Validating a theory of planned behavior questionnaire for assessing changes in professional behaviors of medical students.

Introduction: Teaching professionalism is a fundamental aspect of medical undergraduate education, delivering important domains of professional attitudes, ethics, and behaviors. The effects of educational interventions can be assessed by measuring the change in such domains, but validated assessment tools for these professionalism domains are lacking. In this study, we constructed and conducted expert validation of a modified theory of planned behavior (TPB) questionnaire to assess changes in professional behaviors (PBs) in medical students. Methods: To validate that, we modified an existing TPB questionnaire, and an 18-item questionnaire was subjected to expert panel evaluation using the content validation method. The clarity and relevance of items were assessed using a four-point rating scale (i.e., 1 = not relevant to 4 = highly relevant). Ratings of experts and free-text comments were analyzed. Quantitative evaluation of relevance and clarity was undertaken through analyses of the Item-level Content Validity Index (I-CVI) and Scale-level Content Validity Index (S-CVI). A qualitative assessment of the comments of experts was conducted to refine items, any disagreements were discussed, and a consensus decision was developed among authors for item changes. Results: Quantitative evaluation of the Item-level Content Validity Index (I-CVI) scored 0.9-1 for relevance and 0.7-1 for clarity. Qualitative evaluation resulted in (i) changes to the wording of items (e.g., choices such as "worthless/worthwhile" were replaced with "not important/important"); and (ii) suggestion of the addition of social media in the construct of subjective norms. Discussion: The proposed tool exhibits content validity and can assess TPB constructs in professionalism education. This study of content validity may help to ensure the modified TPB questionnaire accurately measures the TPB constructs, ensuring its effectiveness in accurately measuring the TPB constructs for PB in diversified educational medical institutions.

Association between statin therapy dose intensity and radiation cardiotoxicity in non-small cell lung cancer: Results from the NI-HEART study.

INTRODUCTION: Radiation cardiotoxicity is a dose-limiting toxicity and major survivorship issue for patients with non-small cell lung cancer (NSCLC) completing curative-intent radiotherapy, however patients' cardiovascular baseline is not routinely optimised prior to treatment. In this study we examined the impact of statin therapy on overall survival and post-radiotherapy cardiac events. METHODS: Patients treated between 2015-2020 at a regional center were identified. Clinical notes were interrogated for baseline patient, tumor and cardiac details, and both follow-up cancer control and cardiac events. Three cardiologists verified cardiac events. Radiotherapy planning scans were retrieved for application of validated deep learning-based autosegmentation. Pre-specified Cox regression analyses were generated with varying degrees of adjustment for overall survival. Fine and Gray regression for the risk of cardiac events, accounting for the competing risk of death and cardiac covariables was undertaken. RESULTS: Statin therapy was prescribed to 59% of the 478 included patients. The majority (88%) of patients not prescribed a statin had at least one indication for statin therapy according to cardiovascular guidelines. In total, 340 patients (71%) died and 79 patients (17%) experienced a cardiac event. High-intensity (HR 0.68, 95%CI 0.50-0.91, p = 0.012) and medium-intensity (HR 0.70, 95%CI 0.51-0.97, p = 0.033) statin therapy were associated with improved overall survival after adjustment for patient, cancer, treatment, response and cardiovascular clinical factors. There were no consistent differences in the rate or grade of cardiac events according to statin intensity. CONCLUSIONS: Statin therapy is associated with improved overall survival in patients receiving curative-intent radiotherapy for NSCLC, and there is evidence of a dose-response relationship. This study highlights the importance of a pre-treatment cardiovascular risk assessment in this cohort. Further studies are needed to examine if statin therapy is cardioprotective in patients undergoing treatment for NSCLC with considerable incidental cardiac radiation dose and a low baseline cardiac risk.

Risk and Management of Patients with Cancer and Heart Disease.

