A safety and toxicity assessment of the administration of multiple intracerebral injections of irinotecan or doxorubicin drug-eluting beads

OBJECTIVE Previous research in a rat glioma model has shown that the local intratumoral application of polymerbased drug-eluting beads (DEBs) loaded with doxorubicin or irinotecan suppress tumour growth and prolong survival. For translation into a clinical setting, the present experiment investigates in the healthy cat brain the local and systemic toxicity of a multiple injection shot technique. METHODS Three injection shots were placed, each at a 1 cm distance in the frontal lobe. The DEBs were suspended in an aqueous alginate excipient solution, which becomes subject to a sol-gel transition when injected into the Ca(2+)- rich brain tissue environment. Systemic and local side effects were monitored over a period of two weeks. Injection sites were histologically investigated. RESULTS Gelling of the alginate results in the permanent immobilisation of the microspheres at the implantation site. A distinct local cytotoxic effect of doxorubicin was found with intracerebral and intraventricular haemorrhages, and signs of brain tissue necrosis. In cats injected with irinotecan DEBs, such local adverse side effects did not occur. No signs of systemic toxicity were found with both chemotherapeutics. DISCUSSION We conclude that the multiple injection shot technique with irinotecan DEBs meets feasibility criteria and safety requirements for a clinical application (AU)

How to measure the outcomes of chronic disease management.

The fastest-growing methodology for disease management outcomes measurement is valid, transparent, easy to apply, and freely available in the public domain and this article. It measures the actual goal of disease management, which is to reduce the rate of adverse events associated with the disease(s) being managed. Changes in this rate can be translated into a return on investment using some explicit assumptions about comorbidities and episode costs. Outcomes measured in this way show that in the health plan community as a whole, disease management in the broadest sense is working, as measured by the relative stability in the rate of adverse medical events closely associated with common chronic disease during this decade of increasing prevalence of most of the common chronic conditions.

Assessing return on investment of defined-population disease management interventions.

BACKGROUND: Strategies to reduce health expenditures through the improvement of health and quality of care are in high demand. A group of experts formed a nonpartisan, independent work group, under the sponsorship of the National Managed Health Care Congress. Its goal was to establish a list of easy-to-understand, actionable, and usable recommendations to enable disease management program advocates to conduct basic-level evaluations. RECOMMENDATIONS: The work group made recommendations concerning identification of reference and intervention population, population definitions, quantitative methods and data quality, confounding and bias, and stakeholder agreements/contracting. CASE STUDY: A case study was created to quantitatively illustrate some of the major issues raised by the work group. Five typical errors were simulated by applying different rules to the intervention population than to the reference population: differential inclusion (high versus low risk), differential exclusion (high versus low risk) and differential claims run-out. Compared with the true impact, four of the five errors resulted in a bias toward "intervention effect," while one (differential inclusion of high-risk patients) was biased against the "intervention effect." The direction and magnitude of the bias in natural settings will not necessarily follow this pattern.

Quality and disease management.

Does having a comprehensive list of quality targets as part of the contract incentivize vendors to do the right thing? Not necessarily. However, if a vendor needs incentives to do the right thing in the quality department, one may have picked the wrong vendor and/or negotiated the wrong contract. Conversely, a vendor willing to be measured by the most objective measures possible is a vendor with enough confidence in its own outcomes to be considered an excellent choice as a partner.

Phosphorylcholine-based polymers and their use in the prevention of biofouling.

This article provides an overview of work carried out on the synthesis and non-fouling properties of phosphorylcholine (PC)-containing polymers. The concept of biomimicry is outlined and the major classes of synthetic PC-based materials described. Studies on the interaction of these materials with various proteins are collated and the mechanism for their protein-resistant nature is discussed. Similarly, cellular interactions are also reviewed, with ex-vivo and in-vivo clinical data provided to demonstrate the usefulness of these materials for improving the properties of medical devices.