of serial SCAI stage re-assessment, usually within the first 24 h of shock onset, to predict deterioration and clinical outcomes across shock causes. In parallel, numerous registry-based analyses support the utility of a more precise assessment of the macrocirculation and microcirculation, leveraging invasive haemodynamics, imaging and additional laboratory and clinical markers. The emergence of machine learning and artificial intelligence capabilities offers the opportunity to integrate multimodal data into high fidelity, real-time metrics to more precisely define trajectory and inform our therapeutic decision making. SUMMARY: Whilst the SCAI staging system remains a pivotal tool in cardiogenic shock assessment, communication and reassessment, it is vital that the sophistication with which we measure and assess shock trajectory evolves in parallel our understanding of the complexity and variability of clinical course and clinical outcomes.

In perspective: the patient at the heart of research in acute cardiovascular care.

Patient and public involvement is a fundamental part of research design and is increasingly required by research funders and regulators. In addition to the moral and ethical arguments in its favour, it has the potential to improve the accessibility and transparency of research and to optimize study recruitment and retention. Whilst clinical trials in acute cardiovascular care have traditionally focussed on 'hard' outcomes, such as mortality or major adverse cardiovascular events, there is increasing recognition that these fail to capture the full breadth of patient experience. Patient-centred outcomes aim to measure things of greater value to patients, using validated tools to quantify symptoms, patient self-reports, or novel outcomes such as days alive and outside hospital. This In Perspective commentary explores the rationale behind patient and public involvement and the background to and evidence supporting the use of patient-centred outcomes and discusses potential challenges and how they can be mitigated.

Cognitive Predictors of Delirium on Long-Term Follow-Up after TIA and Stroke: Population-Based Cohort Study.

INTRODUCTION: TIA and stroke cause cognitive impairment with a typical "vascular" pattern, including prominent frontal/executive deficits. Cognitive impairment is associated with increased delirium risk and the few available data suggest that executive dysfunction is important. We therefore determined the predictive value of both severity and pattern of cognitive deficits for delirium on long-term follow-up after TIA/stroke. METHODS: Surviving TIA/stroke participants on October 1, 2013, in the Oxford Vascular Study (OXVASC) were assessed prospectively for delirium during all hospitalizations over the subsequent 6 months. Associations between OXVASC pre-admission mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores, and delirium during hospitalizations on follow-up were determined using logistic regression adjusted for covariates, including demographic factors, history of depression, baseline stroke severity, and admission illness severity. RESULTS: Among 1,565 TIA/stroke survivors, 158 patients (mean/SD age = 79.2/11.5 years) had ≥1 admission and 59 (37%) had ≥1 delirium episode. Mean/SD time between baseline TIA/stroke and admission was 4.7/3.6 years and between most recent OXVASC cognitive testing and admission was 1.7/1.8 years. MMSE and MoCA scores were associated with delirium: odds ratio (OR) = 1.16 (95% CI 1.07-1.27, p < 0.0001 per point decrease in MMSE) and OR = 1.20 (1.11-1.30, p < 0.0001 MoCA) and associations were robust to adjustment for all covariates, including stroke severity: OR = 1.11 (1.01-1.22, p = 0.03, MMSE) and OR = 1.15 (1.05-1.25, p = 0.003, MoCA). All 10 subtests on the MoCA and 4/11 on the MMSE were significantly associated with delirium with highest predictive value for frontal/executive and recall domains. CONCLUSIONS: Cognitive impairment of increasing severity after TIA/stroke predisposed to delirium particularly deficits in frontal/executive domains and recall. Long-term risk of delirium should be considered as part of the overall cerebrovascular disease burden.

Intravenous prostanoids in systemic sclerosis-associated pulmonary arterial hypertension: a single-centre experience.

