Dietary biomarkers may help objectively assessing dietary pattern adherence. This study performed K-means clustering analysis on quantitative food diary data from a dietary intervention study. Standardised dietary data (134 food diaries) from 57 participants were K-means clustered stepwise until fully optimised and cross-validated. The primary endpoint was to develop distinct dietary clusters and to evaluate the performanceof 90 plasma metabolites. The secondary endpoint was to analyse the biomarker-food groups relationships from those distinct dietary patterns. The final two cluster models comprised of 6 specific food types. Cluster 1 included participants with higher intake of fruit and vegetables, legumes, fish and whole grain cereals, and lower intake of meat and sweet foods than Cluster 2. Ten plasma metabolites significantly differed between the clusters (p < 0.05; q < 0.05) with reasonable biomarker performance (receiver operating characteristic (ROC): 0.64-0.72). Docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), α-linolenic acid, citric acid and vitamin C were significantly higher in Cluster 1, whereas adrenic acid, osbond acid, cholesterol, dihomo-γ-linolenic acid (DGLA) and triglycerides were higher in Cluster 2. Five additional metabolites also showed significant differences (p < 0.02; q < 0.11) and were included: palmitic acid, tyrosine, β-carotene, α-carotene and betaine. The DHA-to-Osbond acid ratio was an optimal indicator distinguishing healthy from unhealthy dietary patterns (ROC: 0.78). Combining clustering and metabolite profiling methods effectively identifies biomarkers of particular dietary patterns and highlights several robust food-metabolite correlations.

Aims SCN5A-E1784K (c.5350G>A) is the most common variant associated with the long QT (LQTS) and Brugada syndromes (BrS). It can manifest variably as LQTS, BrS, and/or conduction disorders. This presents a challenge for risk stratification. We aimed to describe clinical and ECG characteristics and identify risk markers that associate with arrhythmic events. Methods and results We undertook a retrospective observational multicentre study of a large cohort of 231 subjects with SCN5A-E1784K from Europe, USA, and Japan. Comprehensive demographic and clinical data, including initial presentation ECG and follow-up, were collected. 'Lethal events' were defined as sudden death, non-fatal cardiac arrest, and documented sustained VT or VF. 'Cardiac events' were defined as arrhythmic syncope plus any lethal events. Clinical characteristics and ECG parameters corrected for age were investigated for association with lethal and/or cardiac events. Fourteen (6%) subjects experienced a lethal event and 45 (19%) a cardiac event. PR interval and QRS duration were associated with lethal and cardiac events. In multivariable models, both PR interval and QRS duration were associated with lethal events, but only QRS duration was associated with cardiac events. Only age-corrected QRS (rQRS) was associated with lethal and cardiac event-free survival from birth after correction for multiple testing. Conclusion Ventricular myocardial conduction appears likely to play a role in the risk of arrhythmic events in patients with SCN5A-E1784K. This provides an important opportunity for the personalization of management and has the potential to guide preventative therapies.

Background: Increasing fruit and vegetable (FV) consumption is associated with reduced cardiovascular disease risk in observational studies but with little evidence from randomised controlled trials (RCTs). The impact of concurrent pharmacological therapy is unknown. Objective: To pool data from six RCTs to examine the effect of increasing FV intake on blood pressure (BP) and lipid profile, also exploring whether effects differed by medication use. Design: Across trials, dietary intake was assessed by diet diaries or histories, lipids by routine biochemical methods and BP by automated monitors. Linear regression provided an estimate of the change in lipid profile or BP associated with a one portion increase in self-reported daily FV intake, with interaction terms fitted for medication use. Results: The pooled sample included a total of 554 participants (308 males and 246 females). Meta-analysis of regression coefficients revealed no significant change in either systolic or diastolic BP per portion FV increase, although there was significant heterogeneity across trials for systolic BP (I-2 = 73%). Neither adjusting for change in body mass index, nor analysis according to use of anti-hypertensive medication altered the relationship. There was no significant change in lipid profile per portion FV increase, although there was a significant reduction in total cholesterol among those not on lipid-lowering therapy (P < 0.05 after Bonferroni correction). Conclusion: Pooled analysis of six individual FV trials showed no impact of increasing intake on BP or lipids, but there was a total cholesterol-lowering effect in those not on lipid-lowering therapy.