Cancer and cardiovascular disease are two of the leading causes of global mortality and morbidity. Medical research has generated powerful lifesaving treatments for patients with cancer; however, such treatments may sometimes be at the expense of the patient's myocardium, leading to heart failure. Anti-cancer drugs, including anthracyclines, can result in deleterious cardiac effects, significantly impacting patients' functional capacity, mental well-being, and quality of life. Recognizing this, recent international guidelines and expert papers published recommendations on risk stratification and care delivery, including that of cardio-oncology services. This review will summarize key evidence with a focus on anthracycline therapy, providing clinical guidance for the non-oncology professional caring for a patient with cancer and heart failure.

Circulating biomarkers for management of cancer therapeutics-related cardiac dysfunction.

Cancer therapeutics-related cardiac dysfunction (CTRCD) has emerged as a major cause of morbidity and mortality in cancer survivors. Effective clinical management of CTRCD is impeded by a lack of sensitive diagnostic and prognostic strategies. Circulating molecular markers could potentially address this need as they are often indicative of cardiac stress before cardiac damage can be detected clinically. A growing understanding of the underlying physiological mechanisms for CTRCD has inspired research efforts to identify novel pathophysiologically relevant biomarkers that may also guide development of cardio-protective therapeutic approaches. The purpose of this review is to evaluate current circulating biomarkers of cardiac stress and their potential role in diagnosis and management of CTRCD. We also discuss some emerging avenues for CTRCD-focused biomarker investigations.

Survival of cancer patients with pre-existing heart disease.

BACKGROUND: While cancer outcomes have improved over time, in Northern Ireland they continue to lag behind those of many other developed economies. The role of comorbid conditions has been suggested as a potential contributory factor in this but issues of data comparability across jurisdictions has inhibited efforts to explore relationships. We use data from a single jurisdiction of the UK using data from - the Northern Ireland Cancer Registry (NICR), to examine the association between mortality (all-cause and cancer specific) and pre-existing cardiovascular diseases among patients with cancer. MATERIALS AND METHODS: All patients diagnosed with cancer (excluding non-melanoma skin cancer) between 2011 and 2014 were identified from Registry records. Those with a pre-existing diagnosis of cardiovascular diseases were identified by record linkage with patient hospital discharge data using ICD10 codes. Survival following diagnosis was examined using descriptive statistics and Cox proportional hazards regression analyses. Analyses examined all-cause mortality and cancer specific mortality for lung, colorectal, breast and prostate cancer. As well as cardiovascular diseases, regression models controlled for age, gender (where appropriate), deprivation (as quintiles), stage at diagnosis and other comorbidities. RESULTS: Almost 35,000 incident cancer cases were diagnosed during the study period of which approximately 23% had a prior heart condition. The pan-cancer hazard ratio for death in the presence of pre-existing cardiovascular diseases was 1.28 (95% CI: 1.18-1.40). All-cause and cancer specific mortality was higher for patients with cardiovascular diseases across lung, female breast, prostate and colorectal cancer groups after controlling for age, gender (where appropriate), deprivation (as quintiles), stage at diagnosis and other comorbidities. CONCLUSION: Pre-existing morbidity may restrict the treatment of cancer for many patients. In this cohort, cancer patients with pre-existing cardiovascular diseases had poorer outcomes than those without cardiovascular diseases. A high prevalence of cardiovascular diseases may contribute to poorer cancer outcomes at a national level.

BSE and BCOS Guideline for Transthoracic Echocardiographic Assessment of Adult Cancer Patients Receiving Anthracyclines and/or Trastuzumab.

The subspecialty of cardio-oncology aims to reduce cardiovascular morbidity and mortality in patients with cancer or following cancer treatment. Cancer therapy can lead to a variety of cardiovascular complications, including left ventricular systolic dysfunction, pericardial disease, and valvular heart disease. Echocardiography is a key diagnostic imaging tool in the diagnosis and surveillance for many of these complications. The baseline assessment and subsequent surveillance of patients undergoing treatment with anthracyclines and/or human epidermal growth factor receptor (HER) 2-positive targeted treatment (e.g., trastuzumab and pertuzumab) form a significant proportion of cardio-oncology patients undergoing echocardiography. This guideline from the British Society of Echocardiography and British Cardio-Oncology Society outlines a protocol for baseline and surveillance echocardiography of patients undergoing treatment with anthracyclines and/or trastuzumab. The methodology for acquisition of images and the advantages and disadvantages of techniques are discussed. Echocardiographic definitions for considering cancer therapeutics-related cardiac dysfunction are also presented.

