Management of atrial fibrillation in diabetes

Diabetes is an important risk factor for cardiovascular morbidity and mortality, and atrial fibrillation is linked to cardiovascular complications. The prevalence of both is increasing and they commonly co‐exist with a longer duration of diabetes and poorer control putting individuals at higher risk of atrial fibrillation. The complications of atrial fibrillation include heart failure and thromboembolism. There is an association between diabetes and atrial fibrillation and there are many theories as to the specific pathophysiology, including sharing similar precursors, but it is not clearly understood. What is understood is that the risk of developing the main consequences of atrial fibrillation can be reduced by treatment. Broadly speaking, this involves controlling the heart rhythm and/or heart rate to improve cardiac function in addition to anticoagulation. The development of risk stratification strategies and direct oral anticoagulants has led to safer anticoagulation with more individuals thought to benefit balanced against any potential risk of bleeding. The evidence base for treatment of atrial fibrillation includes many individuals with diabetes and, in this group, prevention of complications is equally as relevant. In those with diabetes and atrial fibrillation the evidence overwhelmingly supports a treatment strategy similar to that for individuals with atrial fibrillation but without diabetes. This should be done in addition to identifying and treating other cardiovascular risk factors

Effects of a four-week touch rugby and self-paced interval running intervention on health markers in active young men.

Background: Modified team sport activity has been proposed as effective exercise modality for promoting markers of health that are comparable or greater than continuous forms of activity. However, research using modified team sports is currently limited to sedentary populations using 2-3 sessions across a minimum of 8 weeks. Aim: To investigate the effects of a four-week touch rugby and self-paced interval running intervention on a range of health markers in active men. Methods: Sixteen participants (age 26.4 ± 6.4 years) were matched for age, demographic and physical activity before completing a single touch rugby (n = 8) or running (n = 8) session per week for four weeks. Measures of systolic and diastolic blood pressure, resting heart rate (RHR), body composition and biochemical status were recorded pre- and post-intervention. Results: ANCOVA analysis revealed between-group differences for impedance (P = 0.027), fat mass (P = 0.008), percentage body fat (P = 0.008) and fat free mass (P = 0.002), with greater changes after touch rugby. Systolic blood pressure decreased for both groups with greater reductions observed after touch rugby (P = 0.002). No between-group difference was observed for RHR, interleukin-6 or C-reactive protein (P > 0.05). Contrasting internal, external and perceptual loads were observed. Conclusion: The results of this study suggest that a single session of touch rugby over a 4-week period elicited greater improvements in body composition and SBP that self-paced running, with both equally beneficial for improving RHR, diastolic blood pressure and improved inflammatory status in active young men

Toxicity of cancer therapy: what the cardiologist needs to know about angiogenesis inhibitors

Clinical outcomes for patients with a wide range of malignancies have improved substantially over the last two decades. Tyrosine kinase inhibitors (TKIs) are potent signalling cascade inhibitors and have been responsible for significant advances in cancer therapy. By inhibiting vascular endothelial growth factor receptor (VEGFR)-mediated tumour blood vessel growth, VEGFR-TKIs have become a mainstay of treatment for a number of solid malignancies. However, the incidence of VEGFR-TKI-associated cardiovascular toxicity is substantial and previously under-recognised. Almost all patients have an acute rise in blood pressure, and the majority develop hypertension. They are associated with the development of left ventricular systolic dysfunction (LVSD), heart failure and myocardial ischaemia and can have effects on myocardial repolarisation. Attention should be given to rigorous baseline assessment of patients prior to commencing VEGFR-TKIs, with careful consideration of baseline cardiovascular risk factors. Baseline blood pressure measurement, ECG and cardiac imaging should be performed routinely. Hypertension management currently follows national guidelines, but there may be a future role forendothelin-1 antagonism in the prevention or treatment of VEGFR-TKI-associated hypertension. VEGFR-TKI-associated LVSD appears to be independent of dose and is reversible. Patients who develop LVSD and heart failure should be managed with conventional heart failure therapies, but the role of prophylactic therapy is yet to be defined. Serial monitoring of left ventricular function and QT interval require better standardisation and coordinated care. Management of these complex patients requires collaborative, cardio-oncology care to allow the true therapeutic potential from cancer treatment while minimising competing cardiovascular effects

High-Sensitivity Cardiac Troponin and New-Onset Heart Failure: A Systematic Review and Meta-Analysis of 67,063 Patients With 4,165 Incident Heart Failure Events.