OBJECTIVES: The current study evaluates survival rates among SSc-associated pulmonary arterial hypertension (SSc-PAH) patients on i.v. prostanoids, and short-term impact of i.v. prostanoids on clinical and haemodynamic parameters. METHODS: Baseline demographics, invasive and non-invasive data, European Society of Cardiology (ESC) score and REVEAL score of 81 SSc-PAH patients (median age 61 years, interquartile range 54-67 years, 84% females) were prospectively recorded, from November 2006 till November 2020, before initiation of i.v. prostanoids, and at first formal reassessment. Survival data were retrieved from National Health Service Spine and hospital databases. RESULTS: Significant improvements in clinical and haemodynamic parameters in response to i.v. prostanoid therapy were documented. Functional class (FC) (16.6% improved by 1FC, P =0.041), mean pulmonary arterial pressure (-6.5 mmHg, P =0.036), pulmonary vascular resistance (-2.6 WU, P =0.012), cardiac index (Q/m2) (+0.7 l/min/m2, P =0.003) and mixed venous oxygen saturation (SvO2) (+3%, P =0.036) improved. Estimated survival for CTD-PAH patients on i.v. prostanoids was 64%, 31% and 18%, at 1 year, 3 years and 5 years, respectively. Independent baseline predictors of mortality were older age (HR: 1.043, 95% CI: 1.011-1.075, P =0.007), higher N-terminal pro-brain natriuretic peptide levels (HR: 2.191, 95% CI: 1.131-4.243, P =0.020), and lower SvO2 levels (HR: 0.962, 95% CI: 0.926-0.998, P =0.039). High ESC risk or high and very high REVEAL score was associated with significantly worse survival compared with patients with lower risk scores, both at baseline and when reassessed after a median of 6.5 months. CONCLUSIONS: Survival among SSc-PAH patients on i.v. prostanoids remains poor, risk scoring at baseline and after 6.5 months of therapy improves prognostication.

Utility of white matter disease and atrophy on routinely acquired brain imaging for prediction of long-term delirium risk: population-based cohort study.

BACKGROUND: brain imaging done as part of standard care may have clinical utility beyond its immediate indication. Using delirium as an exemplar, we determined the predictive value of baseline brain imaging variables [white matter changes (WMC) and atrophy] for delirium risk on long-term follow-up after transient ischemic attack (TIA)/stroke in a population-based cohort study. METHODS: surviving TIA/stroke participants in the Oxford Vascular Study (OXVASC) were assessed prospectively for delirium during all hospitalisations over 6 months (2013-14). Using logistic regression, independent associations were determined between baseline OXVASC computed tomography or magnetic resonance brain imaging measures of WMC and cerebral atrophy (none/mild versus moderate/severe) and delirium adjusted for age, sex, baseline stroke severity, depression, illness severity and pre-admission cognition. RESULTS: among 1,565 TIA/stroke survivors with 194 hospital admissions (158 patients, mean/standard deviation age at admission = 79.2/11.5 years), delirium occurred in 59 (37%). WMC and atrophy on baseline imaging were associated with delirium [odds ratio (OR) = 3.41, 1.21-5.85, P = 0.001 and OR = 2.50, 1.23-5.08, P = 0.01 (unadjusted) and OR = 2.67, 1.21-5.85, P = 0.02 and OR = 2.18, 1.00-4.73, P = 0.05 (adjusted age and sex)]. Associations were strengthened when analyses were restricted to patients hospitalised within 5 years of baseline brain imaging [OR = 6.04, 2.39-15.24, P < 0.0001 and OR = 4.64, 1.46-14.82, P = 0.009 (unadjusted)] but only WMC remained significant after adjustment for all covariates including pre-admission cognition (OR = 4.83, 1.29-18.13, P = 0.02 for Mini-Mental State Examination and OR = 5.15, 1.26-21.09, P = 0.02 for Montreal Cognitive Assessment). CONCLUSIONS: WMC and atrophy on brain imaging done up to 5 years earlier predicted delirium and may have clinical utility in risk stratification. Associations with WMC but not atrophy were independent of pre-admission cognitive impairment.

Myopericarditis and thyroiditis: a case report.

