Assessing efficiency of public health and medical care provision in OECD countries after a decade of reform

The objective of this study was to examine the change in efficiency of health care systems of 34 OECD countries between 2000 and 2012, a period marked by significant health reform in most OECD countries. This paper uses a novel Dynamic Network Data Envelopment Analysis (DNDEA) model to analyze the efficiency of the public health system and the medical care system of these OECD countries independently along with assessing the efficiency of their overall health system. This helps understand the relative priorities for improving the overall health system. The data for this study was obtained from the OECD Health Facts database. The study findings suggest that countries which improved their public health system were more likely to show overall improvement in efficiency

Racial and Ethnic Differences in Receipt of Immediate Breast Reconstruction Surgery: Do Hospital Characteristics Matter?

Immediate Breast Reconstruction Surgery (IBRS) is associated with better quality of life among women who undergo a mastectomy. Despite insurance coverage for IBRS, utilization of IBRS remains low. Data from publicly available sources for 2010-2012 are used to examine the association between hospital characteristics receipt of IBRS by patients. Minority-serving status, low bed size, for-profit ownership, non-teaching status, high competition, low density of plastic surgeons in the market and non-metropolitan location are associated with lower likelihood of receipt of IBRS. Racial and ethnic minorities are less likely to receive IBRS. A mixed effects logistic regression model with interactions between Black/Hispanic race/ethnicity and hospital variables is estimated to examine whether certain hospital characteristics are associated with disparately low receipt of IBRS for racial and ethnic minorities. Minority-serving hospitals located in markets with a higher density of plastic surgeons and higher competition characteristics are associated with disparately low receipt of IBRS for racial and ethnic minorities. In order to reduce racial/ ethnic differences in receipt of IBRS, it is important to understand which factors contribute the most to these differences. Fairlie decomposition is used to examine the contribution of multi-level factors to racial and ethnic differences in receipt of IBRS. Racial and ethnic differences in being Medicaid insured, residing in low-income neighborhoods and receiving care at minority-serving hospitals are the three largest contributors to racial and ethnic differences in receipt of IBRS. The results from this study have significant implications for access to IBRS among racial and ethnic minority patients

Orbit Fitting and Uncertainties for Kuiper Belt Objects

We present a procedure for determination of positions and orbital elements, and associated uncertainties, of outer Solar System planets. The orbit-fitting procedure is greatly streamlined compared to traditional methods because acceleration can be treated as a perturbation to the inertial motion of the body. These techniques are immediately applicable to Kuiper Belt Objects, for which recovery observations are costly. Our methods produce positional estimates and uncertainty ellipses even in the face of the substantial degeneracies of short-arc orbit fits; the sole a priori assumption is that the orbit should be bound or nearly so. We use these orbit-fitting techniques to derive a strategy for determining Kuiper Belt orbits with a minimal number of observations.Comment: 21 pages AASTeX5, 3 figures, accepted to AJ. Associated software available at http://www.astro.lsa.umich.edu/users/gary

Vehicle-to-Grid Integration for Enhancement of Grid: A Distributed Resource Allocation Approach

In the future grids, to reduce greenhouse gas emissions Electric Vehicles (EVs) seems to be an important means of transportation. One of the major disadvantages of the future grid is the demand-supply mismatch which can be mitigated by incorporating the EVs into the grid. The paper introduces the concept of the Distributed Resource Allocation (DRA) approach for incorporating a large number of Plug-in EV (PEVs) with the power grid utilizing the concept of achieving output consensus. The charging/discharging time of all the participating PEVs are separated with respect to time slots and are considered as strategies. The major aim of the paper is to obtain a favorable charging strategy for each grid-connected PEVs in such a way that it satisfies both grid objectives in terms of load profile smoothening and minimizing of load shifting as well as economic and social interests of vehicle owners i.e. a fair share of the rate of charging for all connected PEVs. The three-fold contribution of the paper in smoothening of load profile, load shifting minimization, and fair charging rate is validated using a representative case study. The results confirm improvement in load profile and also highlight a fair deal in the charging rate for each PEV

Are we over-treating with checkpoint inhibitors?

