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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.

BACKGROUND: Limited data suggest a benefit of population-based screening for cardiovascular disease with respect to the risk of death.METHODS: We performed a population-based, parallel-group, randomized, controlled trial involving men 65 to 74 years of age living in 15 Danish municipalities. The participants were randomly assigned in a 1:2 ratio to undergo screening (the invited group) or not to undergo screening (the control group) for subclinical cardiovascular disease. Randomization was based on computer-generated random numbers and stratified according to municipality. Only the control group was unaware of the trial-group assignments. Screening included noncontrast electrocardiography-gated computed tomography to determine the coronary-artery calcium score and to detect aneurysms and atrial fibrillation, ankle-brachial blood-pressure measurements to detect peripheral artery disease and hypertension, and a blood sample to detect diabetes mellitus and hypercholesterolemia. The primary outcome was death from any cause.RESULTS: A total of 46,611 participants underwent randomization. After exclusion of 85 men who had died or emigrated before being invited to undergo screening, there were 16,736 men in the invited group and 29,790 men in the control group; 10,471 of the men in the invited group underwent screening (62.6%). In intention-to-treat analyses, after a median follow-up of 5.6 years, 2106 men (12.6%) in the invited group and 3915 men (13.1%) in the control group had died (hazard ratio, 0.95; 95% confidence interval [CI], 0.90 to 1.00; P = 0.06). The hazard ratio for stroke in the invited group, as compared with the control group, was 0.93 (95% CI, 0.86 to 0.99); for myocardial infarction, 0.91 (95% CI, 0.81 to 1.03); for aortic dissection, 0.95 (95% CI, 0.61 to 1.49); and for aortic rupture, 0.81 (95% CI, 0.49 to 1.35). There were no significant between-group differences in safety outcomes.CONCLUSIONS: After more than 5 years, the invitation to undergo comprehensive cardiovascular screening did not significantly reduce the incidence of death from any cause among men 65 to 74 years of age. (Funded by the Southern Region of Denmark and others; DANCAVAS ISRCTN Registry number, ISRCTN12157806.).

Quantification of histological information from excised human abdominal aortic aneurysm (AAA) specimens may provide essential information on the degree of infiltration of inflammatory cells in different regions of the AAA. Such information will support mechanistic insight in AAA pathology and can be linked to clinical measures for further development of AAA treatment regimens. We hypothesize that artificial intelligence can support high throughput analyses of histological sections of excised human AAA. We present an analysis framework based on supervised machine learning. We used TensorFlow and QuPath to determine the overall architecture of the AAA: thrombus, arterial wall, and adventitial loose connective tissue. Within the wall and adventitial zones, the content of collagen, elastin, and specific inflammatory cells was quantified. A deep neural network (DNN) was trained on manually annotated, Weigert stained, tissue sections (14 patients) and validated on images from two other patients. Finally, we applied the method on 95 new patient samples. The DNN was able to segment the sections according to the overall wall architecture with Jaccard coefficients after 65 epocs of 92% for the training and 88% for the validation data set, respectively. Precision and recall both reached 92%. The zone areas were highly variable between patients, as were the outputs on total cell count and elastin/collagen fiber content. The number of specific cells or stained area per zone was deterministically determined. However, combining the masks based on the Weigert stainings, with images of immunostained serial sections requires addition of landmark recognition to the analysis path. The combination of digital pathology, the DNN we developed, and landmark registration will provide a strong tool for future analyses of the histology of excised human AAA. In combination with biomechanical testing and microstructurally motivated mathematical models of AAA remodeling, the method has the potential to be a strong tool to provide mechanistic insight in the disease. In combination with each patients’ demographic and clinical profile, the method can be an interesting tool to in supportof a better treatment regime for the patients.

Vagrancy is critical in facilitating range expansion and colonization through exploration and occupation of potentially suitable habitat. Uncovering origins of vagrants will help us better understand not only species-specific vagrant movements, but how the dynamics of a naturally growing population influence vagrancy, and potentially lead to range expansion. Under the premise that occurrence of vagrants is linked to increasing population growth in the core of the breeding range, we assessed the utility of breeding population survey data to predict source populations of vagrants. Lesser Black-backed Gulls (LBBG) (Larus fuscus) served as our focal species due to their dramatic and well-documented history of vagrancy to North America in the last 30 years. We related annual occurrence of vagrants to indices of breeding population size and growth rate of breeding populations. We propose that the fastest growing population is the most likely source of recent vagrants to North America. Our study shows that it is possible to predict potential source populations of vagrants with breeding population data, but breeding surveys require increased standardization across years to improve models. For the Lesser Black-backed Gull, Iceland’s breeding population likely influenced vagrancy during the early years of colonization, but the major increase in vagrants occurred during a period of growth of Greenland’s population, suggesting that Greenland is the source population of the most recent pulse of vagrant LBBG to North America.

Objective: The purpose of this study was to investigate potential vasorelaxant effects of angiotensin AT2-receptor stimulation by the specific AT2-receptor agonist C21 in pericardial resistance arteries from cardiovascular disease patients. Methods: Parietal pericardium was obtained during coronary artery bypass-grafting and/or valve replacement in patients. Pericardial arteries from pigs and mesenteric arteries from C57BL-6J and AT2R deficient (AT2R-/y) mice were used for comparison. Isolated arteries were mounted onto wire myographs, pre-contracted with either K+, phenylephrine, endothelin-1 (ET-1) or the thromboxane agonist U46619, and the relaxing effect of C21 (0.1nM - 10μM) was investigated in the absence or presence of 3nM valsartan (AT1R antagonist), 10μM PD123319 or 10μM M132 (AT2R antagonists). Results: C21 significantly relaxed ET-1 contracted porcine arteries (Emax -37 ± 6 %; -0.87 vs -0.45 N/m relaxation; N=6; P Conclusion: Depended on species, vascular bed and contractile stimulus, C21 relaxes resistance-sized arteries by AT2R stimulation or by TXA2 antagonism. These data together with the low affinity binding of C21 to the TXA2 receptor and its effect on platelet aggregation strongly suggest that C21 is not only a high affinity, selective AT2R agonist, but also a low affinity TXA2 receptor antagonist.