Budget impact of adding ivabradine to standard of care in patients with chronic systolic heart failure in the United States

BACKGROUND: Heart failure (HF) costs $21 billion annually in direct health care costs, 80 OBJECTIVE: To estimate the budget impact of ivabradine from a U.S. commercial payer perspective. METHODS: A budget impact model estimated the per-member-per month (PMPM) impact of introducing ivabradine to existing formularies by comparing a reference scenario (SoC) and a new drug scenario (ivabradine + SoC) in hypothetical 1 million-member commercial and Medicare Advantage plans. In both scenarios, U.S. claims data were used for the reference cumulative annual rates of hospitalizations (HF, non-HF cardiovascular [CV], and non-CV), and hospitalization rates were adjusted using SHIFT data. The model controlled for mortality risk using SHIFT and U.S. life table data, and hospitalization costs were obtained from U.S. claims data: HF-related =$37,507; non-HF CV = $28,951; and non-CV =$17,904. The annualized wholesale acquisition cost of ivabradine was $4,500, with baseline use for this new drug at 2 RESULTS: Based on the approved U.S. indication, approximately 2,000 commercially insured patients from a 1 million-member commercial plan were eligible to receive ivabradine. Ivabradine resulted in a PMPM cost savings of$0.01 and $0.04 in years 1 and 3 of the core model, respectively. After including the acquisition price for ivabradine, the model showed a decrease in total costs in the commercial ($991,256 and $474,499, respectively) and Medicare populations ($13,849,262 and $4,280,291, respectively) in year 1. This decrease was driven by ivabradine’s reduction in hospitalization rates. For the core model, the estimated pharmacy-only PMPM in year 1 was$0.01 for the commercial population and $0.24 for the Medicare Advantage population. CONCLUSIONS: Adding ivabradine to SoC led to lower average annual treatment costs. The negative PMPM budget impact indicates that ivabradine is an affordable option for U.S. payers

Evaporation-induced hydrodynamics control plasmid transfer during surface-associated microbial growth.

Droplet evaporation is a general process in unsaturated environments that results in micro-scale hydrodynamic flows which in turn determine the spatial distributions of microbial cells across surfaces. These spatial distributions can have significant effects on the development and functioning of surface-associated microbial communities, with consequences for important processes such as the spread of plasmids. Here, we experimentally quantified how evaporation-induced hydrodynamic processes modulate the initial deposition patterns of microbial cells (via the coffee ring effect and Marangoni convection) and how these patterns control the spread of an antibiotic resistance-encoding plasmid during surface-associated growth. We found that plasmid spread is a function of the initial density of cells deposited along the droplet periphery, which is a manifestation of the coffee ring effect. Using an individual-based model, we systematically linked how the different initial cell deposition patterns caused by the relative strengths of the coffee ring effect and Marangoni convection determine the extent of plasmid transfer during surface-associated growth. Our study demonstrates that evaporation-induced hydrodynamic processes that are common in nature can alter crucial ecological properties of surface-associated microbial communities and control the proliferation of plasmids, with consequences on the spread of antibiotic resistance and other plasmid-encoded traits

Antimatter and Matter Production in Heavy Ion Collisions at CERN (The NEWMASS Experiment NA52)

Besides the dedicated search for strangelets NA52 measures light (anti)particle and (anti)nuclei production over a wide range of rapidity. Compared to previous runs the statistics has been increased in the 1998 run by more than one order of magnitude for negatively charged objects at different spectrometer rigidities. Together with previous data taking at a rigidity of -20 GeV/c we obtained 10^6 antiprotons 10^3 antideuterons and two antihelium3 without centrality requirements. We measured nuclei and antinuclei (p,d,antiprotons, antideuterons) near midrapidity covering an impact parameter range of b=2-12 fm. Our results strongly indicate that nuclei and antinuclei are mainly produced via the coalescence mechanism. However the centrality dependence of the antibaryon to baryon ratios show that antibaryons are diminished due to annihilation and breakup reactions in the hadron dense environment. The volume of the particle source extracted from coalescence models agrees with results from pion interferometry for an expanding source. The chemical and thermal freeze-out of nuclei and antinuclei appear to coincide with each other and with the thermal freeze-out of hadrons.Comment: 12 pages, 8 figures, to appear in the proceedings of the conference on 'Fundamental Issues in Elementary Matter' Bad Honnef, Germany, Sept. 25-29, 200