Background Historically, high levels of morbidity and mortality have been associated with cardiovascular disease in the Northern Ireland population. Previously reported associations between single nucleotide polymorphisms (SNPs) and cardiovascular disease within other populations have not always been consistent. Objective To investigate associations between 33 SNPs with fatal or non-fatal incident coronary heart disease (CHD) events and all-cause mortality in the Northern Irish participants of the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Method Phase 2 of the PRIME study prospectively evaluated 2,010 men aged 58–74 years in Northern Ireland for more than 10 years for incident CHD events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass, and cardiac death) and more than 15 years for all-cause mortality. SNPs previously reported in association with cardiovascular outcomes were evaluated against incident CHD events and all-cause mortality using Cox’s proportional hazards models adjusted for established cardiovascular disease risk factors. Results During the follow-up period, 177 incident CHD events were recorded, and 821 men died. Both BCMO1 rs6564851 (Hazard ratio [HR] = 0.76; 95% confidence intervals [CI]: 0.60–0.96; P = 0.02) and TGFB1 rs1800469 (HR = 1.30; CI: 1.02–1.65; P = 0.04) were significantly associated with incident CHD events in adjusted models. Only IL1B rs16944 was significantly associated with all-cause mortality (HR = 1.18; CI: 1.05–1.33; P = 0.005). No associations remained significant following Bonferonni correction for multiple testing. Conclusion We report a novel association between BCMO1 rs6564851 and risk of incident CHD events. In addition, TGFB1 rs1800469 and IL1B rs16944 were associated with the risk of incident CHD events and all-cause mortality outcomes respectively, supporting previously reported associations.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings.

Background Simulated participants (SPs) play an important role in simulated assessments of clinical encounters between medical students and patients, most notably in objective structured clinical examinations (OSCEs). SP contributions to OSCEs are invaluable, taking the role of a patient or carer. While SPs in some settings/contexts may rate students, their role has been problematized in the literature for their lack of agency within a standardised format of OSCEs that promotes reliability, objectivity and accountability. In this study, we explored SP experiences for tensions that result from simulated assessments and their potential implications for education. Methods Semi-structured interviews were conducted with seven SPs who were also tasked with providing a global mark for students. They were purposively selected to include women and men of different ages, occupation, education and experience as an SP. The interviews were analysed using a critical thematic analysis using a phenomenological approach. Results SP experiences directly addressed tensions and contradictions around OSCEs. SP participants described their experiences under four themes: industrialising, reducing, performativity and patient safety. OSCEs were compared to an industrial process that promoted efficiency but which bore no resemblance to real-life doctor-patient encounters. They were perceived to have a power and agency that reduced SPs to verbalising scripts to ensure that students were exposed to a standardised simulated experience that also underlined the performative role of SPs as props. These performative and reductionist experiences extended to students, for whom the mark sheet acted as a checklist, promoting standardised responses that lacked genuineness. All of this created a tension for SPs in promoting patient safety by ensuring that those medical students who passed were clinically competent. Conclusions OSCEs often form part of high-stakes exams. As such, they are governed by processes of industrialisation, accountability and standardisation. OSCEs possess a power and agency that can have unintended negative consequences. These include ‘conditioning’ students to adopt behaviours that are not suited to real-life clinical encounters and are not person-centred.

Queen’s University Belfast (QUB) has completed a curriculum review resulting in the most significant revision of the undergraduate medical programme since 1996. The result is ‘C25’ named to reflect the year (2025) when the first students from this programme will graduate. In this article, we will briefly answer why and how the review was completed, focussing on the new components of C25 and the evidence-base that underpins them.

