Association of Patient Out-of-Pocket Costs With Prescription Abandonment and Delay in Fills of Novel Oral Anticancer Agents

High out-of-pocket (OOP) costs may limit access to novel oral cancer medications. In a retrospective study, nearly one third of patients whose OOP costs were $100 to$500 and nearly half of patients whose OOP costs were more than $2,000 failed to pick up their new prescription for an oral cancer medication, compared to 10$10 at the time of purchase. Delays in picking up prescriptions were also more frequent among patients facing higher OOP costs

High Cost Sharing and Specialty Drug Initiation Under Medicare Part D: A Case Study in Patients With Newly Diagnosed Chronic Myeloid Leukemia

Medicare Part D beneficiaries with higher out-of-pocket costs are more likely to delay starting or not start a recommended specialty drug when newly diagnosed with leukemia. Policy changes are needed to ensure optimal access to specialty medications under Medicare Part D

Structure- and ligand-based virtual screening identifies new scaffolds for inhibitors of the oncoprotein MDM2

A major challenge in the field of ligand discovery is to identify chemically useful fragments that can be developed into inhibitors of specific protein-protein interactions. Low molecular weight fragments (with molecular weight less than 250 Da) are likely to bind weakly to a protein's surface. Here we use a new virtual screening procedure which uses a combination of similarity searching and docking to identify chemically tractable scaffolds that bind to the p53-interaction site of MDM2. The binding has been verified using capillary electrophoresis which has proven to be an excellent screening method for such small, weakly binding ligands

New Cytotoxic Oxygenated Sterols from the Marine Bryozoan Cryptosula pallasiana

Six new sterols (1-6), together with seven known sterols (7-13), were isolated from the CCl4 extract of the marine bryozoan Cryptosula pallasiana, four (3-6) of which have already been reported as synthetic sterols. This is the first time that these compounds (3-6) are reported as natural sterols. The structures of the new compounds were determined on the basis of the extensive spectroscopic analysis, including two-dimensional (2D) NMR and HR-ESI-MS data. Compounds 1-4, 7 and 10-13 were evaluated for their cytotoxicity against HL-60 human myeloid leukemia cell line, and all of the evaluated compounds exhibited moderate cytotoxicity to HL-60 cells with a range of IC50 values from 14.73 to 22.11 µg/mL except for compounds 12 and 13

Long-term clinical and cost-effectiveness of psychological intervention for family carers of people with dementia: a single-blind, randomised, controlled trial

Background Two-thirds of people with dementia live at home supported mainly by family carers. These carers frequently develop clinical depression or anxiety, which predicts care breakdown. We aimed to assess the clinical effectiveness (long-term reduction of depression and anxiety symptoms in family carers) and cost-effectiveness of a psychological intervention called START (STrAtegies for RelaTives). Methods We did a randomised, parallel-group trial with masked outcome assessments in three UK mental-health services and one neurological-outpatient dementia service. We included self-identified family carers of people with dementia who had been referred in the previous year and gave support at least once per week to the person with dementia. We randomly assigned these carers, via an online computer-generated randomisation system from an independent clinical trials unit, to either START, an 8-session, manual-based coping intervention delivered by supervised psychology graduates, or treatment as usual (TAU). The primary long-term outcomes were affective symptoms (Hospital Anxiety and Depression Scale total score [HADS-T]) 2 years after randomisation and cost-effectiveness (health and social care perspectives) over 24 months. Analysis was by intention to treat, excluding carers with data missing at both 12 and 24 months. This trial is registered ISCTRN70017938. Findings From November 4, 2009, to June 8, 2011, we recruited 260 carers. 173 carers were randomly assigned to START and 87 to TAU. Of these 260 participants, 209 (80%) were included in the clinical efficacy analysis (140 START, 69 TAU). At 24 months, compared with TAU the START group was significantly better for HADS-T (mean difference −2·58 points, 95% CI −4·26 to −0·90; p=0·003). The intervention is cost effective for both carers and patients (67% probability of cost-effectiveness at the £20 000 per QALY willingness-to-pay threshold, and 70% at the £30 000 threshold). Interpretation START is clinically effective, improving carer mood and anxiety levels for 2 years. Carers in the control TAU group were seven times more likely to have clinically significant depression than those receiving START. START is cost effective with respect to carer and patient outcomes, and National Institute for Health and Care Excellence (NICE) thresholds. The number of people with dementia is rapidly growing, and policy frameworks assume that their families will remain the frontline providers of (unpaid) support. This cost-neutral intervention, which substantially improves family-carers' mental health and quality of life, should therefore be widely available. Funding National Institute for Health Research Health Technology Assessment programme 08/14/06