Quantum dot labeling of mesenchymal stem cells

<p>Abstract</p> <p>Background</p> <p>Mesenchymal stem cells (MSCs) are multipotent cells with the potential to differentiate into bone, cartilage, fat and muscle cells and are being investigated for their utility in cell-based transplantation therapy. Yet, adequate methods to track transplanted MSCs <it>in vivo </it>are limited, precluding functional studies. Quantum Dots (QDs) offer an alternative to organic dyes and fluorescent proteins to label and track cells <it>in vitro </it>and <it>in vivo</it>. These nanoparticles are resistant to chemical and metabolic degradation, demonstrating long term photostability. Here, we investigate the cytotoxic effects of <it>in vitro </it>QD labeling on MSC proliferation and differentiation and use as a cell label in a cardiomyocyte co-culture.</p> <p>Results</p> <p>A dose-response to QDs in rat bone marrow MSCs was assessed in Control (no-QDs), Low concentration (LC, 5 nmol/L) and High concentration (HC, 20 nmol/L) groups. QD yield and retention, MSC survival, proinflammatory cytokines, proliferation and DNA damage were evaluated in MSCs, 24 -120 hrs post QD labeling. In addition, functional integration of QD labeled MSCs in an <it>in vitro </it>cardiomyocyte co-culture was assessed. A dose-dependent effect was measured with increased yield in HC vs. LC labeled MSCs (93 ± 3% vs. 50% ± 15%, p < 0.05), with a larger number of QD aggregates per cell in HC vs. LC MSCs at each time point (p < 0.05). At 24 hrs >90% of QD labeled cells were viable in all groups, however, at 120 hrs increased apoptosis was measured in HC vs. Control MSCs (7.2% ± 2.7% vs. 0.5% ± 0.4%, p < 0.05). MCP-1 and IL-6 levels doubled in HC MSCs when measured 24 hrs after QD labeling. No change in MSC proliferation or DNA damage was observed in QD labeled MSCs at 24, 72 and 120 hrs post labeling. Finally, in a cardiomyocyte co-culture QD labeled MSCs were easy to locate and formed functional cell-to-cell couplings, assessed by dye diffusion.</p> <p>Conclusion</p> <p>Fluorescent QDs label MSC effectively in an <it>in vitro </it>co-culture model. QDs are easy to use, show a high yield and survival rate with minimal cytotoxic effects. Dose-dependent effects suggest limiting MSC QD exposure.</p

role of limbic system in the control of hamster growth

Rostral septal lesions accelerate somatic growth in adult hamsters. This study tested the hypothesis that this effect results from damage to fibers of passage by observing the effects of transections of septohippocampal and septohypothalamic connections on growth. We attempted to identify these fibers further by (a) measuring spectrofluorometrically changes in the monoamine concentrations in hippocampus, cerebral cortex, corpus striatum, and diencephalon, (b) staining the degenerating axons after septal lesions and the two cuts, and (c) examining the correspondence between such damage and the acceleration of growth. Both knife cuts accelerated somatic growth and were associated (as well as septal lesions) with significant depletions of serotonin (-27 to -57%) and norepinephrine (-27 to -60%) in the hippocampus, with less consistent depletions of these monoamines in the cerebral cortex, and with no changes in regional dopamine content. All three procedures were associated with degeneration in the hippocampal formation and its fiber systems. Thus, fibers interconnecting hippocampus and brainstem, and passing through septum, exert tonic suppression over somatic growth in adult hamsters.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23616/1/0000579.pd

