Exercise training improves activity in adolescents with congenital heart disease.

OBJECTIVES: To ascertain if motivational techniques and a structured exercise programme can increase activity in adolescents afflicted with congenital heart disease (CHD). DESIGN: Prospective randomised controlled trial. SETTING: One hundred and forty-three patients aged 12-20 years attending the tertiary centre for paediatric cardiology in Northern Ireland. MAIN OUTCOME MEASURES: Increase in exercise capacity as assessed by duration of exercise stress test, and number of minutes spent in moderate to vigorous physical activity (MVPA) per day. RESULTS: Eighty-six patients were men (60%), mean age was 15.60 ± 2.27 years. Seventy-three percent were considered to have major CHD. Seventy-two participants were randomised to the intervention group. Following intervention, duration of exercise test increased by 1 min 5 s for the intervention group (p value 0.02) along with increase in predicted VO2Max (p value 0.02). There was a significant increase in minutes of MVPA per day for the intervention group from baseline to reassessment (p value <0.001) while MVPA remained much the same for the control group. Fourteen patients met the current recommendation for more than 60 min MVPA per day at baseline. This doubled to 29 participants at reassessment. There were no adverse effects or mortalities reported. CONCLUSIONS: Exercise training is safe, feasible and beneficial in adolescents with CHD. Psychological techniques can be employed to maximise the impact of interventions. TRIAL REGISTRATION NUMBER: ISRCTN27986270.

Educational interventions in neurology: a comprehensive systematic review.

A fear of neurology and neural sciences (neurophobia) may have clinical consequences. There is therefore a need to formulate an evidence-based approach to neurology education. A comprehensive systematic review of educational interventions in neurology was performed. BEI, Cochrane Library, Dialog Datastar, EBSCO Biomedical, EBSCO Psychology & Behavioral Sciences, EMBASE, ERIC, First Search, MDConsult, Medline, Proquest Medical Library and Web of Knowledge databases were searched for all published studies assessing interventions in neurology education among undergraduate students, junior medical doctors and residents up to and including July 2012. Two independent literature searches were performed for relevant studies, which were then classified for level of evidence using the Centre of Evidence-based Medicine criteria and four levels of Kirkpatrick educational outcomes. One systematic review, 16 randomized controlled trials (RCTs), nine non-randomized cohort/follow-up studies, 33 case series or historically controlled studies and three mechanism-based reasoning studies were identified. Educational interventions showed favourable evaluation or assessment outcomes in 15 of 16 (94%) RCTs. Very few studies measured subsequent clinical behaviour (two studies) and patient outcomes (one study). There is very little high quality evidence of demonstrably effective neurology education. However, RCTs are emerging, albeit without meeting comprehensive educational criteria. An improving evidence base in the quality of neurology education will be important to reduce neurophobia.

Nutritional intake and oxidative stress in chronic heart failure.

BACKGROUND AND AIMS: Patients with chronic heart failure (CHF) are known to be at risk of malnutrition, and cardiac cachexia is an adverse prognostic indicator. The aim of this study was to determine the dietary adequacy of CHF patients compared with Dietary Reference Values, to compare the nutritional intake and status of CHF patients to a healthy comparison group, and finally to determine whether nutritional intake and status depended on New York Heart Association (NYHA) functional class. METHODS AND RESULTS: Patients with CHF (n = 39) and a comparison group of 27 healthy participants, who did not have CHF, were asked to complete a four-day food diary, and energy and nutrient intakes were calculated. F(2α)-isoprostanes were measured in urine as an indicator of oxidative stress and antioxidants were measured in serum or plasma. Overall 73% of the CHF patients were consuming less than recommended energy intakes, and more than 50% of these patients were also consuming less than recommended vitamin D, selenium and zinc intakes. Nutrient intake (energy, vitamin B6, D, E, iron, folate and riboflavin) was lower in CHF patients than in the comparison group, with vitamin B6 and folate intake and antioxidant status decreasing, and isoprostane status increasing as NYHA functional class increased. CONCLUSION: The majority of CHF patients do not meet dietary reference values for energy and a range of nutrients, and nutrient intake is lower in CHF patients than in healthy individuals. Dietary inadequacy tends to be increased in those with more severe disease.

Adoption and maintenance of a Mediterranean diet in patients with coronary heart disease from a Northern European population: a pilot randomised trial of different methods of delivering Mediterranean diet advice.