British Society for Echocardiography and British Cardio-Oncology Society guideline for transthoracic echocardiographic assessment of adult cancer patients receiving anthracyclines and/or trastuzumab.

The subspecialty of cardio-oncology aims to reduce cardiovascular morbidity and mortality in patients with cancer or following cancer treatment. Cancer therapy can lead to a variety of cardiovascular complications, including left ventricular systolic dysfunction, pericardial disease, and valvular heart disease. Echocardiography is a key diagnostic imaging tool in the diagnosis and surveillance for many of these complications. The baseline assessment and subsequent surveillance of patients undergoing treatment with anthracyclines and/or human epidermal growth factor (EGF) receptor (HER) 2-positive targeted treatment (e.g. trastuzumab and pertuzumab) form a significant proportion of cardio-oncology patients undergoing echocardiography. This guideline from the British Society of Echocardiography and British Cardio-Oncology Society outlines a protocol for baseline and surveillance echocardiography of patients undergoing treatment with anthracyclines and/or trastuzumab. The methodology for acquisition of images and the advantages and disadvantages of techniques are discussed. Echocardiographic definitions for considering cancer therapeutics-related cardiac dysfunction are also presented.

Association of reduced inner retinal thicknesses with chronic kidney disease.

BACKGROUND: Tissue derived biomarkers may offer utility as indicators of accumulated damage. Reduced thickness of retinal neuronal tissue and the vascular choroid have previously been associated with vascular damage and diabetes. We evaluated associations between retinal thickness, retinal microvascular and choroidal measures, and renal function in a population with a high burden of comorbidity. METHODS: Participants were recruited from nuclear cardiology or renal medicine clinics. Retinal and choroidal thickness were measured from spectral-domain optical coherence tomograms. Retinal microvascular parameters were assessed from digital fundus photographs using a semi-automated software package. MAIN OUTCOME MEASURE: Chronic kidney disease (CKD) categorised as: CKD stages 1-2, eGFR ≥60 ml/min/1.73m2; CKD stage 3, eGFR 30-59 ml/min/1.73m2, and CKD stages 4-5, eGFR ≤29 ml/min/1.73m2. RESULTS: Participants (n = 241) had a mean age of 65 years and a mean eGFR of 66.9 ml/min/1.73m2. Thirty-nine % of the cohort had diabetes and 27% were using diuretics. Thinning of the inner retina and changes to its microvascular blood supply were associated with lower eGFR and CKD stages 4 and 5, while no associations were found between the outer retinal layers or their choroidal blood supply and CKD of any stage. These associations remained following adjustment for age, mean arterial blood pressure, diabetes status, low-density lipoprotein, body mass index, and sex. CONCLUSIONS: Inner retinal thinning and retinal microvascular variation is associated with advanced CKD (stages 4 & 5) independent of important confounding factors, but not with earlier stage CKD (stage 3) and, therefore, its utility as a biomarker for early CKD is not supported in this study.

Protective effects of intermedin/adrenomedullin-2 in a cellular model of human pulmonary arterial hypertension.

