Cardiac resynchronization therapy following Carillon® annuloplasty device for symptomatic heart failure and functional mitral regurgitation: a case report

Background  Symptomatic patients with significant left ventricular systolic dysfunction (LVSD) require a tailored treatment approach. Both functional mitral regurgitation (FMR) and left bundle branch block (LBBB) can develop, contributing to clinical deterioration, and worse prognosis despite optimal medical therapy (OMT). Case summary  We report the case of a symptomatic 60-year-old man on OMT with LVSD and significant FMR. His symptoms and FMR initially improved following transvenous mitral annuloplasty using the Carillon® Mitral Contour System® annuloplasty device. However, he subsequently developed LBBB with associated reduction in exercise capacity, for which he underwent cardiac resynchronization therapy, and ensuing symptom improvement and stabilization. Discussion  Our case describes how targeted device interventions can be combined synergistically to optimize patient symptoms

The REDUCE FMR Trial: A Randomized Sham-Controlled Study of Percutaneous Mitral Annuloplasty in Functional Mitral Regurgitation

Objectives This study sought to evaluate the effects of the Carillon device on mitral regurgitation severity and left ventricular remodeling. Background Functional mitral regurgitation (FMR) complicates heart failure with reduced ejection fraction and is associated with a poor prognosis. Methods In this blinded, randomized, proof-of-concept, sham-controlled trial, 120 patients receiving optimal heart failure medical therapy were assigned to a coronary sinus-based mitral annular reduction approach for FMR or sham. The pre-specified primary endpoint was change in mitral regurgitant volume at 12 months, measured by quantitative echocardiography according to an intention-to-treat analysis. Results Patients (69.8 ± 9.5 years of age) were randomized to either the treatment (n = 87) or the sham-controlled (n = 33) arm. There were no significant differences in baseline characteristics between the groups. In the treatment group, 73 of 87 (84%) had the device implanted. The primary endpoint was met, with a statistically significant reduction in mitral regurgitant volume in the treatment group compared to the control group (decrease of 7.1 ml/beat [95% confidence interval [CI]: −11.7 to −2.5] vs. an increase of 3.3 ml/beat [95% CI: −6.0 to 12.6], respectively; p = 0.049). Additionally, there was a significant reduction in left ventricular volumes in patients receiving the device versus those in the control group (left ventricular end-diastolic volume decrease of 10.4 ml [95% CI: −18.5 to −2.4] vs. an increase of 6.5 ml [95% CI: −5.1 to 18.2]; p = 0.03 and left ventricular end-systolic volume decrease of 6.2 ml [95% CI: −12.8 to 0.4] vs. an increase of 6.1 ml [95% CI: −1.42 to 13.6]; p = 0.04). Conclusions The Carillon device significantly reduced mitral regurgitant volume and left ventricular volumes in symptomatic patients with functional mitral regurgitation receiving optimal medical therapy. (Carillon Mitral Contour System for Reducing Functional Mitral Regurgitation [REDUCE FMR]; NCT02325830

Maternal psychological distress in primary care and association with child behavioural outcomes at age three

Observational studies indicate children whose mothers have poor mental health are at increased risk of socio-emotional behavioural difficulties, but it is unknown whether these outcomes vary by the mothers’ mental health recognition and treatment status. To examine this question, we analysed linked longitudinal primary care and research data from 1078 women enrolled in the Born in Bradford cohort. A latent class analysis of treatment status and self-reported distress broadly categorised women as (a) not having a common mental disorder (CMD) that persisted through pregnancy and the first 2 years after delivery (N = 756, 70.1 %), (b) treated for CMD (N = 67, 6.2 %), or (c) untreated (N = 255, 23.7 %). Compared to children of mothers without CMD, 3-year-old children with mothers classified as having untreated CMD had higher standardised factor scores on the Strengths and Difficulties Questionnaire (d = 0.32), as did children with mothers classified as having treated CMD (d = 0.27). Results were only slightly attenuated in adjusted analyses. Children of mothers with CMD may be at risk for socio-emotional and behavioural difficulties. The development of effective treatments for CMD needs to be balanced by greater attempts to identify and treat women. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00787-015-0777-2) contains supplementary material, which is available to authorized users

Mathematical modelling of polyamine metabolism in bloodstream-form trypanosoma brucei: An application to drug target identification