BACKGROUND: A Mediterranean diet has been shown to protect against coronary heart disease (CHD). Adherence to a Mediterranean diet can be assessed using a Mediterranean diet score. The primary aim of this pilot study was to examine whether CHD patients in a Northern European population would adopt and maintain a Mediterranean diet, with a secondary aim of comparing the effectiveness of different methodologies aimed at improving compliance. METHODS: Sixty-one patients with a diagnosis of CHD were randomised to one of three groups: either to receive conventional dietetic advice for CHD or advice to implement a Mediterranean-style diet using either behavioural counselling or nutritional counselling. Patients received a follow-up assessment at 6 months (adoption) and a subset of patients was followed up at 12 months (maintenance). The primary outcome measure was the between-group difference in the mean change in Mediterranean diet score (MDS). RESULTS: The change in MDS was not significantly different between groups. However, all three groups reported a significant within-group increase in MDS (P < 0.01) at 6 and 12 months follow-up. CONCLUSIONS: All three groups made dietary changes towards a Mediterranean diet, but behavioural counselling did not have significant additional benefit over nutritional counselling in initiating and maintaining dietary change, and neither method offering specific Mediterranean diet advice had any significant benefit in terms of improvement in MDS over conventional dietetic practice.

Genetic polymorphisms in platelet-related proteins and coronary artery disease: investigation of candidate genes, including N-acetylgalactosaminyltransferase 4 (GALNT4) and sulphotransferase 1A1/2 (SULT1A1/2).

BACKGROUND: Both platelet function and heart disease show strong genetic components, many of which remain to be elucidated. MATERIALS AND METHODS: The roles of candidate polymorphisms in ten platelet-associated genes were compared between 1,237 Acute Coronary Syndrome (ACS) cases (with myocardial infarction and unstable angina) and 386 controls, from an Irish Caucasian population. Additionally, 361 stable angina patients were investigated. Two genes of interest were followed up in a separate Irish study of 1,484 individuals (577 with IHD and 907 unaffected). RESULTS: The GALNT4 (N-acetyl galactosaminyl transferase 4) 506I allele was significantly underrepresented in ACS (OR = 0.66, CI = 0.52-0.84; P = 0.001; P = 0.01 after correction for multiple testing), while the SULT1A1 (Sulphotransferase 1A1) 213H allele was associated with risk of ACS (OR = 1.37, CI = 1.08-1.74; P = 0.01; P = 0.1 after correction for multiple testing). Subsequent genotyping of further SNPs in GALNT4 in the family-based (IHD) group revealed that the 506I allele showed the same trend towards protecting against ACS but the haplotypic test over the four commonest haplotypes was not significant (P = 0.55). In contrast, the SULT1A1/SULT1A2 gene complex showed suggestive haplotypic association in the family-based study (P = 0.07), with the greatest increase in risk conferred by the SULT1A2 235T allele (P = 0.025). CONCLUSION: We have identified two risk genes for cardiovascular disease, one of whose (GALNT4) effects may be on either platelet or endothelial function through modifications of PSGL1 or other important glycosylated proteins. The role of sulphotransferases (SULT1A1/2) in cardiovascular disease requires further exploration. Further validation of cardiovascular risks conferred by both genes in other populations (including gene copy number variation) is warranted.

Assessment of aspirin resistance varies on a temporal basis in patients with ischaemic heart disease.

OBJECTIVE: Laboratory tests including optical platelet aggregometry (OPA), platelet function analyser (PFA-100), and thromboxane B2 (TXB2) metabolite levels have been used to define aspirin resistance. This study characterised the prevalence of aspirin resistance in patients with ischaemic heart disease (IHD) and investigated the concordance and repeatability of these tests. DESIGN, SETTING AND PATIENTS: Consecutive outpatients with stable IHD were enrolled. They were commenced on 150 mg aspirin daily (day 0) and had platelet function assessment (OPA and PFA-100) and quantitative analysis of serum/urine TXB2 at day > or =7 and then at a second visit approximately 2 weeks later. MAIN OUTCOME MEASURES: We assessed the prevalence of aspirin resistance by each method, concordance between methods of measuring response to aspirin and association between time points to assess the predictability of response over time. RESULTS: 172 patients (62.7 (SD 8.7) years, 83.1% male) were recruited. At visits 1 and 2, respectively, 1.7% and 4.7% were aspirin resistant by OPA, whereas 22.1% and 20.3% were aspirin resistant by PFA-100. There were poor associations between PFA-100 and OPA, and between TXB2 metabolites and platelet function tests. OPA and PFA-100 results were poorly associated between visits (kappa = 0.16 and kappa = 0.42, respectively) as were TXB2 metabolites, suggesting that aspirin resistance is not predictable over time. CONCLUSIONS: The prevalence of aspirin resistance is dependent on the method of testing. Response varies on a temporal basis, indicating that testing on a single occasion is inadequate to diagnose resistance or guide therapy in a clinical setting.