Stability of strangelet at finite temperature

Using the quark mass density- and temperature dependent model, we have studied the thermodynamical properties and the stability of strangelet at finite temperature. The temperature, charge and strangeness dependences on the stability of strangelet are investigated. We find that the stable strangelets are only occured in the high strangeness and high negative charge region.Comment: 12 pages, 14 figure

Review of Speculative "Disaster Scenarios" at RHIC

We discuss speculative disaster scenarios inspired by hypothetical new fundamental processes that might occur in high energy relativistic heavy ion collisions. We estimate the parameters relevant to black hole production; we find that they are absurdly small. We show that other accelerator and (especially) cosmic ray environments have already provided far more auspicious opportunities for transition to a new vacuum state, so that existing observations provide stringent bounds. We discuss in most detail the possibility of producing a dangerous strangelet. We argue that four separate requirements are necessary for this to occur: existence of large stable strangelets, metastability of intermediate size strangelets, negative charge for strangelets along the stability line, and production of intermediate size strangelets in the heavy ion environment. We discuss both theoretical and experimental reasons why each of these appears unlikely; in particular, we know of no plausible suggestion for why the third or especially the fourth might be true. Given minimal physical assumptions the continued existence of the Moon, in the form we know it, despite billions of years of cosmic ray exposure, provides powerful empirical evidence against the possibility of dangerous strangelet production.Comment: 28 pages, REVTeX; minor revisions for publication (Reviews of Modern Physics, ca. Oct. 2000); email to [email protected]

Multibaryons in the collective coordinate approach to the SU(3) Skyrme model

We obtain the rotational spectrum of strange multibaryon states by performing the SU(3) collective coordinate quantization of the static multi-Skyrmions. These background configurations are given in terms of rational maps, which are very good approximations and share the same symmetries as the exact solutions. Thus, the allowed quantum numbers in the spectra and the structure of the collective Hamiltonians we obtain are also valid in the exact case. We find that the predicted spectra are in overall agreement with those corresponding to the alternative bound state soliton model.Comment: 16 pages, 1 figur

Cold Strangelets Formation with Finite Size Effects in High Energy Heavy-Ion Collisions

We have studied the phase diagram and evolution of a strangelet in equilibrium with a finite hadronic gas. Significant finite size modifications of the phase diagram are found and their parameter dependences are studied. With the inclusion of finite size effects we have also been able to obtain the detailed properties of the cold strangelet emerging in the final stage of the isentropic expansion of a finite strange fireball in high energy heavy-ion collisions.Comment: 19 pages(RevTex), 11 Postscript figures; To appear in Phys. Rev.

Financial impact of ivabradine on reducing heart failure penalties under the Hospital Readmission Reduction Program

Objective: The introduction of the Hospital Readmission Reduction Program (HRRP) has led to renewed interest in developing strategies to reduce 30 day readmissions among patients with heart failure (HF). In this study, a model was developed to investigate whether the addition of ivabradine to a standard-of-care (SoC) treatment regimen for patients with HF would reduce HRRP penalties incurred by a hypothetical hospital with excess 30 day readmissions. Research design: A model using a Monte Carlo simulation framework was developed. Model inputs included national hospital characteristics, hospital-specific characteristics, and the ivabradine treatment effect as quantified by a post hoc analysis of the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT). Results: The model computed an 83% reduction in HF readmission penalty payments in a hypothetical hospital with a readmission rate of 22.95% (excess readmission ratio = 1.056 over the national average readmission rate of 21.73%), translating into net savings of $44,016. A sensitivity analysis indicated that the readmission penalty is affected by the specific characteristics of the hospital, including the readmission rate, size of the ivabradine-eligible population, and ivabradine utilization. Conclusions: The results of this study indicate that the addition of ivabradine to an SoC treatment regimen for patients with HF may lead to a reduction in the penalties incurred by hospitals under the HRRP. This highlights the role ivabradine can play as part of a wider effort to optimize the care of patients with HF