BACKGROUND: Hyperthyroidism is commonly associated with adverse cardiovascular effects, including tachydysrhythmia, heart failure, and hypertension, although the association between hyperthyroidism and myopericarditis is restricted to a small number of case reports. CASE SUMMARY: A 45-year-old Caucasian male with no past medical history was admitted with chest pain. The electrocardiogram demonstrated diffuse ST-segment elevation, the troponin T rose, and he was diagnosed with myopericarditis. He was noted to have markedly deranged thyroid function tests and a diagnosis of hyperthyroidism secondary to Graves' disease was made. He was treated with Bisoprolol, Carbimazole, Prednisolone, Ibuprofen, and Colchicine, his symptoms resolved rapidly and he was discharged. Five weeks later he re-presented with similar symptoms and recurrent pericarditis was diagnosed. His symptoms settled with a repeat course of steroids. DISCUSSION: We hypothesize that there may be an underappreciated link between hyperthyroidism and myopericarditis. Potential pathophysiological mechanisms include viral infection, autoimmunity, or changes in myocardial fat metabolism. Suggested management consists of a combination of current guidelines for the treatment of hyperthyroidism and pericardial disease, with attention to certain disease-drug interactions. Further research is required to evaluate the true incidence of hyperthyroidism-associated myopericarditis, elucidate its pathophysiology and instruct management.

Anakinra treats fulminant myocarditis from Neisseria meningitidis septicaemia and haemophagocytic lymphohistiocytosis: a case report.

BACKGROUND: Fulminant myocarditis is a life-threatening condition characterized by acute cardiac dysfunction requiring pharmacological or mechanical circulatory support. Haemophagocytic lymphohistiocytosis (HLH) is an uncommon state of immune dysregulation and overactivation. Inflammation mediated by interleukin-1 (IL-1) is thought to play a role in the pathogenesis of myocarditis and HLH, and there is some evidence that the IL-1 receptor antagonist Anakinra may play a role in treating both these conditions. CASE SUMMARY: A 26-year-old previously healthy male presented to the Emergency Department with a 3-day history of malaise, headache, vomiting, diarrhoea, and fever. He was profoundly hypotensive on arrival, diagnosed with septic shock, and commenced on broad-spectrum antibiotics and vasopressors. Blood tests showed lymphopenia, thrombocytopenia, low fibrinogen and elevated high sensitivity troponin T, ferritin, and C-reactive protein. Echocardiography demonstrated severely impaired biventricular systolic function and a diagnosis of fulminant myocarditis was made. His condition deteriorated and he required intubation and additional inotropic support. A diagnosis of HLH was made and he was commenced on Anakinra and Methylprednisolone. His condition improved rapidly thereafter. Polymerase chain reaction testing subsequently confirmed infection with Neisseria meningitidis. DISCUSSION: In this case, fulminant myocarditis and HLH were life-threatening manifestations of meningococcal septicaemia, and the patient's condition improved rapidly following administration of the IL-1 receptor antagonist Anakinra. These complications should be borne in mind in septic patients with marked haemodynamic instability and multiorgan dysfunction, and treatment with Anakinra should be considered in those who fail to respond to conventional therapy.

Poor Bone Quality is Associated With Greater Arterial Stiffness: Insights From the UK Biobank.

Osteoporosis and ischemic heart disease (IHD) represent important public health problems. Existing research suggests an association between the two conditions beyond that attributable to shared risk factors, with a potentially causal relationship. In this study, we tested the association of bone speed of sound (SOS) from quantitative heel ultrasound with (i) measures of arterial compliance from cardiovascular magnetic resonance (aortic distensibility [AD]); (ii) finger photoplethysmography (arterial stiffness index [ASI]); and (iii) incident myocardial infarction and IHD mortality in the UK Biobank cohort. We considered the potential mediating effect of a range of blood biomarkers and cardiometabolic morbidities and evaluated differential relationships by sex, menopause status, smoking, diabetes, and obesity. Furthermore, we considered whether associations with arterial compliance explained association of SOS with ischemic cardiovascular outcomes. Higher SOS was associated with lower arterial compliance by both ASI and AD for both men and women. The relationship was most consistent with ASI, likely relating to larger sample size available for this variable (n = 159,542 versus n = 18,229). There was no clear evidence of differential relationship by menopause, smoking, diabetes, or body mass index (BMI). Blood biomarkers appeared important in mediating the association for both men and women, but with different directions of effect and did not fully explain the observed effects. In fully adjusted models, higher SOS was associated with significantly lower IHD mortality in men, but less robustly in women. The association of SOS with ASI did not explain this observation. In conclusion, our findings support a positive association between bone and vascular health with consistent patterns of association in men and women. The underlying mechanisms are complex and appear to vary by sex. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Clinical characteristics and outcomes of critically ill patients with COVID-19 admitted to an intensive care unit in London: A prospective observational cohort study.