Voriconazole-induced pseudoporphyria.

Pseudoporphyria is a bullous photosensitivity, the commonest aetiology being secondary to various ingested medications. Voriconazole is a relatively new second-generation triazole antifungal agent. There have only been two reports of pseudoporphyria secondary to voriconazole. We report the third case of this phenomenon occurring in a lady being treated for disseminated candidal infection.

Antioxidant vitamins C and E ameliorate hyperglycaemia-induced oxidative stress in coronary endothelial cells.

OBJECTIVE: Vitamins C and E have protective features in many disease states associated with enhanced oxidative stress. The aim of this study was to investigate whether vitamin(s) C and/or E modulate hyperglycaemia-induced oxidative stress by regulating enzymatic activities of prooxidant, i.e. NAD(P)H oxidase and/or antioxidant enzymes, namely endothelial nitric oxide synthase (eNOS), superoxide dismutase, catalase and glutathione peroxidase, using coronary microvascular endothelial cells (CMEC). METHODS: CMEC were cultured under normal (5.5 mM) or high glucose (22 mM) concentrations for 7 days. The enzyme activities were determined by specific assays. The levels of O(2) (-) and nitrite were measured by cytochrome c reduction and Griess assays respectively. RESULTS: Hyperglycaemia did not alter eNOS activity or overall nitrite generation, an index of NO production. However, it increased NAD(P)H oxidase and antioxidant enzyme activities (p < 0.05). Specific inhibitors of NAD(P)H oxidase, i.e. phenylarsine oxide (0.1-3 microm) and 4-(2-aminoethyl)benzenesulfonyl fluoride (5-100 microm) and vitamins C and E (0.1-1 microm) significantly reduced prooxidant and antioxidant enzyme activities in CMEC exposed to hyperglycaemia (p < 0.01). The differences in enzyme activities were independent of increases in osmolarity generated by high glucose levels as investigated by using equimolar concentrations of mannitol in parallel experiments. CONCLUSIONS: Vitamins C and E may protect CMEC against hyperglycaemia-induced oxidative stress by concomitantly regulating prooxidant and antioxidant enzyme activities.

The intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism is not associated with ischaemic heart disease: an investigation using family-based tests of association.

The possible role of the K469E polymorphism in the intercellular adhesion molecule-1 (ICAM-1) gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population using two recently described family-based tests of association. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped for the ICAM-1 K469E polymorphism. Using the combined transmission disequilibrium test (TDT)/sib-TDT and the pedigree disequilibrium test (PDT), no association between the ICAM-1 K469E polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the ICAM-1 K469E polymorphism is not associated with IHD.

Lack of association between the -2518G/A polymorphism of the MCP-1 gene and ischaemic heart disease: a family-based investigation.

Using two recently described family-based tests of association, the possible role of the functional -2518G/A polymorphism in the promoter region of the monocyte chemoattractant protein-1 (MCP-1) gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped for the MCP-1 -2518G/A polymorphism. Using the combined transmission disequilibrium test and the pedigree disequilibrium test, no association between the MCP-1 -2518G/A polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the MCP-1 -2518G/A polymorphism is not strongly associated with IHD.

The impact of curricular change on medical students' knowledge of anatomy.

BACKGROUND: In recent years, following the publication of Tomorrow's Doctors, the undergraduate medical curriculum in most UK medical schools has undergone major revision. This has resulted in a significant reduction in the time allocated to the teaching of the basic medical sciences, including anatomy. However, it is not clear what impact these changes have had on medical students' knowledge of surface anatomy. AIM: This study aimed to assess the impact of these curricular changes on medical students' knowledge of surface anatomy. SETTING: Medical student intakes for 1995-98 at the Queen's University of Belfast, UK. METHODS: The students were invited to complete a simple examination paper testing their knowledge of surface anatomy. Results from the student intake of 1995, which undertook a traditional, 'old' curriculum, were compared with those from the student intakes of 1996-98, which undertook a new, 'systems-based' curriculum. To enhance linear response and enable the use of linear models for analysis, all data were adjusted using probit transformations of the proportion (percentage) of correct answers for each item and each year group. RESULTS: The student intake of 1995 (old curriculum) were more likely to score higher than the students who undertook the new, systems-based curriculum. CONCLUSION: The introduction of the new, systems-based course has had a negative impact on medical students' knowledge of surface anatomy.