A resiliency framework for an enterprise cloud

This paper presents a systematic approach to develop a resilient software system which can be developed as emerging services and analytics for resiliency. While using the resiliency as a good example for enterprise cloud security, all resilient characteristics should be blended together to produce greater impacts. A framework, Cloud Computing Adoption Framework (CCAF), is presented in details. CCAF has four major types of emerging services and each one has been explained in details with regard to the individual function and how each one can be integrated. CCAF is an architectural framework that blends software resilience, service components and guidelines together and provides real case studies to produce greater impacts to the organizations adopting Cloud Computing and security. CCAF provides business alignments and provides agility, efficiency and integration for business competitive edge. In order to validate user requirements and system designs, a large scale survey has been conducted with detailed analysis provided for each major question. We present our discussion and conclude that the use of CCAF framework can illustrate software resilience and security improvement for enterprise security. CCAF framework itself is validated as an emerging service for Enterprise Cloud Computing with analytics showing survey analysi

Location Advantages, Governance Quality, Stock Market Development and Firm Characteristics as Antecedents of African M&As

This study explores firm- and country-specific antecedents of African M&As. We use one of the largest datasets to-date consisting of 1,490 unique African firms (11,183 firm-year observations) from 1996 to 2012. Our results suggest that improvements in time-varying country-level factors, including location advantages (market size, human capital and efficiency opportunities), national governance quality, and stock market development are associated with an increase in the volume of M&A activity. Consistent with the resource-curse paradox, high resource endowments are not associated with increased levels of M&A. In support of the management inefficiency but contrary to the traditional firm size hypotheses, African targets are generally characterised by declining stock returns and accounting profitability but are more likely to be larger firms; suggesting the presence of information asymmetry concerns in their selection. Notwithstanding, we find evidence of heterogeneity across countries with inconsistent support for established target prediction hypotheses. A model which combines firm- and country- specific factors better explains observed variations in African M&A activity

The ConSurf-DB: pre-calculated evolutionary conservation profiles of protein structures

ConSurf-DB is a repository for evolutionary conservation analysis of the proteins of known structures in the Protein Data Bank (PDB). Sequence homologues of each of the PDB entries were collected and aligned using standard methods. The evolutionary conservation of each amino acid position in the alignment was calculated using the Rate4Site algorithm, implemented in the ConSurf web server. The algorithm takes into account the phylogenetic relations between the aligned proteins and the stochastic nature of the evolutionary process explicitly. Rate4Site assigns a conservation level for each position in the multiple sequence alignment using an empirical Bayesian inference. Visual inspection of the conservation patterns on the 3D structure often enables the identification of key residues that comprise the functionally important regions of the protein. The repository is updated with the latest PDB entries on a monthly basis and will be rebuilt annually. ConSurf-DB is available online at http://consurfdb.tau.ac.il

Antitumor Peptides from Marine Organisms

The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new antitumor agents in the field of the development of marine bioactive substances. In this review, the progress on studies of antitumor peptides from marine sources is provided. The biological properties and mechanisms of action of different marine peptides are described; information about their molecular diversity is also presented. Novel peptides that induce apoptosis signal pathway, affect the tubulin-microtubule equilibrium and inhibit angiogenesis are presented in association with their pharmacological properties. It is intended to provide useful information for further research in the fields of marine antitumor peptides