Costs of care for persons with opioid dependence in commercial integrated health systems

BACKGROUND: When used in general medical practices, buprenorphine is an effective treatment for opioid dependence, yet little is known about how use of buprenorphine affects the utilization and cost of health care in commercial health systems. METHODS: The objective of this retrospective cohort study was to examine how buprenorphine affects patterns of medical care, addiction medicine services, and costs from the health system perspective. Individuals with two or more opioid-dependence diagnoses per year, in two large health systems (System A: n = 1836; System B: n = 4204) over the time span 2007–2008 were included. Propensity scores were used to help adjust for group differences. RESULTS: Patients receiving buprenorphine plus addiction counseling had significantly lower total health care costs than patients with little or no addiction treatment (mean health care costs with buprenorphine treatment = $13,578; vs. mean health care costs with no addiction treatment =$31,055; p < .0001), while those receiving buprenorphine plus addiction counseling and those with addiction counseling only did not differ significantly in total health care costs (mean costs with counseling only: $17,017; p = .5897). In comparison to patients receiving buprenorphine plus counseling, those with little or no addiction treatment had significantly greater use of primary care (p < .001), other medical visits (p = .001), and emergency services (p = .020). Patients with counseling only (compared to patients with buprenorphine plus counseling) used less inpatient detoxification (p < .001), and had significantly more PC visits (p = .001), other medical visits (p = .005), and mental health visits (p = .002). CONCLUSIONS: Buprenorphine is a viable alternative to other treatment approaches for opioid dependence in commercial integrated health systems, with total costs of health care similar to abstinence-based counseling. Patients with buprenorphine plus counseling had reduced use of general medical services compared to the alternatives

Propranolol Sensitizes Vascular Sarcoma Cells to Doxorubicin by Altering Lysosomal Drug Sequestration and Drug Efflux

Angiosarcoma is a rare cancer of blood vessel–forming cells with a high patient mortality and few treatment options. Although chemotherapy often produces initial clinical responses, outcomes remain poor, largely due to the development of drug resistance. We previously identified a subset of doxorubicin-resistant cells in human angiosarcoma and canine hemangiosarcoma cell lines that exhibit high lysosomal accumulation of doxorubicin. Hydrophobic, weak base chemotherapeutics, like doxorubicin, are known to sequester within lysosomes, promoting resistance by limiting drug accessibility to cellular targets. Drug synergy between the beta adrenergic receptor (β-AR) antagonist, propranolol, and multiple chemotherapeutics has been documented in vitro, and clinical data have corroborated the increased therapeutic potential of propranolol with chemotherapy in angiosarcoma patients. Because propranolol is also a weak base and accumulates in lysosomes, we sought to determine whether propranolol enhanced doxorubicin cytotoxicity via antagonism of β-ARs or by preventing the lysosomal accumulation of doxorubicin. β-AR-like immunoreactivities were confirmed in primary tumor tissues and cell lines; receptor function was verified by monitoring downstream signaling pathways of β-ARs in response to receptor agonists and antagonists. Mechanistically, propranolol increased cytoplasmic doxorubicin concentrations in sarcoma cells by decreasing the lysosomal accumulation and cellular efflux of this chemotherapeutic agent. Equivalent concentrations of the receptor-active S-(−) and -inactive R-(+) enantiomers of propranolol produced similar effects, supporting a β-AR-independent mechanism. Long-term exposure of hemangiosarcoma cells to propranolol expanded both lysosomal size and number, yet cells remained sensitive to doxorubicin in the presence of propranolol. In contrast, removal of propranolol increased cellular resistance to doxorubicin, underscoring lysosomal doxorubicin sequestration as a key mechanism of resistance. Our results support the repurposing of the R-(+) enantiomer of propranolol with weak base chemotherapeutics to increase cytotoxicity and reduce the development of drug-resistant cell populations without the cardiovascular and other side effects associated with antagonism of β-ARs

An Analysis of AERONET Aerosol Absorption Properties and Classifications Representative of Aerosol Source Regions

Partitioning of mineral dust, pollution, smoke, and mixtures using remote sensing techniques can help improve accuracy of satellite retrievals and assessments of the aerosol radiative impact on climate. Spectral aerosol optical depth (tau) and single scattering albedo (omega (sub 0) ) from Aerosol Robotic Network (AERONET) measurements are used to form absorption [i.e., omega (sub 0) and absorption Angstrom exponent (alpha(sub abs))] and size [i.e., extinction Angstrom exponent (alpha(sub ext)) and fine mode fraction of tau] relationships to infer dominant aerosol types. Using the long-term AERONET data set (1999-2010), 19 sites are grouped by aerosol type based on known source regions to: (1) determine the average omega (sub 0) and alpha(sub abs) at each site (expanding upon previous work); (2) perform a sensitivity study on alpha(sub abs) by varying the spectral omega (sub 0); and (3) test the ability of each absorption and size relationship to distinguish aerosol types. The spectral omega (sub 0) averages indicate slightly more aerosol absorption (i.e., a 0.0 < delta omega (sub 0) <= 0.02 decrease) than in previous work and optical mixtures of pollution and smoke with dust show stronger absorption than dust alone. Frequency distributions of alpha(sub abs) show significant overlap among aerosol type categories and at least 10% of the alpha(sub abs) retrievals in each category are below 1.0. Perturbing the spectral omega (sub 0) by +/- 0.03 induces significant alpha(sub abs) changes from the unperturbed value by at least approx. +/- 0.6 for Dust, approx. +/-0.2 for Mixed, and approx. +/-0.1 for Urban/Industrial and Biomass Burning. The omega (sub 0)440nm and alpha(sub ext) 440-870nm relationship shows the best separation among aerosol type clusters, providing a simple technique for determining aerosol type from surface- and future space-based instrumentation

Drawing Trees with Perfect Angular Resolution and Polynomial Area

We study methods for drawing trees with perfect angular resolution, i.e., with angles at each node v equal to 2{\pi}/d(v). We show: 1. Any unordered tree has a crossing-free straight-line drawing with perfect angular resolution and polynomial area. 2. There are ordered trees that require exponential area for any crossing-free straight-line drawing having perfect angular resolution. 3. Any ordered tree has a crossing-free Lombardi-style drawing (where each edge is represented by a circular arc) with perfect angular resolution and polynomial area. Thus, our results explore what is achievable with straight-line drawings and what more is achievable with Lombardi-style drawings, with respect to drawings of trees with perfect angular resolution.Comment: 30 pages, 17 figure

Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages

The assessment of macrophage response to nanoparticles is a central component in the evaluation of new nanoparticle designs for future in vivo application. This work investigates which feature, nanoparticle size or charge, is more predictive of non-specific uptake of nanoparticles by macrophages. This was investigated by synthesizing a library of polymer-coated iron oxide micelles, spanning a range of 30–100 nm in diameter and −23 mV to +9 mV, and measuring internalization into macrophages in vitro. Nanoparticle size and charge both contributed towards non-specific uptake, but within the ranges investigated, size appears to be a more dominant predictor of uptake. Based on these results, a protease-responsive nanoparticle was synthesized, displaying a matrix metalloproteinase-9 (MMP-9)-cleavable polymeric corona. These nanoparticles are able to respond to MMP-9 activity through the shedding of 10–20 nm of hydrodynamic diameter. This MMP-9-triggered decrease in nanoparticle size also led to up to a six-fold decrease in nanoparticle internalization by macrophages and is observable by T2-weighted magnetic resonance imaging. These findings guide the design of imaging or therapeutic nanoparticles for in vivo targeting of macrophage activity in pathologic states