BACKGROUND: Cohorts of severely ill patients with COVID-19 have been described in several countries around the globe, but to date there have been few published reports from the United Kingdom (UK). Understanding the characteristics of the affected population admitted to intensive care units (ICUs) in the UK is crucial to inform clinical decision making, research and planning for future waves of infection. METHODS: We conducted a prospective observational cohort study of all patients with COVID-19 admitted to a large UK ICU from March to May 2020 with follow-up to June 2020. Data were collected from health records using a standardised template. We used multivariable logistic regression to analyse the factors associated with ICU survival. RESULTS: Of the 156 patients included, 112 (72%) were male, 89 (57%) were overweight or obese, 68 (44%) were from ethnic minorities, and 89 (57%) were aged over 60 years of age. 136 (87%) received mechanical ventilation, 77 (57% of those intubated) were placed in the prone position and 95 (70% of those intubated) received neuromuscular blockade. 154 (99%) patients required cardiovascular support and 44 (28%) required renal replacement therapy. Of the 130 patients with completed ICU episodes, 38 (29%) died and 92 (71%) were discharged alive from ICU. In multivariable models, age (OR 1.13 [95% CI 1.07-1.21]), obesity (OR 3.06 [95% CI 1.16-8.74]), lowest P/F ratio on the first day of admission (OR 0.82 [95% CI 0.67-0.98]) and PaCO2 (OR 1.52 [95% CI 1.01-2.39]) were independently associated with ICU death. CONCLUSIONS: Age, obesity and severity of respiratory failure were key determinants of survival in this cohort. Multiorgan failure was prevalent. These findings are important for guiding future research and should be taken into consideration during future healthcare planning in the UK.

Impact of a system-wide multicomponent intervention on administrative diagnostic coding for delirium and other cognitive frailty syndromes: observational prospective study.

BACKGROUND: We determined the impact of a system-wide multicomponent intervention to improve recognition and documentation of cognitive frailty syndromes on hospital administrative coding for delirium. METHODS: A multicomponent intervention including introduction of structured patient assessment including cognitive/delirium screen, regular audit/feedback and educational seminars was undertaken (2012-17). Sensitivity and specificity of administrative International Classification of Diseases, 10th revision (ICD-10) delirium codes for the gold standard of prospectively clinically diagnosed delirium were calculated in consecutive patients admitted to acute medicine over five 8-week cycles (2010-18). RESULTS: Among 1,281 consecutive unselected admissions to acute medicine overall (mean / standard deviation age = 70.0/19.2 years; n=615 (48.0%) male), 320 had clinical delirium diagnosis (n=220 delirium only; n=100 delirium on dementia). Sensitivity of delirium coding increased from 12.8% (95% confidence interval (CI) 5.6-26.7) in 2010 to 60.2% (95% CI 50.1-69.7; ptrend<0.0001) in 2018 while specificity remained at >99% throughout. CONCLUSION: A multicomponent intervention increased sensitivity of hospital administrative diagnostic coding for delirium almost six-fold without increasing the false positive diagnosis rate.

Automated localization and quality control of the aorta in cine CMR can significantly accelerate processing of the UK Biobank population data.

