Prediction of mortality rates in heart failure patients with data mining methods

Heart failure is one of the severe diseases which menace the human health and affectmillions of people. Half of all patients diagnosed with heart failure die within four years. For thepurpose of avoiding life-threatening situations and minimizing the costs, it is important to predictmortality rates of heart failure patients. As part of a HEIF-5 project, a data mining study wasconducted aiming specifically at extracting new knowledge from a group of patients suffering fromheart failure and using it for prediction of mortality rates. The methodology of knowledge discoveryin databases is analyzed within the framework of home telemonitoring. Several data mining methodssuch as a Bayesian network method, a decision tree method, a neural network method and a nearestneighbour method are employed. The accuracy for the data mining methods from the point of view ofavoiding life-threatening situations and minimizing the costs is discussed. It seems that the decisiontree method achieves the best accuracy results and is also interpretable for the clinicians

Commercial users panel

The discussions of motives and requirements for telerobotics application demonstrated that, in many cases, lack of progress was a result not of limited opportunities but of inadequate mechanisms and resources for promoting opportunities. Support for this conclusion came from Telerobotics, Inc., one of the few companies devoted primarily to telerobot systems. They have produced units for such diverse applications as nuclear fusion research, particle accelerators, cryogenics, firefighting, marine biology/undersea systems and nuclear mobile robotics. Mr. Flatau offered evidence that telerobotics research is only rarely supported by the private sector and that it often presents a difficult market. Questions on the mechanisms contained within the NASA technology transfer process for promoting commercial opportunities were fielded by Ray Gilbert and Tom Walters. A few points deserve emphasis: (1) NASA/industry technology transfer occurs in both directions and NASA recognizes the opportunity to learn a great deal from industry in the fields of automation and robotics; (2) promotion of technology transfer projects takes a demand side approach, with requests to industry for specific problem identification. NASA then proposes possible solutions; and (3) comittment ofmotivated and technically qualified people on each end of a technology transfer is essential

Forum: Parental education and child mortality

None supplied

Biomarker profiles of acute heart failure patients with a mid-range ejection fraction

OBJECTIVES: In this study, the authors used biomarker profiles to characterize differences between patients with acute heart failure with a midrange ejection fraction (HFmrEF) and compare them with patients with a reduced (heart failure with a reduced ejection fraction [HFrEF]) and preserved (heart failure with a preserved ejection fraction [HFpEF]) ejection fraction. BACKGROUND: Limited data are available on biomarker profiles in acute HFmrEF. METHODS: A panel of 37 biomarkers from different pathophysiological domains (e.g., myocardial stretch, inflammation, angiogenesis, oxidative stress, hematopoiesis) were measured at admission and after 24 h in 843 acute heart failure patients from the PROTECT trial. HFpEF was defined as left ventricular ejection fraction (LVEF) of ≥50% (n = 108), HFrEF as LVEF of <40% (n = 607), and HFmrEF as LVEF of 40% to 49% (n = 128). RESULTS: Hemoglobin and brain natriuretic peptide levels (300 pg/ml [HFpEF]; 397 pg/ml [HFmrEF]; 521 pg/ml [HFrEF]; ptrend <0.001) showed an upward trend with decreasing LVEF. Network analysis showed that in HFrEF interactions between biomarkers were mostly related to cardiac stretch, whereas in HFpEF, biomarker interactions were mostly related to inflammation. In HFmrEF, biomarker interactions were both related to inflammation and cardiac stretch. In HFpEF and HFmrEF (but not in HFrEF), remodeling markers at admission and changes in levels of inflammatory markers across the first 24 h were predictive for all-cause mortality and rehospitalization at 60 days (pinteraction <0.05). CONCLUSIONS: Biomarker profiles in patients with acute HFrEF were mainly related to cardiac stretch and in HFpEF related to inflammation. Patients with HFmrEF showed an intermediate biomarker profile with biomarker interactions between both cardiac stretch and inflammation markers. (PROTECT-1: A Study of the Selective A1 Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function; NCT00328692)

A network analysis to identify pathophysiological pathways distinguishing ischaemic from non-ischaemic heart failure

