Low fasting plasma insulin is associated with atrial fibrillation in men from a cohort study - the Malmö preventive project

Background: Type 2 diabetes has been associated with increased incidence of atrial fibrillation (AF) and cardiovascular disease. Controversy remains regarding the role of insulin in the epidemiology of AF risk. The aim of the present study was to study the association between fasting plasma insulin (FPI) and incidence of AF, as well as any effect modification by fasting blood glucose (FBG) or 2 h post-load blood glucose and body mass index (BMI). Methods: The study population consisted of 6052 men and 1014 women followed for an average of 26.2 years. There were 983 cases of incident AF. Analysis was performed using Cox regression and competing risks regression approaches. The population was analysed as a whole, and by subgroups according to glucose levels and BMI. Results: After adjustment for age, height, weight, systolic blood pressure and smoking there was a significant inverse association between FPI and AF (hazard ratio; HR) for 4th vs. 1st quartile: 0.69 (95% confidence interval (CI): 0.57-0.83, p < 0.0001) in the cohort as a whole. Among men the corresponding values were HR 0.64 (95% CI 0.52-0.78, p < 0.001) and among women HR 1.16 (95% CI 0.69-1.93, p = 0.58); p-value for interaction 0.06. The protective effects of insulin tended to be weaker in subjects with elevated fasting glucose, implying that the relation between FPI and incident AF could be dependent on the status of individual's glucose metabolism. Conclusions: High levels of FPI are associated with lower risk of incident AF in a middle-aged population with a long follow-up

Community peer-led falls prevention presentations: What do the experts suggest?

Falls among older adults are a major problem. Despite considerable progress in falls prevention research, older adults often show low motivation to engage in recommended preventive strategies. Peer-led falls prevention education for older adults may have potential for bridging the research evidence-practice gap, thereby promoting the uptake of falls prevention strategies. We evaluated peer educators’ presentations of falls prevention education to community-dwelling older adults in regard to established criteria that were consistent with adult learning principles, the framework of health behaviour change, falls prevention guidelines, and recommendations for providing falls prevention information. We conducted a within-stage mixed model study using purposive and snowball sampling techniques to recruit 10 experts to evaluate video recordings of the delivery of three peer-led falls prevention presentations. Each expert viewed three videos and rated them using a questionnaire containing both open-ended and closed items. There was a good level of expert agreement across the questionnaire domains. Though the experts rated some aspects of the presentations highly, they thought that the presentations were mainly didactic in delivery, not consistently personally relevant to the older adult audience, and did not encourage older adults to engage in the preventive strategies that were presented. Based on the experts’ findings, we developed five key themes and recommendations for the effective delivery of peer led falls prevention presentations. These included recommending that peer educators share falls prevention messages in a more interactive and experiential manner and that uptake of strategies should be facilitated by encouraging the older adults to develop a personalised action plan. Findings suggest that if peer-led falls prevention presentations capitalise on older adults’ capability, opportunity, and motivation, the older adults may be more receptive to take up falls prevention messages

saeRS and sarA Act Synergistically to Repress Protease Production and Promote Biofilm Formation in Staphylococcus aureus

Mutation of the staphylococcal accessory regulator (sarA) limits biofilm formation in diverse strains of Staphylococcus aureus, but there are exceptions. One of these is the commonly studied strain Newman. This strain has two defects of potential relevance, the first being mutations that preclude anchoring of the fibronectin-binding proteins FnbA and FnbB to the cell wall, and the second being a point mutation in saeS that results in constitutive activation of the saePQRS regulatory system. We repaired these defects to determine whether either plays a role in biofilm formation and, if so, whether this could account for the reduced impact of sarA in Newman. Restoration of surface-anchored FnbA enhanced biofilm formation, but mutation of sarA in this fnbA-positive strain increased rather than decreased biofilm formation. Mutation of sarA in an saeS-repaired derivative of Newman (P18L) or a Newman saeRS mutant (ΔsaeRS) resulted in a biofilm-deficient phenotype like that observed in clinical isolates, even in the absence of surface-anchored FnbA. These phenotypes were correlated with increased production of extracellular proteases and decreased accumulation of FnbA and/or Spa in the P18L and ΔsaeRS sarA mutants by comparison to the Newman sarA mutant. The reduced accumulation of Spa was reversed by mutation of the gene encoding aureolysin, while the reduced accumulation of FnbA was reversed by mutation of the sspABC operon. These results demonstrate that saeRS and sarA act synergistically to repress the production of extracellular proteases that would otherwise limit accumulation of critical proteins that contribute to biofilm formation, with constitutive activation of saeRS limiting protease production, even in a sarA mutant, to a degree that can be correlated with increased enhanced capacity to form a biofilm. Although it remains unclear whether these effects are mediated directly or indirectly, studies done with an sspA::lux reporter suggest they are mediated at a transcriptional level

Development and Psychometric Evaluation of an Item Bank for Computerized Adaptive Testing of the EORTC Insomnia Dimension in Cancer Patients (EORTC CAT-SL)

