Genetics of Atrial Fibrillation and Possible Implications for Ischemic Stroke

Atrial fibrillation is the most common cardiac arrhythmia mainly caused by valvular, ischemic, hypertensive, and myopathic heart disease. Atrial fibrillation can occur in families suggesting a genetic background especially in younger subjects. Additionally recent studies have identified common genetic variants to be associated with atrial fibrillation in the general population. This cardiac arrhythmia has important public health implications because of its main complications: congestive heart failure and ischemic stroke. Since atrial fibrillation can result in ischemic stroke, one might assume that genetic determinants of this cardiac arrhythmia are also implicated in cerebrovascular disease. Ischemic stroke is a multifactorial, complex disease where multiple environmental and genetic factors interact. Whether genetic variants associated with a risk factor for ischemic stroke also increase the risk of a particular vascular endpoint still needs to be confirmed in many cases. Here we review the current knowledge on the genetic background of atrial fibrillation and the consequences for cerebrovascular disease

Improving students' code correctness and test completeness by informal specifications

The quality of software produced by students is often poor. How to teach students to develop good quality software has long been a topic in computer science education and research. We must conclude that we still do not have a good answer to this question. Specifications are necessary to determine the correctness of software, to develop error-free software and to write complete tests. Several attempts have been made to teach students to write specifications before writing code. So far, that has not proven to be very successful: Students do not like to write a specification and do not see the benefits of writing specifications. In this paper we focus on the use of informal specifications. Instead of teaching students how to write specifications, we teach them how to use informal specifications to develop correct software. The results were surprising: the number of errors in software and the completeness of tests both improved considerably and, most importantly, students really appreciate the specifications. We think that if students appreciate specification, we have a key to teach them how to specify and to appreciate its value.Comment: 14 page

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Raised natriuretic peptides, big-endothelin-1 and improved beta-cell function in type 2 diabetic males with hyperuricaemia.

Urate, a naturally-occurring antioxidant, is a marker/factor for cardiovascular disease. Hyperuricaemia is associated with IR, MetS and endothelial dysfunction. We characterised the associations between neurohormones, uricaemia, and glucose homeostasis in type 2 diabetes mellitus (T2DM) males. Cross-sectional; 705 T2DM males divided into two groups: uric acid or= 7.0 mg/dl (hyperuricaemic; n=229). HOMA beta-cell function (B), insulin sensitivity (S), hyperbolic product (BxS), and (BxS) loss rate were determined alongside neurohormones (Nt-proANP, BNP, Big ET-1 and UII). Mean age and diabetes duration were not different between groups. Hyperuricaemics had more macroangiopathy, total/central adiposity, IR, hypertension, dyslipidemia and MetS prevalence. Nt-proANP and BNP levels were more than twice as high in hyperuricaemics, whereas Big ET-1 and UII were higher by 46% and 14%, respectively. HOMA (BxS) was higher in hyperuricaemics: 31 (16)% vs. 26 (18)% (p=0.0004). BxS loss rate was faster in normouricaemics: 1.36 (0.54)% vs. 1.20 (0.43)%/year(-1) (p<0.0001 ). The proportion with HbA(1C) < 7.0% was 39% (normouricaemics) vs. 49% (hyperuricaemics; p=0.0091). In T2DM males, hyperuricaemia is associated with raised neurohormones together with better beta-cell indices. Urate's dual properties may translate into beneficial (glucose homeostasis) and detrimental (raised neurohormones) effects

Erectile dysfunction, microangiopathy and UKPDS risk in type 2 diabetes.

BACKGROUND: Erectile dysfunction (ED) is a frequent comorbidity in patients with type 2 diabetes mellitus (T2DM), and is now increasingly considered a surrogate marker of endothelial dysfunction as well as a sentinel predictor of new-onset macroangiopathic events. Less attention, however, has been directed at the potential association of ED and microangiopathy in hyperglycaemic states. METHODS: We analyzed 221 consecutive male T2DM outpatients in whom ED was assessed by the International Index of Erectile Function (IIEF-5) questionnaire. ED(+) patients (IIEF-5 1-20; n=83) were compared with an age-matched ED(-) cohort (IIEF-5 21-25; n=51), with similar diabetes duration, in terms of cardiovascular (CV) risk factors, micro-/macroangiopathy and the United Kingdom Prospective Diabetes Study (UKPDS) risk score. RESULTS: Mean age and diabetes duration were 58 and 10 years, respectively. IIEF-5 score (1 S.D) was 23 (1) in ED(-) vs 11 (6) in ED(+). Anamnestic impotence and erectogenic drug use were reported by 52% and 36%, respectively, of ED(+) vs 12% and 8%, respectively, of ED(-) (P<0.0002 and P<0.0001, respectively). The metabolic syndrome prevalence (88% vs 64%; P=0.002) and central adiposity markers (waist, waist/height and visceral fat) were all significantly higher in ED(+). HbA(1c) was similar in both groups: 7.5% (1.3%), and there were also no significant differences in smoking, blood pressure, HOMA insulin sensitivity, cholesterol and glomerular filtration rate. However, prevalences of retinopathy, polyneuropathy and elevated albuminuria, and the composite endpoint of peripheral artery disease, transient ischaemic attacks and/or stroke, were markedly increased in ED(+) (all P<0.05). No differences were observed in coronary artery disease prevalence or in the UKPDS 10-year CV risk between the two ED groups. CONCLUSION: IIEF-5-defined ED in men with T2DM is associated with a marked increase in the metabolic syndrome, central adiposity and microangiopathy. These data suggest that diagnosing ED in T2DM warrants detailed screening and monitoring for microangiopathy in target organs