Aims Heart failure (HF) is frequently caused by an ischaemic event (e.g. myocardial infarction) but might also be caused by a primary disease of the myocardium (cardiomyopathy). In order to identify targeted therapies specific for either ischaemic or non‐ischaemic HF, it is important to better understand differences in underlying molecular mechanisms. Methods and results We performed a biological physical protein–protein interaction network analysis to identify pathophysiological pathways distinguishing ischaemic from non‐ischaemic HF. First, differentially expressed plasma protein biomarkers were identified in 1160 patients enrolled in the BIOSTAT‐CHF study, 715 of whom had ischaemic HF and 445 had non‐ischaemic HF. Second, we constructed an enriched physical protein–protein interaction network, followed by a pathway over‐representation analysis. Finally, we identified key network proteins. Data were validated in an independent HF cohort comprised of 765 ischaemic and 100 non‐ischaemic HF patients. We found 21/92 proteins to be up‐regulated and 2/92 down‐regulated in ischaemic relative to non‐ischaemic HF patients. An enriched network of 18 proteins that were specific for ischaemic heart disease yielded six pathways, which are related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. We identified five key network proteins: acid phosphatase 5, epidermal growth factor receptor, insulin‐like growth factor binding protein‐1, plasminogen activator urokinase receptor, and secreted phosphoprotein 1. Similar results were observed in the independent validation cohort. Conclusions Pathophysiological pathways distinguishing patients with ischaemic HF from those with non‐ischaemic HF were related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. The five key pathway proteins identified are potential treatment targets specifically for patients with ischaemic HF

Trajectories of Changes in Renal Function in Patients with Acute Heart Failure

Aims: Changes in renal function have been associated with differential outcome in patients with acute heart failure (HF). However, individual trajectories of changes in renal function are unknown and it is unclear whether these relate to different clinical characteristics and clinical outcome. Our aim was to investigate the prognostic importance of individual trajectories of changes in renal function in acute HF. Methods and Results: This was a retrospective, observational analysis from the double-blind, randomized, placebo controlled PROTECT trial in acute HF patients. We identified and internally validated 8 different renal trajectories among 1897 patients by visual inspection of inhospital serum creatinine changes. The primary outcome measure was all-cause mortality at 180 days. Mean age was 70±12 years, 70% were male, and mean baseline eGFR was 49.0 mL/min/1.73m2. A total of eight different trajectories were established. The most prevalent trajectories were an inhospital bump (19.0%), a sustained increase (17.6%), and a dip (14.5%) in serum creatinine. Overall, clinical characteristics of patients within different trajectories were remarkably similar. Crude 180-day mortality rates ranged from 12.0% in the trajectory with no significant changes to 18.3% in trajectory of sustained increase without significant differences. Overall, after multivariable adjustment, there was no trajectory of changes in renal function that was associated with significantly better or worse outcomes. Conclusions: Trajectories of changes in renal function in acute HF differ considerably on patient level. Despite these differences, clinical characteristics and outcome were similar, therefore questioning the prognostic importance of changes in renal function in acute HF

Computing prime factors with a Josephson phase qubit quantum processor

A quantum processor (QuP) can be used to exploit quantum mechanics to find the prime factors of composite numbers[1]. Compiled versions of Shor's algorithm have been demonstrated on ensemble quantum systems[2] and photonic systems[3-5], however this has yet to be shown using solid state quantum bits (qubits). Two advantages of superconducting qubit architectures are the use of conventional microfabrication techniques, which allow straightforward scaling to large numbers of qubits, and a toolkit of circuit elements that can be used to engineer a variety of qubit types and interactions[6, 7]. Using a number of recent qubit control and hardware advances [7-13], here we demonstrate a nine-quantum-element solid-state QuP and show three experiments to highlight its capabilities. We begin by characterizing the device with spectroscopy. Next, we produces coherent interactions between five qubits and verify bi- and tripartite entanglement via quantum state tomography (QST) [8, 12, 14, 15]. In the final experiment, we run a three-qubit compiled version of Shor's algorithm to factor the number 15, and successfully find the prime factors 48% of the time. Improvements in the superconducting qubit coherence times and more complex circuits should provide the resources necessary to factor larger composite numbers and run more intricate quantum algorithms.Comment: 5 pages, 3 figure