To further advance assessment of patient-reported outcomes, the European Organisation of Research and Treatment of Cancer (EORTC) Quality of Life Group has developed computerized adaptive test (CAT) versions of all EORTC Quality of Life Core Questionnaire (QLQ-C30) scales/items. The aim of this study was to develop and evaluate an item bank for CAT measurement of insomnia (CAT-SL). In line with the EORTC guidelines, the developmental process comprised four phases: (I) defining the concept insomnia and literature search, (II) selection and formulation of new items, (III) pre-testing and (IV) field-testing, including psychometric analyses of the final item bank. In phase I, the literature search identified 155 items that were compatible with our conceptualisation of insomnia, including both quantity and quality of sleep. In phase II, following a multistep-approach, this number was reduced to 15 candidate items. Pre-testing of these items in cancer patients (phase III) resulted in an item list of 14 items, which were field-tested among 1094 patients in phase IV. Psychometric evaluations showed that eight items could be retained in a unidimensional model. The final item bank yielded greater measurement precision than the original QLQ-C30 insomnia item. It was estimated that administering two or more items from the insomnia item bank with CAT results in a saving in sample size between approximately 15–25%. The 8-item EORTC CAT-SL item bank facilitates precise and efficient measurement of insomnia as part of the EORTC CAT system of health-related quality life assessment in both clinical research and practice

The Efficacy of Exercise in Reducing Depressive Symptoms among Cancer Survivors: A Meta-Analysis

INTRODUCTION: The purpose of this meta-analysis was to examine the efficacy of exercise to reduce depressive symptoms among cancer survivors. In addition, we examined the extent to which exercise dose and clinical characteristics of cancer survivors influence the relationship between exercise and reductions in depressive symptoms. METHODS: We conducted a systematic search identifying randomized controlled trials of exercise interventions among adult cancer survivors, examining depressive symptoms as an outcome. We calculated effect sizes for each study and performed weighted multiple regression moderator analysis. RESULTS: We identified 40 exercise interventions including 2,929 cancer survivors. Diverse groups of cancer survivors were examined in seven exercise interventions; breast cancer survivors were examined in 26; prostate cancer, leukemia, and lymphoma were examined in two; and colorectal cancer in one. Cancer survivors who completed an exercise intervention reduced depression more than controls, d(+) = -0.13 (95% CI: -0.26, -0.01). Increases in weekly volume of aerobic exercise reduced depressive symptoms in dose-response fashion (β = -0.24, p = 0.03), a pattern evident only in higher quality trials. Exercise reduced depressive symptoms most when exercise sessions were supervised (β = -0.26, p = 0.01) and when cancer survivors were between 47-62 yr (β = 0.27, p = 0.01). CONCLUSION: Exercise training provides a small overall reduction in depressive symptoms among cancer survivors but one that increased in dose-response fashion with weekly volume of aerobic exercise in high quality trials. Depressive symptoms were reduced to the greatest degree among breast cancer survivors, among cancer survivors aged between 47-62 yr, or when exercise sessions were supervised

Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes

Genome-wide associations for birth weight and correlations with adult disease

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW ($\textit{P}$  < 5 × 10$^{-8}$). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure ($\textit{R}$ $_{g}$ = -0.22, $\textit{P}$  = 5.5 × 10$^{-13}$), T2D ($\textit{R}$ $_{g}$ = -0.27, $\textit{P}$  = 1.1 × 10$^{-6}$) and coronary artery disease ($\textit{R}$ $_{g}$ = -0.30, $\textit{P}$  = 6.5 × 10$^{-9}$). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions ($\textit{P}$ = 1.9 × 10$^{-4}$). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.For a full list of the funders pelase visit the publisher's website and look at the supplemetary material provided. Some of the funders are: British Heart Foundation, Cancer Research UK, Medical Research Council, National Institutes of Health, Royal Society and Wellcome Trust

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Metacognitive therapy home-based self-help for cardiac rehabilitation patients experiencing anxiety and depressive symptoms : study protocol for a feasibility randomised controlled trial (PATHWAY Home-MCT)

BACKGROUND: Anxiety and depression are common among patients attending cardiac rehabilitation services. Currently available pharmacological and psychological interventions have limited effectiveness in this population. There are presently no psychological interventions for anxiety and depression integrated into cardiac rehabilitation services despite emphasis in key UK National Health Service policy. A new treatment, metacognitive therapy, is highly effective at reducing anxiety and depression in mental health settings. The principal aims of the current study are (1) to evaluate the acceptability of delivering metacognitive therapy in a home-based self-help format (Home-MCT) to cardiac rehabilitation patients experiencing anxiety and depressive symptoms and conduct a feasibility trial of Home-MCT plus usual cardiac rehabilitation compared to usual cardiac rehabilitation; and (2) to inform the design and sample size for a full-scale trial. METHODS: The PATHWAY Home-MCT trial is a single-blind feasibility randomised controlled trial comparing usual cardiac rehabilitation (control) versus usual cardiac rehabilitation plus home-based self-help metacognitive therapy (intervention). Economic and qualitative evaluations will be embedded within the trial. Participants will be assessed at baseline and followed-up at 4 and 12 months. Patients who have been referred to cardiac rehabilitation programmes and have a score of ≥ 8 on the anxiety and/or depression subscales of the Hospital Anxiety and Depression Scale will be invited to take part in the study and written informed consent will be obtained. Participants will be recruited from the National Health Service in the UK. A minimum of 108 participants will be randomised to the intervention and control arms in a 1:1 ratio. DISCUSSION: The Home-MCT feasibility randomised controlled trial will provide evidence on the acceptability of delivering metacognitive therapy in a home-based self-help format for cardiac rehabilitation patients experiencing symptoms of anxiety and/or depression and on the feasibility and design of a full-scale trial. In addition, it will provide provisional point estimates, with appropriately wide measures of uncertainty, relating to the effectiveness and cost-effectiveness of the intervention. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03129282 , Submitted to Registry: 11 April 2017