INTRODUCTION: Aortic distensibility can be calculated using semi-automated methods to segment the aortic lumen on cine CMR (Cardiovascular Magnetic Resonance) images. However, these methods require visual quality control and manual localization of the region of interest (ROI) of ascending (AA) and proximal descending (PDA) aorta, which limit the analysis in large-scale population-based studies. Using 5100 scans from UK Biobank, this study sought to develop and validate a fully automated method to 1) detect and locate the ROIs of AA and PDA, and 2) provide a quality control mechanism. METHODS: The automated AA and PDA detection-localization algorithm followed these steps: 1) foreground segmentation; 2) detection of candidate ROIs by Circular Hough Transform (CHT); 3) spatial, histogram and shape feature extraction for candidate ROIs; 4) AA and PDA detection using Random Forest (RF); 5) quality control based on RF detection probability. To provide the ground truth, overall image quality (IQ = 0-3 from poor to good) and aortic locations were visually assessed by 13 observers. The automated algorithm was trained on 1200 scans and Dice Similarity Coefficient (DSC) was used to calculate the agreement between ground truth and automatically detected ROIs. RESULTS: The automated algorithm was tested on 3900 scans. Detection accuracy was 99.4% for AA and 99.8% for PDA. Aorta localization showed excellent agreement with the ground truth, with DSC ≥ 0.9 in 94.8% of AA (DSC = 0.97 ± 0.04) and 99.5% of PDA cases (DSC = 0.98 ± 0.03). AA×PDA detection probabilities could discriminate scans with IQ ≥ 1 from those severely corrupted by artefacts (AUC = 90.6%). If scans with detection probability < 0.75 were excluded (350 scans), the algorithm was able to correctly detect and localize AA and PDA in all the remaining 3550 scans (100% accuracy). CONCLUSION: The proposed method for automated AA and PDA localization was extremely accurate and the automatically derived detection probabilities provided a robust mechanism to detect low quality scans for further human review. Applying the proposed localization and quality control techniques promises at least a ten-fold reduction in human involvement without sacrificing any accuracy.

Association Between Ambient Air Pollution and Cardiac Morpho-Functional Phenotypes: Insights From the UK Biobank Population Imaging Study.

Background: Exposure to ambient air pollution is strongly associated with increased cardiovascular morbidity and mortality. Little is known about the influence of air pollutants on cardiac structure and function. We aim to investigate the relationship between chronic past exposure to traffic-related pollutants and the cardiac chamber volume, ejection fraction, and left ventricular remodeling patterns after accounting for potential confounders. Methods: Exposure to ambient air pollutants including particulate matter and nitrogen dioxide was estimated from the Land Use Regression models for the years between 2005 and 2010. Cardiac parameters were measured from cardiovascular magnetic resonance imaging studies of 3920 individuals free from pre-existing cardiovascular disease in the UK Biobank population study. The median (interquartile range) duration between the year of exposure estimate and the imaging visit was 5.2 (0.6) years. We fitted multivariable linear regression models to investigate the relationship between cardiac parameters and traffic-related pollutants after adjusting for various confounders. Results: The studied cohort was 62±7 years old, and 46% were men. In fully adjusted models, particulate matter with an aerodynamic diameter <2.5 µm concentration was significantly associated with larger left ventricular end-diastolic volume and end-systolic volume (effect size = 0.82%, 95% CI, 0.09-1.55%, P=0.027; and effect size = 1.28%, 95% CI, 0.15-2.43%, P=0.027, respectively, per interquartile range increment in particulate matter with an aerodynamic diameter <2.5 µm) and right ventricular end-diastolic volume (effect size = 0.85%, 95% CI, 0.12-1.58%, P=0.023, per interquartile range increment in particulate matter with an aerodynamic diameter <2.5 µm). Likewise, higher nitrogen dioxide concentration was associated with larger biventricular volume. Distance from the major roads was the only metric associated with lower left ventricular mass (effect size = -0.74%, 95% CI, -1.3% to -0.18%, P=0.01, per interquartile range increment). Neither left and right atrial phenotypes nor left ventricular geometric remodeling patterns were influenced by the ambient pollutants. Conclusions: In a large asymptomatic population with no prevalent cardiovascular disease, higher past exposure to particulate matter with an aerodynamic diameter <2.5 µm and nitrogen dioxide was associated with cardiac ventricular dilatation, a marker of adverse remodeling that often precedes heart failure development.

Variation in lung function and alterations in cardiac structure and function-Analysis of the UK Biobank cardiovascular magnetic resonance imaging substudy.

