The relation between repeated 6-minute walk test performance and outcome in patients with chronic heart failure

Objective: To assess the prognostic implications of the 6-minute walk test (6-MWT) distance measured twice, one year apart, in a large sample of patients with chronic heart failure (CHF) followed for an extended period ( > . 8. years from baseline). Material and methods: Patients undertook a 6-MWT at baseline and at one year, and were followed up for 8. years from baseline. Results: Six hundred patients (median [inter-quartile range, IQR]) (age 78 [72-84] years; 75% males; body mass index 27 [25-31] kg·m -2 ; left ventricular ejection fraction 34 [26-38] %) were included. At baseline, median 6-MWT distance was 232 (60-386) m. There was no significant change in 6-MWT distance at one year (change -12m; P=0.533). During a median follow-up of 8.0years in survivors, 396patients had died (66%). Four variables were independent predictors of all-cause mortality in a multivariable Cox model (adjusted for body mass index, age, QRS duration, left ventricular ejection fraction); increasing NT pro-BNP, decreasing 6-MWT distance at 1year, decreasing haemoglobin, and increasing urea. Conclusions: Distance walked during the 6-MWT is an independent predictor of all-cause mortality in patients with CHF. In survivors, the 6-MWT distance is stable at 1 year. The 6-MWT distance at 1 year carries similar prognostic information. © 2014 Elsevier Masson SAS

Exercise dose and all-cause mortality within extended cardiac rehabilitation: a cohort study.

AIMS: To investigate the relationship between exercise participation, exercise 'dose' expressed as metabolic equivalent (MET) hours (h) per week, and prognosis in individuals attending an extended, community-based exercise rehabilitation programme. METHODS: Cohort study of 435 participants undertaking exercise-based cardiac rehabilitation (CR) in Leeds, West Yorkshire, UK between 1994 and 2006, followed up to 1 November 2013. MET intensity of supervised exercise was estimated utilising serial submaximal exercise test results and corresponding exercise prescriptions. Programme participation was routinely monitored. Cox regression analysis including time-varying and propensity score adjustment was applied to identify predictors of long-term, all-cause mortality across exercise dose and programme duration groups. RESULTS: There were 133 events (31%) during a median follow-up of 14 years (range, 1.2 to 18.9 years). The significant univariate association between exercise dose and all-cause mortality was attenuated following multivariable adjustment for other predictors, including duration in the programme. Longer-term adherence to supervised exercise training (>36 months) was associated with a 33% lower mortality risk (multivariate-adjusted HR: 0.67; 95% CI: 0.47 to 0.97; p=0.033) compared with all lesser durations of CR (3, 12, 36 months), even after adjustment for baseline fitness, comorbidities and survivor bias. CONCLUSION: Exercise dose (MET-h per week) appears less important than long-term adherence to supervised exercise for the reduction of long-term mortality risk. Extended, supervised CR programmes within the community may play a key role in promoting long-term exercise maintenance and other secondary prevention therapies for survival benefit

Submaximal fitness and mortality risk reduction in coronary heart disease: a retrospective cohort study of community-based exercise rehabilitation.

To examine the association between submaximal cardiorespiratory fitness (sCRF) and all-cause mortality in a cardiac rehabilitation (CR) cohort.Retrospective cohort study of participants entering CR between 26 May 1993 and 16 October 2006, followed up to 1 November 2013 (median 14 years, range 1.2-19.4 years).A community-based CR exercise programme in Leeds, West Yorkshire, UK.A cohort of 534 men (76%) and 136 women with a clinical diagnosis of coronary heart disease (CHD), aged 22-82 years, attending CR were evaluated for the association between baseline sCRF and all-cause mortality. 416 participants with an exercise test following CR (median 14 weeks) were examined for changes in sCRF and all-cause mortality.All-cause mortality and change in sCRF expressed in estimated metabolic equivalents (METs).Baseline sCRF was a strong predictor of all-cause mortality; compared to the lowest sCRF group (<5 METs for women and <6 METs for men), mortality risk was 41% lower in those with moderate sCRF (HR 0.59; 95% CI 0.42 to 0.83) and 60% lower (HR 0.40; 95% CI 0.25 to 0.64) in those with higher sCRF levels (≥7 METs women and ≥8 METs for men). Although improvement in sCRF at 14 weeks was not associated with a significant mortality risk reduction (HR 0.91; 95% CI 0.79 to 1.06) for the whole cohort, in those with the lowest sCRF (and highest all-cause mortality) at baseline, each 1-MET improvement was associated with a 27% age-adjusted reduction in mortality risk (HR 0.73; 95% CI 0.57 to 0.94).Higher baseline sCRF is associated with a reduced risk of all-cause mortality over 14 years in adults with CHD. Improving fitness through exercise-based CR is associated with significant risk reduction for the least fit

Dynamics of antimicrobial resistance in intestinal Escherichia coli from children in community settings in South Asia and sub-Saharan Africa.

