Prevalence, predictors and prognostic implications of PR interval prolongation in patients with heart failure

Aims: To determine the prevalence, incidence, predictors and prognostic implications of PR interval prolongation in patients referred with suspected heart failure. Methods and Results: Consecutive patients referred with suspected heart failure were prospectively enrolled. After excluding patients with implantable cardiac devices and atrial fibrillation, 1420 patients with heart failure and reduced ejection fraction (HeFREF) [age: median 71 (interquartile range IQR: 63-78) years; men: 71%; NT-ProBNP: 1319 (583-3378) ng/L], 1094 with heart failure and normal ejection fraction (HeFNEF) [age: 76 (70-82) years; men: 47%; NT-ProBNP: 547 (321-1171) ng/L], and 1150 without heart failure [age: 68 (60-75) years; men: 51%; NT-ProBNP: 86 (46-140) ng/L] were included. The prevalence of first degree heart block [heart-rate corrected PR interval (PRc) >200 ms] was higher in patients with heart failure (21% HeFREF, 20% HeFNEF, 9% without heart failure). In patients with HeFREF or HeFNEF, longer baseline PRc was associated with greater age, male sex, and longer QRS duration and, in those with HeFREF, treatment with amiodarone or digoxin. Patients with heart failure in the longest PRc quartile had worse survival compared to shorter PRc quartiles but PRc was not independently associated with survival in multivariable analysis. For patients without heart failure, shorter baseline PRc was independently associated with worse survival. Conclusion: PRc prolongation is common in patients with HeFREF or HeFNEF and associated with worse survival, although not an independent predictor of outcome. The results of clinical trials investigating the therapeutic potential of shortening the PR interval by pacing are awaited

Incorporating corrosion measurement in hip wear simulators: An added complication or a necessity?

Corrosion is not routinely considered in the assessment of the degradation or the lifetime of total hip replacement bearing surfaces. Biomechanical simulations are becoming ever more complex and are taking into account motion cycles that represent activities beyond a simple walking gait at 1 Hz, marking a departure from the standard ISO BS 14242. However, the degradation is still very often referred to as wear, even though the material loss occurs due to a combination of tribological and corrosion processes and their interactions. This article evaluates how, by incorporating real-time corrosion measurements in total hip replacement simulations, pre-clinical evaluations and research studies can both yield much more information and accelerate the process towards improved implants

The quest for the solar g modes

Solar gravity modes (or g modes) -- oscillations of the solar interior for which buoyancy acts as the restoring force -- have the potential to provide unprecedented inference on the structure and dynamics of the solar core, inference that is not possible with the well observed acoustic modes (or p modes). The high amplitude of the g-mode eigenfunctions in the core and the evanesence of the modes in the convection zone make the modes particularly sensitive to the physical and dynamical conditions in the core. Owing to the existence of the convection zone, the g modes have very low amplitudes at photospheric levels, which makes the modes extremely hard to detect. In this paper, we review the current state of play regarding attempts to detect g modes. We review the theory of g modes, including theoretical estimation of the g-mode frequencies, amplitudes and damping rates. Then we go on to discuss the techniques that have been used to try to detect g modes. We review results in the literature, and finish by looking to the future, and the potential advances that can be made -- from both data and data-analysis perspectives -- to give unambiguous detections of individual g modes. The review ends by concluding that, at the time of writing, there is indeed a consensus amongst the authors that there is currently no undisputed detection of solar g modes.Comment: 71 pages, 18 figures, accepted by Astronomy and Astrophysics Revie

Inherited variants in regulatory T cell genes and outcome of ovarian cancer.

Although ovarian cancer is the most lethal of gynecologic malignancies, wide variation in outcome following conventional therapy continues to exist. The presence of tumor-infiltrating regulatory T cells (Tregs) has a role in outcome of this disease, and a growing body of data supports the existence of inherited prognostic factors. However, the role of inherited variants in genes encoding Treg-related immune molecules has not been fully explored. We analyzed expression quantitative trait loci (eQTL) and sequence-based tagging single nucleotide polymorphisms (tagSNPs) for 54 genes associated with Tregs in 3,662 invasive ovarian cancer cases. With adjustment for known prognostic factors, suggestive results were observed among rarer histological subtypes; poorer survival was associated with minor alleles at SNPs in RGS1 (clear cell, rs10921202, p = 2.7×10(-5)), LRRC32 and TNFRSF18/TNFRSF4 (mucinous, rs3781699, p = 4.5×10(-4), and rs3753348, p = 9.0×10(-4), respectively), and CD80 (endometrioid, rs13071247, p = 8.0×10(-4)). Fo0r the latter, correlative data support a CD80 rs13071247 genotype association with CD80 tumor RNA expression (p = 0.006). An additional eQTL SNP in CD80 was associated with shorter survival (rs7804190, p = 8.1×10(-4)) among all cases combined. As the products of these genes are known to affect induction, trafficking, or immunosuppressive function of Tregs, these results suggest the need for follow-up phenotypic studies

Lifestyle interventions are feasible in patients with colorectal cancer with potential short-term health benefits:a systematic review