Proliferation of pulmonary fibroblasts (PF) and distal migration of smooth muscle cells (PSM) are hallmarks of pulmonary arterial hypertension (PAH). Intermedin/adrenomedullin-2 (IMD/AM2) belongs to the Calcitonin Gene-Related Peptide (CGRP)/Adrenomedullin (AM) superfamily. These peptides act via Calcitonin-Like Receptors (CLR) combined with one of three Receptor activity-modifying proteins (RAMPs). IMD/AM2 is a potent pulmonary vasodilator in animal studies. The aim was to describe expression of IMD/AM2, AM and receptor components in human pulmonary vascular cells and to elucidate effects of IMD/AM2 on human PSM migration and PF proliferation. Gene expression was detected by immunofluorescence, immunoblotting and qRT-PCR. Normotension and hypertension were simulated by applying pulsatile mechanical stretch (Flexcell® apparatus). Viable cell numbers were determined by dye exclusion. PSM chemotaxis was measured via Dunn chamber. IMD/AM2 protein was co-expressed with AM and their receptor components in pulmonary artery and microvascular endothelial (PAEC, PMVEC) and non-endothelial cells (PF, PSM), and localised to vesicles. IMD/AM2 was secreted under basal conditions, most abundantly from PF and PMVEC. Secretion from PF and PSM was enhanced by stretch. IMD/AM2 mRNA expression increased in response to hypertensive stretch of PSM. IMD/AM2 inhibited PDGF (10-7 M)-mediated PSM migration maximally at 3 × 10-10 M and PF proliferation maximally at 3 × 10-9 M. Angiotensin II (5 × 10-8 M), normotensive and hypertensive stretch augmented PF proliferation. IMD/AM2 (10-9 M) abolished the proliferative effects of Angiotensin II and normotensive stretch and attenuated the proliferative effect of hypertensive stretch alone and combined with angiotensin II. These findings indicate an important counter-regulatory role for IMD/AM2 in PAH.

The Risk of Cardiovascular Disease in Prostate Cancer Patients Receiving Androgen Deprivation Therapies.

BACKGROUND: Androgen deprivation therapy (ADT), with a proven role in prostate cancer management, has been associated with various cardiovascular diseases. However, few studies have investigated these associations by type of ADT, particularly for newer ADTs such as the gonadotropin-releasing hormone (GnRH) antagonist degarelix. We investigated the risk of cardiovascular disease by type of ADT in a real-world setting. METHODS: We identified men newly diagnosed with prostate cancer, from 2009 to 2015, from the Scottish Cancer Registry and ADTs from the nationwide Prescribing Information System. Cardiovascular events were based upon hospitalization (from hospital records) or death from cardiovascular disease (from death records). We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular events with time-varying ADT exposure, comparing ADT users with untreated patients, after adjusting for potential confounders, including prior cardiovascular disease. RESULTS: The cohort contained 20,216 prostate cancer patients, followed for 73,570 person-years, during which there were 3,853 cardiovascular events. ADT was associated with a 30% increase in cardiovascular events (adjusted HR = 1.3; 95% CI = 1.2, 1.4). This reflected increases in cardiovascular events associated with GnRH agonists (adjusted HR = 1.3; 95% CI = 1.2, 1.4), degarelix (adjusted HR = 1.5; 95% CI = 1.2, 1.9), but not bicalutamide monotherapy (adjusted HR = 1.0; 95% CI = 0.82, 1.3). CONCLUSIONS: There were increased risks of cardiovascular disease with the use of GnRH agonists and degarelix, but not with bicalutamide monotherapy. This is the first study to observe increased cardiovascular risks with degarelix, but the cause of this association is unclear and merits further investigation.

Serum amyloid A levels are associated with polymorphic variants in the serum amyloid A 1 and 2 genes.

BACKGROUND: Serum amyloid A (SAA) is secreted by liver hepatocytes in response to increased inflammation whereupon it associates with high-density lipoprotein (HDL) and alters the protein and lipid composition of HDL negating some of its anti-atherogenic properties. AIMS: To identify variants within the SAA gene that may be associated with SAA levels and/or cardiovascular disease (CVD). METHODS: We identified exonic variants within the SAA genes by deoxyribonucleic acid (DNA) Sanger sequencing. We tested the association between SAA variants and serum SAA levels in 246 individuals with and without CVD. RESULTS: Increased SAA was associated with rs2468844 (beta [ß] = 1.73; confidence intervals [CI], 1.14-1.75; p = 0.01), rs1136747 (ß = 1.53 (CI, 1.11-1.73); p = 0.01) and rs149926073 (ß = 3.37 (CI, 1.70-4.00); p = 0.02), while rs1136745 was significantly associated with decreased SAA levels (ß = 0.70 (CI, 0.53-0.94); p = 0.02). Homozygous individuals with the SAA1.3 haplotype had significantly lower levels of SAA compared with those with SAA1.1 or SAA1.5 (ß = 0.43 (CI, 0.22-0.85); p = 0.02) while SAA1.3/1.5 heterozygotes had significantly higher SAA levels compared with those homozygous for SAA1.1 (ß = 2.58 (CI, 1.19-5.57); p = 0.02). CONCLUSIONS: We have identified novel genetic variants in the SAA genes associated with SAA levels, a biomarker of inflammation and chronic disease. The utility of SAA as a biomarker for inflammation and chronic disease may be influenced by underlying genetic variation in baseline levels.

