Cost-effectiveness analysis of sacubitril/valsartan vs enalapril in patients with heart failure and reduced ejection fraction

Importance  The angiotensin receptor neprilysin inhibitor sacubitril/valsartan was associated with a reduction in cardiovascular mortality, all-cause mortality, and hospitalizations compared with enalapril. Sacubitril/valsartan has been approved for use in heart failure (HF) with reduced ejection fraction in the United States and cost has been suggested as 1 factor that will influence the use of this agent. Objective  To estimate the cost-effectiveness of sacubitril/valsartan vs enalapril in the United States. Design, Setting, and Participants  Data from US adults (mean [SD] age, 63.8 [11.5] years) with HF with reduced ejection fraction and characteristics similar to those in the PARADIGM-HF trial were used as inputs for a 2-state Markov model simulated HF. Risks of all-cause mortality and hospitalization from HF or other reasons were estimated with a 30-year time horizon. Quality of life was based on trial EQ-5D scores. Hospital costs combined Medicare and private insurance reimbursement rates; medication costs included the wholesale acquisition cost for sacubitril/valsartan and enalapril. A discount rate of 3% was used. Sensitivity analyses were performed on key inputs including: hospital costs, mortality benefit, hazard ratio for hospitalization reduction, drug costs, and quality-of-life estimates. Main Outcomes and Measures  Hospitalizations, quality-adjusted life-years (QALYs), costs, and incremental costs per QALY gained. Results  The 2-state Markov model of US adult patients (mean age, 63.8 years) calculated that there would be 220 fewer hospital admissions per 1000 patients with HF treated with sacubitril/valsartan vs enalapril over 30 years. The incremental costs and QALYs gained with sacubitril/valsartan treatment were estimated at $35 512 and 0.78, respectively, compared with enalapril, equating to an incremental cost-effectiveness ratio (ICER) of$45 017 per QALY for the base-case. Sensitivity analyses demonstrated ICERs ranging from $35 357 to$75 301 per QALY. Conclusions and Relevance  For eligible patients with HF with reduced ejection fraction, the Markov model calculated that sacubitril/valsartan would increase life expectancy at an ICER consistent with other high-value accepted cardiovascular interventions. Sensitivity analyses demonstrated sacubitril/valsartan would remain cost-effective vs enalapril

Uranium nitride-silicide advanced nuclear fuel: Higher efficiency and greater safety

The development of new nuclear fuel compositions is being driven by an interest in improving efficiency/lowering cost and increasing safety margins. Nuclear fuel efficiency is in large measure a function of the atomic density of the uranium, that is, the more fissionable uranium available per unit volume the less fuel volume that is required. Proliferation concerns limit the concentration of fissile 235U, and thus attention is directed to higher overall uranium content fuel. Among the options are the high temperature phases U3Si2 and composite UN- U3Si2 where the design would have the more water-stable U3Si2 surround the more soluble, but higher uranium density UN grains. (Uranium metal of course has the highest atomic density, however its low melting point, high degree of swelling under irradiation, and chemical reactivity eliminate it from consideration.) Another advantage of the nitride and silicide phases are their high thermal conductivity, greatly exceeding the current standard UO2 fuel, with the high conductivity potentially allowing the fuel to operate at a higher power density. Please click Additional Files below to see the full abstract

The employee as 'Dish of the Day’:human resource management and the ethics of consumption

This article examines the ethical implications of the growing integration of consumption into the heart of the employment relationship. Human resource management (HRM) practices increasingly draw upon the values and practices of consumption, constructing employees as the ‘consumers’ of ‘cafeteria-style’ benefits and development opportunities. However, at the same time employees are expected to market themselves as items to be consumed on a corporate menu. In relation to this simultaneous position of consumer/consumed, the employee is expected to actively engage in the commodification of themselves, performing an appropriate organizational identity as a necessary part of being a successful employee. This article argues that the relationship between HRM and the simultaneously consuming/consumed employee affects the conditions of possibility for ethical relations within organizational life. It is argued that the underlying ‘ethos’ for the integration of consumption values into HRM practices encourages a self-reflecting, self-absorbed subject, drawing upon a narrow view of individualised autonomy and choice. Referring to Levinas’ perspective that the primary ethical relation is that of responsibility and openness to the Other, it is concluded that these HRM practices affect the possibility for ethical being