The dynamics of antimicrobial resistance (AMR) in developing countries are poorly understood, especially in community settings, due to a sparsity of data on AMR prevalence and genetics. We used a combination of phenotyping, genomics and antimicrobial usage data to investigate patterns of AMR amongst atypical enteropathogenic Escherichia coli (aEPEC) strains isolated from children younger than five years old in seven developing countries (four in sub-Saharan Africa and three in South Asia) over a three-year period. We detected high rates of AMR, with 65% of isolates displaying resistance to three or more drug classes. Whole-genome sequencing revealed a diversity of known genetic mechanisms for AMR that accounted for >95% of phenotypic resistance, with comparable rates amongst aEPEC strains associated with diarrhoea or asymptomatic carriage. Genetic determinants of AMR were associated with the geographic location of isolates, not E. coli lineage, and AMR genes were frequently co-located, potentially enabling the acquisition of multi-drug resistance in a single step. Comparison of AMR with antimicrobial usage data showed that the prevalence of resistance to fluoroquinolones and third-generation cephalosporins was correlated with usage, which was higher in South Asia than in Africa. This study provides much-needed insights into the frequency and mechanisms of AMR in intestinal E. coli in children living in community settings in developing countries

Ultraviolet photochemistry of 2-bromothiophene explored using universal ionization detection and multi-mass velocity-map imaging with a PImMS2 sensor

This project is funded by EPSRC Programme Grant No. EP/L005913/1. The raw ion events data and calculation log files can be retrieved from the University of Bristol’s research data repository and can be accessed using the following DOI:10.5523/bris.k35bi3pqsdbh2b5moo2e3puxf.The ultraviolet photochemistry of 2-bromothiophene (C4H3SBr) has been studied across the wavelength range 265-245 nm using a velocity-map imaging (VMI) apparatus recently modified for multi-mass imaging and vacuum ultraviolet (VUV, 118.2 nm) universal ionization. At all wavelengths, molecular products arising from the loss of atomic bromine were found to exhibit recoil velocities and anisotropies consistent with those reported elsewhere for the Br fragment [J. Chem. Phys. 142, 224303 (2015)]. Comparison between the momentum distributions of the Br and C4H3S fragments suggests that bromine is formed primarily in its ground (2P3/2) spin-orbit state. These distributions match well at high momentum, but relatively fewer slow moving molecular fragments were detected. This is explained by the observation of a second substantial ionic product, C3H3+. Analysis of ion images recorded simultaneously for several ion masses and the results of high-level ab initio calculations suggest that this fragment ion arises from dissociative ionization (by the VUV probe laser) of the most internally excited C4H3S fragments. This study provides an excellent benchmark for the recently modified VMI instrumentation and offers a powerful demonstration of the emerging field of multi-mass VMI using event-triggered, high frame-rate sensors, and universal ionization.Publisher PDFPeer reviewe

Increased resistance to biotrophic pathogens in the Arabidopsis constitutive induced resistance 1 mutant is EDS1 and PAD4-dependent and modulated by environmental temperature

The Arabidopsis constitutive induced resistance 1 ( cir1 ) mutant displays salicylic acid (SA)-dependent constitutive expression of defence genes and enhanced resistance to biotrophic pathogens. To further characterise the role of CIR1 in plant immunity we conducted epistasis analyses with two key components of the SA-signalling branch of the defence network, ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1) and PHYTOALEXIN DEFICIENT4 (PAD4). We demonstrate that the constitutive defence phenotypes of cir1 require both EDS1 and PAD4, indicating that CIR1 lies upstream of the EDS1-PAD4 regulatory node in the immune signalling network. In light of this finding we examined EDS1 expression in cir1 and observed increased protein, but not mRNA levels in this mutant, suggesting that CIR1 might act as a negative regulator of EDS1 via a post-transcriptional mechanism. Finally, as environmental temperature is known to influence the outcome of plant-pathogen interactions, we analysed cir1 plants grown at 18, 22 or 25°C. We found that susceptibility to Pseudomonas syringae pv. tomato ( Pst ) DC3000 is modulated by temperature in cir1 . Greatest resistance to this pathogen (relative to PR-1:LUC control plants) was observed at 18°C, while at 25°C no difference in susceptibility between cir1 and control plants was apparent. The increase in resistance to Pst DC3000 at 18°C correlated with a stunted growth phenotype, suggesting that activation of defence responses may be enhanced at lower temperatures in the cir1 mutant

Characterising the application of the “progressive overload” principle of exercise training within cardiac rehabilitation: A United Kingdom-based community programme

Background: Recent concerns have cast doubt over the effectiveness of cardiac rehabilitation [CR] programmes for improving cardiorespiratory fitness [CRF] in patients with a history of cardiac disease in the United Kingdom [UK]. We aimed to characterise the weekly progression of exercise training dose over an 8-week Phase III CR programme as we felt this may be partly responsible for the lack of improvement in CRF reported in previous studies. Design: Observational study. Methods: We evaluated a community-based Phase III CR programme in the UK. During each training session, patients wore an Apple Watch and the weekly progression of exercise training dose/load was quantified. The analysis was based on 332 individual training sessions. Exercise intensity [% heart rate reserve] during the cardiovascular [CV] exercise training component [%HRR-CV], CV training duration; estimated changes in cardiorespiratory fitness [change in estimated metabolic equivalents (METs)]; session rating of perceived exertion [sRPE], sRPE training load [sRPE-TL], and exercise training impulse [TRIMP] were evaluated. Results: Thirty cardiac patients [83% male; age [SD] 67.0 [10.0] years; body mass index [SD] 28.3 [4.6] kg∙m-2] were recruited to an 8-week programme [16 sessions in total]. Bayesian repeated-measures ANOVA indicated anecdotal evidence for the alternative hypothesis for changes in %HRR-CV (BF10 = 0.61), sRPE (BF10 = 1.1), and change in estimated METs (BF10 = 1.2) during CR. Conversely, Bayesian repeated-measures ANOVA showed extreme evidence for changes in CV training duration (BF10 = 2.438e+26), TRIMP (BF10 = 71436), and sRPE-TL (BF10 = 779570). Conclusion: The key exercise training principle of progressive overload was only partially applied. Increases observed in exercise dose were due to increases in the duration of CV training, rather than combined with increases in exercise intensity [%HRR-CV and sRPE]. Accordingly, allied health professionals must ensure that exercise intensity is more consistently progressed to optimise the exercise stimulus and improvements in CRF and patient outcomes