Improving the Diagnosis of Culprit Left Circumflex Occlusion With Acute Myocardial Infarction in Patients With a Nondiagnostic 12-Lead ECG at Presentation: A Retrospective Cohort Study.

Background Left circumflex culprit is often missed by the standard 12-lead ECG . Extended lead systems (body surface potential map [ BSPM ]) should improve the diagnosis of culprit left circumflex stenosis with myocardial infarction. Methods and Results Retrospective analysis of a hospital research registry (August 2000-August 2010) comprising consecutive patients with (1) ischemic-type chest pain at rest; (2) 12-lead ECG and 80-lead BSPM at first medical contact; and (3) cardiac troponin-T 12 hours after symptom onset and/or creatine kinase MB fraction, were undertaken. Enrolled in the cohort were patients with culprit left circumflex stenosis (thrombolysis in myocardial infarction flow grade 0/1) at angiography. Acute myocardial infarction AMI was defined as cardiac troponin-T ≥0.1 µg/L and/or creatine kinase MB fraction >2 upper limits of normal. Enrolled were 482 patients: 168 had exclusion criteria. Of the remaining 314 (age 64±11 years; 62% male), 254 (81%) had AMI : of these, 231 had BSPM STE -sensitivity 0.91, specificity 0.72, positive predictive value 0.93, negative predictive value 0.65, and c-statistic 0.803 for AMI ( P<0.001). Of those with BSPM STE and AMI (n=231), STE was most frequently detected in the posterior (n=111, 48%), lateral (n=53, 23%), inferior (n=39, 17%), and right ventricular (n=21, 9%) territories. Conclusions Among patients with 12-lead ECG non-ST-segment-elevation myocardial infarction and culprit left circumflex stenosis, initial BSPM identifies ST-segment elevation beyond the territory of the 12-lead ECG . Greater use of the BSPM may result in earlier identification of AMI , which may lead to more rapid reperfusion.

Dietary Micronutrient Intake and Micronutrient Status in Patients With Chronic Stable Heart Failure: An Observational Study.

BACKGROUND: Observational studies suggest that patients with heart failure have a tendency to a reduced status of a number of micronutrients and that this may be associated with an adverse prognosis. A small number of studies also suggest that patients with heart failure may have reduced dietary intake of micronutrients, a possible mechanism for reduced status. OBJECTIVE: The aims of this study were to assess dietary micronutrient intake and micronutrient status in a group of patients with heart failure. METHODS: Dietary intake was assessed in 79 outpatients with chronic stable heart failure with a reduced ejection fraction using a validated food frequency questionnaire. Blood concentrations of a number of micronutrients, including vitamin D, were measured in fasting blood samples, drawn at the time of food frequency questionnaire completion. RESULTS: More than 20% of patients reported intakes less than the reference nutrient intake or recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, and iodine. More than 5% of patients reported intakes less than the lower reference nutrient intake or minimum recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, selenium, and iodine. Vitamin D deficiency (plasma total 25-hydroxy-vitamin D concentration <50 nmol/L) was observed in 75.6% of patients. CONCLUSIONS: Vitamin D deficiency was common in this group of patients with heart failure. Based on self-reported dietary intake, a substantial number of individuals may not have been consuming enough vitamin D and a modest number of individuals may not have been consuming enough riboflavin, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, or iodine to meet their dietary needs.

Epicardial potentials computed from the body surface potential map using inverse electrocardiography and an individualised torso model improve sensitivity for acute myocardial infarction diagnosis.

