Biofilms in surface waters primarily consist of allochthonous microorganisms. Under conditions of pollution faecally derived bacteria may interact with these biofilms. Total coliform bacteria, ...Escherichia coli and intestinal enterococci are used to monitor source water quality, indicating faecal pollution and the possible presence of enteric pathogens. In the present study the occurrence of faecal indicators was investigated in biofilms (epilithic biofilms, sediments) of German rivers. All of the biofilms contained significant concentrations of these bacteria, which were several orders of magnitude lower compared with the total cell number and the number of culturable heterotrophic plate count bacteria indicating that faecal indicator bacteria represented a minor fraction of the whole biofilm communities. The biofilms displayed approximately two orders of magnitude higher concentrations of total coliforms, E. coli and enterococci compared with the overlying water. Identification of coliform and enterococcal isolates from the biofilms revealed the presence of species which are known to be opportunistic pathogens. Overall, the results of the present study show that faecal indicator bacteria can survive in the presence of high cell densities of the authochthonous microflora in epilithic biofilms and sediments, suggesting that these biofilms may act as a reservoir for bacterial pathogens in polluted rivers.
Aortic dilations (ectasias and aneurysms) may occur on any segment of the aorta. Pathogenesis varies between locations, suggesting that etiology and risk factors may differ. Despite this discrepancy, ...guidelines recommend screening of the whole aorta if 1 segmental dilation is discovered.
The purpose of this study was to determine the most dominant predictors for dilations at the ascending, arch, descending, and abdominal part of the aorta, and to establish comprehensive risk factor profiles for each aortic segment.
Individuals aged 60-74 years were randomly selected to participate in DANCAVAS I+II (Danish Cardiovascular Multicenter Screening Trials). Participants underwent cardiovascular risk assessments, including blood samples, blood pressure readings, medical records, and noncontrast computed tomography scans. Adjusted odds ratios for potential risk factors of dilations were estimated by multivariate logistic analyses.
The study population consisted of 14,989 participants (14,235 men, 754 women) with an average age of 68 ± 4 years. The highest adjusted odd ratios for having any aortic dilation were observed when coexisting aortic dilations were present. Other noteworthy predictors included coexisting iliac dilations, hypertension, increasing body surface area, male sex, familial disposition, and atrial fibrillation, which were present in various combinations for the different aortic parts. Smoking and acute myocardial infarction were inversely associated with ascending and abdominal dilations. Diabetes was a shared protective factor.
Risk factors differ for aortic dilations between locations. The most dominant predictor for having a dilation at any aortic segment is the presence of an aortic dilation elsewhere. This supports current guidelines when recommending a full screening of the aorta if a focal aortic dilation is discovered.
The DANISH study (Danish Study to Assess the Efficacy of ICDs Implantable Cardioverter Defibrillators in Patients With Non-Ischemic Systolic Heart Failure on Mortality) did not demonstrate an overall ...effect on all-cause mortality with ICD implantation. However, the prespecified subgroup analysis suggested a possible age-dependent association between ICD implantation and mortality with survival benefit seen only in the youngest patients. The nature of this relationship between age and outcome of a primary prevention ICD in patients with nonischemic systolic heart failure warrants further investigation.
All 1116 patients from the DANISH study were included in this prespecified subgroup analysis. We assessed the relationship between ICD implantation and mortality by age, and an optimal age cutoff was estimated nonparametrically with selection impact curves. Modes of death were divided into sudden cardiac death and nonsudden death and compared between patients younger and older than this age cutoff with the use of χ
analysis.
Median age of the study population was 63 years (range, 21-84 years). There was a linearly decreasing relationship between ICD and mortality with age (hazard ratio HR, 1.03; 95% confidence interval CI, 1.003-1.06;
=0.03). An optimal age cutoff for ICD implantation was present at ≤70 years. There was an association between reduced all-cause mortality and ICD in patients ≤70 years of age (HR, 0.70; 95% CI, 0.51-0.96;
=0.03) but not in patients >70 years of age (HR, 1.05; 95% CI, 0.68-1.62;
=0.84). For patients ≤70 years old, the sudden cardiac death rate was 1.8 (95% CI, 1.3-2.5) and nonsudden death rate was 2.7 (95% CI, 2.1-3.5) events per 100 patient-years, whereas for patients >70 years old, the sudden cardiac death rate was 1.6 (95% CI, 0.8-3.2) and nonsudden death rate was 5.4 (95% CI, 3.7-7.8) events per 100 patient-years. This difference in modes of death between the 2 age groups was statistically significant (
=0.01).
In patients with systolic heart failure not caused by ischemic heart disease, the association between the ICD and survival decreased linearly with increasing age. In this study population, an age cutoff for ICD implantation at ≤70 years yielded the highest survival for the population as a whole.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT00542945.