BACKGROUND: Reduced lung function is common and associated with increased cardiovascular morbidity and mortality, even in asymptomatic individuals without diagnosed respiratory disease. Previous studies have identified relationships between lung function and cardiovascular structure in individuals with pulmonary disease, but the relationships in those free from diagnosed cardiorespiratory disease have not been fully explored. METHODS: UK Biobank is a prospective cohort study of community participants in the United Kingdom. Individuals self-reported demographics and co-morbidities, and a subset underwent cardiovascular magnetic resonance (CMR) imaging and spirometry. CMR images were analysed to derive ventricular volumes and mass. The relationships between CMR-derived measures and spirometry and age were modelled with multivariable linear regression, taking account of the effects of possible confounders. RESULTS: Data were available for 4,975 individuals, and after exclusion of those with pre-existing cardiorespiratory disease and unacceptable spirometry, 1,406 were included in the analyses. In fully-adjusted multivariable linear models lower FEV1 and FVC were associated with smaller left ventricular end-diastolic (-5.21ml per standard deviation (SD) change in FEV1, -5.69ml per SD change in FVC), end-systolic (-2.34ml, -2.56ml) and stroke volumes (-2.85ml, -3.11ml); right ventricular end-diastolic (-5.62ml, -5.84ml), end-systolic (-2.47ml, -2.46ml) and stroke volumes (-3.13ml, -3.36ml); and with lower left ventricular mass (-2.29g, -2.46g). Changes of comparable magnitude and direction were observed per decade increase in age. CONCLUSIONS: This study shows that reduced FEV1 and FVC are associated with smaller ventricular volumes and reduced ventricular mass. The changes seen per standard deviation change in FEV1 and FVC are comparable to one decade of ageing.

The impact of menopausal hormone therapy (MHT) on cardiac structure and function: Insights from the UK Biobank imaging enhancement study.

BACKGROUND: The effect of menopausal hormone therapy (MHT)-previously known as hormone replacement therapy-on cardiovascular health remains unclear and controversial. This cross-sectional study examined the impact of MHT on left ventricular (LV) and left atrial (LA) structure and function, alterations in which are markers of subclinical cardiovascular disease, in a population-based cohort. METHODS: Post-menopausal women who had never used MHT and those who had used MHT ≥3 years participating in the UK Biobank who had undergone cardiovascular magnetic resonance (CMR) imaging and free of known cardiovascular disease were included. Multivariable linear regression was performed to examine the relationship between cardiac parameters and MHT use ≥3 years. To explore whether MHT use on each of the cardiac outcomes differed by age, multivariable regression models were constructed with a cross-product of age and MHT fitted as an interaction term. RESULTS: Of 1604 post-menopausal women, 513 (32%) had used MHT ≥3 years. In the MHT cohort, median age at menopause was 50 (IQR: 45-52) and median duration of MHT was 8 years. In the non-MHT cohort, median age at menopause was 51 (IQR: 48-53). MHT use was associated with significantly lower LV end-diastolic volume (122.8 ml vs 119.8 ml, effect size = -2.4%, 95% CI: -4.2% to -0.5%; p = 0.013) and LA maximal volume (60.2 ml vs 57.5 ml, effect size = -4.5%, 95% CI: -7.8% to -1.0%; p = 0.012). There was no significant difference in LV mass. MHT use significantly modified the effect between age and CMR parameters; MHT users had greater decrements in LV end-diastolic volume, LV end-systolic volume and LA maximal volume with advancing age. CONCLUSIONS: MHT use was not associated with adverse, subclinical changes in cardiac structure and function. Indeed, significantly smaller LV and LA chamber volumes were observed which have been linked to favourable cardiovascular outcomes. These findings represent a novel approach to examining MHT's effect on the cardiovascular system.

Meta-analysis of transcriptomic datasets identifies genes enriched in the mammalian circadian pacemaker.