INTRODUCTION: Epicardial potentials (EPs) derived from the body surface potential map (BSPM) improve acute myocardial infarction (AMI) diagnosis. In this study, we compared EPs derived from the 80-lead BSPM using a standard thoracic volume conductor model (TVCM) with those derived using a patient-specific torso model (PSTM) based on body mass index (BMI). METHODS: Consecutive patients presenting to both the emergency department and pre-hospital coronary care unit between August 2009 and August 2011 with acute ischaemic-type chest pain at rest were enrolled. At first medical contact, 12-lead electrocardiograms and BSPMs were recorded. The BMI for each patient was calculated. Cardiac troponin T (cTnT) was sampled 12 hours after symptom onset. Patients were excluded from analysis if they had any ECG confounders to interpretation of the ST-segment. A cardiologist assessed the 12-lead ECG for ST-segment elevation myocardial infarction by Minnesota criteria and the BSPM. BSPM ST-elevation (STE) was ⩾0.2 mV in anterior, ⩾0.1 mV in lateral, inferior, right ventricular or high right anterior and ⩾0.05 mV in posterior territories. To derive EPs, the BSPM data were interpolated to yield values at 352 nodes of a Dalhousie torso. Using an inverse solution based on the boundary element method, EPs at 98 cardiac nodes positioned within a standard TVCM were derived. The TVCM was then scaled to produce a PSTM using a model developed from computed tomography in 48 patients of varying BMIs, and EPs were recalculated. EPs >0.3 mV defined STE. A cardiologist blinded to both the 12-lead ECG and BSPM interpreted the EP map. AMI was defined as cTnT ⩾0.1 µg/L. RESULTS: Enrolled were 400 patients (age 62 ± 13 years; 57% male); 80 patients had exclusion criteria. Of the remaining 320 patients, the BMI was an average of 27.8 ± 5.6 kg/m2. Of these, 180 (56%) had AMI. Overall, 132 had Minnesota STE on ECG (sensitivity 65%, specificity 89%) and 160 had BSPM STE (sensitivity 81%, specificity 90%). EP STE occurred in 165 patients using TVCM (sensitivity 88%, specificity 95%; p < 0.001) and in 206 patients using PSTM (sensitivity 98%, specificity 79%; p < 0.001). Of those with AMI by cTnT and EPs ⩽0.3 mV using TVCM ( n = 22), 18 (82%) patients had EPs >0.3 mV when an individualised PSTM was used. CONCLUSION: Among patients presenting with ischaemic-type chest pain at rest, EPs derived from BSPM using a novel PSTM significantly improve sensitivity for AMI diagnosis.

Plasma levels of intermedin (adrenomedullin-2) in healthy human volunteers and patients with heart failure.

Intermedin/adrenomedullin-2 (IMD) is a member of the adrenomedullin/CGRP peptide family. Less is known about the distribution of IMD than for other family members within the mammalian cardiovascular system, particularly in humans. The aim was to evaluate plasma IMD levels in healthy subjects and patients with chronic heart failure. IMD and its precursor fragments, preproIMD(25-56) and preproIMD(57-92), were measured by radioimmunoassay in 75 healthy subjects and levels of IMD were also compared to those of adrenomedullin (AM) and mid-region proadrenomedullin(45-92) (MRproAM(45-92)) in 19 patients with systolic heart failure (LVEF<45%). In healthy subjects, plasma levels (mean+SE) of IMD (6.3+0.6 pg ml(-1)) were lower than, but correlated with those of AM (25.8+1.8 pg ml(-1); r=0.49, p<0.001). Plasma preproIMD(25-56) (39.6+3.1 pg ml(-1)), preproIMD(57-92) (25.9+3.8 pg ml(-1)) and MRproAM(45-92) (200.2+6.7 pg ml(-1)) were greater than their respective bioactive peptides. IMD levels correlated positively with BMI but not age, and were elevated in heart failure (9.8+1.3 pg ml(-1), p<0.05), similarly to MRproAM(45-92) (329.5+41.9 pg ml(-1), p<0.001) and AM (56.8+10.9 pg ml(-1), p<0.01). IMD levels were greater in heart failure patients with concomitant renal impairment (11.3+1.8 pg ml(-1)) than those without (6.5+1.0 pg ml(-1); p<0.05). IMD and AM were greater in patients receiving submaximal compared with maximal heart failure drug therapy and were decreased after 6 months of cardiac resynchronization therapy. In conclusion, IMD is present in the plasma of healthy subjects less abundantly than AM, but is similarly correlated weakly with BMI. IMD levels are elevated in heart failure, especially with concomitant renal impairment, and tend to be reduced by high intensity drug or pacing therapy.