Handedness, insulin sensitivity and pancreatic B-cell function in Type 2 diabetes.

Background Laterality is associated with various health conditions. No study has addressed the influence of handedness on Type 2 diabetes mellitus (T2DM) phenotype, including glucose homeostasis, glucose-lowering therapies and metabolic control. Methods Five hundred and seventy-six consecutive adult T2DM outpatients underwent homeostasis model assessment (HOMA) of pancreatic B-cell function (B), insulin sensitivity (S), hyperbolic product (B x S) and age-standardized B x S deficit. Right-handed patients (87.5%; RH; n = 504) had similar age, gender, diabetes duration and education than non-right-handed patients (12.5%; non-RH; n = 72). Results Non-RH were more insulin-sensitive: 66% (39%) vs. 52% (36%) [mean (1 sd); P = 0.0024] and had significantly higher B x S and lower age-adjusted B x S deficit: 35% (20%) vs. 26% (17%) and 1.08% (0.40%) vs. 1.32% (0.55%)/year (non-RH; P = 0.0005 and P < 0.0001, respectively). Conclusions Non-right-handed T2DM patients are more insulin-sensitive, have higher hyperbolic product and less age-standardized B x S deficit. These may modulate glucose-lowering therapy requirements and glycaemic control

Cross-cultural Adaptation and Validation of Haem-A-QoL in Côte d'Ivoire

INTRODUCTION: Health-related quality (HRQoL) evaluations are considered essential outcomes in the assessment of people with haemophilia. In developing countries, reliable HRQoL data are even more critical whilst enabling government agencies to develop national haemophilia care programmes. However, validated tools are not yet available in sub-Saharan African countries. AIMS: This study sought to perform a cultural adaptation and validation of the Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) in Côte d'Ivoire. METHODS: The process comprised several steps, such as linguistic adaptation, cognitive debriefing interviews with adult haemophilia patients and psychometric testing, including reliability (internal consistency, test-retest reliability) and validity assessments (convergent with EQ-5D-5L, criterion with HJHS 2.1, known-groups). RESULTS: The final Ivoirian Haem-A-QoL version was obtained in December 2017 following linguistic adaptation and cognitive debriefings with six participants. The validation process included 25 patients, mainly haemophilia A patients (88%) with severe forms (80%). All participants received on-demand treatment, with joint impairment observed in 92%. Internal consistency and test-retest reliability of the Ivoirian Haem-A-QoL were very good. A Pearson correlation analysis revealed a moderate negative correlation between EQ-VAS and total Haem-A-QoL scores and a moderate positive correlation between HJHS 2.1 and total Haem-A-QoL scores. CONCLUSIONS: A cross-culturally adapted and validated Haem-A-QoL version in Côte d'Ivoire is now available, enabling measurement of intervention outcomes in the targeted population and Ivorian participation to multisite international trials. However, further work is needed to ensure optimal understanding of HRQoL questionnaires, previously developed in culturally distinct countries, with almost unlimited access to different treatment regimens

Haemophilia care in Europe: the ESCHQoL study.

The aim of this study was to determine the clinical conditions of patients with haemophilia within Europe as recommended by the European Commission. In this multicentre, cross-sectional, ambispective study, conducted within 21 European countries patients' clinical data were collected, amongst others haemophilia type, severity, treatment pattern, use of factor products, bleeding, orthopaedic joint scores and infections. A total of 1400 patients, 84.3% with haemophilia A and 15.7% with haemophilia B were enrolled by 42 centres between 2004 and 2006. Thereof, 417 were children (30.0%) and 983 were adults (70.0%). About 70% of patients had severe factor deficiency (5 IU; region 2: 2-5 IU; region 3: <2 IU. Paediatric and adult patients in region 3 had median numbers of three and eight joint bleeds, respectively, with worse joint scores compared to region 1 with zero and one bleed. Prophylactic therapy was used in only 31.3% children and 8.9% adults with severe haemophilia in region 3 compared to 93.7% and 54.1%, respectively, in region 1. Statistical analysis revealed that residence in areas with low factor consumption/availability is the most prominent risk factor for joint disease. Access of European patients with haemophilia to optimal care with safe factor VIII concentrates is limited and depends on the region of residence