Stepped-care approach to treating MS: a managed care treatment algorithm.

OBJECTIVE: To introduce a model treatment algorithm for use in the managed care setting as a strategy to provide ongoing disease management and long-term care for patients with multiple sclerosis (MS), with the goal of delaying disease progression and the associated disability and cognitive dysfunction. SUMMARY: MS is a chronic inflammatory disorder of the central nervous system that is associated with progressive disability and cognitive dysfunction. Currently, management of MS involves planning an effective long-term treatment strategy that can delay the progression of the disease. This article reviews a typical stepped-care approach to treating MS that is based on the concept of a platform drug, which is an agent that provides baseline immunomodulatory action throughout the course of the disease. Considerations for selecting a platform therapy include the effect on the full spectrum of MS (disability, relapses, lesion load, and atrophy as well as patient compliance and the potential impact of neutralizing antibodies [NAbs]). Currently, 4 first-line therapies are approved for relapsing MS: the 3 interferon beta (IFNbeta) products and glatiramer acetate. Of these, the IFNbetas are generally recommended as platform therapy because all have shown significant effects on relapses, magnetic resonance imaging parameters of the disease, and because intramuscular (i.m.) IFNbeta-1a (Avonex) and subcutaneous (s.c.) IFNbeta-1a (Rebif) have been shown to slow the progression of sustained disability. Patients being treated with IFNbetas can develop NAbs to the drug, which can lead to a loss of efficacy and subsequent occurrence of breakthrough disease. The 3 different formulations of IFNbeta are associated with a varying incidence of NAbs (i.m. IFNbeta-1a, 5%; s.c. IFNbeta-1a, 24%; IFNbeta-1b [Betaseron], 45%). Antibodies also form against glatiramer acetate, although their clinical significance needs to be elucidated. As the disease progresses or has periods of aggressive activity, the stepped-care approach is to add other agents onto the platform therapy to improve control of the disease. CONCLUSION: Stepped care, as outlined in this model treatment algorithm for the managed care setting, is an effective method to achieve the fundamental goal of MS treatment, that is, to delay disease progression and the associated disability and cognitive impairment.

Tumor vascularity in the prognostic assessment of primary cutaneous melanoma.

PURPOSE: The vascular supply of the primary tumor is recognized to play an important role in the progression of a number of solid tumors. However, the role of tumor vascularity in the prognostic assessment of melanoma remains unclear. The purpose of this study was to determine the prognostic impact of patterns of vascularity on the outcome associated with cutaneous melanoma. PATIENTS AND METHODS: Tumor vascularity was documented prospectively using routine histopathologic analysis of 417 primary cutaneous melanomas from the University of California at San Francisco Melanoma Center database. Four patterns of tumor vascularity were recorded: absent, sparse, moderate, and prominent. RESULTS: Increasing tumor vascularity significantly increased the risk of relapse and death associated with melanoma, corresponding to reduced relapse-free and overall survival. By multivariate analysis, tumor vascularity was the most important determinant of overall survival, surpassing tumor thickness. Increasing tumor vascularity was associated with increased incidence of ulceration in the primary tumor. CONCLUSION: Tumor vascularity is an important prognostic factor in melanoma, rivaling tumor thickness. Increasing tumor vascularity is highly correlated with ulceration, possibly helping to explain the biologic basis of this known prognostic factor.

Spatial analysis of West Nile virus: rapid risk assessment of an introduced vector-borne zoonosis.

The distribution of human risk for West Nile virus was determined by spatial analysis of the initial case distribution for the New York City area in 1999 using remote sensing and geographic information system technologies. Cluster analysis revealed the presence of a statistically significant grouping of cases, which also indicates the area of probable virus introduction. Within the cluster, habitat suitability for potentially infective adult mosquitoes was measured by the amount of vegetation cover using satellite imagery. Logistic regression analysis revealed satellite-derived vegetation abundance to be significantly and positively associated with the presence of human cases. The logistic model was used to estimate the spatial distribution of human risk for West Nile virus throughout New York City. Accuracy of the resulting risk map was cross-validated using virus-positive mosquito sample sites. These new epidemiological methods aid in rapid entry point identification and spatial prediction of human risk of infection for introduced vector-borne pathogens.