PurposeThe aim of this study was to quantify the potential cost savings to Medicare of shifting the site of treatment for worsening heart failure (HF) from inpatient to outpatient (OP) settings for a subset of worsening HF episodes among the Medicare fee-for-service (FFS) population.Materials and methodsA cross-sectional analysis of a random 5% sample of 2014 FFS Medicare beneficiaries was conducted. Incidence and cost of worsening HF episodes in both inpatient and OP settings were identified. These results were used to calculate cost savings associated with shifting a proportion of worsening HF episodes from the inpatient to OP settings.ResultsA total of 151,908 HF beneficiaries were identified. The estimated annual cost for the treatment of worsening HF across both inpatient and OP settings ranged from US$9.3 billion to US$17.0 billion or 2.4%–4.3% of total Medicare FFS spend. The cost saving associated with shifting worsening HF treatment from inpatient hospital setting to OP settings was US$667.5 million or 0.17% of total Medicare spend when 10% of HF admissions were targeted and 60% of targeted HF admissions were successfully shifted. The cost savings increased to US$2.098 billion or 0.53% of total Medicare spend when 20% of HF admissions were targeted and 90% of targeted HF admissions were successfully shifted.ConclusionTreatment options that can shift costly hospital admissions for worsening HF treatment to less expensive OP settings potentially lead to significant cost savings to Medicare. Pursuit of OP therapy options for treating worsening HF might be considered a viable alternative.

Cardiovascular events in Medicare fee-for-service beneficiaries with T2DM contribute substantially to Medicare cardiovascular events, resource utilization, and cost.

Introduction Drug-induced proarrhythmic potential is an important regulatory criterion in safety pharmacology. The application of in silico approaches to predict proarrhythmic potential of new compounds is under consideration as part of future guidelines. Current approaches simulate electrophysiology of a single human adult ventricular cardiomyocyte. However, drug-induced proarrhythmic potential can be different when cardiomyocytes are surrounded by non-muscle cells. Incorporating fibroblasts in models of myocardium is important particularly for predicting a drugs cardiac liability in the aging population – a growing population who take more medications and exhibit increased cardiac fibrosis. In this study, we used computational models to investigate the effects of fibroblast coupling on the electrophysiology and response to drugs of cardiomyocytes. Methods A computational model of cardiomyocyte electrophysiology and ion handling (O’Hara et al. 2011) is coupled to a passive model of fibroblast electrophysiology to test the effects of dofetilide block on the rapid delayed rectifier K+ channel. Results are compared to model results without fibroblast coupling to see how fibroblasts affect cardiomyocyte action potential duration at 90% repolarization (APD90) and propensity for early after depolarization (EAD). Results Simulation results show an increase in cardiomyocyte APD90 with increasing concentration of three drugs that affect cardiac function: dofetilide, vardenafil and nebivolol, when no fibroblasts are coupled to the cardiomyocyte. Coupling fibroblasts to cardiomyocytes markedly shortens APD90. Moreover, increasing the number of fibroblasts can augment the shortening effect. Discussion Coupling cardiomyocytes and fibroblasts are predicted to decrease proarrhythmic susceptibility under dofetilide, vardenafil and nebivolol block. However, this result is sensitive to parameters which define the electrophysiological function of the fibroblast. Fibroblast membrane capacitance and conductance (CFB and GFB) have less of an effect on APD90 than the fibroblast resting membrane potential (EFB). This study suggests that in both theoretical models and experimental tissue constructs that represent cardiac tissue, both cardiomyocytes and nonmuscle cells should be considered when testing cardiac pharmacological agents.

The team makes the following further research suggestions:  Using predetermined scenarios, evaluate organizations' definitions and interpretations of their roles across US government CWMD efforts  Review/analyze US agencies' roles with international partners  Evaluate US consequence management (CM) efforts 109 743, 758, and 774. "Export Control Modernization: Strategic Trade Authorization License Exception." Federal Register 9 December 2010: 76653-76666. Online.

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