Objective The main objective of this study was to ascertain if a structured intervention programme can improve the biophysical health of young children with congenital heart disease (CHD). The primary end point was an increase in measureable physical activity levels following the intervention.Methods Patients aged 5–10 years with CHD were identified and invited to participate. Participants completed a baseline biophysical assessment, including a formal exercise stress test and daily activity monitoring using an accelerometer. Following randomisation, the intervention group attended a 1 day education session and received an individual written exercise plan to be continued over the 4-month intervention period. The control group continued with their usual level of care. After 4 months, all participants were reassessed in the same manner as at baseline.Results One hundred and sixty-three participants (mean age 8.4 years) were recruited, 100 of whom were male (61.3%). At baseline, the majority of the children were active with good exercise tolerance. The cyanotic palliated subgroup participants, however, were found to have lower levels of daily activity and significantly limited peak exercise performance compared with the other subgroups. One hundred and fifty-two participants (93.2%) attended for reassessment. Following the intervention, there was a significant improvement in peak exercise capacity in the intervention group. There was also a trend towards increased daily activity levels.Conclusion Overall physical activity levels are well preserved in the majority of young children with CHD. A structured intervention programme significantly increased peak exercise capacity and improved attitudes towards positive lifestyle changes.

The inherited basis of certain cardiac conditions is a rapidly expanding area of knowledge development and future innovations in care pathways are anticipated. Understanding the genetic basis of disease can have significant benefit. Inherited cardiac conditions encompasses cardiomyopathies, arrhythmic syndromes, aortopathies, and others and are defined by their clinical and genetic heterogeneity. Sudden cardiac death is a tragic outcome of some inherited cardiac conditions and therefore effective screening and primary prevention is vitally important. There is also a risk of poor psychological outcomes and changes to family and social function. Congenital heart disease is a collection of gross structural abnormalities of the heart or intrathoracic great vessels that have actual or potential functional significance. Congenital heart disease comprises a wide spectrum of simple, moderate, and complex severity lesions. The population of patients with congenital heart disease is growing, which results in an increased demand for nursing care. While treatment options have improved in many cases, the impact of inherited cardiac conditions and congenital heart diseases is multifaceted and lifelong. Caring for patients with these conditions requires a holistic and ongoing assessment, a distinct patient- and family-centred approach, and shared decision-making from all professionals in the interdisciplinary team.

Mental ill health is currently one of the leading causes of disease burden worldwide. A growing body of data has emerged supporting the role of diet, especially polyphenols, which have anxiolytic and antidepressant-like properties. The aim of the present study was to assess the effect of a high polyphenol diet (HPD) compared to a low polyphenol diet (LPD) on aspects of psychological well-being in the Polyphenol Intervention Trial (PPhIT). Ninety-nine mildly hypertensive participants aged 40–65 years were enrolled in a four-week LPD washout period and then randomised to either an LPD or an HPD for eight weeks. Both at baseline and the end of intervention, participants’ lifestyle and psychological well-being were assessed. The participants in the HPD group reported a decrease in depressive symptoms, as assessed by the Beck Depression Inventory-II, and an improvement in physical component and mental health component scores as assessed with 36-Item Short Form Survey. No differences in anxiety, stress, self-esteem or body image perception were observed. In summary, the study findings suggest that the adoption of a polyphenol-rich diet could potentially lead to beneficial effects including a reduction in depressive symptoms and improvements in general mental health status and physical health in hypertensive participants.

