Phase I study of pegylated liposomal doxorubicin and the multidrug-resistance modulator, valspodar

Valspodar, a P-glycoprotein modulator, affects pharmacokinetics of doxorubicin when administered in combination, resulting in doxorubicin dose reduction. In animal models, valspodar has minimal interaction with pegylated liposomal doxorubicin (PEG-LD). To determine any pharmacokinetic interaction in humans, we designed a study to determine maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics of total doxorubicin, in PEG-LD and valspodar combination therapy in patients with advanced malignancies. Patients received PEG-LD 20–25 mg m−2 intravenously over 1 h for cycle one. In subsequent 2-week cycles, valspodar was administered as 72 h continuous intravenous infusion with PEG-LD beginning at 8 mg m−2 and escalated in an accelerated titration design to 25 mg m−2. Pharmacokinetic data were collected with and without valspodar. A total of 14 patients completed at least two cycles of therapy. No DLTs were observed in six patients treated at the highest level of PEG-LD 25 mg m−2. The most common toxicities were fatigue, nausea, vomiting, mucositis, palmar plantar erythrodysesthesia, diarrhoea, and ataxia. Partial responses were observed in patients with breast and ovarian carcinoma. The mean (range) total doxorubicin clearance decreased from 27 (10–73) ml h−1 m−2 in cycle 1 to 18 (3–37) ml h−1 m−2 with the addition of valspodar in cycle 2 (P=0.009). Treatment with PEG-LD 25 mg m−2 in combination with valspodar results in a moderate prolongation of total doxorubicin clearance and half-life but did not increase the toxicity of this agent

Development of risk maps to minimize uranium exposures in the Navajo Churchrock mining district

© 2009 deLemos et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The Linear Programming Relaxation Permutation Symmetry Group of an Orthogonal Array Defining Integer Linear Program

There is always a natural embedding of $S_{s}\wr S_{k}$ into the linear programming (LP) relaxation permutation symmetry group of an orthogonal array integer linear programming (ILP) formulation with equality constraints. The point of this paper is to prove that in the $2$ -level, strength- $1$ case the LP relaxation permutation symmetry group of this formulation is isomorphic to $S_{2}\wr S_{k}$ for all $k$ , and in the $2$ -level, strength- $2$ case it is isomorphic to $S_{2}^{k}\rtimes S_{k+1}$ for $k\geqslant 4$ . The strength- $2$ result reveals previously unknown permutation symmetries that cannot be captured by the natural embedding of $S_{2}\wr S_{k}$ . We also conjecture a complete characterization of the LP relaxation permutation symmetry group of the ILP formulation

Viscosupplementation for Osteoarthritis of the Knee: A Key Opinion Leader Panel Discussion

With a sharp rise in the prevalence of osteoarthritis of the knee (OAK) in a younger population, new management strategies are needed to preserve mobility, improve patients\u27 quality of life, and reduce the effects of potential disease-related comorbidities. Viscosupplementation with the use of hyaluronic acid (HA) injection is a treatment option for OAK that can provide lubrication and elastic shock absorption, leading to potential pain relief, improved function, and reduced stiffness. A key opinion leader (KOL) panel discussion was held December 3, 2016, with the objective of sharing opinions, ideas, information, and trends regarding OAK and the potential treatment and management offered by viscosupplementation. The panel concluded that viscosupplementation with HA injections presents a viable, cost-effective, and safe alternative for the treatment of OAK.DISCLOSURES: This panel discussion and report was facilitated by Magellan Rx Manage-ment and funded by Sanofi. Bert and Ruane report fees from Sanofi outside of this project. Sgaglione reports royalty payments from Zimmer Biomet and Wolters Kluwer. Dasa has received fees from Bioventus and Myoscience. All the authors received an honorarium for work on this project. Lopes is employed by Magellan Rx Management

Reading Behavior and Compliance Among Ecuadorian University Students: A National Study

Un estudio sobre el comportamiento de lectura y el cumplimiento de lectura entre 2.600 estudiantes en cinco universidades en Ecuador encontró que su comportamiento de lectura y cumplimiento de lectura fueron mejores que entre los estudiantes en los Estados Unidos, a pesar de los desafíos que existen en la educación superior ecuatoriana. Se incluyen sugerencias para futuras investigaciones, en particular con respecto a mejorar las habilidades de gestión del tiempo de los estudiantes como una forma de mejorar su cumplimiento de lectura. © El autor (es) 2019.A study into reading behavior and reading compliance among 2,600 students in five universities in Ecuador found that their reading behavior and reading compliance were better than among students in the United States, despite the challenges that exist in Ecuadorian higher education. Suggestions for future research, in particular with regard to improving students’ time management skills as a way to enhance their reading compliance, are included. © The Author(s) 2019