Rivaroxaban in patients with heart failure, sinus rhythm, and coronary disease

Background: Heart failure is associated with activation of thrombin-related pathways, which predicts a poor prognosis. We hypothesized that treatment with rivaroxaban, a factor Xa inhibitor, could reduce thrombin generation and improve outcomes for patients with worsening chronic heart failure and underlying coronary artery disease. Methods: In this double-blind, randomized trial, 5022 patients who had chronic heart failure, a left ventricular ejection fraction of 40% or less, coronary artery disease, and elevated plasma concentrations of natriuretic peptides and who did not have atrial fibrillation were randomly assigned to receive rivaroxaban at a dose of 2.5 mg twice daily or placebo in addition to standard care after treatment for an episode of worsening heart failure. The primary efficacy outcome was the composite of death from any cause, myocardial infarction, or stroke. The principal safety outcome was fatal bleeding or bleeding into a critical space with a potential for causing permanent disability. Results: Over a median follow-up period of 21.1 months, the primary end point occurred in 626 (25.0%) of 2507 patients assigned to rivaroxaban and in 658 (26.2%) of 2515 patients assigned to placebo (hazard ratio, 0.94; 95% confidence interval [CI], 0.84 to 1.05; P=0.27). No significant difference in all-cause mortality was noted between the rivaroxaban group and the placebo group (21.8% and 22.1%, respectively; hazard ratio, 0.98; 95% CI, 0.87 to 1.10). The principal safety outcome occurred in 18 patients who took rivaroxaban and in 23 who took placebo (hazard ratio, 0.80; 95% CI, 0.43 to 1.49; P=0.48). Conclusions: Rivaroxaban at a dose of 2.5 mg twice daily was not associated with a significantly lower rate of death, myocardial infarction, or stroke than placebo among patients with worsening chronic heart failure, reduced left ventricular ejection fraction, coronary artery disease, and no atrial fibrillation. (Funded by Janssen Research and Development; COMMANDER HF ClinicalTrials.gov number, NCT01877915.

Distinct pathophysiological pathways in women and men with heart failure

Aims: Clinical differences between women and men have been described in heart failure (HF). However, less is known about the underlying pathophysiological mechanisms. In this study, we compared multiple circulating biomarkers to gain better insights into differential HF pathophysiology between women and men. Methods and Results: In 537 women and 1485 men with HF, we compared differential expression of a panel of 363 biomarkers. Then, we performed a pathway over-representation analysis to identify differential biological pathways in women and men. Findings were validated in an independent HF cohort (575 women, 1123 men). In both cohorts, women were older and had higher ejection fraction (LVEF). In the index and validation cohorts respectively, we found 14/363 and 12/363 biomarkers that were relatively up-regulated in women, while 21/363 and 14/363 were up-regulated in men. In both cohorts, the strongest up-regulated biomarkers in women were leptin and fatty acid binding protein-4, compared to matrix metalloproteinase-3 in men. Similar findings were replicated in a subset of patients from both cohorts matched by age and LVEF. Pathway over-representation analysis revealed increased activity of pathways associated with lipid metabolism in women, and neuroinflammatory response in men (all p < 0.0001). Conclusion: In two independent cohorts of HF patients, biomarkers associated with lipid metabolic pathways were observed in women, while biomarkers associated with neuro-inflammatory response were more active in men. Differences in inflammatory and metabolic pathways may contribute to sex differences in clinical phenotype observed in HF, and provide useful insights towards development of tailored HF therapies

The causes of stalling fertility transitions

An examination of fertility trends in countries with multiple DHS surveys found that in the 1990s fertility stalled in mid-transition in seven countries: Bangladesh, Colombia, Dominican Republic, Ghana, Kenya, Peru, and Turkey. An analysis of trends in the determinants of fertility revealed a systematic pattern of leveling off or near leveling in a number of determinants, including contraceptive use, the demand for contraception, and wanted fertility. Findings suggest no major deterioration in contraceptive access during the stall, but levels of unmet need and unwanted fertility are relatively high and improvements in access to family planning methods would therefore be desirable. No significant link was found between the presence of a stall and trends in socioeconomic development, but at the onset of the stall the level of fertility was low relative to the level of development in all but one of the stalling countries