Endothelium-derived intermedin/adrenomedullin-2 protects human ventricular cardiomyocytes from ischaemia-reoxygenation injury predominantly via the AM1 receptor.

Application of intermedin/adrenomedullin-2 (IMD/AM-2) protects cultured human cardiac vascular cells and fibroblasts from oxidative stress and simulated ischaemia-reoxygenation injury (I-R), predominantly via adrenomedullin AM1 receptor involvement; similar protection had not been investigated previously in human cardiomyocytes (HCM). Expression of IMD, AM and their receptor components was studied in HCM. Receptor subtype involvement in protection by exogenous IMD against injury by simulated I-R was investigated using receptor component-specific siRNAs. Direct protection by endogenous IMD against HCM injury, both as an autocrine factor produced in HCM themselves and as a paracrine factor released from HCMEC co-cultured with HCM, was investigated using peptide-specific siRNA for IMD. IMD, AM and their receptor components (CLR, RAMPs1-3) were expressed in HCM. IMD 1nmol L(-1), applied either throughout ischaemia (3h) and re-oxygenation (1h) or during re-oxygenation (1h) alone, attenuated HCM injury (P<0.05); cell viabilities were 59% and 61% respectively vs. 39% in absence of IMD. Cytoskeletal disruption, protein carbonyl formation and caspase activity followed similar patterns. Pre-treatment (4 days) of HCM with CLR and RAMP2 siRNAs attenuated (P<0.05) protection by exogenous IMD. Pre-treatment of HCMEC with IMD (and AM) siRNA augmented (P<0.05) I-R injury: cell viabilities were 22% (and 32%) vs. 39% untreated HCMEC. Pre-treatment of HCM with IMD (and AM) siRNA did not augment HCM injury: cell viabilities were 37% (and 39%) vs. 39% untreated HCM. Co-culture with HCMEC conferred protection from injury on HCM; such protection was attenuated when HCMEC were pre-treated with IMD (but not AM) siRNA before co-culture. Although IMD is present in HCM, IMD derived from HCMEC and acting in a paracrine manner, predominantly via AM1 receptors, makes a marked contribution to cardiomyocyte protection by the endogenous peptide against acute I-R injury.

Serum- and HDL3-serum amyloid A and HDL3-LCAT activity are influenced by increased CVD-burden.

BACKGROUND: High density lipoproteins (HDL) protect against cardiovascular disease (CVD). However, increased serum amyloid-A (SAA) related inflammation may negate this property. This study investigated if SAA was related to CVD-burden. METHODS: Subjects referred to the rapid chest pain clinic (n = 240) had atherosclerotic burden assessed by cardiac computerised tomography angiography. Subjects were classified as: no-CVD (n = 106), non-obstructive-CVD, stenosis<50% (n = 58) or moderate/significant-CVD, stenosis ≥50% (n = 76). HDL was subfractionated into HDL2 and HDL3 by rapid-ultracentrifugation. SAA-concentration was measured by ELISA and lecithin cholesterol acyltransferase (LCAT) activity measured by a fluorimetric assay. RESULTS: We illustrated that serum-SAA and HDL3-SAA-concentration were higher and HDL3-LCAT-activity lower in the moderate/significant-CVD-group, compared to the no-CVD and non-obstructive-CVD-groups (percent differences: serum-SAA, +33% & +30%: HDL3-SAA, +65% and +39%: HDL3-LCAT, -6% & -3%; p < 0.05 for all comparisons). We also identified a positive correlation between serum-SAA and HDL3-SAA (r = 0.698; p < 0.001) and a negative correlation between HDL3-SAA and HDL3-LCAT-activity (r = -0.295; p = 0.003), while CVD-burden positively correlated with serum-SAA (r = 0.150; p < 0.05) and HDL3-SAA (r = 0.252; p < 0.001) and negatively correlated with HDL3-LCAT-activity (r = -0.182; p = 0.006). Additionally, multivariate regression analysis adjusted for age, gender, CRP and serum-SAA illustrated that HDL3-SAA was significantly associated with modifying CVD-risk of moderate/significant CVD-risk (p < 0.05). CONCLUSION: This study has demonstrated increased SAA-related inflammation in subjects with moderate/significant CVD-burden, which appeared to impact on the antiatherogenic potential of HDL. We suggest that SAA may be a useful biomarker to illustrate increased CVD-burden, although this requires further investigation.