Purpose: Lifestyle interventions have been proposed to improve cancer survivorship in patients with colorectal cancer (CRC), but with treatment pathways becoming increasingly multi-modal and prolonged, opportunities for interventions may be limited. This systematic review assessed the evidence for the feasibility of performing lifestyle interventions in CRC patients and evaluated any short- and long-term health benefits. Methods: Using PRISMA Guidelines, selected keywords identified randomised controlled studies (RCTs) of lifestyle interventions [smoking, alcohol, physical activity (PA) and diet/excess body weight] in CRC patients. These electronic databases were searched in June 2015: Dynamed, Cochrane Database, OVID MEDLINE, OVID EMBASE, and PEDro. Results: Fourteen RCTs were identified: PA RCTs (n = 10) consisted mainly of telephone-prompted walking or cycling interventions of varied durations, predominately in adjuvant setting; dietary/excess weight interventions RCTs (n = 4) focused on low-fat and/or high-fibre diets within a multi-modal lifestyle intervention. There were no reported RCTs in smoking or alcohol cessation/reduction. PA and/or dietary/excess weight interventions reported variable recruitment rates, but good adherence and retention/follow-up rates, leading to short-term improvements in dietary quality, physical, psychological and quality-of-life parameters. Only one study assessed long-term follow-up, finding significantly improved cancer-specific survival after dietary intervention. Conclusions: This is the first systematic review on lifestyle interventions in patients with CRC finding these interventions to be feasible with improvements in short-term health. Future work should focus on defining the optimal type of intervention (type, duration, timing and intensity) that not only leads to improved short-term outcomes but also assesses long-term survival

Underrepresentation of Elderly People in Randomised Controlled Trials. The Example of Trials of 4 Widely Prescribed Drugs

BACKGROUND: We aimed to determine the representation of elderly people in published reports of randomized controlled trials (RCTs). We focused on trials of 4 medications--pioglitazone, rosuvastatin, risedronate, and valsartan-frequently used by elderly patients with chronic medical conditions. METHODS AND FINDINGS: We selected all reports of RCTs indexed in PubMed from 1966 to April 2008 evaluating one of the 4 medications of interest. Estimates of the community-based "on-treatment" population were from a national health insurance database (SNIIR-AM) covering approximately 86% of the population in France. From this database, we evaluated data claims from January 2006 to December 2007 for 1,958,716 patients who received one of the medications of interest for more than 6 months. Of the 155 RCT reports selected, only 3 studies were exclusively of elderly patients (2 assessing valsartan; 1 risedronate). In only 4 of 37 reports (10.8%) for pioglitazone, 4 of 22 (18.2%) for risedronate, 3 of 29 (10.3%) for rosuvastatine and 9 of 67 (13.4%) for valsartan, the proportion of patients aged 65 or older was within or above that treated in clinical practice. In 62.2% of the reports for pioglitazone, 40.9% for risedronate, 37.9% for rosuvastatine, and 70.2% for valsartan, the proportion of patients aged 65 or older was lower than half that in the treated population. The representation of elderly people did not differ by publication date or sample size. CONCLUSIONS: Elderly patients are poorly represented in RCTs of drugs they are likely to receive

A haplotype of polymorphisms in ASE-1, RAI and ERCC1 and the effects of tobacco smoking and alcohol consumption on risk of colorectal cancer: a danish prospective case-cohort study

<p>Abstract</p> <p>Background</p> <p>Single nucleotide polymorphisms (SNPs) are the most frequent type of genetic variation in the human genome, and are of interest for the study of susceptibility to and protection from diseases. The haplotype at chromosome 19q13.2-3 encompassing the three SNPs <it>ASE-1 </it>G-21A, <it>RAI </it>IVS1 A4364G and <it>ERCC1 </it>Asn118Asn have been associated with risk of breast cancer and lung cancer. Haplotype carriers are defined as the homozygous carriers of <it>RAI </it>IVS1 A4364G^A, <it>ERCC1 </it>Asn118Asn^Tand <it>ASE-1 </it>G-21A^G. We aimed to evaluate whether the three polymorphisms and the haplotype are associated to risk of colorectal cancer, and investigated gene-environment associations between the polymorphisms and the haplotype and smoking status at enrolment, smoking duration, average smoking intensity and alcohol consumption, respectively, in relation to risk of colorectal cancer.</p> <p>Methods</p> <p>Associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were examined, as well as gene-environment interaction, in a Danish case-cohort study including 405 cases and a comparison group of 810 persons. Incidence rate ratio (IRR) were estimated by the Cox proportional hazards model stratified according to gender, and two-sided 95% confidence intervals (CI) and p-values were calculated based on robust estimates of the variance-covariance matrix and Wald's test of the Cox regression parameter.</p> <p>Results</p> <p>No consistent associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were found. No statistically significant interactions between the genotypes and the lifestyle exposures smoking or alcohol consumption were observed.</p> <p>Conclusion</p> <p>Our results suggest that the <it>ASE-1 </it>G-21A, <it>RAI </it>IVS1 A4364G and <it>ERCC1 </it>Asn118Asn polymorphisms and the previously identified haplotype are not associated with risk of colorectal cancer. We found no evidence of gene-environment interaction between the three polymorphisms and the haplotype and smoking intensity and alcohol consumption, respectively, in relation to the risk of colorectal cancer.</p