OBJECTIVE:To investigate periodontitis as a risk factor for prevalent and incident coronary heart disease (CHD) in a group of middle-aged men from Northern Ireland. METHODS:A representative sample of 1400 dentate men had a comprehensive periodontal examination between 2001 and 2003. Prevalent and incident CHD events were validated by independent cardiologists. Logistic regression was used to assess the cross-sectional relationship between periodontitis and prevalent CHD and Cox's proportional hazards analysis to assess the longitudinal relationship between periodontitis and incident CHD. RESULTS:The mean age of the men at baseline was 63.7 (SD 3.0) years. Of the 1400 men examined, 126 (9%) had prevalent CHD. After adjusting for confounding variables, men with highest mean CAL (Q4) had an odds ratio of 2.15 (95% CI 1.15-4.02), p = 0.02 for prevalent CHD in comparison to men with the lowest CAL (Q1). During a median follow-up of 12.7 years, 137 (10.8%) of the 1274 men free of CHD at baseline had an incident CHD event. After adjusting for confounding variables, the hazard ratio for incident CHD in men in Q4 versus Q1 CAL categories was 1.36 (95% CI 0.81-2.29), p = 0.24. CONCLUSIONS:In this group of dentate men, periodontitis was associated with prevalent CHD. However, there was no association with incident CHD.

BACKGROUND:Brugada syndrome (BrS) is characterized by the type 1 Brugada ECG pattern. Pathogenic rare variants in SCN5A (mutations) are identified in 20% of BrS families in whom incomplete penetrance and genotype-negative phenotype-positive individuals are observed. E1784K-SCN5A is the most common SCN5A mutation identified. We determined the association of a BrS genetic risk score (BrS-GRS) and SCN5A mutation type on BrS phenotype in BrS families with SCN5A mutations. METHODS:Subjects with a spontaneous type 1 pattern or positive/negative drug challenge from cohorts harboring SCN5A mutations were recruited from 16 centers (n=312). Single nucleotide polymorphisms previously associated with BrS at genome-wide significance were studied in both cohorts: rs11708996, rs10428132, and rs9388451. An additive linear genetic model for the BrS-GRS was assumed (6 single nucleotide polymorphism risk alleles). RESULTS:In the total population (n=312), BrS-GRS ≥4 risk alleles yielded an odds ratio of 4.15 for BrS phenotype ([95% CI, 1.45-11.85]; P=0.0078). Among SCN5A-positive individuals (n=258), BrS-GRS ≥4 risk alleles yielded an odds ratio of 2.35 ([95% CI, 0.89-6.22]; P=0.0846). In SCN5A-negative relatives (n=54), BrS-GRS ≥4 alleles yielded an odds ratio of 22.29 ([95% CI, 1.84-269.30]; P=0.0146). Among E1784K-SCN5A positive family members (n=79), hosting ≥4 risk alleles gave an odds ratio=5.12 ([95% CI, 1.93-13.62]; P=0.0011). CONCLUSIONS:Common genetic variation is associated with variable expressivity of BrS phenotype in SCN5A families, explaining in part incomplete penetrance and genotype-negative phenotype-positive individuals. SCN5A mutation genotype and a BrS-GRS associate with BrS phenotype, but the strength of association varies according to presence of a SCN5A mutation and severity of loss of function.

The Mediterranean diet (MD) is a dietary pattern well-known for its benefits in disease prevention. Monitoring adherence to the MD could be improved by discovery of novel dietary biomarkers. The MEDiterranean Diet in Northern Ireland (MEDDINI) intervention study monitored the adherence of participants to the MD for up to 12 months. This investigation aimed to profile plasma metabolites, correlating each against the MD score of participants (n = 58). Based on an established 14-point scale MD score, subjects were classified into two groups (“low” and “high”). 1H-Nuclear Magnetic Resonance (1H-NMR) metabolomic analysis found that citric acid was the most significant metabolite (p = 5.99 × 10−4*; q = 0.03), differing between ‘low’ and ‘high’. Furthermore, five additional metabolites significantly differed (p < 0.05; q < 0.35) between the two groups. Discriminatory metabolites included: citric acid, pyruvic acid, betaine, mannose, acetic acid and myo-inositol. Additionally, the top five most influential metabolites in multivariate models were also citric acid, pyruvic acid, betaine, mannose and myo-inositol. Metabolites significantly correlated with the consumption of certain food types. For example, citric acid positively correlated fruit, fruit juice and vegetable constituents of the diet, and negatively correlated with sweet foods alone or when combined with carbonated drinks. Citric acid was the best performing biomarker and this was enhanced by paired ratio with pyruvic acid. The present study demonstrates the utility of metabolomic profiling for effectively assessing adherence to MD and the discovery of novel dietary biomarkers.