The Essentials of Cardiac Computerized Tomography.

Cardiac computerized tomography (CT) has evolved from a research tool to an important diagnostic investigation in cardiology, and is now recommended in European, US, and UK guidelines. This review is designed to give the reader an overview of the current state of cardiac CT. The role of cardiac CT is multifaceted, and includes risk stratification, disease detection, coronary plaque quantification, defining congenital heart disease, planning for structural intervention, and, more recently, assessment of ischemia. This paper addresses basic principles as well as newer evidence.

A Reappraisal of the Safety and Cost-Effectiveness of Statin Therapy in Primary Prevention.

Statins are among the most investigated drugs of all time. There is now a wealth of evidence supporting their use in the primary and secondary prevention arenas. The reduction in event recurrence has since been demonstrated across all levels of risk and in elderly patients. As a result, it is now accepted practice for statins to be prescribed universally in secondary prevention unless contraindicated. The extension of this policy into the primary prevention setting is more problematic, with moral and financial issues arising from the long-term treatment of many young apparently healthy individuals. For these reasons it is necessary to prove not only the financial sustainability of such a strategy but also the long-term safety of statins and the degree of benefit that might be expected.

How should teaching on whole person medicine, including spiritual issues, be delivered in the undergraduate medical curriculum in the United Kingdom?

BACKGROUND: Although the General Medical Council recommends that United Kingdom medical students are taught 'whole person medicine', spiritual care is variably recognised within the curriculum. Data on teaching delivery and attainment of learning outcomes is lacking. This study ascertained views of Faculty and students about spiritual care and how to teach and assess competence in delivering such care. METHODS: A questionnaire comprising 28 questions exploring attitudes to whole person medicine, spirituality and illness, and training of healthcare staff in providing spiritual care was designed using a five-point Likert scale. Free text comments were studied by thematic analysis. The questionnaire was distributed to 1300 students and 106 Faculty at Queen's University Belfast Medical School. RESULTS: 351 responses (54 staff, 287 students; 25 %) were obtained. >90 % agreed that whole person medicine included physical, psychological and social components; 60 % supported inclusion of a spiritual component within the definition. Most supported availability of spiritual interventions for patients, including access to chaplains (71 %), counsellors (62 %), or members of the patient's faith community (59 %). 90 % felt that personal faith/spirituality was important to some patients and 60 % agreed that this influenced health. However 80 % felt that doctors should never/rarely share their own spiritual beliefs with patients and 67 % felt they should only do so when specifically invited. Most supported including training on provision of spiritual care within the curriculum; 40-50 % felt this should be optional and 40 % mandatory. Small group teaching was the favoured delivery method. 64 % felt that teaching should not be assessed, but among assessment methods, reflective portfolios were most favoured (30 %). Students tended to hold more polarised viewpoints but generally were more favourably disposed towards spiritual care than Faculty. Respecting patients' values and beliefs and the need for guidance in provision of spiritual care were identified in the free-text comments. CONCLUSIONS: Students and Faculty generally recognise a spiritual dimension to health and support provision of spiritual care to appropriate patients. There is lack of consensus whether this should be delivered by doctors or left to others. Spiritual issues impacting patient management should be included in the curriculum; agreement is lacking about how to deliver and assess.