Anti-PD-1 antibodies offer potentially life-saving treatment for some cancer patients, but their chronic administration generates high and ever-increasing costs. Despite licensing for long-term use, optimal treatment duration is unknown. We challenge the need for long-term treatment duration, using evidence from melanoma research, both published and in process

Development of Targeted Alpha Particle Therapy for Solid Tumors

Abstract: Targeted alpha-particle therapy (TAT) aims to selectively deliver radionuclides emitting α-particles (cytotoxic payload) to tumors by chelation to monoclonal antibodies, peptides or small molecules that recognize tumor-associated antigens or cell-surface receptors. Because of the high linear energy transfer (LET) and short range of alpha (α) particles in tissue, cancer cells can be significantly damaged while causing minimal toxicity to surrounding healthy cells. Recent clinical studies have demonstrated the remarkable efficacy of TAT in the treatment of metastatic, castration-resistant prostate cancer. In this comprehensive review, we discuss the current consensus regarding the properties of the α-particle-emitting radionuclides that are potentially relevant for use in the clinic; the TAT-mediated mechanisms responsible for cell death; the different classes of targeting moieties and radiometal chelators available for TAT development; current approaches to calculating radiation dosimetry for TATs; and lead optimization via medicinal chemistry to improve the TAT radiopharmaceutical properties. We have also summarized the use of TATs in pre-clinical and clinical studies to dat

Monitoring melanoma recurrence with circulating tumor DNA: a proof of concept from three case studies

Background: A significant number of melanoma patients experience recurrence to distant sites, despite having had surgical treatment of the primary lesion, with curative intent. Monitoring of patients for early evidence of disease recurrence would significantly improve management of the disease, allowing timely therapeutic intervention. Circulating tumor DNA (ctDNA) is becoming a well-recognized biomarker for monitoring malignancies and has, in a few studies, been shown to signify disease recurrence earlier than conventional methods. Methods: We performed a retrospective analysis of plasma ctDNA using droplet digital PCR (ddPCR) in 30 primary melanoma patients with tumors harboring BRAF, NRAS or TERT promoter mutations. Mutant specific ctDNA, measured during clinical disease course, was compared with disease status in patients with confirmed disease recurrence (n = 3) and in those with no evidence of disease recurrence (n = 27). Results: Mutant specific ctDNA was detected in all three patients with disease recurrence at the time of clinically confirmed progression. In one case, plasma ctDNA detection preceded clinical identification of recurrence by an interval of 4 months. CtDNA was not detected in patients who were asymptomatic and had no radiological evidence of recurrence. Conclusions: This study demonstrates promising results for the use of ctDNA as an informative monitoring tool for melanoma patients having undergone tumor resection of an early stage primary tumor. The clinical utility of ctDNA for monitoring disease recurrence warrants investigation in prospective studies as it may improve patient outcome

Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study.

BACKGROUND: Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial in melanoma. METHODS: Eligible patients had advanced melanoma that progressed after ICI and targeted therapy, where appropriate. Melanoma lesions were resected (resected tumor diameter ≥1.5 cm) and shipped to a central good manufacturing practice facility for 22-day lifileucel manufacturing. Patients received a non-myeloablative lymphodepletion regimen, a single lifileucel infusion, and up to six doses of high-dose interleukin-2. The primary endpoint was IRC-assessed ORR (Response Evaluation Criteria in Solid Tumors V.1.1). RESULTS: The Full Analysis Set consisted of 153 patients treated with lifileucel, including longer-term follow-up on the 66 patients previously reported. Patients had received a median of 3.0 lines of prior therapy (81.7% received both anti-programmed cell death protein 1 and anti-cytotoxic lymphocyte-associated protein 4) and had high disease burden at baseline (median target lesion sum of diameters (SOD): 97.8 mm; lactate dehydrogenase (LDH) >upper limit of normal: 54.2%). ORR was 31.4% (95% CI: 24.1% to 39.4%), with 8 complete responses and 40 partial responses. Median duration of response was not reached at a median study follow-up of 27.6 months, with 41.7% of the responses maintained for ≥18 months. Median overall survival and progression-free survival were 13.9 and 4.1 months, respectively. Multivariable analyses adjusted for Eastern Cooperative Oncology Group performance status demonstrated that elevated LDH and target lesion SOD >median were independently correlated with ORR (p=0.008); patients with normal LDH and SOD <median had greater likelihood of response than those with either (OR=2.08) or both (OR=4.42) risk factors. The most common grade 3/4 treatment-emergent adverse events (≥30%) were thrombocytopenia (76.9%), anemia (50.0%), and febrile neutropenia (41.7%). CONCLUSIONS: Investigational lifileucel demonstrated clinically meaningful activity in heavily pretreated patients with advanced melanoma and high tumor burden. Durable responses and a favorable safety profile support the potential benefit of one-time lifileucel TIL cell therapy in patients with limited treatment options in ICI-refractory disease