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Preparation of case reports during student attachments has the attraction of reflecting real life clinical practice, but lacks standardisation when used in summative assessment. This study examined the occurrence and nature of feedback after the introduction of a new system of formative case reports in Third Year clinical attachments. Quantitative and qualitative methods were used to compare the new system to previous practice. Comparison of questionnaire responses demonstrated more and earlier feedback in the New Third Year, which was likely to be delivered at a meeting rather than as written comment. In the New Third Year, the quality of feedback was better and several markers of high quality feedback were rated more highly. There was no difference, however, in students' confidence in their ability to assess patients. The qualitative data from the New Third Year documented much excellent feedback but also examples of poor practice as well as inconsistency of advice. In conclusion, a relatively simple intervention effected radical changes to feedback practice and attitudes, although it is not known if the clinical skills of students improved.

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.

Context Inherited Cardiac Conditions (ICCs) are genetic diseases affecting the heart, associated with an increased risk of sudden cardiac death. The Northern Ireland regional ICC service, where patients with ICCs and their first degree relatives are assessed and offered genetic testing to identify the causative DNA mutation undertook this service development to reduce the time from genetic testing to result discussion. Assessment of problem and analysis of its causes Auditing of genetic testing between August and October 2015 identified a delay of 86 days from laboratory report to discussion with the patient due to a lack of outpatient clinic capacity. The ICC multidisciplinary team designed an altered approach to genetic counselling and delivery of results to make optimal use of already available resources and introduced a novel telephone clinic. The pilot telephone clinic launched in April 2016 with subsequent increasing capacity and then a repeat audit during the same time period in 2016 after implementation of the telephone clinic service was undertaken. • The average time delay from genetic results to patient discussion was reduced from 85.7 to 43.8 days. A qualitative assessment by patient satisfaction survey (response rate 20/47 (43%)) was extremely positive. • 100% of responders felt happy to receive their results by telephone • 100% indicated they would wish to receive results by telephone in the future. Effects of Changes Implementation of a telephone clinic has achieved the goal of significantly reduced waiting times (49% shorter) with excellent service quality, demonstrating that meaningful improvements can be made with minimal changes to practice and without significant additional resources. Future development of this service includes plans to increase capacity further and transform it into a nurse-led service.

Objectives There is previous epidemiological evidence that intake of polyphenol-rich foods has been associated with reduced cardiovascular disease risk. We aimed to investigate the effect of increasing dietary polyphenol intake on microvascular function in hypertensive participants. Methods All participants completed a 4-week run-in phase, consuming <2 portions of fruit and vegetables (F&V) daily and avoiding berries and dark chocolate. Subjects were then randomised to continue with the low-polyphenol diet for 8 weeks or to consume a high-polyphenol diet of six portions F&V (including one portion of berries/day and 50 g of dark chocolate). Endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside) vasodilator responses were assessed by venous occlusion plethysmography. Compliance with the intervention was measured using food diaries and biochemical markers. Results Final analysis of the primary endpoint was conducted on 92 participants. Between-group comparison of change in maximum % response to ACh revealed a significant improvement in the high-polyphenol group (p=0.02). There was a significantly larger increase in vitamin C, carotenoids and epicatechin in the high-polyphenol group (between-group difference p<0.001; p<0.001; p=0.008, respectively). Conclusions This study has shown that increasing the polyphenol content of the diet via consumption of F&V, berries and dark chocolate results in a significant improvement in an established marker of cardiovascular risk in hypertensive participants. Trial registration number NCT01319786.