OBJECTIVES: The aim of this study was to systematically collate and appraise the available evidence regarding the association between high-sensitivity cardiac troponin (hs-cTn) and incident heart failure (HF) and the added value of hs-cTn in HF prediction. BACKGROUND: Identification of subjects at high risk for HF and early risk factor modification with medications such as angiotensin-converting enzyme inhibitors may delay the onset of HF. Hs-cTn has been suggested as a prognostic marker for the incidence of first-ever HF in asymptomatic subjects. METHODS: PubMed, Embase, and Web of Science were systematically searched for prospective cohort studies published before January 2017 that reported associations between hs-cTn and incident HF in subjects without baseline HF. Study-specific multivariate-adjusted hazard ratios (HRs) were pooled using random-effects meta-analysis. RESULTS: Data were collated from 16 studies with a total of 67,063 subjects and 4,165 incident HF events. The average age was 57 years, and 47% were women. Study quality was high (Newcastle-Ottawa score 8.2 of 9). In a comparison of participants in the top third with those in the bottom third of baseline values of hs-cTn, the pooled multivariate-adjusted HR for incident HF was 2.09 (95% confidence interval [CI]: 1.76 to 2.48; p < 0.001). Between-study heterogeneity was high, with an I2 value of 80%. HRs were similar in men and women (2.29 [95% CI: 1.64 to 3.21] vs. 2.18 [95% CI: 1.68 to 2.81]) and for hs-cTnI and hs-cTnT (2.09 [95% CI: 1.53 to 2.85] vs. 2.11 [95% CI: 1.69 to 2.63]) and across other study-level characteristics. Further adjustment for B-type natriuretic peptide yielded a similar HR of 2.08 (95% CI: 1.64 to 2.65). Assay of hs-cTn in addition to conventional risk factors provided improvements in the C index of 1% to 3%. CONCLUSIONS: Available prospective studies indicate a strong association of hs-cTn with the risk of first-ever HF and significant improvements in HF prediction

Hypertension and prohypertensive antineoplastic therapies in cancer patients

The development of a wide range of novel antineoplastic therapies has improved the prognosis for patients with a wide range of malignancies, which has increased the number of cancer survivors substantially. Despite the oncological benefit, cancer survivors are exposed to short- and long-term adverse cardiovascular toxicities associated with anticancer therapies. Systemic hypertension, the most common comorbidity among cancer patients, is a major contributor to the increased risk for developing these adverse cardiovascular events. Cancer and hypertension have common risk factors, have overlapping pathophysiological mechanisms and hypertension may also be a risk factor for some tumor types. Many cancer therapies have prohypertensive effects. Although some of the mechanisms by which these antineoplastic agents lead to hypertension have been characterized, further preclinical and clinical studies are required to investigate the exact pathophysiology and the optimal management of hypertension associated with anticancer therapy. In this way, monitoring and management of hypertension before, during, and after cancer treatment can be improved to minimize cardiovascular risks. This is vital to optimize cardiovascular health in patients with cancer and survivors, and to ensure that advances in terms of cancer survivorship do not come at the expense of increased cardiovascular toxicities