© 2013 Gu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThis article has been made available through the Brunel Open Access Publishing Fund.We present the first computational kinetic model of polyamine metabolism in bloodstream-form Trypanosoma brucei, the causative agent of human African trypanosomiasis. We systematically extracted the polyamine pathway from the complete metabolic network while still maintaining the predictive capability of the pathway. The kinetic model is constructed on the basis of information gleaned from the experimental biology literature and defined as a set of ordinary differential equations. We applied Michaelis-Menten kinetics featuring regulatory factors to describe enzymatic activities that are well defined. Uncharacterised enzyme kinetics were approximated and justified with available physiological properties of the system. Optimisation-based dynamic simulations were performed to train the model with experimental data and inconsistent predictions prompted an iterative procedure of model refinement. Good agreement between simulation results and measured data reported in various experimental conditions shows that the model has good applicability in spite of there being gaps in the required data. With this kinetic model, the relative importance of the individual pathway enzymes was assessed. We observed that, at low-to-moderate levels of inhibition, enzymes catalysing reactions of de novo AdoMet (MAT) and ornithine production (OrnPt) have more efficient inhibitory effect on total trypanothione content in comparison to other enzymes in the pathway. In our model, prozyme and TSHSyn (the production catalyst of total trypanothione) were also found to exhibit potent control on total trypanothione content but only when they were strongly inhibited. Different chemotherapeutic strategies against T. brucei were investigated using this model and interruption of polyamine synthesis via joint inhibition of MAT or OrnPt together with other polyamine enzymes was identified as an optimal therapeutic strategy.The work was carried out under a PhD programme partly funded by Prof. Ray Welland, School of Computing Science, University of Glasgo

Changing gender roles and attitudes and their implications for well-being around the new millennium

<b>Purpose</b><p></p> Given evidence that gender role attitudes (GRAs) and actual gender roles impact on well-being, we examine associations between GRAs, three roles (marital status, household chore division, couple employment) and psychological distress in working-age men and women. We investigate time-trends reflecting broader social and economic changes, by focusing on three age groups at two dates.<p></p> <b>Methods</b><p></p> We used British Household Panel Survey data from 20- to 64-year-olds in heterosexual couple households in 1991 (N = 5,302) and 2007 (N = 6,621). We examined: levels of traditional GRAs according to gender, age, date, household and employment roles; associations which GRAs and roles had with psychological distress (measured via the GHQ-12); whether psychological distress increased when GRAs conflicted with actual roles; and whether any of these associations differed according to gender, age or date.<p></p> <b>Results</b><p></p> Gender traditionalism was lower among women, younger people, those participating in 2007 and in ‘less traditional’ relationships and households. Psychological distress was higher among those with more traditional GRAs and, particularly among men, for those not employed, and there was some evidence of different patterns of association according to age-group. There was limited evidence, among women only, of increased psychological distress when GRAs and actual roles conflicted and/or reductions when GRAs and roles agreed, particularly in respect of household chores and paid employment.<p></p> <b>Conclusions</b><p></p> Although some aspects of gender roles and attitudes (traditionalism and paid employment) are associated with well-being, others (marital status and household chores), and attitude-role consistency, may have little impact on the well-being of contemporary UK adults.<p></p&gt

A randomized double-blind trial of an interventional device treatment of functional mitral regurgitation in patients with symptomatic congestive heart failure-Trial design of the REDUCE FMR study

The Carillon Mitral Contour System has been studied in 3 nonrandomized trials in patients with symptomatic congestive heart failure and functional mitral regurgitation. The REDUCE FMR study is a uniquely designed, double-blind trial evaluating the impact of the Carillon device on reducing regurgitant volume, as well as assessing the safety and clinical efficacy of this device. Carillon is a coronary sinus-based indirect annuloplasty device. Eligible patients undergo an invasive venogram to assess coronary sinus vein suitability for the Carillon device. If the venous dimensions are suitable, they are randomized on a 3:1 basis to receive a device or not. Patients and assessors are blinded to the treatment assignment. The primary end point is the difference in regurgitant volume at 1 year between the implanted and nonimplanted groups. Other comparisons include clinical parameters such as heart failure hospitalizations, 6-minute walk test, Kansas City Cardiomyopathy Questionnaire (KCCQ), and other echocardiographic parameters. An exercise echo substudy will also be included