Circulating cardiac troponin I levels measured by a novel highly sensitive assay in acute decompensated heart failure: insights from the ASCEND-HF trial

Background: Circulating cardiac troponin levels (cTn), representative of myocardial injury, are commonly elevated in heart failure (HF) and related to adverse clinical events. However, whether cTn represents a spectrum of risk in HF is unclear. Methods: Baseline, 48–72 hour, and 30 day plasma cTnI was measured by a novel highly-sensitive assay in 900 subjects with acute decompensated HF (ADHF) in ASCEND-HF. Multivariable models determined the relationship between cTnI and outcomes. Results: The median(interquartile range) cTnI was 16.4 (9.3-31.6) ng/L at baseline, 14.1 (7.8-29.7) ng/L at 48-72 hours, and 11.6 (6.8-22.5) ng/L at 30 days. After additional adjustment for amino terminal pro-B-type natriuretic peptide (NT-proBNP) to established risk predictors, both baseline and 48-72 hour cTnI were associated with higher risk for death or worsening HF prior to discharge (OR 1.25, P=0.03 and OR 1.43, P=0.001, respectively). However, only cTnI at 30 days was associated 180-day death (HR 1.25, P=0.007). There were no curvilinear associations between changing cTnI and clinical outcomes. Conclusions: Circulating cTnI level was associated with clinical outcomes in ADHF, but these observations diminished with additional adjustment for NT-proBNP. Although they likely represent a spectrum of risk in ADHF, these findings question the implications of changing cTnI levels during treatment

The Infrared Array Camera (IRAC) for the Spitzer Space Telescope

The Infrared Array Camera (IRAC) is one of three focal plane instruments in the Spitzer Space Telescope. IRAC is a four-channel camera that obtains simultaneous broad-band images at 3.6, 4.5, 5.8, and 8.0 microns. Two nearly adjacent 5.2x5.2 arcmin fields of view in the focal plane are viewed by the four channels in pairs (3.6 and 5.8 microns; 4.5 and 8 microns). All four detector arrays in the camera are 256x256 pixels in size, with the two shorter wavelength channels using InSb and the two longer wavelength channels using Si:As IBC detectors. IRAC is a powerful survey instrument because of its high sensitivity, large field of view, and four-color imaging. This paper summarizes the in-flight scientific, technical, and operational performance of IRAC.Comment: 7 pages, 3 figures. Accepted for publication in the ApJS. A higher resolution version is at http://cfa-www.harvard.edu/irac/publication

Rationale, design and conduct of a randomised controlled trial evaluating a primary care-based complex intervention to improve the quality of life of heart failure patients: HICMan (Heidelberg Integrated Case Management) : study protocol

Background: Chronic congestive heart failure (CHF) is a complex disease with rising prevalence, compromised quality of life (QoL), unplanned hospital admissions, high mortality and therefore high burden of illness. The delivery of care for these patients has been criticized and new strategies addressing crucial domains of care have been shown to be effective on patients' health outcomes, although these trials were conducted in secondary care or in highly organised Health Maintenance Organisations. It remains unclear whether a comprehensive primary care-based case management for the treating general practitioner (GP) can improve patients' QoL. Methods/Design: HICMan is a randomised controlled trial with patients as the unit of randomisation. Aim is to evaluate a structured, standardized and comprehensive complex intervention for patients with CHF in a 12-months follow-up trial. Patients from intervention group receive specific patient leaflets and documentation booklets as well as regular monitoring and screening by a prior trained practice nurse, who gives feedback to the GP upon urgency. Monitoring and screening address aspects of disease-specific selfmanagement, (non)pharmacological adherence and psychosomatic and geriatric comorbidity. GPs are invited to provide a tailored structured counselling 4 times during the trial and receive an additional feedback on pharmacotherapy relevant to prognosis (data of baseline documentation). Patients from control group receive usual care by their GPs, who were introduced to guidelineoriented management and a tailored health counselling concept. Main outcome measurement for patients' QoL is the scale physical functioning of the SF-36 health questionnaire in a 12-month follow-up. Secondary outcomes are the disease specific QoL measured by the Kansas City Cardiomyopathy questionnaire (KCCQ), depression and anxiety disorders (PHQ-9, GAD-7), adherence (EHFScBS and SANA), quality of care measured by an adapted version of the Patient Chronic Illness Assessment of Care questionnaire (PACIC) and NTproBNP. In addition, comprehensive clinical data are collected about health status, comorbidity, medication and health care utilisation. Discussion: As the targeted patient group is mostly cared for and treated by GPs, a comprehensive primary care-based guideline implementation including somatic, psychosomatic and organisational aspects of the delivery of care (HICMAn) is a promising intervention applying proven strategies for optimal care. Trial registration: Current Controlled Trials ISRCTN30822978