Single coronary artery: a familial clustering.

A 59 year old man undergoing investigation for chest pain was found at elective coronary angiography to have a single coronary artery; the left coronary had a normal distribution, with the right coronary originating as a continuation of the atrioventricular circumflex. His 30 year old daughter was admitted for elective coronary angiography for further investigation of a dilated cardiomyopathy. She was also found to have a single coronary artery. However, in her case, the right and left coronary arteries arose from the right sinus of Valsalva; the right coronary had a normal distribution, the left coronary passed anterior to the pulmonary trunk and aorta.

Investigation of the C242T polymorphism of NAD(P)H oxidase p22 phox gene and ischaemic heart disease using family-based association methods.

Ischaemic heart disease is a complex phenotype arising from the interaction of genetic and environmental factors. Excessive production of reactive oxygen species leading to endothelial dysfunction is believed to be important in the pathogenesis of ischaemic heart disease. The NAD(P)H oxidase system generates superoxide anions in vascular cells; however, the role of the C242T polymorphism of the NAD(P)H oxidase p22 phox gene in ischaemic heart disease is unclear due to contradictory results from case-control studies. Consequently, we applied family-based association tests to investigate the role of this polymorphism in ischaemic heart disease in a well-defined Irish population. A total of 1023 individuals from 388 families (discordant sibships and parent/child trios) were recruited. Linkage disequilibrium between the polymorphism and ischaemic heart disease was tested using the combined transmission disequilibrium test (TDT)/sib-TDT (cTDT) and pedigree disequilibrium test (PDT). Both cTDT and PDT analyses found no statistically significant excess transmission of either allele to affected individuals (P =0.30 and P =0.28, respectively). Using robust family-based association tests specifically designed for the study of complex diseases, we found no evidence that the C242T polymorphism of the p22 phox gene has a significant role in the development of ischaemic heart disease in our population.

Off-pump coronary artery bypass grafting. Excellent results in a group of selected high-risk patients.

BACKGROUND: Off-pump coronary artery bypass grafting (OPCABG) has assumed an increasing role in many surgical practices. The ideal candidate has not been defined, but high-risk patients seem to benefit most when cardiopulmonary bypass (CPB), aortic cross clamping and cardioplegic arrest are avoided. METHODS: Fourteen high-risk patients (age 52 to 81 years, 1 female, EF 44%+/-8, Parsonnet score 23+/-4) were studied. They presented with acute coronary syndroms on platelet glycoprotein IIb/IIIa antagonists, acute myocardial infarction, worsening renal failure, decompensating ischemic cardiomyopathy, religious beliefs and denial of blood transfusion, and severe peripheral/cerebrovascular disease (total bilateral internal carotid artery occlusion and/or >90% stenosis). These patients underwent OPCABG via sternotomy with the intention of complete coronary revascularization. RESULTS: An average of 2.3 grafts/patient were performed and the posterior descending artery (PDA) and marginal branches of the circumflex artery (LCX) were grafted in 79% of the patients. There were 3 events of intraoperative cardiac arrest precipitated by occlusion of right coronary artery (RCA) or positioning a cardiomegaly heart leading to immediate intravascular shunting (2) and/or conversion to CPB (1). One patient was converted to CPB and graft revision (intraoperative ultrasound and probing). The mortality rate was 0% and one stroke was observed on post-operative day 1. Coronary angiography (n=6) showed no significant stenosis. CONCLUSIONS: OPCABG complete revascularization is feasible in high-risk patients with low morbidity and mortality and excellent early RESULTS: OPCABG may be indicated in patients on platelet receptor antagonists preventing bleeding complications. Cardiomegaly can cause difficult off-pump LCX and PDA exposure and stabilization. RCA grafting off-pump is less tolerated and PDA grafting is preferred. High-risk patients for CPB are the ones who may benefit the most from OPCABG.

The prevalence and types of coronary artery anomalies in Northern Ireland.

Coronary artery anomalies are uncommon, with a reported prevalence ranging from 0.2% to 1.6%. It is important that those who undertake coronary angiographic procedures are aware of the spectrum of these anomalies. Interventional percutaneous coronary revascularisation procedures are widely used in the management of patients with symptomatic coronary atherosclerosis. The presence of a coronary artery anomaly may make these procedures technically challenging. We have reviewed the Cardiac catheterisation database at the Royal Victoria Hospital, Belfast, and report the prevalence and types of these anomalies.