Microarray scanner calibration curves: characteristics and implications

BACKGROUND: Microarray-based measurement of mRNA abundance assumes a linear relationship between the fluorescence intensity and the dye concentration. In reality, however, the calibration curve can be nonlinear. RESULTS: By scanning a microarray scanner calibration slide containing known concentrations of fluorescent dyes under 18 PMT gains, we were able to evaluate the differences in calibration characteristics of Cy5 and Cy3. First, the calibration curve for the same dye under the same PMT gain is nonlinear at both the high and low intensity ends. Second, the degree of nonlinearity of the calibration curve depends on the PMT gain. Third, the two PMTs (for Cy5 and Cy3) behave differently even under the same gain. Fourth, the background intensity for the Cy3 channel is higher than that for the Cy5 channel. The impact of such characteristics on the accuracy and reproducibility of measured mRNA abundance and the calculated ratios was demonstrated. Combined with simulation results, we provided explanations to the existence of ratio underestimation, intensity-dependence of ratio bias, and anti-correlation of ratios in dye-swap replicates. We further demonstrated that although Lowess normalization effectively eliminates the intensity-dependence of ratio bias, the systematic deviation from true ratios largely remained. A method of calculating ratios based on concentrations estimated from the calibration curves was proposed for correcting ratio bias. CONCLUSION: It is preferable to scan microarray slides at fixed, optimal gain settings under which the linearity between concentration and intensity is maximized. Although normalization methods improve reproducibility of microarray measurements, they appear less effective in improving accuracy

All Our Babies Cohort Study: recruitment of a cohort to predict women at risk of preterm birth through the examination of gene expression profiles and the environment

<p>Abstract</p> <p>Background</p> <p>Preterm birth is the leading cause of perinatal morbidity and mortality. Risk factors for preterm birth include a personal or familial history of preterm delivery, ethnicity and low socioeconomic status yet the ability to predict preterm delivery before the onset of preterm labour evades clinical practice. Evidence suggests that genetics may play a role in the multi-factorial pathophysiology of preterm birth. The All Our Babies Study is an on-going community based longitudinal cohort study that was designed to establish a cohort of women to investigate how a women's genetics and environment contribute to the pathophysiology of preterm birth. Specifically this study will examine the predictive potential of maternal leukocytes for predicting preterm birth in non-labouring women through the examination of gene expression profiles and gene-environment interactions.</p> <p>Methods/Design</p> <p>Collaborations have been established between clinical lab services, the provincial health service provider and researchers to create an interdisciplinary study design for the All Our Babies Study. A birth cohort of 2000 women has been established to address this research question. Women provide informed consent for blood sample collection, linkage to medical records and complete questionnaires related to prenatal health, service utilization, social support, emotional and physical health, demographics, and breast and infant feeding. Maternal blood samples are collected in PAXgene™ RNA tubes between 18-22 and 28-32 weeks gestation for transcriptomic analyses.</p> <p>Discussion</p> <p>The All Our Babies Study is an example of how investment in clinical-academic-community partnerships can improve research efficiency and accelerate the recruitment and data collection phases of a study. Establishing these partnerships during the study design phase and maintaining these relationships through the duration of the study provides the unique opportunity to investigate the multi-causal factors of preterm birth. The overall All Our Babies Study results can potentially lead to healthier pregnancies, mothers, infants and children.</p

A Journey of Hope: giving research participants a voice to share their experiences and improve community engagement around advanced HIV disease in Uganda

Over the last decade excellent progress has been made globally in HIV management thanks to antiretroviral therapy (ART) rollout and international guidelines now recommending immediate initiation of ART in people living with HIV. Despite this, advanced HIV disease (CD4 less than 200 cells/mL) and opportunistic infections remain a persistent challenge and contribute significantly to HIV-associated mortality, which equates to 23,000 deaths in Uganda in 2018 alone. Our Meningitis Research Team based in Uganda is committed to conducting clinical trials to answer important questions regarding diagnostics and management of HIV-associated opportunistic infections, including tuberculosis and cryptococcal meningitis. However, clinical research is impossible without research participants and results are meaningless unless they are translated into benefits for those affected by the disease. Therefore, we held a series of community engagement events with the aims of 1) giving research participants a voice to share their experiences of clinical research and messages of hope around advanced HIV disease with the community, 2) dispelling myths and stigma around HIV, and 3) raising awareness about the complications of advanced HIV disease and local clinical research and recent scientific advances. The purpose of this Open Letter is to describe our community engagement experience in Uganda, where we aimed to give clinical research participants a greater voice to share their experiences. These activities build upon decades of work in HIV community engagement and lays a platform for future research and engagement activities.</ns4:p