Adolescents with metabolic syndrome have a history of low aerobic fitness and physical activity levels

Abstract: Purpose: Metabolic syndrome (MS) is a clustering of cardiovascular disease risk factors that identifies individuals with the highest risk for heart disease. Two factors that may influence the MS are physical activity and aerobic fitness. This study determined if adolescent with the MS had low levels of aerobic fitness and physical activity as children. Methods: This longitudinal, exploratory study had 389 participants: 51% girls, 84% Caucasian, 12% African American, 1% Hispanic, and 3% other races, from the State of North Carolina. Habitual physical activity (PA survey), aerobic fitness (VO2max), body mass index (BMI), blood pressure, and lipids obtained at 7–10 y of age were compared to their results obtained 7 y later at ages 14–17 y. Results: Eighteen adolescents (4.6%) developed 3 or more characteristics of the MS. Logistic regression, adjusting for BMI percentile, blood pressure, and cholesterol levels, found that adolescents with the MS were 6.08 (95%CI = 1.18–60.08) times more likely to have low aerobic fitness as children and 5.16 (95%CI = 1.06–49.66) times more likely to have low PA levels. Conclusion: Low levels of childhood physical activity and aerobic fitness are associated with the presence of the metabolic syndrome in adolescents. Thus, efforts need to begin early in childhood to increase exercise

Validation of Up-the-Ramp Sampling with Cosmic Ray Rejection on IR Detectors

We examine cosmic ray rejection methodology on data collected from InSb and Si:As detectors. The application of an Up-the-Ramp sampling technique with cosmic ray identification and mitigation is the focus of this study. This technique is valuable for space-based observatories which are exposed to high-radiation environments. We validate the Up-the-Ramp approach on radiation-test data sets with InSb and Si:As detectors which were generated for SIRTF. The Up-the-Ramp sampling method studied in this paper is over 99.9% effective at removing cosmic rays and preserves the structure and photometric quality of the image to well within the measurement error.Comment: 30 pages, 13 figures. Accepted for publication in the PASP, 25 October 200

Intergenerational effects of cocaine on maternal aggressive behavior and brain oxytocin in rat dams: Research Report

Gestational cocaine treatment results in significantly increased maternal aggression towards an intruder by postpartum day six, while acute postpartum treatment dose dependently decreases maternal aggressive (MA) behavior. Both increased and decreased aggression in the cocaine-treated dams are correlated with either decreased or increased levels of oxytocin in the amygdala, respectively. The current study was an effort to determine whether the effect of gestational cocaine on maternal aggression is transient or would continue into the postpartum period; whether an intermittent cocaine treatment regimen, which incorporates gestational and postpartum intermittent cocaine treatment, would differ from chronic daily gestational treatment; and finally, whether next generation female offspring of cocaine-treated or control dams would have altered MA behavior and oxytocin system changes attributable to either prenatal drug exposure, rearing condition or both. We now report no increase in maternal aggression following chronic gestational treatment and significantly lower levels of aggression in intermittently treated dams on postpartum day eight, with no significant effects in either group on postpartum day 12. Young adult female offspring of the cocaine-treated and control dams, who reared their own natural litters and were tested on postpartum day eight for maternal aggression, had higher levels of maternal aggression towards an intruder attributable to both prenatal cocaine exposure and rearing condition. Higher aggression in cocaine-reared next generation dams was associated with lower levels of oxytocin in the amygdala. Intergenerational effects of cocaine were apparent with respect to aggression and oxytocin system changes