The master circadian pacemaker in mammals is located in the suprachiasmatic nuclei (SCN) which regulate physiology and behaviour, as well as coordinating peripheral clocks throughout the body. Investigating the function of the SCN has often focused on the identification of rhythmically expressed genes. However, not all genes critical for SCN function are rhythmically expressed. An alternative strategy is to characterize those genes that are selectively enriched in the SCN. Here, we examined the transcriptome of the SCN and whole brain (WB) of mice using meta-analysis of publicly deposited data across a range of microarray platforms and RNA-Seq data. A total of 79 microarrays were used (24 SCN and 55 WB samples, 4 different microarray platforms), alongside 17 RNA-Seq data files (7 SCN and 10 WB). 31 684 MGI gene symbols had data for at least one platform. Meta-analysis using a random effects model for weighting individual effect sizes (derived from differential expression between relevant SCN and WB samples) reliably detected known SCN markers. SCN-enriched transcripts identified in this study provide novel insights into SCN function, including identifying genes which may play key roles in SCN physiology or provide SCN-specific drivers.

Leadership and management in UK medical school curricula.

Purpose Although medical leadership and management (MLM) is increasingly being recognised as important to improving healthcare outcomes, little is understood about current training of medical students in MLM skills and behaviours in the UK. The paper aims to discuss these issues. Design/methodology/approach This qualitative study used validated structured interviews with expert faculty members from medical schools across the UK to ascertain MLM framework integration, teaching methods employed, evaluation methods and barriers to improvement. Findings Data were collected from 25 of the 33 UK medical schools (76 per cent response rate), with 23/25 reporting that MLM content is included in their curriculum. More medical schools assessed MLM competencies on admission than at any other time of the curriculum. Only 12 schools had evaluated MLM teaching at the time of data collection. The majority of medical schools reported barriers, including overfilled curricula and reluctance of staff to teach. Whilst 88 per cent of schools planned to increase MLM content over the next two years, there was a lack of consensus on proposed teaching content and methods. Research limitations/implications There is widespread inclusion of MLM in UK medical schools' curricula, despite the existence of barriers. This study identified substantial heterogeneity in MLM teaching and assessment methods which does not meet students' desired modes of delivery. Examples of national undergraduate MLM teaching exist worldwide, and lessons can be taken from these. Originality/value This is the first national evaluation of MLM in undergraduate medical school curricula in the UK, highlighting continuing challenges with executing MLM content despite numerous frameworks and international examples of successful execution.

Methodological Factors in Determining Risk of Dementia After Transient Ischemic Attack and Stroke: (III) Applicability of Cognitive Tests.

BACKGROUND AND PURPOSE: Cognitive assessment is recommended after stroke but there are few data on the applicability of short cognitive tests to the full spectrum of patients. We therefore determined the rates, causes, and associates of untestability in a population-based study of all transient ischemic attack (TIA) and stroke. METHODS: Patients with TIA or stroke prospectively recruited (2002-2007) into the Oxford Vascular Study had ≥1 short cognitive test (mini-mental state examination, telephone interview of cognitive status, Montreal cognitive assessment, and abbreviated mental test score) at baseline and on follow-up to 5 years. RESULTS: Among 1097 consecutive assessed survivors (mean: age/SD, 74.8/12.1 years; 378 TIA), numbers testable with a short cognitive test at baseline, 1, 6, 12, and 60 months were 835/1097 (76%), 778/947 (82%), 756/857 (88%), 692/792 (87%), and 472/567 (83%). Eighty-eight percent (331/378) of assessed patients with TIA were testable at baseline compared with only 46% (133/290) of major stroke (P<0.001). Untestability was also associated with older age, premorbid dependency, death on follow-up, and with both pre- and postevent dementia (all P<0.01). Untestability (and problems with testing) were commonly caused by acute stroke effects at baseline (153/262 [58%]: dysphasia/anarthria/hemiparesis=84 [32%], drowsiness=58 [22%], and acute confusion=11 [4%]), whereas sensory deficits caused relatively more problems with testing at later time points (24/63 [38%] at 5 years). CONCLUSIONS: Substantial numbers of patients with TIA and stroke are untestable with short cognitive tests. Future studies should report data on untestable patients and those with problems with testing in whom the likelihood of dementia is high.