Class 1 cytokine receptors regulate essential biological processes through complex intracellular signalling networks. However, the structural platform for understanding their functions is currently ...incomplete as structure-function studies of the intracellular domains (ICDs) are critically lacking. The present study provides the first comprehensive structural characterization of any cytokine receptor ICD and demonstrates that the human prolactin (PRL) receptor (PRLR) and growth hormone receptor (GHR) ICDs are intrinsically disordered throughout their entire lengths. We show that they interact specifically with hallmark lipids of the inner plasma membrane leaflet through conserved motifs resembling immuno receptor tyrosine-based activation motifs (ITAMs). However, contrary to the observations made for ITAMs, lipid association of the PRLR and GHR ICDs was shown to be unaccompanied by changes in transient secondary structure and independent of tyrosine phosphorylation. The results of the present study provide a new structural platform for studying class 1 cytokine receptors and may implicate the membrane as an active component regulating intracellular signalling.
Abstract
Aims
A recent trial has shown that screening of men for cardiovascular disease (CVD) may reduce all-cause mortality. This study assesses the cost effectiveness of such screening vs. no ...screening from the perspective of European healthcare systems.
Methods and results
Randomized controlled trial-based cost-effectiveness evaluation with a mean 5.7 years of follow-up. Screening was based on low-dose computed tomography to detect coronary artery calcification and aortic/iliac aneurysms, limb blood pressure measurement to detect peripheral artery disease and hypertension, telemetric assessment of the heart rhythm to detect atrial fibrillation, and measurements of the cholesterol and HgbA1c levels. Censoring-adjusted incremental costs, life years (LY), and quality-adjusted LY (QALY) were estimated and used for cost-effectiveness analysis. The incremental cost of screening for the entire health care sector was €207 95% confidence interval (CI) −24; 438, P = 0.078 per invitee for which gains of 0.019 LY (95% CI −0.007; 0.045, P = 0.145) and 0.023 QALY (95% CI −0.001; 0.046, P = 0.051) were achieved. The corresponding incremental cost-effectiveness ratios were of €10 812 per LY and €9075 per QALY, which would be cost effective at probabilities of 0.73 and 0.83 for a willingness to pay of €20 000. Assessment of population heterogeneity showed that cost effectiveness could be more attractive for younger men without CVD at baseline.
Conclusions
Comprehensive screening for CVD is overall cost effective at conventional thresholds for willingness to pay and also competitive to the cost effectiveness of common cancer screening programmes. The screening target group, however, needs to be settled.
DANISH (The Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators ICDs in Patients With Nonischemic Systolic Heart Failure on Mortality) found that primary-prevention ICD ...implantation was not associated with an overall survival benefit in patients with nonischemic systolic heart failure during a median follow-up of 5.6 years, although there was a beneficial effect on all-cause mortality in patients ≤70 years. This study presents an additional 4 years of follow-up data from DANISH.
In DANISH, 556 patients with nonischemic systolic heart failure were randomized to receive an ICD and 560 to receive usual clinical care and followed until June 30, 2016. In this long-term follow-up study, patients were followed until May 18, 2020. Analyses were conducted for the overall population and according to age (≤70 and >70 years).
During a median follow-up of 9.5 years (25th-75th percentile, 7.9-10.9 years), 208/556 patients (37%) in the ICD group and 226/560 patients (40%) in the control group died. Compared with the control group, the ICD group did not have significantly lower all-cause mortality (hazard ratio HR 0.89, 95% CI, 0.74-1.08;
= 0.24). In patients ≤70 years (n = 829), all-cause mortality was lower in the ICD group than the control group (117/389 30% versus 158/440 36%; HR, 0.78 95% CI, 0.61-0.99;
= 0.04), whereas in patients >70 years (n = 287), all-cause mortality was not significantly different between the ICD and control group (91/167 54% versus 68/120 57%; HR, 0.92 95% CI, 0.67-1.28;
= 0.75). Cardiovascular death showed similar trends (overall, 147/556 26% versus 164/560 29%; HR, 0.87 95% CI, 0.70-1.09;
= 0.20; ≤70 years, 87/389 22% versus 122/440 28%; HR, 0.75 95% CI, 0.57-0.98;
= 0.04; >70 years, 60/167 36% versus 42/120 35%; HR, 0.97 95% CI, 0.65-1.45;
= 0.91). The ICD group had a significantly lower incidence of sudden cardiovascular death in the overall population (35/556 6% versus 57/560 10%; HR, 0.60 95% CI, 0.40-0.92;
= 0.02) and in patients ≤70 years (19/389 5% versus 49/440 11%; HR, 0.42 95% CI, 0.24-0.71;
= 0.0008), but not in patients >70 years (16/167 10% versus 8/120 7%; HR, 1.34 95% CI, 0.56-3.19;
= 0.39).
During a median follow-up of 9.5 years, ICD implantation did not provide an overall survival benefit in patients with nonischemic systolic heart failure. In patients ≤70 years, ICD implantation was associated with a lower incidence of all-cause mortality, cardiovascular death, and sudden cardiovascular death. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00542945.
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